Feature

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

A version of this article first appeared on Medscape.com.

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

A version of this article first appeared on Medscape.com.

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

A version of this article first appeared on Medscape.com.

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

A version of this article first appeared on WebMD.com.

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

A version of this article first appeared on WebMD.com.

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

A version of this article first appeared on WebMD.com.

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

A version of this article first appeared on Medscape.com.

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

A version of this article first appeared on Medscape.com.

Fourteen mental health organizations have formed a coalition to press federal and state officials to tackle the ongoing and growing mental health crisis that is accompanying the COVID-19 pandemic.

The coalition is offering a road map, A Unified Vision for Transforming Mental Health and Substance Abuse Care, which spells out “immediate and long-term changes that will lead to a mental health care system capable of saving our nation,” they said in a statement.

The group includes CEOs from the American Psychiatric Association, the American Psychological Association, the Massachusetts Association for Mental Health, Meadows Mental Health Policy Institute, Mental Health America, the National Association for Behavioral Healthcare, the National Alliance on Mental Illness, the National Council for Behavioral Health, One Mind, Peg’s Foundation, the Steinberg Institute, The Kennedy Forum, the Treatment Advocacy Center, and the Well Being Trust.

They have been meeting in weekly sessions since the beginning of the pandemic. The groups have come together in the spirit of previous efforts to address major health crises, including the 1970s war on cancer and the campaign to curtail the HIV/AIDS epidemic in the 1980s, they report.

The coalition reported that since the pandemic began the prevalence of depression symptoms has jumped threefold, overdose deaths have increased in 40 states, and 25% of young adults have had suicidal ideation.

“It requires immediate action by the new administration, as well as state and local governments in all 50 states, and an acknowledged, consistent commitment to fix what’s broken in our system of care,” Daniel H. Gillison Jr, CEO of the National Alliance on Mental Illness, said in a statement.
 

SAMHSA chief ‘grateful’

Elinore McCance-Katz, MD, PhD, who is the assistant secretary for mental health and substance use and leads the Substance Abuse and Mental Health Services Administration, U.S. Department of Health & Human Services, applauded the coalition.

“I am very grateful that these organizations are stepping up and putting out a report like this,” Dr. McCance-Katz told this news organization. “I hope that they will continue this kind of advocacy and leadership on these issues going forward,” she said, adding that the need for mental health care and substance use disorders will be much greater going forward because of the pandemic.
 

Seven policy areas

The group’s 17-page strategic plan emphasizes interventions and methods that have already been tried and tested, focusing on seven policy areas:

• Early identification and prevention, especially for families and young people, by, for instance, bringing telehealth into schools and community centers.
• Rapid deployment of emergency crisis response and  prevention, including speeding up the implementation of the new 988 number for the National Suicide Prevention Lifeline.
• Leveling inequities in access to care by addressing social and political constructs and historical systemic injustices such as racism.
• Integrating physical and mental health care and substance use services to ensure “whole-person” well-being.
• Achieving parity in payment by health plans for mental health and substance-use coverage.
• Assuring evidence-based standards of treatments and care.
• Increasing the number and diversity of the mental health care workforce, peer support, and community-based programs.

Dr. McCance-Katz said the United States needs more resources, especially to increase the workforce, which has already been insufficient and will be even more so in the near future as the effects of the pandemic continue to ripple out.

SAMHSA received $425 million in the first COVID-19 relief package signed into law in March – the CARES Act. The money was distributed to states and used for direct care for people with serious mental illness and substance-use disorders who could not otherwise get care because of virus-related restrictions, and for boosting support for mental health support lines, said Dr. McCance-Katz.

A senior SAMHSA spokesperson said the agency is “hopeful that we will see additional resources in the upcoming stimulus for mental health and substance abuse” that Congress is still working on.

“We need bold steps from our government and the business community alike,” former Rep. Patrick J. Kennedy, founder of The Kennedy Forum, said in the statement from the new coalition. “We encourage all state governments to engage with mental health leaders, bring them into pandemic-related responses, and actively facilitate their communication with communities across the country,” said Mr. Kennedy, who is a part of the new coalition.

Mr. Kennedy is also cochair of the Action Alliance’s Mental Health and Suicide Prevention National Response to COVID-19, which unveiled its own six-priority Action Plan earlier in December.

A version of this article first appeared on Medscape.com.

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

A version of this article first appeared on Medscape.com.

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

A version of this article first appeared on Medscape.com.

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

A version of this article first appeared on Medscape.com.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Levels of nicotine and marijuana vaping among adolescents remain elevated but did not increase significantly in the past year, data from the annual Monitoring the Future survey show.

The 2020 survey included responses from 11,821 individuals in 112 schools across the United States from Feb. 11, 2020, to March 14, 2020, at which time data collection ended prematurely because of the COVID-19 pandemic. The results represent approximately 25% of the usual data collection.

A key positive finding in this year’s survey was the relatively stable levels of nicotine vaping from 2019 to 2020, following a trend of notably increased use annually since vaping was added to the survey in 2017.

During the years 2017-2019, the percentage of teens who reported vaping nicotine in the past 12 months increased from 7.5% to 16.5% among 8th graders, from 15.8% to 30.7% among 10th graders, and from 18.8% to 35.3% among 12th graders. However, in 2020, the percentages of teens who reported past-year nicotine vaping were relatively steady at 16.6%, 30.7%, and 34.5%, for 8th-, 10th-, and 12th-grade students, respectively. In addition, reports of daily or near-daily nicotine vaping (defined as 20 occasions in the past 30 days) decreased significantly, from 6.8% to 3.6% among 10th graders and from 11.6% to 5.3% among 12th graders.

“The rapid rise of teen nicotine vaping in recent years has been unprecedented and deeply concerning since we know that nicotine is highly addictive and can be delivered at high doses by vaping devices, which may also contain other toxic chemicals that may be harmful when inhaled,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in a press release accompanying the release of the findings. “It is encouraging to see a leveling off of this trend though the rates still remain very high.”

Reports of past-year marijuana vaping remained similar to 2019 levels after a twofold increase in the past 2 years, according to the survey. In early 2020, 8.1%, 19.1%, and 22.1% of 8th, 10th, and 12th graders reported past-year use. However, daily marijuana vaping decreased by more than half from 2019, to 1.1% among 10th graders and 1.5% among 12th graders.

Past-year use of the JUUL devices specifically also declined among older teens, from 28.7% in 2019 to 20% in 2020 among 10th graders and from 28.4% in 2019 to 22.7% in 2020 among 12th graders.

Other trends this year included the increased past-year use of amphetamines, inhalants, and cough medicines among 8th graders, and relatively low reported use among 12th graders of LSD (3.9%), synthetic cannabinoids (2.4%), cocaine (2.9%), ecstasy (1.8%), methamphetamine (1.4%), and heroin (0.3%).

The findings were published in JAMA Pediatrics.

 

Early data show progress

“The MTF survey is the most referenced and reliable longitudinal study reporting current use of tobacco, drugs, and alcohol among young people,” said Mark S. Gold, MD, of Washington University, St. Louis, in an interview.

“The new data, collected before data collection stopped prematurely due to the COVID-19 pandemic, suggests that some progress is being made in slowing the increase in substance use among these, the most vulnerable,” he said.

“The best news was that nicotine vaping decreased significantly after its meteoric increase over the past few years,” Dr. Gold emphasized. “Past-year vaping of marijuana remained steady at alarming levels in 2020, with 8.1% of 8th graders, 19.1% of 10th graders, and 22.1% of 12th graders reporting past-year use, following a two-fold increase over the past 2 years.” The use of all forms of marijuana, including smoking and vaping, did not significantly change in any of the three grades for lifetime use, past 12-month use, past 30-day use, and daily use from 2019 to 2020.

“Teen alcohol use has not significantly changed over the past 5 years,” and cigarette smoking in the last 30 days did not significantly change from 2019 to 2020, said Dr. Gold. However, “as with adults, psychostimulant use is increasing. Past year nonmedical use of amphetamines among 8th graders increased, from 3.5% in 2017 to 5.3% in 2020.”
 

COVID-era limitations

“The data suggest that pre-COVID pandemic vaping, smoking cigarettes, marijuana, and alcohol use had stabilized,” Dr. Gold said. “However, it is very difficult to predict what the COVID era data will show as many young people are at home, on the streets, and unsupervised; while adult substance misuse, substance use disorders, and overdoses are increasing. Drug supplies and access have increased for alcohol, cannabis, vaping, and tobacco as have supply synthetics like methamphetamine and fentanyl.”

In addition, “access to evaluation, intervention, and treatment have been curtailed during the pandemic,” Dr. Gold said. “The loss of peer role models, daily routine, and teacher or other adult supervision and interventions may interact with increasing despair, social isolation, depression, and anxiety in ways that are unknown. “It will not be clear until the next survey if perceived dangerousness has changed in ways that can protect these 8th, 10th, and 12th graders and increase the numbers of never users or current nonusers.”

The Monitoring the Future survey is conducted each year by the University of Michigan’s Institute for Social Research, Ann Arbor, and supported by NIDA, part of the National Institutes of Health. Dr. Gold had no relevant financial conflicts to disclose.

Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).

Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.

However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.

The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.

These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.

“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.

Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”

To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.

The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).

The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
 

One in five people will develop cancer

The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.

Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.

Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.

“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.

The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.

A version of this article first appeared on Medscape.com.

Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).

Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.

However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.

The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.

These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.

“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.

Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”

To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.

The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).

The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
 

One in five people will develop cancer

The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.

Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.

Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.

“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.

The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.

A version of this article first appeared on Medscape.com.

Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).

Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.

However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.

The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.

These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.

“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.

Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”

To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.

The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).

The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
 

One in five people will develop cancer

The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.

Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.

Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.

“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.

The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.

A version of this article first appeared on Medscape.com.

A proposal to lower Medicare Part B reimbursements for 50 physician-administered drugs and biologics to what drug manufacturers receive for them in other wealthy nations seems unlikely to take effect as planned on January 1, 2021. The proposal has been strongly opposed by the pharmaceutical industry as well as oncologists and other physicians who use the products most often.

At least four lawsuits have been filed in US district courts to block the move, including from Regeneron, manufacturer of the ophthalmic biologic aflibercept, the first agent on the list; the Community Oncology Alliance; the Biotechnology Innovation Organization, California Life Sciences Association, and Biocom; and Pharmaceutical Research and Manufacturers of America, the Association of Community Cancer Centers, the Global Colon Cancer Association, and National Infusion Center Association.

The proposal could hit oncologists/hematologists particularly hard because they are the primary prescribers of about 30 of the 50 agents on the list, including mainstay breast, lung, and prostate cancer treatments and newer immunotherapies. In its filing for injunctive relieve, the Community Oncology Alliance, a trade group for community oncologists, said the proposal exposes “the health and safety of cancer patients and other patients with potentially life-threatening diseases to real danger.”
 

Hearings are imminent

Hearings on the proposal, which was published by the Centers for Medicare & Medicaid Services (CMS) on November 27 following an executive order September 13, are scheduled for coming days. The first hearing is scheduled for December 18.

Given the looming implementation date, judges are likely to rule quickly on the motions for injunctive relief, said attorney Rachel Sachs, a health law expert and associate professor at the Washington University School of Law, St. Louis, Missouri. The odds are in plaintiffs’ favor based on procedural and Constitutional grounds. “It’s extremely unlikely to survive” the legal onslaught, she told Medscape Medical News.

Among the many issues raised in court filings, the proposal was released as an interim final rule (IFR), meaning it would take effect outside of the usual process of proposed rule, comment period, revision, then implementation. The law allows for bypassing normal rule-making requirements with an IFR, but they are meant for emergency situations — several have been issued in response to the COVID-19 pandemic — and the government must be able to show that delay would be “impracticable, unnecessary, or contrary to the public interest,” Sachs explained.

In contrast, some form of CMS’s new proposal, dubbed the “Most Favored Nation” (MFN) model for drug reimbursements, has been under consideration by the Trump administration since 2018.

“The way the [Trump] administration rolled this rule out at pretty much the last minute opens them up to greater legal challenges than if they pursued more normal regulatory pathways, which they had the opportunity to do. They are attempting to implement this on a time frame that is unprecedented for as large a change as this is,” said Juliette Cubanski, PhD, deputy director of Medicare policy at the Kaiser Family Foundation, San Francisco, California.
 

Reimbursement less than acquisition costs

In the proposal, CMS sought to offset the higher prices that pharmaceutical companies charge in the United States when compared with other developed nations — the prices are about double on average.

“One of the largest drivers of increasing Medicare spending is the growing prices for physician-administered separately payable Medicare Part B drugs, which have risen an average of 11.5% annually since 2015, with total spending of approximately $30 billion in 2019,” the agency said in a fact sheet. This is due in large part to “lack of competitive market forces on Medicare Part B drug costs,” it added.

The 50 agents covered by the new proposal are the ones Part B spends the most on, almost $3 billion in 2019 for aflibercept alone, followed closely by pembrolizumab, an immunotherapy used in many different cancer types.

A full list of the drugs and biologicals included in the proposal is on page 50 of the IFR.

CMS estimated that its move would cut reimbursements by approximately 65% once fully implemented in 4 years and save $87.8 billion over the 7 years of the proposed model, as well as reduce cost sharing for beneficiaries.

This model puts the onus on providers to negotiate down drug prices with companies to meet proposed reimbursement limits. However, if companies do not lower their prices, acquisition costs could be substantially lower than reimbursements.

Prescribers and their practices would either have to take the financial hit or stop offering the pharmaceuticals, in which case patients would have to do without, try a different option, or seek care elsewhere, including facilities excluded from the proposal: children’s hospitals, critical access hospitals, cancer hospitals, federally qualified health centers, rural health clinics, and extended neoplastic disease care hospitals.

CMS estimates that in the first year of MFN reimbursements, 9% of beneficiaries would forgo MFN therapies, growing to 19% by year 3, figures that were included in cost savings estimates.

The reimbursement cuts are meant to motivate manufactures to lower prices, but “we have not seen this occur with similar efforts in the past, and drug prices have continued to rise,” said American College of Rheumatology President David Karp, MD, PhD, in a press release. Many of the agents on the list are used by rheumatologists.

Under current policy, Medicare Part B prescribers are reimbursed manufactures’ average sales price plus a 6% add-on. Under the new proposal, reimbursements would be pegged to the lowest price charged among nations of the Organization for Economic Co-operation and Development with a gross domestic product per capita of at least 60% of the US price. In addition to the United States, there are 36 other member countries, including Canada, the United Kingdom, Japan, and Germany.

To remove incentives to prescribe more expensive drugs, the 6% add-on would be replaced with a flat add-on payment per dose, pegged at $148.73 for the first quarter of 2021. There is a hardship exemption for providers if the reimbursement cuts are too drastic, but that involves a lot of paperwork.

This article first appeared on Medscape.com.

A proposal to lower Medicare Part B reimbursements for 50 physician-administered drugs and biologics to what drug manufacturers receive for them in other wealthy nations seems unlikely to take effect as planned on January 1, 2021. The proposal has been strongly opposed by the pharmaceutical industry as well as oncologists and other physicians who use the products most often.

At least four lawsuits have been filed in US district courts to block the move, including from Regeneron, manufacturer of the ophthalmic biologic aflibercept, the first agent on the list; the Community Oncology Alliance; the Biotechnology Innovation Organization, California Life Sciences Association, and Biocom; and Pharmaceutical Research and Manufacturers of America, the Association of Community Cancer Centers, the Global Colon Cancer Association, and National Infusion Center Association.

The proposal could hit oncologists/hematologists particularly hard because they are the primary prescribers of about 30 of the 50 agents on the list, including mainstay breast, lung, and prostate cancer treatments and newer immunotherapies. In its filing for injunctive relieve, the Community Oncology Alliance, a trade group for community oncologists, said the proposal exposes “the health and safety of cancer patients and other patients with potentially life-threatening diseases to real danger.”
 

Hearings are imminent

Hearings on the proposal, which was published by the Centers for Medicare & Medicaid Services (CMS) on November 27 following an executive order September 13, are scheduled for coming days. The first hearing is scheduled for December 18.

Given the looming implementation date, judges are likely to rule quickly on the motions for injunctive relief, said attorney Rachel Sachs, a health law expert and associate professor at the Washington University School of Law, St. Louis, Missouri. The odds are in plaintiffs’ favor based on procedural and Constitutional grounds. “It’s extremely unlikely to survive” the legal onslaught, she told Medscape Medical News.

Among the many issues raised in court filings, the proposal was released as an interim final rule (IFR), meaning it would take effect outside of the usual process of proposed rule, comment period, revision, then implementation. The law allows for bypassing normal rule-making requirements with an IFR, but they are meant for emergency situations — several have been issued in response to the COVID-19 pandemic — and the government must be able to show that delay would be “impracticable, unnecessary, or contrary to the public interest,” Sachs explained.

In contrast, some form of CMS’s new proposal, dubbed the “Most Favored Nation” (MFN) model for drug reimbursements, has been under consideration by the Trump administration since 2018.

“The way the [Trump] administration rolled this rule out at pretty much the last minute opens them up to greater legal challenges than if they pursued more normal regulatory pathways, which they had the opportunity to do. They are attempting to implement this on a time frame that is unprecedented for as large a change as this is,” said Juliette Cubanski, PhD, deputy director of Medicare policy at the Kaiser Family Foundation, San Francisco, California.
 

Reimbursement less than acquisition costs

In the proposal, CMS sought to offset the higher prices that pharmaceutical companies charge in the United States when compared with other developed nations — the prices are about double on average.

“One of the largest drivers of increasing Medicare spending is the growing prices for physician-administered separately payable Medicare Part B drugs, which have risen an average of 11.5% annually since 2015, with total spending of approximately $30 billion in 2019,” the agency said in a fact sheet. This is due in large part to “lack of competitive market forces on Medicare Part B drug costs,” it added.

The 50 agents covered by the new proposal are the ones Part B spends the most on, almost $3 billion in 2019 for aflibercept alone, followed closely by pembrolizumab, an immunotherapy used in many different cancer types.

A full list of the drugs and biologicals included in the proposal is on page 50 of the IFR.

CMS estimated that its move would cut reimbursements by approximately 65% once fully implemented in 4 years and save $87.8 billion over the 7 years of the proposed model, as well as reduce cost sharing for beneficiaries.

This model puts the onus on providers to negotiate down drug prices with companies to meet proposed reimbursement limits. However, if companies do not lower their prices, acquisition costs could be substantially lower than reimbursements.

Prescribers and their practices would either have to take the financial hit or stop offering the pharmaceuticals, in which case patients would have to do without, try a different option, or seek care elsewhere, including facilities excluded from the proposal: children’s hospitals, critical access hospitals, cancer hospitals, federally qualified health centers, rural health clinics, and extended neoplastic disease care hospitals.

CMS estimates that in the first year of MFN reimbursements, 9% of beneficiaries would forgo MFN therapies, growing to 19% by year 3, figures that were included in cost savings estimates.

The reimbursement cuts are meant to motivate manufactures to lower prices, but “we have not seen this occur with similar efforts in the past, and drug prices have continued to rise,” said American College of Rheumatology President David Karp, MD, PhD, in a press release. Many of the agents on the list are used by rheumatologists.

Under current policy, Medicare Part B prescribers are reimbursed manufactures’ average sales price plus a 6% add-on. Under the new proposal, reimbursements would be pegged to the lowest price charged among nations of the Organization for Economic Co-operation and Development with a gross domestic product per capita of at least 60% of the US price. In addition to the United States, there are 36 other member countries, including Canada, the United Kingdom, Japan, and Germany.

To remove incentives to prescribe more expensive drugs, the 6% add-on would be replaced with a flat add-on payment per dose, pegged at $148.73 for the first quarter of 2021. There is a hardship exemption for providers if the reimbursement cuts are too drastic, but that involves a lot of paperwork.

This article first appeared on Medscape.com.

A proposal to lower Medicare Part B reimbursements for 50 physician-administered drugs and biologics to what drug manufacturers receive for them in other wealthy nations seems unlikely to take effect as planned on January 1, 2021. The proposal has been strongly opposed by the pharmaceutical industry as well as oncologists and other physicians who use the products most often.

At least four lawsuits have been filed in US district courts to block the move, including from Regeneron, manufacturer of the ophthalmic biologic aflibercept, the first agent on the list; the Community Oncology Alliance; the Biotechnology Innovation Organization, California Life Sciences Association, and Biocom; and Pharmaceutical Research and Manufacturers of America, the Association of Community Cancer Centers, the Global Colon Cancer Association, and National Infusion Center Association.

The proposal could hit oncologists/hematologists particularly hard because they are the primary prescribers of about 30 of the 50 agents on the list, including mainstay breast, lung, and prostate cancer treatments and newer immunotherapies. In its filing for injunctive relieve, the Community Oncology Alliance, a trade group for community oncologists, said the proposal exposes “the health and safety of cancer patients and other patients with potentially life-threatening diseases to real danger.”
 

Hearings are imminent

Hearings on the proposal, which was published by the Centers for Medicare & Medicaid Services (CMS) on November 27 following an executive order September 13, are scheduled for coming days. The first hearing is scheduled for December 18.

Given the looming implementation date, judges are likely to rule quickly on the motions for injunctive relief, said attorney Rachel Sachs, a health law expert and associate professor at the Washington University School of Law, St. Louis, Missouri. The odds are in plaintiffs’ favor based on procedural and Constitutional grounds. “It’s extremely unlikely to survive” the legal onslaught, she told Medscape Medical News.

Among the many issues raised in court filings, the proposal was released as an interim final rule (IFR), meaning it would take effect outside of the usual process of proposed rule, comment period, revision, then implementation. The law allows for bypassing normal rule-making requirements with an IFR, but they are meant for emergency situations — several have been issued in response to the COVID-19 pandemic — and the government must be able to show that delay would be “impracticable, unnecessary, or contrary to the public interest,” Sachs explained.

In contrast, some form of CMS’s new proposal, dubbed the “Most Favored Nation” (MFN) model for drug reimbursements, has been under consideration by the Trump administration since 2018.

“The way the [Trump] administration rolled this rule out at pretty much the last minute opens them up to greater legal challenges than if they pursued more normal regulatory pathways, which they had the opportunity to do. They are attempting to implement this on a time frame that is unprecedented for as large a change as this is,” said Juliette Cubanski, PhD, deputy director of Medicare policy at the Kaiser Family Foundation, San Francisco, California.
 

Reimbursement less than acquisition costs

In the proposal, CMS sought to offset the higher prices that pharmaceutical companies charge in the United States when compared with other developed nations — the prices are about double on average.

“One of the largest drivers of increasing Medicare spending is the growing prices for physician-administered separately payable Medicare Part B drugs, which have risen an average of 11.5% annually since 2015, with total spending of approximately $30 billion in 2019,” the agency said in a fact sheet. This is due in large part to “lack of competitive market forces on Medicare Part B drug costs,” it added.

The 50 agents covered by the new proposal are the ones Part B spends the most on, almost $3 billion in 2019 for aflibercept alone, followed closely by pembrolizumab, an immunotherapy used in many different cancer types.

A full list of the drugs and biologicals included in the proposal is on page 50 of the IFR.

CMS estimated that its move would cut reimbursements by approximately 65% once fully implemented in 4 years and save $87.8 billion over the 7 years of the proposed model, as well as reduce cost sharing for beneficiaries.

This model puts the onus on providers to negotiate down drug prices with companies to meet proposed reimbursement limits. However, if companies do not lower their prices, acquisition costs could be substantially lower than reimbursements.

Prescribers and their practices would either have to take the financial hit or stop offering the pharmaceuticals, in which case patients would have to do without, try a different option, or seek care elsewhere, including facilities excluded from the proposal: children’s hospitals, critical access hospitals, cancer hospitals, federally qualified health centers, rural health clinics, and extended neoplastic disease care hospitals.

CMS estimates that in the first year of MFN reimbursements, 9% of beneficiaries would forgo MFN therapies, growing to 19% by year 3, figures that were included in cost savings estimates.

The reimbursement cuts are meant to motivate manufactures to lower prices, but “we have not seen this occur with similar efforts in the past, and drug prices have continued to rise,” said American College of Rheumatology President David Karp, MD, PhD, in a press release. Many of the agents on the list are used by rheumatologists.

Under current policy, Medicare Part B prescribers are reimbursed manufactures’ average sales price plus a 6% add-on. Under the new proposal, reimbursements would be pegged to the lowest price charged among nations of the Organization for Economic Co-operation and Development with a gross domestic product per capita of at least 60% of the US price. In addition to the United States, there are 36 other member countries, including Canada, the United Kingdom, Japan, and Germany.

To remove incentives to prescribe more expensive drugs, the 6% add-on would be replaced with a flat add-on payment per dose, pegged at $148.73 for the first quarter of 2021. There is a hardship exemption for providers if the reimbursement cuts are too drastic, but that involves a lot of paperwork.

This article first appeared on Medscape.com.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Coronavirus vaccines have become a reality, as they are now being approved and authorized for use in a growing number of countries including the United States. The U.S. Food and Drug Administration has just issued emergency authorization for the use of the COVID-19 vaccine produced by Pfizer and BioNTech. Close behind is the vaccine developed by Moderna, which has also applied to the FDA for emergency authorization.

scyther5/thinkstock

The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, and the FDA has said that the 95% credible interval for the vaccine efficacy was 90.3%-97.6%. But as with many initial clinical trials, whether for drugs or vaccines, not all populations were represented in the trial cohort, including individuals who are immunocompromised. At the current time, it is largely unknown how safe or effective the vaccine may be in this large population, many of whom are at high risk for serious COVID-19 complications.

At a special session held during the recent annual meeting of the American Society of Hematology, Anthony Fauci, MD, the nation’s leading infectious disease expert, said that individuals with compromised immune systems, whether because of chemotherapy or a bone marrow transplant, should plan to be vaccinated when the opportunity arises.

In response to a question from ASH President Stephanie J. Lee, MD, of the Fred Hutchinson Cancer Center, Seattle, Dr. Fauci emphasized that, despite being excluded from clinical trials, this population should get vaccinated. “I think we should recommend that they get vaccinated,” he said. “I mean, it is clear that, if you are on immunosuppressive agents, history tells us that you’re not going to have as robust a response as if you had an intact immune system that was not being compromised. But some degree of immunity is better than no degree of immunity.”

That does seem to be the consensus among experts who spoke in interviews: that as long as these are not live attenuated vaccines, they hold no specific risk to an immunocompromised patient, other than any factors specific to the individual that could be a contraindication.

“Patients, family members, friends, and work contacts should be encouraged to receive the vaccine,” said William Stohl, MD, PhD, chief of the division of rheumatology at the University of Southern California, Los Angeles. “Clinicians should advise patients to obtain the vaccine sooner rather than later.”
 

Kevin C. Wang, MD, PhD, of the department of dermatology at Stanford (Calif.) University, agreed. “I am 100% with Dr. Fauci. Everyone should get the vaccine, even if it may not be as effective,” he said. “I would treat it exactly like the flu vaccines that we recommend folks get every year.”

Dr. Wang noted that he couldn’t think of any contraindications unless the immunosuppressed patients have a history of severe allergic reactions to prior vaccinations. “But I would even say patients with history of cancer, upon recommendation of their oncologists, are likely to be suitable candidates for the vaccine,” he added. “I would say clinicians should approach counseling the same way they counsel patients for the flu vaccine, and as far as I know, there are no concerns for systemic drugs commonly used in dermatology patients.”

However, guidance has not yet been issued from either the FDA or the Centers for Disease Control and Prevention regarding the use of the vaccine in immunocompromised individuals. Given the lack of data, the FDA has said that “it will be something that providers will need to consider on an individual basis,” and that individuals should consult with physicians to weigh the potential benefits and potential risks.

The CDC’s Advisory Committee on Immunization Practices has said that clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies. The CDC itself has not yet released its formal guidance on vaccine use.


 

COVID-19 vaccines

Vaccines typically require years of research and testing before reaching the clinic, but this year researchers embarked on a global effort to develop safe and effective coronavirus vaccines in record time. Both the Pfizer/BioNTech and Moderna vaccines have only a few months of phase 3 clinical trial data, so much remains unknown about them, including their duration of effect and any long-term safety signals. In addition to excluding immunocompromised individuals, the clinical trials did not include children or pregnant women, so data are lacking for several population subgroups.

But these will not be the only vaccines available, as the pipeline is already becoming crowded. U.S. clinical trial data from a vaccine jointly being developed by Oxford-AstraZeneca, could potentially be ready, along with a request for FDA emergency use authorization, by late January 2021.

In addition, China and Russia have released vaccines, and there are currently 61 vaccines being investigated in clinical trials and at least 85 preclinical products under active investigation.

The vaccine candidates are using both conventional and novel mechanisms of action to elicit an immune response in patients. Conventional methods include attenuated inactivated (killed) virus and recombinant viral protein vaccines to develop immunity. Novel approaches include replication-deficient, adenovirus vector-based vaccines that contain the viral protein, and mRNA-based vaccines, such as the Pfizer and Moderna vaccines, that encode for a SARS-CoV-2 spike protein.

“The special vaccine concern for immunocompromised individuals is introduction of a live virus,” Dr. Stohl said. “Neither the Moderna nor Pfizer vaccines are live viruses, so there should be no special contraindication for such individuals.”

Live vaccine should be avoided in immunocompromised patients, and currently, live SARS-CoV-2 vaccines are only being developed in India and Turkey.

It is not unusual for vaccine trials to begin with cohorts that exclude participants with various health conditions, including those who are immunocompromised. These groups are generally then evaluated in phase 4 trials, or postmarketing surveillance. While the precise number of immunosuppressed adults in the United States is not known, the numbers are believed to be rising because of increased life expectancy among immunosuppressed adults as a result of advances in treatment and new and wider indications for therapies that can affect the immune system.

According to data from the 2013 National Health Interview Survey, an estimated 2.7% of U.S. adults are immunosuppressed. This population covers a broad array of health conditions and medical specialties; people living with inflammatory or autoimmune conditions, such as inflammatory rheumatic diseases (rheumatoid arthritis, axial spondyloarthritis, lupus); inflammatory bowel disease (Crohn’s disease and ulcerative colitis); psoriasis; multiple sclerosis; organ transplant recipients; patients undergoing chemotherapy; and life-long immunosuppression attributable to HIV infection.

As the vaccines begin to roll out and become available, how should clinicians advise their patients, in the absence of any clinical trial data?


 

Risk vs. benefit

Gilaad Kaplan, MD, MPH, a gastroenterologist and professor of medicine at the University of Calgary (Alta.), noted that the inflammatory bowel disease (IBD) community has dealt with tremendous anxiety during the pandemic because many are immunocompromised because of the medications they use to treat their disease.

“For example, many patients with IBD are on biologics like anti-TNF [tumor necrosis factor] therapies, which are also used in other immune-mediated inflammatory diseases such as rheumatoid arthritis,” he said. “Understandably, individuals with IBD on immunosuppressive medications are concerned about the risk of severe complications due to COVID-19.”

The entire IBD community, along with the world, celebrated the announcement that multiple vaccines are protective against SARS-CoV-2, he noted. “Vaccines offer the potential to reduce the spread of COVID-19, allowing society to revert back to normalcy,” Dr. Kaplan said. “Moreover, for vulnerable populations, including those who are immunocompromised, vaccines offer the potential to directly protect them from the morbidity and mortality associated with COVID-19.”

That said, even though the news of vaccines are extremely promising, some cautions must be raised regarding their use in immunocompromised populations, such as persons with IBD. “The current trials, to my knowledge, did not include immunocompromised individuals and thus, we can only extrapolate from what we know from other trials of different vaccines,” he explained. “We know from prior vaccines studies that the immune response following vaccination is less robust in those who are immunocompromised as compared to a healthy control population.”

Dr. Kaplan also pointed to recent reports of allergic reactions that have been reported in healthy individuals. “We don’t know whether side effects, like allergic reactions, may be different in unstudied populations,” he said. “Thus, the medical and scientific community should prioritize clinical studies of safety and effectiveness of COVID-19 vaccines in immunocompromised populations.”

So, what does this mean for an individual with an immune-mediated inflammatory disease like Crohn’s disease or ulcerative colitis who is immunocompromised? Dr. Kaplan explained that it is a balance between the potential harm of being infected with COVID-19 and the uncertainty of receiving a vaccine in an understudied population. For those who are highly susceptible to dying from COVID-19, such as an older adult with IBD, or someone who faces high exposure, such as a health care worker, the potential protection of the vaccine greatly outweighs the uncertainty.

“However, for individuals who are at otherwise lower risk – for example, young and able to work from home – then waiting a few extra months for postmarketing surveillance studies in immunocompromised populations may be a reasonable approach, as long as these individuals are taking great care to avoid infection,” he said.
 

No waiting needed

Joel M. Gelfand, MD, MSCE, professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, feels that the newly approved vaccine should be safe for most of his patients.

“Patients with psoriatic disease should get the mRNA-based COVID-19 vaccine as soon as possible based on eligibility as determined by the CDC and local public health officials,” he said. “It is not a live vaccine, and therefore patients on biologics or other immune-modulating or immune-suppressing treatment can receive it.”

However, the impact of psoriasis treatment on immune response to the mRNA-based vaccines is not known. Dr. Gelfand noted that, extrapolating from the vaccine literature, there is some evidence that methotrexate reduces response to the influenza vaccine. “However, the clinical significance of this finding is not clear,” he said. “Since the mRNA vaccine needs to be taken twice, a few weeks apart, I do not recommend interrupting or delaying treatment for psoriatic disease while undergoing vaccination for COVID-19.”

Given the reports of allergic reactions, he added that it is advisable for patients with a history of life-threatening allergic reactions such as anaphylaxis or who have been advised to carry an epinephrine autoinjector, to talk with their health care provider to determine if COVID-19 vaccination is medically appropriate.

The National Psoriasis Foundation has issued guidance on COVID-19, explained Steven R. Feldman, MD, PhD, professor of dermatology, pathology, and social sciences & health policy at Wake Forest University, Winston-Salem, N.C., who is also a member of the committee that is working on those guidelines and keeping them up to date. “We are in the process of updating the guidelines with information on COVID vaccines,” he said.

He agreed that there are no contraindications for psoriasis patients to receive the vaccine, regardless of whether they are on immunosuppressive treatment, even though definitive data are lacking. “Fortunately, there’s a lot of good data coming out of Italy that patients with psoriasis on biologics do not appear to be at increased risk of getting COVID or of having worse outcomes from COVID,” he said.

Patients are going to ask about the vaccines, and when counseling them, clinicians should discuss the available data, the residual uncertainty, and patients’ concerns should be considered, Dr. Feldman explained. “There may be some concern that steroids and cyclosporine would reduce the effectiveness of vaccines, but there is no concern that any of the drugs would cause increased risk from nonlive vaccines.”

He added that there is evidence that “patients on biologics who receive nonlive vaccines do develop antibody responses and are immunized.”


 

Boosting efficacy

Even prior to making their announcement, the American College of Rheumatology had said that they would endorse the vaccine for all patients, explained rheumatologist Brett Smith, DO, from Blount Memorial Physicians Group and East Tennessee Children’s Hospital, Alcoa. “The vaccine is safe for all patients, but the problem may be that it’s not as effective,” he said. “But we don’t know that because it hasn’t been tested.”

With other vaccines, biologic medicines are held for 2 weeks before and afterwards, to get the best response. “But some patients don’t want to stop the medication,” Dr. Smith said. “They are afraid that their symptoms will return.”

As for counseling patients as to whether they should receive this vaccine, he explained that he typically doesn’t try to sway patients one way or another until they are really high risk. “When I counsel, it really depends on the individual situation. And for this vaccine, we have to be open to the fact that many people have already made up their mind.”

There are a lot of questions regarding the vaccine. One is the short time frame of development. “Vaccines typically take 6-10 years to come on the market, and this one is now available after a 3-month study,” Dr. Smith said. “Some have already decided that it’s too new for them.”

The process is also new, and patients need to understand that it doesn’t contain an active virus and “you can’t catch coronavirus from it.”

Dr. Smith also explained that, because the vaccine may be less effective in a person using biologic therapies, there is currently no information available on repeat vaccination. “These are all unanswered questions,” he said. “If the antibodies wane in a short time, can we be revaccinated and in what time frame? We just don’t know that yet.”

Marcelo Bonomi, MD, a medical oncologist from The Ohio State University Comprehensive Cancer Center, Columbus, explained that one way to ensure a more optimal response to the vaccine would be to wait until the patient has finished chemotherapy.* “The vaccine can be offered at that time, and in the meantime, they can take other steps to avoid infection,” he said. “If they are very immunosuppressed, it isn’t worth trying to give the vaccine.”

Cancer patients should be encouraged to stay as healthy as possible, and to wear masks and social distance. “It’s a comprehensive approach. Eat healthy, avoid alcohol and tobacco, and exercise. [These things] will help boost the immune system,” Dr. Bonomi said. “Family members should be encouraged to get vaccinated, which will help them avoid infection and exposing the patient.”

Jim Boonyaratanakornkit, MD, PhD, an infectious disease specialist who cares for cancer patients at the Fred Hutchinson Cancer Research Center, agreed. “Giving a vaccine right after a transplant is a futile endeavor,” he said. “We need to wait 6 months to have an immune response.”

He pointed out there may be a continuing higher number of cases, with high levels peaking in Washington in February and March. “Close friends and family should be vaccinated if possible,” he said, “which will help interrupt transmission.”

The vaccines are using new platforms that are totally different, and there is no clear data as to how long the antibodies will persist. “We know that they last for at least 4 months,” said Dr. Boonyaratanakornkit. “We don’t know what level of antibody will protect them from COVID-19 infection. Current studies are being conducted, but we don’t have that information for anyone yet.”
 

*Correction, 1/7/21: An earlier version of this article misattributed quotes from Dr. Marcelo Bonomi.

Researchers have worked at record-breaking speed to not only identify and characterize the novel coronavirus, but also to develop potential vaccines; it is a race that another trio of scientists, awarded the 2020 Nobel Prize in Medicine, know well after their own decades-long marathon to crack the code of hepatitis C.

The RNA virus vexed researchers like Harvey J. Alter, MD; Michael Houghton, PhD; and Charles M. Rice, PhD, for years. Unlike today’s parallel sequencing and polymerase chain reaction, screening at the time was tedious and painstaking. But they were all in for some big highs, some dead-ends, and a little inspiration by way of author Lewis Carroll.

“Our undertaking was a success,” Dr. Alter said in an interview, “because everyone got on board.” Investigators, the Food and Drug Administration, and blood banks all worked together. It was a national effort, he added.

The Laureates will share the $1 million prize that recognizes their achievement. This is the second time that scientists who have devoted their time to the pursuit of viral hepatitis have been honored.

Two main types of infectious hepatitis were identified in the 1940s. The first, hepatitis A, is transmitted by polluted water or food and generally has little long-term effect on the patient. The second, transmitted through blood and other bodily fluids, is a much more serious threat.

In the 1960s, Baruch Blumberg, MD, ascertained that blood-borne hepatitis was caused by an insidious virus – hepatitis B – which silently causes liver complications in otherwise healthy people years after infection. Dr. Blumberg’s discovery led to the development of diagnostic tests and an effective vaccine; he was awarded the Nobel Prize in Physiology or Medicine in 1976.

At that time, Dr. Alter was working at the National Institutes of Health in Bethesda, Md., studying the occurrence of hepatitis in patients who had received blood transfusions. Globally, blood-borne hepatitis was causing more than a million deaths each year.

When screening began in 1969 to prevent people with hepatitis A or hepatitis B from donating blood, many recipients were spared from developing liver inflammation after transfusion. However, some people were still getting sick and researchers began to suspect that something dubbed “non-A, non-B” was lurking in donated blood.

As scientists were tracking it down in the micro world, public health officials and others tried to block the presumed virus in the macro world. In the United States, this meant changing blood-donation practices. When it became clear that as many as one in five transfusion recipients developed hepatitis, probably as the result of a virus, the blood donation system switched from being a paid enterprise to a volunteer activity.

It was anticipated that this would eliminate one source of the virus – users of street drugs – and it did; rates of transmission after transfusion dropped by half. By the 1980s, researchers had figured out that donors carrying the mysterious pathogen often had elevated levels of antibodies to the hepatitis B virus or elevated levels of ALT. Blood banks then began testing prospective donors and cut the incidence of non-A, non-B hepatitis by another half.

When Dr. Alter and his team got to work studying chimpanzees, they were able to confirm that the non-A, non-B agent was transmittable by blood transfusion. But the next step proved insurmountable. “People knew what the virus would look like if we found it, but we couldn’t find it,” Dr. Alter said.

“Then Chiron came along and cloned it,” he recounts.

The tiny start-up company was housed in a few rented rooms in an abandoned plant in Emeryville, Calif. This is where Nobel Laureate Dr. Houghton and coworkers Qui-Lim Choo, PhD, and George Kuo, PhD, spent 7 years chasing the mystery pathogen. When every traditional method to pin it down failed, the team tried some nontraditional approaches.

They found success when they painstakingly cloned genomic fragments from the blood of an infected chimpanzee and then screened this library using serum isolated from affected patients. The hope was that antibodies in the serum samples would stick to the viral genetic material and create a signpost indicating its presence.

This “fishing expedition” was disappointing at first, said Dr. Choo, now vice president of research at Nansha Biologics Limited in Hong Kong. “We didn’t catch any fish.”

He likened the pursuit, which took place under growing pressure from upper management, to that in “The Imitation Game,” the film that depicted Alan Turing’s effort to decrypt German intelligence messages for the British government during World War II.

The effort wasn’t working out and the team was down. So to keep spirits up, Dr. Kuo shared a snippet of the Lewis Carroll poem “The Hunting of the Snark.” It just happened to encapsulate the frustrations of their pursuit while also encouraging perseverance: “For the Snark’s a peculiar creature, that won’t / Be caught in a commonplace way. / Do all that you know, and try all that you don’t: / Not a chance must be wasted today!”

Those words motivated the team to keep going, to try different approaches and, ultimately, to find the hepatitis C virus, said Dr. Kuo, now retired.

During the tedious process of screening millions of clones, Dr. Choo spotted a single likely area on one of the plates that his “gut feeling” told him would contain the viral material. And it did. The pathogen – RNA packed in a lipid coat – was a member of the Flaviviridae family.

In 1989, the team reported that they’d identified a new flavivirus associated with posttransfusion hepatitis, and published their findings in Science. Later that year, an antibody test for it was described in Science by the team, which included Dr. Alter.

The success was a “fantastic feeling,” mused Dr. Houghton, now a virologist at the University of Alberta, Edmonton. “I’ve often said that, from 1989 to 1991, I was high just on the discovery.” After that, “researchers and the pharmaceutical industry did a great job coming up with really effective antivirals.”

“Mike, with his team, took 7 years to get this tiny little piece of viral genome, which reacted with convalescent patient serum, and used that to build up the sequence. That’s where I come into it,” said Dr. Rice, professor of virology at Rockefeller University, New York, and the third scientist in the Nobel Prize–winning trio.

The next step was to confirm that this was causing the hepatitis in patients who received blood transfusions. Over the course of several years, Dr. Rice and colleagues at the Washington University, St. Louis, engineered a version of the virus that retained its replicating capacity and injected it into chimpanzees. The animals developed hepatitis, confirming that this flavivirus was indeed the cause. More than 8 years after the virus was identified, scientists had proof of its infectiousness.

“We finally knew the structure of the viral genome,” said Dr. Rice. “We showed that the sequence was sufficient to initiate infection and cause disease.”

Those findings, published in 1997 in Science, were the key final step in the search for a molecular target for therapies and, maybe someday, a vaccine.

For the first time in history, hepatitis C can now be cured, raising hopes that the virus will be eradicated from the world population. But obstacles remain as the World Health Organization works toward its goal of eliminating hepatitis C–related disease by 2030.

Rates have actually risen in the United States as the opioid epidemic has taken hold because the virus is common in people who use street drugs and are at increased risk for behaviors that lead to transmission.

The prevalence of chronic hepatitis C now hovers around 1%. In 2019, it affected an estimated 3.8 million Americans, and more than 39,000 people died of hepatitis C–related causes. Of all deaths from liver cancer in 2019, 39% were attributable to hepatitis C.

This “silent killer” can take years to develop, which dampens the sense of immediacy to help, said Jean-Michel Piedagnel, director of the Drugs for Neglected Diseases nonprofit initiative.

People infected with hepatitis C are often part of marginalized groups. There isn’t typically a common demographic factor to unite them in advocacy.

And even though treatment can cost as little as $200 in countries where generic drugs are available, money can still be an issue, Mr. Piedagnel pointed out.

The COVID-19 response shows how quickly health systems can evolve in a crisis and adapt. “If there is political will, means can be found, said Cary James, CEO at the World Hepatitis Alliance.

The incredible speed of vaccine development for SARS-CoV-2 has impressed the Nobel Laureates, who have yet to see a vaccine for hepatitis C.

Dr. Houghton said he hopes this momentum will perpetuate new emergency filings for hepatitis C vaccines.

If even a tiny fraction of the money that’s gone into COVID-19 were used, Dr. Rice pointed out, “we’d have a hep C vaccine by now.”

A version of this article first appeared on Medscape.com

Researchers have worked at record-breaking speed to not only identify and characterize the novel coronavirus, but also to develop potential vaccines; it is a race that another trio of scientists, awarded the 2020 Nobel Prize in Medicine, know well after their own decades-long marathon to crack the code of hepatitis C.

The RNA virus vexed researchers like Harvey J. Alter, MD; Michael Houghton, PhD; and Charles M. Rice, PhD, for years. Unlike today’s parallel sequencing and polymerase chain reaction, screening at the time was tedious and painstaking. But they were all in for some big highs, some dead-ends, and a little inspiration by way of author Lewis Carroll.

“Our undertaking was a success,” Dr. Alter said in an interview, “because everyone got on board.” Investigators, the Food and Drug Administration, and blood banks all worked together. It was a national effort, he added.

The Laureates will share the $1 million prize that recognizes their achievement. This is the second time that scientists who have devoted their time to the pursuit of viral hepatitis have been honored.

Two main types of infectious hepatitis were identified in the 1940s. The first, hepatitis A, is transmitted by polluted water or food and generally has little long-term effect on the patient. The second, transmitted through blood and other bodily fluids, is a much more serious threat.

In the 1960s, Baruch Blumberg, MD, ascertained that blood-borne hepatitis was caused by an insidious virus – hepatitis B – which silently causes liver complications in otherwise healthy people years after infection. Dr. Blumberg’s discovery led to the development of diagnostic tests and an effective vaccine; he was awarded the Nobel Prize in Physiology or Medicine in 1976.

At that time, Dr. Alter was working at the National Institutes of Health in Bethesda, Md., studying the occurrence of hepatitis in patients who had received blood transfusions. Globally, blood-borne hepatitis was causing more than a million deaths each year.

When screening began in 1969 to prevent people with hepatitis A or hepatitis B from donating blood, many recipients were spared from developing liver inflammation after transfusion. However, some people were still getting sick and researchers began to suspect that something dubbed “non-A, non-B” was lurking in donated blood.

As scientists were tracking it down in the micro world, public health officials and others tried to block the presumed virus in the macro world. In the United States, this meant changing blood-donation practices. When it became clear that as many as one in five transfusion recipients developed hepatitis, probably as the result of a virus, the blood donation system switched from being a paid enterprise to a volunteer activity.

It was anticipated that this would eliminate one source of the virus – users of street drugs – and it did; rates of transmission after transfusion dropped by half. By the 1980s, researchers had figured out that donors carrying the mysterious pathogen often had elevated levels of antibodies to the hepatitis B virus or elevated levels of ALT. Blood banks then began testing prospective donors and cut the incidence of non-A, non-B hepatitis by another half.

When Dr. Alter and his team got to work studying chimpanzees, they were able to confirm that the non-A, non-B agent was transmittable by blood transfusion. But the next step proved insurmountable. “People knew what the virus would look like if we found it, but we couldn’t find it,” Dr. Alter said.

“Then Chiron came along and cloned it,” he recounts.

The tiny start-up company was housed in a few rented rooms in an abandoned plant in Emeryville, Calif. This is where Nobel Laureate Dr. Houghton and coworkers Qui-Lim Choo, PhD, and George Kuo, PhD, spent 7 years chasing the mystery pathogen. When every traditional method to pin it down failed, the team tried some nontraditional approaches.

They found success when they painstakingly cloned genomic fragments from the blood of an infected chimpanzee and then screened this library using serum isolated from affected patients. The hope was that antibodies in the serum samples would stick to the viral genetic material and create a signpost indicating its presence.

This “fishing expedition” was disappointing at first, said Dr. Choo, now vice president of research at Nansha Biologics Limited in Hong Kong. “We didn’t catch any fish.”

He likened the pursuit, which took place under growing pressure from upper management, to that in “The Imitation Game,” the film that depicted Alan Turing’s effort to decrypt German intelligence messages for the British government during World War II.

The effort wasn’t working out and the team was down. So to keep spirits up, Dr. Kuo shared a snippet of the Lewis Carroll poem “The Hunting of the Snark.” It just happened to encapsulate the frustrations of their pursuit while also encouraging perseverance: “For the Snark’s a peculiar creature, that won’t / Be caught in a commonplace way. / Do all that you know, and try all that you don’t: / Not a chance must be wasted today!”

Those words motivated the team to keep going, to try different approaches and, ultimately, to find the hepatitis C virus, said Dr. Kuo, now retired.

During the tedious process of screening millions of clones, Dr. Choo spotted a single likely area on one of the plates that his “gut feeling” told him would contain the viral material. And it did. The pathogen – RNA packed in a lipid coat – was a member of the Flaviviridae family.

In 1989, the team reported that they’d identified a new flavivirus associated with posttransfusion hepatitis, and published their findings in Science. Later that year, an antibody test for it was described in Science by the team, which included Dr. Alter.

The success was a “fantastic feeling,” mused Dr. Houghton, now a virologist at the University of Alberta, Edmonton. “I’ve often said that, from 1989 to 1991, I was high just on the discovery.” After that, “researchers and the pharmaceutical industry did a great job coming up with really effective antivirals.”

“Mike, with his team, took 7 years to get this tiny little piece of viral genome, which reacted with convalescent patient serum, and used that to build up the sequence. That’s where I come into it,” said Dr. Rice, professor of virology at Rockefeller University, New York, and the third scientist in the Nobel Prize–winning trio.

The next step was to confirm that this was causing the hepatitis in patients who received blood transfusions. Over the course of several years, Dr. Rice and colleagues at the Washington University, St. Louis, engineered a version of the virus that retained its replicating capacity and injected it into chimpanzees. The animals developed hepatitis, confirming that this flavivirus was indeed the cause. More than 8 years after the virus was identified, scientists had proof of its infectiousness.

“We finally knew the structure of the viral genome,” said Dr. Rice. “We showed that the sequence was sufficient to initiate infection and cause disease.”

Those findings, published in 1997 in Science, were the key final step in the search for a molecular target for therapies and, maybe someday, a vaccine.

For the first time in history, hepatitis C can now be cured, raising hopes that the virus will be eradicated from the world population. But obstacles remain as the World Health Organization works toward its goal of eliminating hepatitis C–related disease by 2030.

Rates have actually risen in the United States as the opioid epidemic has taken hold because the virus is common in people who use street drugs and are at increased risk for behaviors that lead to transmission.

The prevalence of chronic hepatitis C now hovers around 1%. In 2019, it affected an estimated 3.8 million Americans, and more than 39,000 people died of hepatitis C–related causes. Of all deaths from liver cancer in 2019, 39% were attributable to hepatitis C.

This “silent killer” can take years to develop, which dampens the sense of immediacy to help, said Jean-Michel Piedagnel, director of the Drugs for Neglected Diseases nonprofit initiative.

People infected with hepatitis C are often part of marginalized groups. There isn’t typically a common demographic factor to unite them in advocacy.

And even though treatment can cost as little as $200 in countries where generic drugs are available, money can still be an issue, Mr. Piedagnel pointed out.

The COVID-19 response shows how quickly health systems can evolve in a crisis and adapt. “If there is political will, means can be found, said Cary James, CEO at the World Hepatitis Alliance.

The incredible speed of vaccine development for SARS-CoV-2 has impressed the Nobel Laureates, who have yet to see a vaccine for hepatitis C.

Dr. Houghton said he hopes this momentum will perpetuate new emergency filings for hepatitis C vaccines.

If even a tiny fraction of the money that’s gone into COVID-19 were used, Dr. Rice pointed out, “we’d have a hep C vaccine by now.”

A version of this article first appeared on Medscape.com

Researchers have worked at record-breaking speed to not only identify and characterize the novel coronavirus, but also to develop potential vaccines; it is a race that another trio of scientists, awarded the 2020 Nobel Prize in Medicine, know well after their own decades-long marathon to crack the code of hepatitis C.

The RNA virus vexed researchers like Harvey J. Alter, MD; Michael Houghton, PhD; and Charles M. Rice, PhD, for years. Unlike today’s parallel sequencing and polymerase chain reaction, screening at the time was tedious and painstaking. But they were all in for some big highs, some dead-ends, and a little inspiration by way of author Lewis Carroll.

“Our undertaking was a success,” Dr. Alter said in an interview, “because everyone got on board.” Investigators, the Food and Drug Administration, and blood banks all worked together. It was a national effort, he added.

The Laureates will share the $1 million prize that recognizes their achievement. This is the second time that scientists who have devoted their time to the pursuit of viral hepatitis have been honored.

Two main types of infectious hepatitis were identified in the 1940s. The first, hepatitis A, is transmitted by polluted water or food and generally has little long-term effect on the patient. The second, transmitted through blood and other bodily fluids, is a much more serious threat.

In the 1960s, Baruch Blumberg, MD, ascertained that blood-borne hepatitis was caused by an insidious virus – hepatitis B – which silently causes liver complications in otherwise healthy people years after infection. Dr. Blumberg’s discovery led to the development of diagnostic tests and an effective vaccine; he was awarded the Nobel Prize in Physiology or Medicine in 1976.

At that time, Dr. Alter was working at the National Institutes of Health in Bethesda, Md., studying the occurrence of hepatitis in patients who had received blood transfusions. Globally, blood-borne hepatitis was causing more than a million deaths each year.

When screening began in 1969 to prevent people with hepatitis A or hepatitis B from donating blood, many recipients were spared from developing liver inflammation after transfusion. However, some people were still getting sick and researchers began to suspect that something dubbed “non-A, non-B” was lurking in donated blood.

As scientists were tracking it down in the micro world, public health officials and others tried to block the presumed virus in the macro world. In the United States, this meant changing blood-donation practices. When it became clear that as many as one in five transfusion recipients developed hepatitis, probably as the result of a virus, the blood donation system switched from being a paid enterprise to a volunteer activity.

It was anticipated that this would eliminate one source of the virus – users of street drugs – and it did; rates of transmission after transfusion dropped by half. By the 1980s, researchers had figured out that donors carrying the mysterious pathogen often had elevated levels of antibodies to the hepatitis B virus or elevated levels of ALT. Blood banks then began testing prospective donors and cut the incidence of non-A, non-B hepatitis by another half.

When Dr. Alter and his team got to work studying chimpanzees, they were able to confirm that the non-A, non-B agent was transmittable by blood transfusion. But the next step proved insurmountable. “People knew what the virus would look like if we found it, but we couldn’t find it,” Dr. Alter said.

“Then Chiron came along and cloned it,” he recounts.

The tiny start-up company was housed in a few rented rooms in an abandoned plant in Emeryville, Calif. This is where Nobel Laureate Dr. Houghton and coworkers Qui-Lim Choo, PhD, and George Kuo, PhD, spent 7 years chasing the mystery pathogen. When every traditional method to pin it down failed, the team tried some nontraditional approaches.

They found success when they painstakingly cloned genomic fragments from the blood of an infected chimpanzee and then screened this library using serum isolated from affected patients. The hope was that antibodies in the serum samples would stick to the viral genetic material and create a signpost indicating its presence.

This “fishing expedition” was disappointing at first, said Dr. Choo, now vice president of research at Nansha Biologics Limited in Hong Kong. “We didn’t catch any fish.”

He likened the pursuit, which took place under growing pressure from upper management, to that in “The Imitation Game,” the film that depicted Alan Turing’s effort to decrypt German intelligence messages for the British government during World War II.

The effort wasn’t working out and the team was down. So to keep spirits up, Dr. Kuo shared a snippet of the Lewis Carroll poem “The Hunting of the Snark.” It just happened to encapsulate the frustrations of their pursuit while also encouraging perseverance: “For the Snark’s a peculiar creature, that won’t / Be caught in a commonplace way. / Do all that you know, and try all that you don’t: / Not a chance must be wasted today!”

Those words motivated the team to keep going, to try different approaches and, ultimately, to find the hepatitis C virus, said Dr. Kuo, now retired.

During the tedious process of screening millions of clones, Dr. Choo spotted a single likely area on one of the plates that his “gut feeling” told him would contain the viral material. And it did. The pathogen – RNA packed in a lipid coat – was a member of the Flaviviridae family.

In 1989, the team reported that they’d identified a new flavivirus associated with posttransfusion hepatitis, and published their findings in Science. Later that year, an antibody test for it was described in Science by the team, which included Dr. Alter.

The success was a “fantastic feeling,” mused Dr. Houghton, now a virologist at the University of Alberta, Edmonton. “I’ve often said that, from 1989 to 1991, I was high just on the discovery.” After that, “researchers and the pharmaceutical industry did a great job coming up with really effective antivirals.”

“Mike, with his team, took 7 years to get this tiny little piece of viral genome, which reacted with convalescent patient serum, and used that to build up the sequence. That’s where I come into it,” said Dr. Rice, professor of virology at Rockefeller University, New York, and the third scientist in the Nobel Prize–winning trio.

The next step was to confirm that this was causing the hepatitis in patients who received blood transfusions. Over the course of several years, Dr. Rice and colleagues at the Washington University, St. Louis, engineered a version of the virus that retained its replicating capacity and injected it into chimpanzees. The animals developed hepatitis, confirming that this flavivirus was indeed the cause. More than 8 years after the virus was identified, scientists had proof of its infectiousness.

“We finally knew the structure of the viral genome,” said Dr. Rice. “We showed that the sequence was sufficient to initiate infection and cause disease.”

Those findings, published in 1997 in Science, were the key final step in the search for a molecular target for therapies and, maybe someday, a vaccine.

For the first time in history, hepatitis C can now be cured, raising hopes that the virus will be eradicated from the world population. But obstacles remain as the World Health Organization works toward its goal of eliminating hepatitis C–related disease by 2030.

Rates have actually risen in the United States as the opioid epidemic has taken hold because the virus is common in people who use street drugs and are at increased risk for behaviors that lead to transmission.

The prevalence of chronic hepatitis C now hovers around 1%. In 2019, it affected an estimated 3.8 million Americans, and more than 39,000 people died of hepatitis C–related causes. Of all deaths from liver cancer in 2019, 39% were attributable to hepatitis C.

This “silent killer” can take years to develop, which dampens the sense of immediacy to help, said Jean-Michel Piedagnel, director of the Drugs for Neglected Diseases nonprofit initiative.

People infected with hepatitis C are often part of marginalized groups. There isn’t typically a common demographic factor to unite them in advocacy.

And even though treatment can cost as little as $200 in countries where generic drugs are available, money can still be an issue, Mr. Piedagnel pointed out.

The COVID-19 response shows how quickly health systems can evolve in a crisis and adapt. “If there is political will, means can be found, said Cary James, CEO at the World Hepatitis Alliance.

The incredible speed of vaccine development for SARS-CoV-2 has impressed the Nobel Laureates, who have yet to see a vaccine for hepatitis C.

Dr. Houghton said he hopes this momentum will perpetuate new emergency filings for hepatitis C vaccines.

If even a tiny fraction of the money that’s gone into COVID-19 were used, Dr. Rice pointed out, “we’d have a hep C vaccine by now.”

A version of this article first appeared on Medscape.com

Many types of plastics pose an unrecognized threat to human health by leaching endocrine-disrupting chemicals, and a new report from the Endocrine Society and the International Pollutants Elimination Network presents their dangers and risks.

curtoicurto/Getty Images

Written in a consumer-friendly form designed to guide public interest groups and policy makers, the report also can be used by clinicians to inform discussions with patients about the potential dangers of plastics and how they can reduce their exposure to endocrine-disrupting chemicals.

The report, Plastics, EDCs, & Health, defines endocrine-disrupting chemicals (EDCs) as “an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Hormones in the body must be released at specific times, and therefore interference with their normal activity can have profound effects on health in areas including growth and reproductive development, according to the report.

The available data show “more and more information about the different chemicals and the different effects they are having,” said lead author, Jodi Flaws, PhD, of the University of Illinois at Urbana-Champaign, in a virtual press conference accompanying the release of the report.

Although numerous EDCs have been identified, a recent study suggested that many potentially dangerous chemical additives remain unknown because they are identified as confidential or simply not well described, the report authors said. In addition, creation of more plastic products will likely lead to increased exposure to EDCs and make health problems worse, said report coauthor Pauliina Damdimopoulou, PhD, of the Karolinska Institutet in Stockholm.
 

Lesser-known EDCs populate consumer products

Most consumers are aware of bisphenol A and phthalates as known EDCs, said Dr. Flaws, but the report identifies other lesser-known EDCs including per- and polyfluoroalkyl substances (PFAS), dioxins, flame retardants, and UV stabilizers.

For example, PFAS have been used for decades in a range of consumer products including stain resistant clothes, fast food wrappers, carpet and furniture treatments, cookware, and firefighting foams, according to the report. Consequently, PFAS have become common in many water sources including surface water, drinking water, and ground water because of how they are disposed. “Consumption of fish and other aquatic creatures caught in waterways contaminated with PFAS also poses heightened risks due to bioaccumulation of persistent chemicals in these animals,” the report authors noted. Human exposures to PFAS have been documented in urine, serum, plasma, placenta, umbilical cord, breast milk, and fetal tissues, they added.

Brominated flame retardants are another lesser-known EDC highlighted in the report. These chemical additives are used in plastics such as electronics cases to reduce the spread of fire, as well as in furniture foam and other building materials, the authors wrote. UV stabilizers, which also have been linked to health problems, often are used in manufacturing cars and other machinery.

Microplastics create large risk

Microplastics, defined as plastic particles less than 5 mm in diameter, are another source of exposure to EDCs that is not well publicized, according to the report. Plastic waste disposal often leads to the release of microplastics, which can infiltrate soil and water. Plastic waste is often dumped or burned; outdoor burning of plastic causes emission of dioxins into the air and ground.

“Not only do microplastics contain endogenous chemical additives, which are not bound to the microplastic and can leach out of the microplastic and expose the population, they can also bind and accumulate toxic chemicals from the surrounding environment such as sea water and sediment,” the report authors said.

Recycling is not an easy answer, either. Often more chemicals are created and released during the process of using plastics to make other plastics, according to the report.

Overall, more awareness of the potential for increased exposure to EDCs and support of strategies to seek out alternatives to hazardous chemicals is needed at the global level, the authors wrote. For example, the European Union has proposed a chemicals strategy that includes improved classification of EDCs and banning identified EDCs in consumer products.

New data support ongoing dangers

“It was important to produce the report at this time because several new studies came out on the effects of EDCs from plastics on human health,” Dr. Flaws said in an interview. “Further, there was not previously a single source that brought together all the information in a manner that was targeted towards the public, policy makers, and others,” she said.

Dr. Flaws said that what has surprised her most in the recent research is the fact that plastics contain such a range of chemicals and EDCs.

“A good take-home message [from the report] is that plastics can contain endocrine-disrupting chemicals that can interfere with normal hormones and lead to adverse health outcomes,” she said. “I suggest limiting the use of plastics as much as possible. I know this is very hard to do, so if someone needs to use plastic, they should not heat food or drink in plastic containers,” she emphasized. Individuals also can limit reuse of plastics over and over,” she said. “Heating and repeated use/washing often causes plastics to leach EDCs into food and drink that we then get into our bodies.”

Additional research is needed to understand the mechanisms by which EDCs from plastics cause damage, Dr. Flaws emphasized. “Given that it is not possible to eliminate plastics at this time, if we understood mechanisms of action, we could develop ways to prevent toxicity or treat EDC-induced adverse health outcomes,” she said. “We also need research designed to develop plastics or ‘green materials’ that do not contain endocrine disruptors and do not cause health problems or damage the environment,” she noted.

The report was produced as a joint effort of the Endocrine Society and International Pollutants Elimination Network. The report authors had no financial conflicts to disclose.

Many types of plastics pose an unrecognized threat to human health by leaching endocrine-disrupting chemicals, and a new report from the Endocrine Society and the International Pollutants Elimination Network presents their dangers and risks.

curtoicurto/Getty Images

Written in a consumer-friendly form designed to guide public interest groups and policy makers, the report also can be used by clinicians to inform discussions with patients about the potential dangers of plastics and how they can reduce their exposure to endocrine-disrupting chemicals.

The report, Plastics, EDCs, & Health, defines endocrine-disrupting chemicals (EDCs) as “an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Hormones in the body must be released at specific times, and therefore interference with their normal activity can have profound effects on health in areas including growth and reproductive development, according to the report.

The available data show “more and more information about the different chemicals and the different effects they are having,” said lead author, Jodi Flaws, PhD, of the University of Illinois at Urbana-Champaign, in a virtual press conference accompanying the release of the report.

Although numerous EDCs have been identified, a recent study suggested that many potentially dangerous chemical additives remain unknown because they are identified as confidential or simply not well described, the report authors said. In addition, creation of more plastic products will likely lead to increased exposure to EDCs and make health problems worse, said report coauthor Pauliina Damdimopoulou, PhD, of the Karolinska Institutet in Stockholm.
 

Lesser-known EDCs populate consumer products

Most consumers are aware of bisphenol A and phthalates as known EDCs, said Dr. Flaws, but the report identifies other lesser-known EDCs including per- and polyfluoroalkyl substances (PFAS), dioxins, flame retardants, and UV stabilizers.

For example, PFAS have been used for decades in a range of consumer products including stain resistant clothes, fast food wrappers, carpet and furniture treatments, cookware, and firefighting foams, according to the report. Consequently, PFAS have become common in many water sources including surface water, drinking water, and ground water because of how they are disposed. “Consumption of fish and other aquatic creatures caught in waterways contaminated with PFAS also poses heightened risks due to bioaccumulation of persistent chemicals in these animals,” the report authors noted. Human exposures to PFAS have been documented in urine, serum, plasma, placenta, umbilical cord, breast milk, and fetal tissues, they added.

Brominated flame retardants are another lesser-known EDC highlighted in the report. These chemical additives are used in plastics such as electronics cases to reduce the spread of fire, as well as in furniture foam and other building materials, the authors wrote. UV stabilizers, which also have been linked to health problems, often are used in manufacturing cars and other machinery.

Microplastics create large risk

Microplastics, defined as plastic particles less than 5 mm in diameter, are another source of exposure to EDCs that is not well publicized, according to the report. Plastic waste disposal often leads to the release of microplastics, which can infiltrate soil and water. Plastic waste is often dumped or burned; outdoor burning of plastic causes emission of dioxins into the air and ground.

“Not only do microplastics contain endogenous chemical additives, which are not bound to the microplastic and can leach out of the microplastic and expose the population, they can also bind and accumulate toxic chemicals from the surrounding environment such as sea water and sediment,” the report authors said.

Recycling is not an easy answer, either. Often more chemicals are created and released during the process of using plastics to make other plastics, according to the report.

Overall, more awareness of the potential for increased exposure to EDCs and support of strategies to seek out alternatives to hazardous chemicals is needed at the global level, the authors wrote. For example, the European Union has proposed a chemicals strategy that includes improved classification of EDCs and banning identified EDCs in consumer products.

New data support ongoing dangers

“It was important to produce the report at this time because several new studies came out on the effects of EDCs from plastics on human health,” Dr. Flaws said in an interview. “Further, there was not previously a single source that brought together all the information in a manner that was targeted towards the public, policy makers, and others,” she said.

Dr. Flaws said that what has surprised her most in the recent research is the fact that plastics contain such a range of chemicals and EDCs.

“A good take-home message [from the report] is that plastics can contain endocrine-disrupting chemicals that can interfere with normal hormones and lead to adverse health outcomes,” she said. “I suggest limiting the use of plastics as much as possible. I know this is very hard to do, so if someone needs to use plastic, they should not heat food or drink in plastic containers,” she emphasized. Individuals also can limit reuse of plastics over and over,” she said. “Heating and repeated use/washing often causes plastics to leach EDCs into food and drink that we then get into our bodies.”

Additional research is needed to understand the mechanisms by which EDCs from plastics cause damage, Dr. Flaws emphasized. “Given that it is not possible to eliminate plastics at this time, if we understood mechanisms of action, we could develop ways to prevent toxicity or treat EDC-induced adverse health outcomes,” she said. “We also need research designed to develop plastics or ‘green materials’ that do not contain endocrine disruptors and do not cause health problems or damage the environment,” she noted.

The report was produced as a joint effort of the Endocrine Society and International Pollutants Elimination Network. The report authors had no financial conflicts to disclose.

Many types of plastics pose an unrecognized threat to human health by leaching endocrine-disrupting chemicals, and a new report from the Endocrine Society and the International Pollutants Elimination Network presents their dangers and risks.

curtoicurto/Getty Images

Written in a consumer-friendly form designed to guide public interest groups and policy makers, the report also can be used by clinicians to inform discussions with patients about the potential dangers of plastics and how they can reduce their exposure to endocrine-disrupting chemicals.

The report, Plastics, EDCs, & Health, defines endocrine-disrupting chemicals (EDCs) as “an exogenous chemical, or mixture of chemicals, that interferes with any aspect of hormone action.” Hormones in the body must be released at specific times, and therefore interference with their normal activity can have profound effects on health in areas including growth and reproductive development, according to the report.

The available data show “more and more information about the different chemicals and the different effects they are having,” said lead author, Jodi Flaws, PhD, of the University of Illinois at Urbana-Champaign, in a virtual press conference accompanying the release of the report.

Although numerous EDCs have been identified, a recent study suggested that many potentially dangerous chemical additives remain unknown because they are identified as confidential or simply not well described, the report authors said. In addition, creation of more plastic products will likely lead to increased exposure to EDCs and make health problems worse, said report coauthor Pauliina Damdimopoulou, PhD, of the Karolinska Institutet in Stockholm.
 

Lesser-known EDCs populate consumer products

Most consumers are aware of bisphenol A and phthalates as known EDCs, said Dr. Flaws, but the report identifies other lesser-known EDCs including per- and polyfluoroalkyl substances (PFAS), dioxins, flame retardants, and UV stabilizers.

For example, PFAS have been used for decades in a range of consumer products including stain resistant clothes, fast food wrappers, carpet and furniture treatments, cookware, and firefighting foams, according to the report. Consequently, PFAS have become common in many water sources including surface water, drinking water, and ground water because of how they are disposed. “Consumption of fish and other aquatic creatures caught in waterways contaminated with PFAS also poses heightened risks due to bioaccumulation of persistent chemicals in these animals,” the report authors noted. Human exposures to PFAS have been documented in urine, serum, plasma, placenta, umbilical cord, breast milk, and fetal tissues, they added.

Brominated flame retardants are another lesser-known EDC highlighted in the report. These chemical additives are used in plastics such as electronics cases to reduce the spread of fire, as well as in furniture foam and other building materials, the authors wrote. UV stabilizers, which also have been linked to health problems, often are used in manufacturing cars and other machinery.

Microplastics create large risk

Microplastics, defined as plastic particles less than 5 mm in diameter, are another source of exposure to EDCs that is not well publicized, according to the report. Plastic waste disposal often leads to the release of microplastics, which can infiltrate soil and water. Plastic waste is often dumped or burned; outdoor burning of plastic causes emission of dioxins into the air and ground.

“Not only do microplastics contain endogenous chemical additives, which are not bound to the microplastic and can leach out of the microplastic and expose the population, they can also bind and accumulate toxic chemicals from the surrounding environment such as sea water and sediment,” the report authors said.

Recycling is not an easy answer, either. Often more chemicals are created and released during the process of using plastics to make other plastics, according to the report.

Overall, more awareness of the potential for increased exposure to EDCs and support of strategies to seek out alternatives to hazardous chemicals is needed at the global level, the authors wrote. For example, the European Union has proposed a chemicals strategy that includes improved classification of EDCs and banning identified EDCs in consumer products.

New data support ongoing dangers

“It was important to produce the report at this time because several new studies came out on the effects of EDCs from plastics on human health,” Dr. Flaws said in an interview. “Further, there was not previously a single source that brought together all the information in a manner that was targeted towards the public, policy makers, and others,” she said.

Dr. Flaws said that what has surprised her most in the recent research is the fact that plastics contain such a range of chemicals and EDCs.

“A good take-home message [from the report] is that plastics can contain endocrine-disrupting chemicals that can interfere with normal hormones and lead to adverse health outcomes,” she said. “I suggest limiting the use of plastics as much as possible. I know this is very hard to do, so if someone needs to use plastic, they should not heat food or drink in plastic containers,” she emphasized. Individuals also can limit reuse of plastics over and over,” she said. “Heating and repeated use/washing often causes plastics to leach EDCs into food and drink that we then get into our bodies.”

Additional research is needed to understand the mechanisms by which EDCs from plastics cause damage, Dr. Flaws emphasized. “Given that it is not possible to eliminate plastics at this time, if we understood mechanisms of action, we could develop ways to prevent toxicity or treat EDC-induced adverse health outcomes,” she said. “We also need research designed to develop plastics or ‘green materials’ that do not contain endocrine disruptors and do not cause health problems or damage the environment,” she noted.

The report was produced as a joint effort of the Endocrine Society and International Pollutants Elimination Network. The report authors had no financial conflicts to disclose.