COVID-19 Updates

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

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

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

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

The first report on responses to COVID-19 vaccination among patients with cancer suggests that, for these patients, the immune response that occurs after the first dose of vaccine is reduced, in comparison with the response that occurs in healthy individuals.

The new findings, which are soon to be published as a preprint, cast doubt on the current U.K. policy of delaying the second dose of the vaccine.

Delaying the second dose can leave most patients with cancer wholly or partially unprotected, according to the researchers. Moreover, such a delay has implications for transmission of SARS-CoV-2 in the cancer patient’s environs as well as for the evolution of virus variants that could be of concern, the researchers concluded.

The data come from a British study that included 151 patients with cancer and 54 healthy control persons. All participants received the COVID-19 mRNA BNT162b2 vaccine (Pfizer-BioNTech).

This vaccine requires two doses. The first few participants in this study were given the second dose 21 days after they had received the first dose, but then national guidelines changed, and the remaining participants had to wait 12 weeks to receive their second dose.

The researchers reported that, among health controls, the immune efficacy of the first dose was very high (97% efficacious). By contrast, among patients with solid tumors, the immune efficacy of a single dose was strikingly low (39%), and it was even lower in patients with hematologic malignancies (13%).

The second dose of vaccine greatly and rapidly increased the immune efficacy in patients with solid tumors (95% within 2 weeks of receiving the second dose), the researchers added.

Too few patients with hematologic cancers had received the second dose before the study ended for clear conclusions to be drawn. Nevertheless, the available data suggest that 50% of patients with hematologic cancers who had received the booster at day 21 were seropositive at 5 weeks vs. only 8% of those who had not received the booster.

“Our data provide the first real-world evidence of immune efficacy following one dose of the Pfizer vaccine in immunocompromised patient populations [and] clearly show that the poor one-dose efficacy in cancer patients can be rescued with an early booster at day 21,” commented senior author Sheeba Irshad, MD, senior clinical lecturer, King’s College London.

“Based on our findings, we would recommend an urgent review of the vaccine strategy for clinically extremely vulnerable groups. Until then, it is important that cancer patients continue to observe all public health measures in place, such as social distancing and shielding when attending hospitals, even after vaccination,” Dr. Irshad added.

The paper, with first author Leticia Monin-Aldama, PhD, is scheduled to appear on the preprint server medRxiv. It has not undergone peer review. The paper was distributed to journalists, with comments from experts not involved in the study, by the UK Science Media Centre.

These data are “of immediate importance” to patients with cancer, commented Shoba Amarnath, PhD, Newcastle University research fellow, Laboratory of T-cell Regulation, Newcastle University Center for Cancer, Newcastle upon Tyne, England.

“These findings are consistent with our understanding. … We know that the immune system within cancer patients is compromised as compared to healthy controls,” Dr. Amarnath said. “The data in the study support the notion that, in solid cancer patients, a considerable delay in second dose will extend the period when cancer patients are at risk of SARS-CoV-2 infection.”

Although more data are required, “this study does raise the issue of whether patients with cancer, other diseases, or those undergoing therapies that affect the body’s immune response should be fast-tracked for their second vaccine dose,” commented Lawrence Young, PhD, professor of molecular oncology and director of the Warwick Cancer Research Center, University of Warwick, Coventry, England.

Stephen Evans, MSc, professor of pharmacoepidemiology, London School of Hygiene and Tropical Medicine, underlined that the study is “essentially” observational and “inevitable limitations must be taken into account.

“Nevertheless, these results do suggest that the vaccines may well not protect those patients with cancer as well as those without cancer,” Mr. Evans said. He added that it is “important that this population continues to observe all COVID-19–associated measures, such as social distancing and shielding when attending hospitals, even after vaccination.”

Study details

Previous studies have shown that some patients with cancer have prolonged responses to SARS-CoV-2 infection, with ongoing immune dysregulation, inefficient seroconversion, and prolonged viral shedding.

There are few data, however, on how these patients respond to COVID-19 vaccination. The authors point out that, among the 18,860 individuals who received the Pfizer vaccine during its development trials, “none with an active oncological diagnosis was included.”

To investigate this issue, they launched the SARS-CoV-2 for Cancer Patients (SOAP-02) study.

The 151 patients with cancer who participated in this study were mostly elderly, the authors noted (75% were older than 65 years; the median age was 73 years). The majority (63%) had solid-tumor malignancies. Of those, 8% had late-stage disease and had been living with their cancer for more than 24 months.

The healthy control persons were vaccine-eligible primary health care workers who were not age matched to the cancer patients.

All participants received the first dose of vaccine; 31 (of 151) patients with cancer and 16 (of 54) healthy control persons received the second dose on day 21.

The remaining participants were scheduled to receive their second dose 12 weeks later (after the study ended), in line with the changes in the national guidelines.

The team reported that, approximately 21 days after receiving the first vaccine dose, the immune efficacy of the vaccine was estimated to be 97% among healthy control persons vs. 39% for patients with solid tumors and only 13% for those with hematologic malignancies (P < .0001 for both).

T-cell responses, as assessed via interferon-gamma and/or interleukin-2 production, were observed in 82% of healthy control persons, 71% of patients with solid tumors, and 50% of those with hematologic cancers.

Vaccine boosting at day 21 resulted in immune efficacy of 100% for healthy control persons and 95% for patients with solid tumors. In contrast, only 43% of those who did not receive the second dose were seropositive 2 weeks later.

Further analysis suggested that participants who did not have a serologic response were “spread evenly” across different cancer types, but the reduced responses were more frequent among patients who had received the vaccine within 15 days of cancer treatment, especially chemotherapy, and had undergone intensive treatments.

The SOAP study is sponsored by King’s College London and Guy’s and St. Thomas Trust Foundation NHS Trust. It is funded from grants from the KCL Charity, Cancer Research UK, and program grants from Breast Cancer Now. The investigators have disclosed no relevant financial relationships.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

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

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

Pregnant patients with COVID-19 infections were more likely to experience severe disease if they had preexisting comorbidities, such as chronic hypertension, asthma, or pregestational diabetes, according to findings from a new study presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

The study included outcomes for the largest multistate cohort of pregnant patients with COVID-19 outside of what the Centers for Disease Control and Prevention is tracking. Its findings also mirrored those of a multicenter, retrospective study in Washington state, published in the American Journal of Obstetrics & Gynecology. That study also found that pregnant patients hospitalized for COVID-19 were more likely to have comorbidities, and both studies found an increased likelihood of preterm birth among pregnant patients with severe or critical disease.
 

Disease severity linked to risk of perinatal complications

In the abstract presented at the SMFM meeting, more severe disease was associated with older age and a higher median body mass index, as seen in the general population, but the researchers found no differences in disease severity occurred by race or ethnicity, Torri D. Metz, MD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, told attendees of the conference. The researchers also found that perinatal complications were more prevalent in those with severe or critical COVID-19 disease but not in those with mild or moderate disease. Vertical COVID-19 transmission from mother to child was rare.

The observational study included all patients who had a singleton pregnancy, had a positive SARS-CoV-2 test, and delivered between March 1 and July 31, 2020, at one of the 33 U.S. hospitals in the NICHD Maternal-Fetal Medicine Units Network, spread across 14 states. The researchers used electronic medical records to determine incidence of cesarean delivery, postpartum hemorrhage, hypertensive disorders of pregnancy, preterm birth (less than 37 weeks), maternal death, infant death, and positive infant COVID-19 test. They tracked mothers through 6 weeks post partum and newborns through delivery hospitalization.

Of 1,291 patients in the cohort, 1,219 received their first positive COVID-19 test during pregnancy. The others tested positive while in the hospital for delivery or within a month and a half after discharge. Limiting their analysis to those who developed COVID-19 while pregnant prior to delivery, nearly half (47%) were asymptomatic.

The disease was mild in 27%, moderate in 14%, severe in 8%, and critical in 4%. The researchers used the National Institutes of Health classifications for severity and included deaths in the critical group. The most common symptom was a cough, reported by a third of the patients (34%). Four of six maternal deaths that occurred were caused by COVID-19.

Compared with an average age of 28 in those without symptoms, the mean age was 29 in those with mild/moderate disease and 30 in those with severe/critical disease (P = .006). Similarly, the mean BMI was 28.3 in asymptomatic patients, 29 in those with mild/moderate disease, and 32.3 in those with severe/critical disease (P < .001). Despite a diverse cohort – 53% Hispanic, 23% Black, and 15% White – the researches found no racial/ethnic trends in disease severity.

Patients who had asthma, chronic obstructive pulmonary disorder, pregestational diabetes, chronic hypertension, chronic liver disease, or a seizure disorder were all significantly more likely to have critical/severe disease than mild/moderate disease, and more likely to have mild/moderate disease than asymptomatic (P values ranged from < .001 to .02).

The mothers with critical or severe illness were 1.6 times more likely to have cesarean births and to have hypertensive disorders of pregnancy, and they were twice as likely to have postpartum hemorrhage (P < .001; P = .007). Those with mild or moderate disease, however, had no increased risks for perinatal complications over asymptomatic patients.

Critical or severe illness was also associated with more than triple the risk of preterm birth (adjusted risk ratio, 3.6; P < .001). Newborns of mothers with critical or severe illness also had three times greater risk of neonatal ICU admission (ARR, 3.1; P <. 001) and weighed an average 385 g less than newborns of asymptomatic mothers. COVID-19 rate among infants was only 1% during delivery hospitalization.

Since the study cutoff was July 30 and COVID infections only became prevalent in March, the researchers were unable to evaluate women for outcomes resulting from COVID infections in early pregnancy, such as congenital anomalies or early miscarriage, Dr. Metz said. In addition, since many of the sites are urban centers, the data may not be generalizable to rural areas.

Peter S. Bernstein, MD, MPH, of Montefiore Medical Center, New York, asked whether the increased cesarean deliveries and preterm births in the group of women with severe disease were caused by usual obstetric causes or the treatment of COVID-19 infection. Dr. Metz said the vast majority of preterm deliveries were indicated, but only a small proportion were induced for COVID-19 alone. “A lot had hypertensive disorders of pregnancies or PPROM, so it’s partly driven by the infection itself but also partly driven by some of those perinatal complications,” she said.
 

Similar findings in Washington

In the Washington study, among 240 pregnant patients with confirmed COVID-19 infection between March 1 and July 30, 2020, 1 in 11 developed severe or critical disease, and 1 in 10 were hospitalized. The pregnant patients had more than triple the risk of hospitalization compared with adults of similar ages in the general population (10% vs. 2.8%; rate ratio, 3.5). Similar to the multistate NICHD study, women were more likely to be hospitalized if they had asthma, hypertension, type 2 diabetes, autoimmune disease, or class III obesity.

Three mothers died of COVID-19, resulting in a case fatality rate 13.6 times greater than nonpregnant patients with COVID-19 in the general population. The absolute difference in the rate was 1.2%. As seen in the NICHD study, preterm birth was more common in mothers with severe or critical COVID-19. Nearly half (45.4%) of mothers with severe or critical COVID-19 delivered preterm compared to 5.2% in those with mild COVID-19 (P < .001).

“Our finding that deaths in pregnant patients contributed disproportionately to deaths from COVID-19 among 20- to 39-year-olds in Washington state is similar to what was observed during the influenza A virus H1N1 2009 pandemic,” Erica M. Lokken, PhD, MS, of the departments of global health and ob.gyn. at the University of Washington, Seattle, and colleagues wrote in the Washington study. But they noted that it took 8 months into the pandemic before pregnant patients were identified as a high-risk group for COVID-19.

“Given the similarity in clinical course between COVID-19 and IAV H1N1 2009 with an increased risk for mortality during pregnancy and the postpartum period, we strongly recommend that pregnant patients should be considered a high-risk population to novel highly pathogenic respiratory viruses until proven otherwise by population-based studies with good ascertainment of pregnancy status,” they wrote.

Judette Louis, MD, MPH, associate professor of ob.gyn. and department chair at the University of South Florida, Tampa, said in an interview that the findings in these studies were fairly expected, but it’s important to have data from such a large cohort as the one presented at SMFM.

“It confirmed that those who had severe disease were more likely to have chronic medical conditions, mirroring what we saw in the general population who isn’t pregnant,” Dr. Louis said. “I thought this was very crucial because as pregnant women are trying to decide whether they should get the COVID vaccine, this provides support to say that if you’re pregnant, you’re more likely to have severe disease [if you have] other chronic medical conditions.”

The findings also confirm the importance of pregnant people taking precautions to avoid infection.

“Even though these individuals are, as a group, in an age cohort that mostly has asymptomatic disease, for some of them, it results in severe disease and even maternal death,” she said. “They should still take it seriously if they’re pregnant.”

The SMFM abstract study was funded by the NICHD. The Washington study was funded by the University of Washington Population Health Initiative, the National Institutes of Health, and philanthropic gift funds. One coauthor of the Washington study is on a Pfizer and GlaxoSmithKline advisory board for immunizations. No other authors or individuals interviewed reported any disclosures.

In 2020, COVID-19 disrupted our medical system, and life in general. In the 1980s, the AIDS epidemic devastated communities and overwhelmed hospitals. There were lessons learned from the AIDS epidemic that can be applied to the current situation.

Patients with HIV-spectrum illness faced stigmatization and societal indifference, including rejection by family members, increased rates of suicide, fears of sexual and/or intrauterine transmission, substance abuse issues, and alterations of body image for those with wasting syndromes and disfiguring Kaposi lesions. AIDS prevention strategies such as the provision of condoms and needle exchange programs were controversial, and many caregivers exposed to contaminated fluids had to endure months of antiretroviral treatment.

Similar to the AIDS epidemic, the COVID-19 pandemic has had significant psychological implications for patients and caregivers. Patients with COVID-19 infections also face feelings of guilt over potentially exposing a family member to the virus; devastating socioeconomic issues; restrictive hospital visitation policies for family members; disease news oversaturation; and feelings of hopelessness. People with AIDS in the 1980s faced the possibility of dying alone, and there was initial skepticism about medications to treat HIV—just as some individuals are now uneasy about recently introduced coronavirus vaccines.

Looking back on the AIDS epidemic should teach us to prioritize attending to the mental health of sufferers and caregivers and depoliticizing prevention strategies.

The similarities of both diseases allow us some foresight on how to deal with current COVID-19 issues. Looking back on the AIDS epidemic should teach us to prioritize attending to the mental health of sufferers and caregivers, creating advocacy and support groups for when a patient’s family is unavailable, instilling public confidence in treatment options, maintaining staff morale, addressing substance abuse (due to COVID-related stress), and depoliticizing prevention strategies. Addressing these issues is especially critical for minority populations.

As respected medical care leaders, we can provide and draw extra attention to the needs of patients’ family members and health care personnel during this COVID-19 pandemic. Hopefully, the distribution of vaccines will shorten some of our communal and professional distress.

Robert Frierson, MD
Steven Lippmann, MD
Louisville, KY

In 2020, COVID-19 disrupted our medical system, and life in general. In the 1980s, the AIDS epidemic devastated communities and overwhelmed hospitals. There were lessons learned from the AIDS epidemic that can be applied to the current situation.

Patients with HIV-spectrum illness faced stigmatization and societal indifference, including rejection by family members, increased rates of suicide, fears of sexual and/or intrauterine transmission, substance abuse issues, and alterations of body image for those with wasting syndromes and disfiguring Kaposi lesions. AIDS prevention strategies such as the provision of condoms and needle exchange programs were controversial, and many caregivers exposed to contaminated fluids had to endure months of antiretroviral treatment.

Similar to the AIDS epidemic, the COVID-19 pandemic has had significant psychological implications for patients and caregivers. Patients with COVID-19 infections also face feelings of guilt over potentially exposing a family member to the virus; devastating socioeconomic issues; restrictive hospital visitation policies for family members; disease news oversaturation; and feelings of hopelessness. People with AIDS in the 1980s faced the possibility of dying alone, and there was initial skepticism about medications to treat HIV—just as some individuals are now uneasy about recently introduced coronavirus vaccines.

Looking back on the AIDS epidemic should teach us to prioritize attending to the mental health of sufferers and caregivers and depoliticizing prevention strategies.

The similarities of both diseases allow us some foresight on how to deal with current COVID-19 issues. Looking back on the AIDS epidemic should teach us to prioritize attending to the mental health of sufferers and caregivers, creating advocacy and support groups for when a patient’s family is unavailable, instilling public confidence in treatment options, maintaining staff morale, addressing substance abuse (due to COVID-related stress), and depoliticizing prevention strategies. Addressing these issues is especially critical for minority populations.

As respected medical care leaders, we can provide and draw extra attention to the needs of patients’ family members and health care personnel during this COVID-19 pandemic. Hopefully, the distribution of vaccines will shorten some of our communal and professional distress.

Robert Frierson, MD
Steven Lippmann, MD
Louisville, KY

In 2020, COVID-19 disrupted our medical system, and life in general. In the 1980s, the AIDS epidemic devastated communities and overwhelmed hospitals. There were lessons learned from the AIDS epidemic that can be applied to the current situation.

Patients with HIV-spectrum illness faced stigmatization and societal indifference, including rejection by family members, increased rates of suicide, fears of sexual and/or intrauterine transmission, substance abuse issues, and alterations of body image for those with wasting syndromes and disfiguring Kaposi lesions. AIDS prevention strategies such as the provision of condoms and needle exchange programs were controversial, and many caregivers exposed to contaminated fluids had to endure months of antiretroviral treatment.

Similar to the AIDS epidemic, the COVID-19 pandemic has had significant psychological implications for patients and caregivers. Patients with COVID-19 infections also face feelings of guilt over potentially exposing a family member to the virus; devastating socioeconomic issues; restrictive hospital visitation policies for family members; disease news oversaturation; and feelings of hopelessness. People with AIDS in the 1980s faced the possibility of dying alone, and there was initial skepticism about medications to treat HIV—just as some individuals are now uneasy about recently introduced coronavirus vaccines.

Looking back on the AIDS epidemic should teach us to prioritize attending to the mental health of sufferers and caregivers and depoliticizing prevention strategies.

The similarities of both diseases allow us some foresight on how to deal with current COVID-19 issues. Looking back on the AIDS epidemic should teach us to prioritize attending to the mental health of sufferers and caregivers, creating advocacy and support groups for when a patient’s family is unavailable, instilling public confidence in treatment options, maintaining staff morale, addressing substance abuse (due to COVID-related stress), and depoliticizing prevention strategies. Addressing these issues is especially critical for minority populations.

As respected medical care leaders, we can provide and draw extra attention to the needs of patients’ family members and health care personnel during this COVID-19 pandemic. Hopefully, the distribution of vaccines will shorten some of our communal and professional distress.

Robert Frierson, MD
Steven Lippmann, MD
Louisville, KY

Because of significant reduction in delivery of recommended childhood immunization during the pandemic, there is a risk for resurgence of vaccine preventable infections, including measles, pertussis, and polio, which can result in significant morbidity and mortality in children, reported Amy G. Feldman, MD, of Children’s Hospital Colorado, Aurora, and associates.

Yangna/Thinkstock

Will loss of herd immunity lead to vaccine deserts?

When asked to comment, pediatric infectious disease specialist Christopher J. Harrison, MD, said, “My concern is that we may see expansion of what I call ‘vaccine deserts.’ Vaccine deserts occur in underserved communities, areas with pockets of vaccine-hesitant families or among selected groups with difficult access to health care. These vaccine deserts have held a higher density of vulnerables due to low vaccine uptake, often giving rise to outbreaks of vaccine-preventable diseases, e.g., measles, mumps, pertussis. They are usually due to an index case arriving from another vaccine desert (a developing country or a developed country, U.S. or foreign) where the disease is still endemic or pockets of vaccine hesitancy/refusal exist. When detected, local outbreaks result in rapid responses from public/private health collaborations that limit the outbreak. But what if vaccine deserts became more generalized in the U.S. because of loss of vaccine-induced herd immunity in many more or larger areas of our communities because of pandemic-driven lack of vaccinations? That pandemic-driven indirect damage would further stress the health care system and the economy. And it may first show up in the older children whose vaccines were deferred in the first 4-6 months of the pandemic.”

Dr. Feldman and associates cited findings from a collaborative survey conducted by UNICEF, the World Health Organization, Gavi the Vaccine Alliance, the CDC, the Sabin Vaccine Institute, and the Johns Hopkins Bloomberg School of Public Health, which found that immunization programs experienced moderate to severe disruptions or terminations in at least 68 of 129 low and middle-income countries surveyed. According to the WHO, CDC, Red Cross, and GAVI, 94 million people presently are estimated to be at risk as a consequence of not receiving their measles vaccines following the suspensions.

“These national and international declines in routine immunizations have placed the global community at significant risk for outbreaks of vaccine-preventable infections (VPIs) including measles, polio, and pertussis, diseases which are more deadly, more contagious and have a higher reproductive factor (R0) amongst children than COVID-19,” the authors observed.

Dr. Feldman and associates outlined the horrible devastation that these VPI can cause in children, including significantly higher morbidity and mortality than adults, especially among those with immunodeficiencies. Neurologic deficits, paralysis, intellectual disabilities, and vision and hearing loss are just some of the permanent effects conveyed. “It is concerning to imagine how measles could spread across the United States when social distancing restriction[s] are relaxed and unvaccinated children return to school and usual community engagement,” they noted.
 

Collaborative engagement key to course correction

The authors found that primary care providers and public health communities are working not only to restore vaccine administration but also to restore confidence that vaccine delivery is safe in spite of COVID. In addition to recommending specific risk mitigation strategies for clinicians, they also suggested individual practitioners use electronic health records to identify patients with COVID-related lapses in vaccination, employ electronic health record–based parent notification of overdue immunizations, and offer distance-friendly vaccination options that include parking lot or drive-up window vaccine delivery.

Additionally, Dr. Feldman and colleagues recommended that local, state, regional, and national health systems use public service announcements via television and digital as well as social media platforms to convey important messages about the considerable health risks associated with vaccine avoidance and the availability of free or reduced-cost vaccination programs through the federally funded Vaccines For Children program for parents out of work or without insurance. Equally important is messaging around encouraging vaccine opportunities during all health care visits, whether they be subspecialty, urgent care, emergency room, or inpatient visits. In areas where access to clinics is limited, they urged the use of mobile clinics as well as additional focus on providing medical homes to children with poor access to care.

“A partial but expanding safety net may be developing spontaneously, i.e., practices and clinics based on a patient-centered medical home (PCMH) model,” noted Dr. Harrison, professor of pediatrics, University of Missouri-Kansas City, in an interview. “When lagging vaccinations were reported in mid-2020, we checked with a local hospital–based urban clinic and two suburban private practices modeled on PCMH. Each had noted a drastic drop in well checks in the first months of the pandemic. But with ill visits nearly nonexistent, they doubled down on maintaining health maintenance visits. Even though staff and provider work hours were limited, and families were less enthusiastic about well checks, momentum appears to have grown so that, by later in 2020, vaccine uptake rates were again comparable to 2019. So, some already seem to have answered the call, but practices/clinics remain hampered by months of reduced revenue needed to support staff, providers, PPE supplies, and added infection control needs,” he said.The study was funded by the Agency for Healthcare Research Quality. Dr. Isakov disclosed relationships with various pharmaceutical companies outside the submitted work. The other authors had no relevant disclosures. Dr. Harrison’s institution receives grant funding from GSK, Merck, and Pfizer for pediatric vaccine trials and pneumococcal seroprevalence studies on which he is an investigator.

pdnews@mdedge.com

Because of significant reduction in delivery of recommended childhood immunization during the pandemic, there is a risk for resurgence of vaccine preventable infections, including measles, pertussis, and polio, which can result in significant morbidity and mortality in children, reported Amy G. Feldman, MD, of Children’s Hospital Colorado, Aurora, and associates.

Yangna/Thinkstock

Will loss of herd immunity lead to vaccine deserts?

When asked to comment, pediatric infectious disease specialist Christopher J. Harrison, MD, said, “My concern is that we may see expansion of what I call ‘vaccine deserts.’ Vaccine deserts occur in underserved communities, areas with pockets of vaccine-hesitant families or among selected groups with difficult access to health care. These vaccine deserts have held a higher density of vulnerables due to low vaccine uptake, often giving rise to outbreaks of vaccine-preventable diseases, e.g., measles, mumps, pertussis. They are usually due to an index case arriving from another vaccine desert (a developing country or a developed country, U.S. or foreign) where the disease is still endemic or pockets of vaccine hesitancy/refusal exist. When detected, local outbreaks result in rapid responses from public/private health collaborations that limit the outbreak. But what if vaccine deserts became more generalized in the U.S. because of loss of vaccine-induced herd immunity in many more or larger areas of our communities because of pandemic-driven lack of vaccinations? That pandemic-driven indirect damage would further stress the health care system and the economy. And it may first show up in the older children whose vaccines were deferred in the first 4-6 months of the pandemic.”

Dr. Feldman and associates cited findings from a collaborative survey conducted by UNICEF, the World Health Organization, Gavi the Vaccine Alliance, the CDC, the Sabin Vaccine Institute, and the Johns Hopkins Bloomberg School of Public Health, which found that immunization programs experienced moderate to severe disruptions or terminations in at least 68 of 129 low and middle-income countries surveyed. According to the WHO, CDC, Red Cross, and GAVI, 94 million people presently are estimated to be at risk as a consequence of not receiving their measles vaccines following the suspensions.

“These national and international declines in routine immunizations have placed the global community at significant risk for outbreaks of vaccine-preventable infections (VPIs) including measles, polio, and pertussis, diseases which are more deadly, more contagious and have a higher reproductive factor (R0) amongst children than COVID-19,” the authors observed.

Dr. Feldman and associates outlined the horrible devastation that these VPI can cause in children, including significantly higher morbidity and mortality than adults, especially among those with immunodeficiencies. Neurologic deficits, paralysis, intellectual disabilities, and vision and hearing loss are just some of the permanent effects conveyed. “It is concerning to imagine how measles could spread across the United States when social distancing restriction[s] are relaxed and unvaccinated children return to school and usual community engagement,” they noted.
 

Collaborative engagement key to course correction

The authors found that primary care providers and public health communities are working not only to restore vaccine administration but also to restore confidence that vaccine delivery is safe in spite of COVID. In addition to recommending specific risk mitigation strategies for clinicians, they also suggested individual practitioners use electronic health records to identify patients with COVID-related lapses in vaccination, employ electronic health record–based parent notification of overdue immunizations, and offer distance-friendly vaccination options that include parking lot or drive-up window vaccine delivery.

Additionally, Dr. Feldman and colleagues recommended that local, state, regional, and national health systems use public service announcements via television and digital as well as social media platforms to convey important messages about the considerable health risks associated with vaccine avoidance and the availability of free or reduced-cost vaccination programs through the federally funded Vaccines For Children program for parents out of work or without insurance. Equally important is messaging around encouraging vaccine opportunities during all health care visits, whether they be subspecialty, urgent care, emergency room, or inpatient visits. In areas where access to clinics is limited, they urged the use of mobile clinics as well as additional focus on providing medical homes to children with poor access to care.

“A partial but expanding safety net may be developing spontaneously, i.e., practices and clinics based on a patient-centered medical home (PCMH) model,” noted Dr. Harrison, professor of pediatrics, University of Missouri-Kansas City, in an interview. “When lagging vaccinations were reported in mid-2020, we checked with a local hospital–based urban clinic and two suburban private practices modeled on PCMH. Each had noted a drastic drop in well checks in the first months of the pandemic. But with ill visits nearly nonexistent, they doubled down on maintaining health maintenance visits. Even though staff and provider work hours were limited, and families were less enthusiastic about well checks, momentum appears to have grown so that, by later in 2020, vaccine uptake rates were again comparable to 2019. So, some already seem to have answered the call, but practices/clinics remain hampered by months of reduced revenue needed to support staff, providers, PPE supplies, and added infection control needs,” he said.The study was funded by the Agency for Healthcare Research Quality. Dr. Isakov disclosed relationships with various pharmaceutical companies outside the submitted work. The other authors had no relevant disclosures. Dr. Harrison’s institution receives grant funding from GSK, Merck, and Pfizer for pediatric vaccine trials and pneumococcal seroprevalence studies on which he is an investigator.

pdnews@mdedge.com

Because of significant reduction in delivery of recommended childhood immunization during the pandemic, there is a risk for resurgence of vaccine preventable infections, including measles, pertussis, and polio, which can result in significant morbidity and mortality in children, reported Amy G. Feldman, MD, of Children’s Hospital Colorado, Aurora, and associates.

Yangna/Thinkstock

Will loss of herd immunity lead to vaccine deserts?

When asked to comment, pediatric infectious disease specialist Christopher J. Harrison, MD, said, “My concern is that we may see expansion of what I call ‘vaccine deserts.’ Vaccine deserts occur in underserved communities, areas with pockets of vaccine-hesitant families or among selected groups with difficult access to health care. These vaccine deserts have held a higher density of vulnerables due to low vaccine uptake, often giving rise to outbreaks of vaccine-preventable diseases, e.g., measles, mumps, pertussis. They are usually due to an index case arriving from another vaccine desert (a developing country or a developed country, U.S. or foreign) where the disease is still endemic or pockets of vaccine hesitancy/refusal exist. When detected, local outbreaks result in rapid responses from public/private health collaborations that limit the outbreak. But what if vaccine deserts became more generalized in the U.S. because of loss of vaccine-induced herd immunity in many more or larger areas of our communities because of pandemic-driven lack of vaccinations? That pandemic-driven indirect damage would further stress the health care system and the economy. And it may first show up in the older children whose vaccines were deferred in the first 4-6 months of the pandemic.”

Dr. Feldman and associates cited findings from a collaborative survey conducted by UNICEF, the World Health Organization, Gavi the Vaccine Alliance, the CDC, the Sabin Vaccine Institute, and the Johns Hopkins Bloomberg School of Public Health, which found that immunization programs experienced moderate to severe disruptions or terminations in at least 68 of 129 low and middle-income countries surveyed. According to the WHO, CDC, Red Cross, and GAVI, 94 million people presently are estimated to be at risk as a consequence of not receiving their measles vaccines following the suspensions.

“These national and international declines in routine immunizations have placed the global community at significant risk for outbreaks of vaccine-preventable infections (VPIs) including measles, polio, and pertussis, diseases which are more deadly, more contagious and have a higher reproductive factor (R0) amongst children than COVID-19,” the authors observed.

Dr. Feldman and associates outlined the horrible devastation that these VPI can cause in children, including significantly higher morbidity and mortality than adults, especially among those with immunodeficiencies. Neurologic deficits, paralysis, intellectual disabilities, and vision and hearing loss are just some of the permanent effects conveyed. “It is concerning to imagine how measles could spread across the United States when social distancing restriction[s] are relaxed and unvaccinated children return to school and usual community engagement,” they noted.
 

Collaborative engagement key to course correction

The authors found that primary care providers and public health communities are working not only to restore vaccine administration but also to restore confidence that vaccine delivery is safe in spite of COVID. In addition to recommending specific risk mitigation strategies for clinicians, they also suggested individual practitioners use electronic health records to identify patients with COVID-related lapses in vaccination, employ electronic health record–based parent notification of overdue immunizations, and offer distance-friendly vaccination options that include parking lot or drive-up window vaccine delivery.

Additionally, Dr. Feldman and colleagues recommended that local, state, regional, and national health systems use public service announcements via television and digital as well as social media platforms to convey important messages about the considerable health risks associated with vaccine avoidance and the availability of free or reduced-cost vaccination programs through the federally funded Vaccines For Children program for parents out of work or without insurance. Equally important is messaging around encouraging vaccine opportunities during all health care visits, whether they be subspecialty, urgent care, emergency room, or inpatient visits. In areas where access to clinics is limited, they urged the use of mobile clinics as well as additional focus on providing medical homes to children with poor access to care.

“A partial but expanding safety net may be developing spontaneously, i.e., practices and clinics based on a patient-centered medical home (PCMH) model,” noted Dr. Harrison, professor of pediatrics, University of Missouri-Kansas City, in an interview. “When lagging vaccinations were reported in mid-2020, we checked with a local hospital–based urban clinic and two suburban private practices modeled on PCMH. Each had noted a drastic drop in well checks in the first months of the pandemic. But with ill visits nearly nonexistent, they doubled down on maintaining health maintenance visits. Even though staff and provider work hours were limited, and families were less enthusiastic about well checks, momentum appears to have grown so that, by later in 2020, vaccine uptake rates were again comparable to 2019. So, some already seem to have answered the call, but practices/clinics remain hampered by months of reduced revenue needed to support staff, providers, PPE supplies, and added infection control needs,” he said.The study was funded by the Agency for Healthcare Research Quality. Dr. Isakov disclosed relationships with various pharmaceutical companies outside the submitted work. The other authors had no relevant disclosures. Dr. Harrison’s institution receives grant funding from GSK, Merck, and Pfizer for pediatric vaccine trials and pneumococcal seroprevalence studies on which he is an investigator.

pdnews@mdedge.com

COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.

They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.

The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.

There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”

There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.

There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.

A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.

copyright DesignPics/Thinkstock

No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.

The guidance includes some recommendations for specific osteoporosis medications.

• Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
• Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
• Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
• Teriparatide and abaloparatide should be continued.
• Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
• Raloxifene should be continued in patients receiving COVID-19 vaccination.

Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

Dr. Jan De Beur has no relevant financial disclosures.

COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.

They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.

The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.

There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”

There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.

There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.

A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.

copyright DesignPics/Thinkstock

No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.

The guidance includes some recommendations for specific osteoporosis medications.

• Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
• Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
• Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
• Teriparatide and abaloparatide should be continued.
• Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
• Raloxifene should be continued in patients receiving COVID-19 vaccination.

Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

Dr. Jan De Beur has no relevant financial disclosures.

COVID-19 vaccines are safe and effective for patients taking osteoporosis medications, according to joint guidance from six endocrine and osteoporosis societies and foundations.

They noted, though, that some timing modifications with certain medications should be considered to help distinguish between adverse events from the medication versus the vaccine.

The American Society for Bone and Mineral Research “is an international organization, so we brought together our sister societies that have a vested interested in bone health. Vaccination is happening worldwide, and we wanted to present a united front and united recommendations about how to handle osteoporosis medications appropriately during vaccination,” said Suzanne Jan De Beur, MD, who is president of ASBMR and an associate professor of medicine at Johns Hopkins University, Baltimore.

There has been quite a lot of concern from the community about vaccine and medications, from both physicians and patients wondering whether treatments and vaccines should occur in a certain order, and whether there should be a time gap between the two, said Dr. Jan De Beur. “There was a dearth of information about the best practices for osteoporosis treatment management during vaccination, and we didn’t want people missing their opportunity for a vaccine, and we also didn’t want them unnecessarily delaying their osteoporosis treatment.”

There is no evidence that osteoporosis therapies affect the risk or severity of COVID-19 disease, nor do they appear to change the disease course. Osteoporosis itself does not appear associated with increased risk of infection or severe outcomes, so patients with osteoporosis do not need to be prioritized for vaccination based on that condition alone.

There is no evidence that osteoporosis therapies affect the safety or efficacy of vaccination, but given that vaccine availability is currently inconsistent, patients may need to make temporary changes to their osteoporosis regimens to ensure they can receive vaccine when it is available, such as ensuring a delay between medication and vaccination injections.

A key reason for a delay between injectable or infusion medications and a vaccine is to distinguish between adverse events that could occur, so that an adverse reaction to vaccine isn’t mistaken for an adverse reaction to a drug. Nevertheless, the real world is messy. Dr. Jan De Beur noted a recent patient who arrived at her clinic for an injectable treatment who had just received a COVID-19 vaccination that morning. “We decided to put the injection in the other arm, rather than reschedule the person and put them through the risk of coming back. We could distinguish between injection-site reactions, at least,” she said.

copyright DesignPics/Thinkstock

No changes should be made to general bone health therapies, such as calcium and vitamin D supplementation, weight-bearing exercises, and maintenance of a balanced diet.

The guidance includes some recommendations for specific osteoporosis medications.

• Oral bisphosphonates: Alendronate, risedronate, and ibandronate should be continued.
• Intravenous bisphosphonates: a 7-day interval (4-day minimum) is recommended between intravenous bisphosphonate (zoledronic acid and ibandronate) infusion and COVID-19 vaccination in order to distinguish potential autoimmune or inflammatory reactions that could be attributable to either intravenous bisphosphonate or the vaccine.
• Denosumab: There should be a 4- to 7-day delay between denosumab infusion and COVID-19 vaccination to account for injection-site reactions. Another option is to have denosumab injected into the contralateral arm or another site like the abdomen or upper thigh, if spacing the injections is not possible. In any case, denosumab injections should be performed within 7 months of the previous dose.
• Teriparatide and abaloparatide should be continued.
• Romosozumab: There should be a 4- to 7-day delay between a romosozumab injection and COVID-19 vaccine, or romosozumab can be injected in the abdomen (with the exception of a 2-inch area around the naval) or thigh if spacing is not possible.
• Raloxifene should be continued in patients receiving COVID-19 vaccination.

Guidance signatories include ASBMR, the American Association of Clinical Endocrinology, the Endocrine Society, the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

Dr. Jan De Beur has no relevant financial disclosures.

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Both high and low serum sodium levels are associated with adverse outcomes for hospitalized patients with COVID-19, new research suggests.

In the retrospective study of 488 patients hospitalized with COVID-19 at one of two London hospitals between February and May 2020, hypernatremia (defined as serum sodium level >145 mmol/L) at any time point during hospital stay was associated with a threefold increase in inpatient mortality.

Hyponatremia (serum sodium level <135 mmol/L) was associated with twice the likelihood of requiring advanced ventilatory support. In-hospital mortality was also increased among patients with hypovolemic hyponatremia.

“Serum sodium values could be used in clinical practice to identify patients with COVID-19 at high risk of poor outcomes who would benefit from more intensive monitoring and judicious rehydration,” Ploutarchos Tzoulis, MD, PhD, and colleagues wrote in their article, which was published online on Feb. 24, 2021, in the Journal of Clinical Endocrinology and Metabolism.

The findings will be presented at the upcoming news conference held by the Endocrine Society
 

Should sodium be included in a risk calculator for COVID-19?

Dr. Tzoulis, professor of endocrinology at the University College London Medical School, said in an interview that “sodium could be incorporated in risk calculators across other routine biomarkers, such as white cell count, lymphocytes, and CRP [C-reactive protein], in order to provide a tool for dynamic risk stratification throughout the clinical course of COVID-19 and assist clinical decision-making.”

Moreover, he said, “we should follow less conservative strategies in the rate and amount of fluid resuscitation in order to prevent hypernatremia, which is induced by negative fluid balance and can often be iatrogenic.”

Asked to comment, Steven Q. Simpson, MD, professor of medicine in the division of pulmonary, critical care, and sleep medicine at the University of Kansas, Kansas City, said that the article is missing key results that would assist in interpreting of the findings.

“Data regarding diuretic use and sparing of fluid administration are not in the paper. ... It is simply not possible to tell whether serum sodium is a ‘predictor’ ... or if it is a side effect of other issues or actions taken by physicians in patients who are progressing poorly.

“To say that sodium needs to be included in a risk calculator is to subtly suggest that there is some causal association with mortality, and that has quite clearly not been established,” stressed Dr. Simpson, who is president of the American College of Chest Physicians but was not speaking for the organization.

He added: “The data are interesting, but not actionable. It is common practice in critical care medicine to adjust water and salt intake to maintain serum sodium within the normal range, so the paper really doesn’t change any behavior.”

Dr. Tzoulis said in an interview that, despite not having electronic medical record data on diuretic use or fluid input and output, “our acute physicians and intensivists at both study sites have been adamant that they’ve not routinely used diuretics in COVID-19 patients. Diuretics have been sparingly used in our cohort, and also the frequency of pulmonary edema was reported as below 5%.”

Regarding volume of fluid intake, Dr. Tzoulis noted, “At our hospital sites, the strategy has been that of cautious fluid resuscitation. In fact, the amount of fluid given has been reported by our physicians and intensivists as ‘on purpose much more conservative than the usual one adopted in patients with community-acquired pneumonia at risk of respiratory failure.’ ”
 

Hyper- and hyponatremia linked to adverse COVID-19 outcomes

In the study, 5.3% of the 488 patients had hypernatremia at hospital presentation, and 24.6% had hyponatremia. Of note, only 19% of those with hyponatremia underwent laboratory workup to determine the etiology. Of those, three quarters had hypovolemic hyponatremia, determined on the basis of a urinary sodium cutoff of 30 mmol/L.

The total in-hospital mortality rate was 31.1%. There was a strong, although nonsignificant, trend toward higher mortality in association with sodium status at admission. Death rates were 28.4%, 30.8%, and 46.1% for those who were normonatremic, hyponatremic, and hypernatremic, respectively (P = .07). Baseline serum sodium levels didn’t differ between survivors (137 mmol/L) and nonsurvivors (138 mmol/L).

In multivariable analysis, the occurrence of hypernatremia at any point during the first 5 days in the hospital was among three independent risk factors for higher in-hospital mortality (adjusted hazard ratio, 2.74; P = .02). The other risk factors were older age and higher CRP level.

Overall, hyponatremia was not associated with death (P = .41).

During hospitalization, 37.9% of patients remained normonatremic; 36.9% experienced hyponatremia; 10.9% had hypernatremia; and 14.3% had both conditions at some point during their stay.

In-hospital mortality was 21% among those with normonatremia, compared with 56.6% for those with hypernatremia (odds ratio, 3.05; P = .0038) and 45.7% for those with both (OR, 2.25; P < .0001).

The 28.3% mortality rate in the overall group that experienced hyponatremia didn’t differ significantly from the 21.1% in the normonatremic group (OR, 1.34; P = .16). However, the death rate was 40.9% among the subgroup that developed hypovolemic hyponatremia, significantly higher than the normonatremic group (OR, 2.59, P = .0017).

The incidence of hyponatremia decreased from 24.6% at admission to 14.1% 5 days later, whereas the frequency of hypernatremia rose from 5.3% to 13.8%.
 

Key finding: Link between hospital-acquired hypernatremia and death

“The key novel finding of our study was that hospital-acquired hypernatremia, rather than hypernatremia at admission, was a predictor for in-hospital mortality, with the worst prognosis being reported in patients with the largest increase in serum sodium in the first 5 days of hospitalization,” noted Dr. Tzoulis and colleagues.

Hypernatremia was present in 29.6% of nonsurvivors, compared with 5.2% in survivors.

Among 120 patients with hyponatremia at admission, 31.7% received advanced respiratory support, compared with 17.5% and 7.7% of those with normonatremia or hypernatremia, respectively (OR, 2.18; P = .0011).

In contrast, there was no difference in the proportions needing ventilatory support between those with hypernatremia and those with normonatremia (16.7% vs. 12.4%; OR, 1.44; P = .39).

Acute kidney injury occurred in 181 patients (37.1%). It was not related to serum sodium concentration at any time point.

Dr. Tzoulis and Dr. Simpson disclosed no relevant financial relationships.

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

Seven weeks appears to be the ideal amount of time to delay surgery, when possible, after someone tests positive for COVID-19, researchers in the United Kingdom report.

BraunS/Getty Images

Risk for death was about 3.5 to 4 times higher in the first 6 weeks after surgery among more than 3,000 people with a preoperative COVID-19 diagnosis compared with patients without COVID-19. After 7 weeks, the 30-day mortality rate dropped to a baseline level.

The study was published online March 9 in Anaesthesia.

Surgery should be further delayed for people who remain symptomatic at 7 weeks post diagnosis, lead author Dmitri Nepogodiev, MBChB, said in an interview.

“In this group we recommend waiting until COVID-19 symptoms resolve, if possible. However, our study did not capture specific data on long COVID … so we are unable to make specific recommendations for this group,” said Dr. Nepogodiev, research fellow at the NIHR Global Health Research Unit on Global Surgery at the University of Birmingham (England).

“This should be an area for future research,” he added.

The international, multicenter, prospective cohort study is notable for its sheer size – more than 15,000 investigators reported outcomes for 140,231 surgical patients from 1,674 hospitals across 116 countries. In total, 2.2% of these patients tested positive for SARS-CoV-2 prior to surgery.

Surgery of any type performed in October 2020 was assessed. A greater proportion of patients with a preoperative COVID-19 diagnosis had emergency surgery, 44%, compared with 30% of people who never had a COVID-19 diagnosis.

Most patients were asymptomatic at the time of surgery, either because they never experienced COVID-19 symptoms or their symptoms resolved. The 30-day mortality rate was the primary outcome.
 

Death rates among surgical patients with preoperative COVID-19 diagnosis

Comparing the timing of surgery after COVID-19 diagnosis vs. 30-day mortality yielded the following results:

• 0 to 2 weeks – 9.1% mortality.
• 3 to 4 weeks – 6.9%.
• 5 to 6 weeks – 5.5%.
• 7 weeks or longer – 2.0%..

For comparison, the 30-day mortality rate for surgical patients without a preoperative COVID-19 diagnosis was 1.4%. A COVID-19 diagnosis more than 7 weeks before surgery did not make a significant difference on outcomes.
 

The ‘why’ remains unknown

The reasons for the association between a COVID-19 diagnosis and higher postoperative death rates remain unknown. However, Dr. Nepogodiev speculated that it could be related to “some degree of lung injury, even if patients are initially asymptomatic.”

Intubation and mechanical ventilation during surgery could exacerbate the existing lung injury, he said, thereby leading to more severe COVID-19.

In fact, Dr. Nepogodiev and colleagues found that postoperative pulmonary complications followed a pattern similar to the findings on death. They reported higher rates of pneumonia, acute respiratory distress syndrome, and unexpected reventilation in the first 6 weeks following a COVID-19 diagnosis. Again, at 7 weeks and beyond, the rates returned to be relatively the same as those for people who never had COVID-19.

“Waiting for 7 or more weeks may allow time for the initial COVID-19 injury to resolve,” Dr. Nepogodiev said.
 

‘An important study’

“This is an important study of postoperative mortality among patients recovered from COVID-19,” Adrian Diaz, MD, MPH, said in an interview when asked to comment.

The large cohort and numerous practice settings are among the strengths of the research, said Dr. Diaz, of the University of Michigan Institute for Healthcare Policy and Innovation in Ann Arbor. He was lead author of a June 2020 review article on elective surgery in the time of COVID-19, published in The American Journal of Surgery.

“As with nearly all studies of this nature, results must be interpreted on a case-by-case basis for individual patients. However, this study does add important information for patients and providers in helping them have an informed discussion on the timing of surgery,” said Dr. Diaz, a fellow in the Center for Healthcare Outcomes and Policy and a resident in general surgery at the Ohio State University, Columbus.

Dr. Nepogodiev and colleagues included both urgent and elective surgeries in the study. Dr. Diaz said this was a potential limitation because emergency operations “should never be delayed, by definition.” Lack of indications for the surgeries and information on cause of death were additional limitations.

Future research should evaluate any benefit in delaying surgery longer than 7 or more weeks, Dr. Diaz added, perhaps looking specifically at 10, 12, or 14 weeks, or considering outcomes as a continuous variable. This would help health care providers “garner more insight into risk and benefits of delaying surgery beyond 7 weeks.”

Dr. Nepogodiev and Dr. Diaz disclosed no relevant financial relationships. The study had multiple funding sources, including the National Institute for Health Research Global Health Research Unit, the Association of Upper Gastrointestinal Surgeons, the British Association of Surgical Oncology, and Medtronic.

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

Seven weeks appears to be the ideal amount of time to delay surgery, when possible, after someone tests positive for COVID-19, researchers in the United Kingdom report.

BraunS/Getty Images

Risk for death was about 3.5 to 4 times higher in the first 6 weeks after surgery among more than 3,000 people with a preoperative COVID-19 diagnosis compared with patients without COVID-19. After 7 weeks, the 30-day mortality rate dropped to a baseline level.

The study was published online March 9 in Anaesthesia.

Surgery should be further delayed for people who remain symptomatic at 7 weeks post diagnosis, lead author Dmitri Nepogodiev, MBChB, said in an interview.

“In this group we recommend waiting until COVID-19 symptoms resolve, if possible. However, our study did not capture specific data on long COVID … so we are unable to make specific recommendations for this group,” said Dr. Nepogodiev, research fellow at the NIHR Global Health Research Unit on Global Surgery at the University of Birmingham (England).

“This should be an area for future research,” he added.

The international, multicenter, prospective cohort study is notable for its sheer size – more than 15,000 investigators reported outcomes for 140,231 surgical patients from 1,674 hospitals across 116 countries. In total, 2.2% of these patients tested positive for SARS-CoV-2 prior to surgery.

Surgery of any type performed in October 2020 was assessed. A greater proportion of patients with a preoperative COVID-19 diagnosis had emergency surgery, 44%, compared with 30% of people who never had a COVID-19 diagnosis.

Most patients were asymptomatic at the time of surgery, either because they never experienced COVID-19 symptoms or their symptoms resolved. The 30-day mortality rate was the primary outcome.
 

Death rates among surgical patients with preoperative COVID-19 diagnosis

Comparing the timing of surgery after COVID-19 diagnosis vs. 30-day mortality yielded the following results:

• 0 to 2 weeks – 9.1% mortality.
• 3 to 4 weeks – 6.9%.
• 5 to 6 weeks – 5.5%.
• 7 weeks or longer – 2.0%..

For comparison, the 30-day mortality rate for surgical patients without a preoperative COVID-19 diagnosis was 1.4%. A COVID-19 diagnosis more than 7 weeks before surgery did not make a significant difference on outcomes.
 

The ‘why’ remains unknown

The reasons for the association between a COVID-19 diagnosis and higher postoperative death rates remain unknown. However, Dr. Nepogodiev speculated that it could be related to “some degree of lung injury, even if patients are initially asymptomatic.”

Intubation and mechanical ventilation during surgery could exacerbate the existing lung injury, he said, thereby leading to more severe COVID-19.

In fact, Dr. Nepogodiev and colleagues found that postoperative pulmonary complications followed a pattern similar to the findings on death. They reported higher rates of pneumonia, acute respiratory distress syndrome, and unexpected reventilation in the first 6 weeks following a COVID-19 diagnosis. Again, at 7 weeks and beyond, the rates returned to be relatively the same as those for people who never had COVID-19.

“Waiting for 7 or more weeks may allow time for the initial COVID-19 injury to resolve,” Dr. Nepogodiev said.
 

‘An important study’

“This is an important study of postoperative mortality among patients recovered from COVID-19,” Adrian Diaz, MD, MPH, said in an interview when asked to comment.

The large cohort and numerous practice settings are among the strengths of the research, said Dr. Diaz, of the University of Michigan Institute for Healthcare Policy and Innovation in Ann Arbor. He was lead author of a June 2020 review article on elective surgery in the time of COVID-19, published in The American Journal of Surgery.

“As with nearly all studies of this nature, results must be interpreted on a case-by-case basis for individual patients. However, this study does add important information for patients and providers in helping them have an informed discussion on the timing of surgery,” said Dr. Diaz, a fellow in the Center for Healthcare Outcomes and Policy and a resident in general surgery at the Ohio State University, Columbus.

Dr. Nepogodiev and colleagues included both urgent and elective surgeries in the study. Dr. Diaz said this was a potential limitation because emergency operations “should never be delayed, by definition.” Lack of indications for the surgeries and information on cause of death were additional limitations.

Future research should evaluate any benefit in delaying surgery longer than 7 or more weeks, Dr. Diaz added, perhaps looking specifically at 10, 12, or 14 weeks, or considering outcomes as a continuous variable. This would help health care providers “garner more insight into risk and benefits of delaying surgery beyond 7 weeks.”

Dr. Nepogodiev and Dr. Diaz disclosed no relevant financial relationships. The study had multiple funding sources, including the National Institute for Health Research Global Health Research Unit, the Association of Upper Gastrointestinal Surgeons, the British Association of Surgical Oncology, and Medtronic.

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

Seven weeks appears to be the ideal amount of time to delay surgery, when possible, after someone tests positive for COVID-19, researchers in the United Kingdom report.

BraunS/Getty Images

Risk for death was about 3.5 to 4 times higher in the first 6 weeks after surgery among more than 3,000 people with a preoperative COVID-19 diagnosis compared with patients without COVID-19. After 7 weeks, the 30-day mortality rate dropped to a baseline level.

The study was published online March 9 in Anaesthesia.

Surgery should be further delayed for people who remain symptomatic at 7 weeks post diagnosis, lead author Dmitri Nepogodiev, MBChB, said in an interview.

“In this group we recommend waiting until COVID-19 symptoms resolve, if possible. However, our study did not capture specific data on long COVID … so we are unable to make specific recommendations for this group,” said Dr. Nepogodiev, research fellow at the NIHR Global Health Research Unit on Global Surgery at the University of Birmingham (England).

“This should be an area for future research,” he added.

The international, multicenter, prospective cohort study is notable for its sheer size – more than 15,000 investigators reported outcomes for 140,231 surgical patients from 1,674 hospitals across 116 countries. In total, 2.2% of these patients tested positive for SARS-CoV-2 prior to surgery.

Surgery of any type performed in October 2020 was assessed. A greater proportion of patients with a preoperative COVID-19 diagnosis had emergency surgery, 44%, compared with 30% of people who never had a COVID-19 diagnosis.

Most patients were asymptomatic at the time of surgery, either because they never experienced COVID-19 symptoms or their symptoms resolved. The 30-day mortality rate was the primary outcome.
 

Death rates among surgical patients with preoperative COVID-19 diagnosis

Comparing the timing of surgery after COVID-19 diagnosis vs. 30-day mortality yielded the following results:

• 0 to 2 weeks – 9.1% mortality.
• 3 to 4 weeks – 6.9%.
• 5 to 6 weeks – 5.5%.
• 7 weeks or longer – 2.0%..

For comparison, the 30-day mortality rate for surgical patients without a preoperative COVID-19 diagnosis was 1.4%. A COVID-19 diagnosis more than 7 weeks before surgery did not make a significant difference on outcomes.
 

The ‘why’ remains unknown

The reasons for the association between a COVID-19 diagnosis and higher postoperative death rates remain unknown. However, Dr. Nepogodiev speculated that it could be related to “some degree of lung injury, even if patients are initially asymptomatic.”

Intubation and mechanical ventilation during surgery could exacerbate the existing lung injury, he said, thereby leading to more severe COVID-19.

In fact, Dr. Nepogodiev and colleagues found that postoperative pulmonary complications followed a pattern similar to the findings on death. They reported higher rates of pneumonia, acute respiratory distress syndrome, and unexpected reventilation in the first 6 weeks following a COVID-19 diagnosis. Again, at 7 weeks and beyond, the rates returned to be relatively the same as those for people who never had COVID-19.

“Waiting for 7 or more weeks may allow time for the initial COVID-19 injury to resolve,” Dr. Nepogodiev said.
 

‘An important study’

“This is an important study of postoperative mortality among patients recovered from COVID-19,” Adrian Diaz, MD, MPH, said in an interview when asked to comment.

The large cohort and numerous practice settings are among the strengths of the research, said Dr. Diaz, of the University of Michigan Institute for Healthcare Policy and Innovation in Ann Arbor. He was lead author of a June 2020 review article on elective surgery in the time of COVID-19, published in The American Journal of Surgery.

“As with nearly all studies of this nature, results must be interpreted on a case-by-case basis for individual patients. However, this study does add important information for patients and providers in helping them have an informed discussion on the timing of surgery,” said Dr. Diaz, a fellow in the Center for Healthcare Outcomes and Policy and a resident in general surgery at the Ohio State University, Columbus.

Dr. Nepogodiev and colleagues included both urgent and elective surgeries in the study. Dr. Diaz said this was a potential limitation because emergency operations “should never be delayed, by definition.” Lack of indications for the surgeries and information on cause of death were additional limitations.

Future research should evaluate any benefit in delaying surgery longer than 7 or more weeks, Dr. Diaz added, perhaps looking specifically at 10, 12, or 14 weeks, or considering outcomes as a continuous variable. This would help health care providers “garner more insight into risk and benefits of delaying surgery beyond 7 weeks.”

Dr. Nepogodiev and Dr. Diaz disclosed no relevant financial relationships. The study had multiple funding sources, including the National Institute for Health Research Global Health Research Unit, the Association of Upper Gastrointestinal Surgeons, the British Association of Surgical Oncology, and Medtronic.

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

MYTH: I shouldn’t get the vaccine because of potential long-term side effects

We know that 68 million people in the United States and 244 million people worldwide have already received messenger RNA (mRNA) SARS-CoV-2 vaccines (Pfizer/BioNTech and Moderna). So for the short-term side effects we already know more than we would know about most vaccines.

What about the long-term side effects? There are myths that these vaccines somehow could cause autoimmunity. This came from three publications where the possibility of mRNA vaccines to produce autoimmunity was brought up as a discussion point.^1-3 There was no evidence given in these publications, it was raised only as a hypothetical possibility.

There’s no evidence that mRNA or replication-defective DNA vaccines (AstraZeneca/Oxford and Johnson & Johnson) produce autoimmunity. Moreover, the mRNA and replication-defective DNA, once it’s inside of the muscle cell, is gone within a few days. What’s left after ribosome processing is the spike (S) protein as an immunogen. We’ve been vaccinating with proteins for 50 years and we haven’t seen autoimmunity.
 

MYTH: The vaccines aren’t safe because they were developed so quickly

These vaccines were developed at “warp speed” – that doesn’t mean they were developed without all the same safety safeguards that the Food and Drug Administration requires. The reason it happened so fast is because the seriousness of the pandemic allowed us, as a community, to enroll the patients into the studies fast. In a matter of months, we had all the studies filled. In a normal circumstance, that might take 2 or 3 years. And all of the regulatory agencies – the National Institutes of Health, the FDA, the Centers for Disease Control and Prevention – were ready to take the information and put a panel of specialists together and immediately review the data. No safety steps were missed. The same process that’s always required of phase 1, of phase 2, and then at phase 3 were accomplished.

The novelty of these vaccines was that they could be made so quickly. Messenger RNA vaccines can be made in a matter of days and then manufactured in a matter of 2 months. The DNA vaccines has a similar timeline trajectory.
 

MYTH: There’s no point in getting the vaccines because we still have to wear masks

Right now, out of an abundance of caution, until it’s proven that we don’t have to wear masks, it’s being recommended that we do so for the safety of others. Early data suggest that this will be temporary. In time, I suspect it will be shown that, after we receive the vaccine, it will be shown that we are not contagious to others and we’ll be able to get rid of our masks.

MYTH: I already had COVID-19 so I don’t need the vaccine

Some people have already caught the SARS-CoV-2 virus that causes this infection and so they feel that they’re immune and they don’t need to get the vaccine. Time will tell if that’s the case. Right now, we don’t know for sure. Early data suggest that a single dose of vaccine in persons who have had the infection may be sufficient. Over time, what happens in the vaccine field is we measure the immunity from the vaccine, and from people who’ve gotten the infection, and we find that there’s a measurement in the blood that correlates with protection. Right now, we don’t know that correlate of protection level. So, out of an abundance of caution, it’s being recommended that, even if you had the disease, maybe you didn’t develop enough immunity, and it’s better to get the vaccine than to get the illness a second time.

MYTH: The vaccines can give me SARS-CoV-2 infection

The new vaccines for COVID-19, released under emergency use Authorization, are mRNA and DNA vaccines. They are a blueprint for the Spike (S) protein of the virus. In order to become a protein, the mRNA, once it’s inside the cell, is processed by ribosomes. The product of the ribosome processing is a protein that cannot possibly cause harm as a virus. It’s a little piece of mRNA inside of a lipid nanoparticle, which is just a casing to protect the mRNA from breaking down until it’s injected in the body. The replication defective DNA vaccines (AstraZeneca/Oxford and Johnson & Johnson) are packaged inside of virus cells (adenoviruses). The DNA vaccines involve a three-step process:

• 1. The adenovirus, containing replication-defective DNA that encodes mRNA for the Spike (S) protein, is taken up by the host cells where it must make its way to the nucleus of the muscle cell.
• 2. The DNA is injected into the host cell nucleus and in the nucleus the DNA is decoded to an mRNA.
• 3. The mRNA is released from the nucleus and transported to the cell cytoplasm where the ribosomes process the mRNA in an identical manner as mRNA vaccines.

MYTH: The COVID-19 vaccines can alter my DNA

The mRNA and replication-defective DNA vaccines never interact with your DNA. mRNA vaccines never enter the nucleus. Replication-defective DNA vaccines cannot replicate and do not interact with host DNA. The vaccines can’t change your DNA.

Here is a link to YouTube videos I made on this topic: https://youtube.com/playlist?list=PLve-0UW04UMRKHfFbXyEpLY8GCm2WyJHD.

Here is a photo of me receiving my first SARS-CoV-2 shot (Moderna) in January 2021. I received my second shot in February. I am a lot less anxious. I hope my vaccine card will be a ticket to travel in the future.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts of interest to report.

References

1. Peck KM and Lauring AS. J Virol. 2018. doi: 10.1128/JVI.01031-17.

2. Pepini T et al. J Immunol. 2017 May 15. doi: 10.4049/jimmunol.1601877.

3. Theofilopoulos AN et al. Annu Rev Immunol. 2005. doi: 10.1146/annurev.immunol.23.021704.115843.

MYTH: I shouldn’t get the vaccine because of potential long-term side effects

We know that 68 million people in the United States and 244 million people worldwide have already received messenger RNA (mRNA) SARS-CoV-2 vaccines (Pfizer/BioNTech and Moderna). So for the short-term side effects we already know more than we would know about most vaccines.

What about the long-term side effects? There are myths that these vaccines somehow could cause autoimmunity. This came from three publications where the possibility of mRNA vaccines to produce autoimmunity was brought up as a discussion point.^1-3 There was no evidence given in these publications, it was raised only as a hypothetical possibility.

There’s no evidence that mRNA or replication-defective DNA vaccines (AstraZeneca/Oxford and Johnson & Johnson) produce autoimmunity. Moreover, the mRNA and replication-defective DNA, once it’s inside of the muscle cell, is gone within a few days. What’s left after ribosome processing is the spike (S) protein as an immunogen. We’ve been vaccinating with proteins for 50 years and we haven’t seen autoimmunity.
 

MYTH: The vaccines aren’t safe because they were developed so quickly

These vaccines were developed at “warp speed” – that doesn’t mean they were developed without all the same safety safeguards that the Food and Drug Administration requires. The reason it happened so fast is because the seriousness of the pandemic allowed us, as a community, to enroll the patients into the studies fast. In a matter of months, we had all the studies filled. In a normal circumstance, that might take 2 or 3 years. And all of the regulatory agencies – the National Institutes of Health, the FDA, the Centers for Disease Control and Prevention – were ready to take the information and put a panel of specialists together and immediately review the data. No safety steps were missed. The same process that’s always required of phase 1, of phase 2, and then at phase 3 were accomplished.

The novelty of these vaccines was that they could be made so quickly. Messenger RNA vaccines can be made in a matter of days and then manufactured in a matter of 2 months. The DNA vaccines has a similar timeline trajectory.
 

MYTH: There’s no point in getting the vaccines because we still have to wear masks

Right now, out of an abundance of caution, until it’s proven that we don’t have to wear masks, it’s being recommended that we do so for the safety of others. Early data suggest that this will be temporary. In time, I suspect it will be shown that, after we receive the vaccine, it will be shown that we are not contagious to others and we’ll be able to get rid of our masks.

MYTH: I already had COVID-19 so I don’t need the vaccine

Some people have already caught the SARS-CoV-2 virus that causes this infection and so they feel that they’re immune and they don’t need to get the vaccine. Time will tell if that’s the case. Right now, we don’t know for sure. Early data suggest that a single dose of vaccine in persons who have had the infection may be sufficient. Over time, what happens in the vaccine field is we measure the immunity from the vaccine, and from people who’ve gotten the infection, and we find that there’s a measurement in the blood that correlates with protection. Right now, we don’t know that correlate of protection level. So, out of an abundance of caution, it’s being recommended that, even if you had the disease, maybe you didn’t develop enough immunity, and it’s better to get the vaccine than to get the illness a second time.

MYTH: The vaccines can give me SARS-CoV-2 infection

The new vaccines for COVID-19, released under emergency use Authorization, are mRNA and DNA vaccines. They are a blueprint for the Spike (S) protein of the virus. In order to become a protein, the mRNA, once it’s inside the cell, is processed by ribosomes. The product of the ribosome processing is a protein that cannot possibly cause harm as a virus. It’s a little piece of mRNA inside of a lipid nanoparticle, which is just a casing to protect the mRNA from breaking down until it’s injected in the body. The replication defective DNA vaccines (AstraZeneca/Oxford and Johnson & Johnson) are packaged inside of virus cells (adenoviruses). The DNA vaccines involve a three-step process:

• 1. The adenovirus, containing replication-defective DNA that encodes mRNA for the Spike (S) protein, is taken up by the host cells where it must make its way to the nucleus of the muscle cell.
• 2. The DNA is injected into the host cell nucleus and in the nucleus the DNA is decoded to an mRNA.
• 3. The mRNA is released from the nucleus and transported to the cell cytoplasm where the ribosomes process the mRNA in an identical manner as mRNA vaccines.

MYTH: The COVID-19 vaccines can alter my DNA

The mRNA and replication-defective DNA vaccines never interact with your DNA. mRNA vaccines never enter the nucleus. Replication-defective DNA vaccines cannot replicate and do not interact with host DNA. The vaccines can’t change your DNA.

Here is a link to YouTube videos I made on this topic: https://youtube.com/playlist?list=PLve-0UW04UMRKHfFbXyEpLY8GCm2WyJHD.

Here is a photo of me receiving my first SARS-CoV-2 shot (Moderna) in January 2021. I received my second shot in February. I am a lot less anxious. I hope my vaccine card will be a ticket to travel in the future.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts of interest to report.

References

1. Peck KM and Lauring AS. J Virol. 2018. doi: 10.1128/JVI.01031-17.

2. Pepini T et al. J Immunol. 2017 May 15. doi: 10.4049/jimmunol.1601877.

3. Theofilopoulos AN et al. Annu Rev Immunol. 2005. doi: 10.1146/annurev.immunol.23.021704.115843.

MYTH: I shouldn’t get the vaccine because of potential long-term side effects

We know that 68 million people in the United States and 244 million people worldwide have already received messenger RNA (mRNA) SARS-CoV-2 vaccines (Pfizer/BioNTech and Moderna). So for the short-term side effects we already know more than we would know about most vaccines.

What about the long-term side effects? There are myths that these vaccines somehow could cause autoimmunity. This came from three publications where the possibility of mRNA vaccines to produce autoimmunity was brought up as a discussion point.^1-3 There was no evidence given in these publications, it was raised only as a hypothetical possibility.

There’s no evidence that mRNA or replication-defective DNA vaccines (AstraZeneca/Oxford and Johnson & Johnson) produce autoimmunity. Moreover, the mRNA and replication-defective DNA, once it’s inside of the muscle cell, is gone within a few days. What’s left after ribosome processing is the spike (S) protein as an immunogen. We’ve been vaccinating with proteins for 50 years and we haven’t seen autoimmunity.
 

MYTH: The vaccines aren’t safe because they were developed so quickly

These vaccines were developed at “warp speed” – that doesn’t mean they were developed without all the same safety safeguards that the Food and Drug Administration requires. The reason it happened so fast is because the seriousness of the pandemic allowed us, as a community, to enroll the patients into the studies fast. In a matter of months, we had all the studies filled. In a normal circumstance, that might take 2 or 3 years. And all of the regulatory agencies – the National Institutes of Health, the FDA, the Centers for Disease Control and Prevention – were ready to take the information and put a panel of specialists together and immediately review the data. No safety steps were missed. The same process that’s always required of phase 1, of phase 2, and then at phase 3 were accomplished.

The novelty of these vaccines was that they could be made so quickly. Messenger RNA vaccines can be made in a matter of days and then manufactured in a matter of 2 months. The DNA vaccines has a similar timeline trajectory.
 

MYTH: There’s no point in getting the vaccines because we still have to wear masks

Right now, out of an abundance of caution, until it’s proven that we don’t have to wear masks, it’s being recommended that we do so for the safety of others. Early data suggest that this will be temporary. In time, I suspect it will be shown that, after we receive the vaccine, it will be shown that we are not contagious to others and we’ll be able to get rid of our masks.

MYTH: I already had COVID-19 so I don’t need the vaccine

Some people have already caught the SARS-CoV-2 virus that causes this infection and so they feel that they’re immune and they don’t need to get the vaccine. Time will tell if that’s the case. Right now, we don’t know for sure. Early data suggest that a single dose of vaccine in persons who have had the infection may be sufficient. Over time, what happens in the vaccine field is we measure the immunity from the vaccine, and from people who’ve gotten the infection, and we find that there’s a measurement in the blood that correlates with protection. Right now, we don’t know that correlate of protection level. So, out of an abundance of caution, it’s being recommended that, even if you had the disease, maybe you didn’t develop enough immunity, and it’s better to get the vaccine than to get the illness a second time.

MYTH: The vaccines can give me SARS-CoV-2 infection

The new vaccines for COVID-19, released under emergency use Authorization, are mRNA and DNA vaccines. They are a blueprint for the Spike (S) protein of the virus. In order to become a protein, the mRNA, once it’s inside the cell, is processed by ribosomes. The product of the ribosome processing is a protein that cannot possibly cause harm as a virus. It’s a little piece of mRNA inside of a lipid nanoparticle, which is just a casing to protect the mRNA from breaking down until it’s injected in the body. The replication defective DNA vaccines (AstraZeneca/Oxford and Johnson & Johnson) are packaged inside of virus cells (adenoviruses). The DNA vaccines involve a three-step process:

• 1. The adenovirus, containing replication-defective DNA that encodes mRNA for the Spike (S) protein, is taken up by the host cells where it must make its way to the nucleus of the muscle cell.
• 2. The DNA is injected into the host cell nucleus and in the nucleus the DNA is decoded to an mRNA.
• 3. The mRNA is released from the nucleus and transported to the cell cytoplasm where the ribosomes process the mRNA in an identical manner as mRNA vaccines.

MYTH: The COVID-19 vaccines can alter my DNA

The mRNA and replication-defective DNA vaccines never interact with your DNA. mRNA vaccines never enter the nucleus. Replication-defective DNA vaccines cannot replicate and do not interact with host DNA. The vaccines can’t change your DNA.

Here is a link to YouTube videos I made on this topic: https://youtube.com/playlist?list=PLve-0UW04UMRKHfFbXyEpLY8GCm2WyJHD.

Here is a photo of me receiving my first SARS-CoV-2 shot (Moderna) in January 2021. I received my second shot in February. I am a lot less anxious. I hope my vaccine card will be a ticket to travel in the future.

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He has no conflicts of interest to report.

References

1. Peck KM and Lauring AS. J Virol. 2018. doi: 10.1128/JVI.01031-17.

2. Pepini T et al. J Immunol. 2017 May 15. doi: 10.4049/jimmunol.1601877.

3. Theofilopoulos AN et al. Annu Rev Immunol. 2005. doi: 10.1146/annurev.immunol.23.021704.115843.

Patients dying without their loved ones, families forced to remotely decide goals of care without the physical presence or human connection of the care team, overworked staff physically isolated from their critically ill patients, and at-risk community members with uncertain and undocumented goals for care are among the universal challenges confronted by hospitals and hospitalists during this COVID-19 pandemic. Partnerships among hospital medicine (HM) and palliative care (PC) teams at Dell Medical School/Dell Seton Medical Center thrive on mutually shared core values of patient centered care – compassion, empathy, and humanity.

A key PC-HM collaboration was adapting our multidisciplinary huddle to focus on communication effectiveness and efficiency in the medical intensive care unit (MICU). Expanded interprofessional and cross-specialty collaboration promoted streamlined, succinct, and standardized communication with patients’ families while their loved ones were critically ill with COVID-19. The PC team attended daily MICU multidisciplinary huddles, attentive to both the medical and psychosocial updates for each patient. During huddles, residents or HM providers were asked to end their presentation with a clinical status “headline” and solicited feedback from the multidisciplinary team before messaging to the family. The PC team then communicated with families a succinct and cohesive medical update and continuously explored goals of care. This allowed the HM team, often overwhelmed with admissions, co-managing intensive care patients, and facilitating safe discharges, to focus on urgent issues while PC provided continuity and personalized support for patients and families. PC’s ability to synthesize and summarize clinical information from multiple teams and then provide cohesive updates in patient-friendly language modeled important communication skills for learners and simultaneously benefited HM providers.

Our chaplains, too, were central to facilitating timely, proactive conversations and documentation of Medical Power of Attorney (MPOA) for patients with COVID-19 admitted to our hospital. HM prioritized early admission conversations with patients to counsel them on severity of illness, prognosis based on risk factors, to elucidate wishes for intubation or resuscitation, and to capture their desired medical decision maker. HM was notified of all COVID and PUI admissions, allowing us to speak with even critically ill patients in the ER or ICU prior to intubation in order to quickly and accurately capture patients’ wishes for treatment and delegate decision makers. Our chaplains supported and supplemented these efforts by diligently and dutifully soliciting, hearing, and documenting patient MPOA delegates, with over 50% MPOA completion by 24 hours of hospitalization.

Another early PC-HM project, “Meet My Loved One,” was adapted from the University of Alabama at Birmingham Palliative and Comfort Unit. The absence of families visiting the ICU and sharing pictures, stories, anecdotes of our patients left a deeply felt, dehumanizing void in the halls and rooms of our hospital. To fill this space with life and humanity, furloughed medical students on their “transition of care” electives contacted family members of their “continuity” patients focusing primarily on those patients expected to have prolonged ICU or hospital stays and solicited personal, humanizing information about our patients. Questions included: “What is your loved one’s preferred name or nickname?” and “What are three things we should know to take better care of your loved one?” With family permission, we posted this information on the door outside the patient’s room. Nursing staff, in particular, appreciated getting to know their patients more personally and families appreciated the staff’s desire to know their loved one as an individual.

It is also important to acknowledge setbacks. Early efforts to engage technology proved more foe than friend. We continue to struggle with using our iPads for video visits. Most of our families prefer “WhatsApp” for video communication, which is not compatible with operating systems on early versions of the iPad, which were generously and widely donated by local school systems. Desperate to allow families to connect, many providers resorted to using personal devices to facilitate video visits and family meetings. And we discovered that many video visits caused more not less family angst, especially for critically ill patients. Families often required preparation and coaching on what to expect and how to interact with intubated, sedated, proned, and paralyzed loved ones.

Our hospital medicine and palliative care teams have an established strong partnership. The COVID-19 pandemic created novel communication challenges but our shared mission toward patient-centered care allowed us to effectively collaborate to bring the patients goals of care to the forefront aligning patients, families, physicians, nurses, and staff during the COVID-19 surge.

Dr. Johnston is associate professor at Dell Medical School at The University of Texas in Austin. She practices hospital medicine and inpatient palliative care at Dell Seton Medical Center. Dr. Cooremans is a resident physician at Dell Medical School. Dr. Salib is the internal medicine clerkship director and an associate professor at Dell Medical School. Dr. Nieto is an assistant professor and associate chief of the Division of Hospital Medicine at Dell Medical School. Dr. Patel is an assistant professor at Dell Medical School. This article is part of a series written by members of the Division of Hospital Medicine at Dell Medical School, exploring lessons learned from the coronavirus pandemic and outlining an approach for creating COVID-19 Centers of Excellence. The article first appeared in The Hospital Leader, the official blog of SHM.

Patients dying without their loved ones, families forced to remotely decide goals of care without the physical presence or human connection of the care team, overworked staff physically isolated from their critically ill patients, and at-risk community members with uncertain and undocumented goals for care are among the universal challenges confronted by hospitals and hospitalists during this COVID-19 pandemic. Partnerships among hospital medicine (HM) and palliative care (PC) teams at Dell Medical School/Dell Seton Medical Center thrive on mutually shared core values of patient centered care – compassion, empathy, and humanity.

A key PC-HM collaboration was adapting our multidisciplinary huddle to focus on communication effectiveness and efficiency in the medical intensive care unit (MICU). Expanded interprofessional and cross-specialty collaboration promoted streamlined, succinct, and standardized communication with patients’ families while their loved ones were critically ill with COVID-19. The PC team attended daily MICU multidisciplinary huddles, attentive to both the medical and psychosocial updates for each patient. During huddles, residents or HM providers were asked to end their presentation with a clinical status “headline” and solicited feedback from the multidisciplinary team before messaging to the family. The PC team then communicated with families a succinct and cohesive medical update and continuously explored goals of care. This allowed the HM team, often overwhelmed with admissions, co-managing intensive care patients, and facilitating safe discharges, to focus on urgent issues while PC provided continuity and personalized support for patients and families. PC’s ability to synthesize and summarize clinical information from multiple teams and then provide cohesive updates in patient-friendly language modeled important communication skills for learners and simultaneously benefited HM providers.

Our chaplains, too, were central to facilitating timely, proactive conversations and documentation of Medical Power of Attorney (MPOA) for patients with COVID-19 admitted to our hospital. HM prioritized early admission conversations with patients to counsel them on severity of illness, prognosis based on risk factors, to elucidate wishes for intubation or resuscitation, and to capture their desired medical decision maker. HM was notified of all COVID and PUI admissions, allowing us to speak with even critically ill patients in the ER or ICU prior to intubation in order to quickly and accurately capture patients’ wishes for treatment and delegate decision makers. Our chaplains supported and supplemented these efforts by diligently and dutifully soliciting, hearing, and documenting patient MPOA delegates, with over 50% MPOA completion by 24 hours of hospitalization.

Another early PC-HM project, “Meet My Loved One,” was adapted from the University of Alabama at Birmingham Palliative and Comfort Unit. The absence of families visiting the ICU and sharing pictures, stories, anecdotes of our patients left a deeply felt, dehumanizing void in the halls and rooms of our hospital. To fill this space with life and humanity, furloughed medical students on their “transition of care” electives contacted family members of their “continuity” patients focusing primarily on those patients expected to have prolonged ICU or hospital stays and solicited personal, humanizing information about our patients. Questions included: “What is your loved one’s preferred name or nickname?” and “What are three things we should know to take better care of your loved one?” With family permission, we posted this information on the door outside the patient’s room. Nursing staff, in particular, appreciated getting to know their patients more personally and families appreciated the staff’s desire to know their loved one as an individual.

It is also important to acknowledge setbacks. Early efforts to engage technology proved more foe than friend. We continue to struggle with using our iPads for video visits. Most of our families prefer “WhatsApp” for video communication, which is not compatible with operating systems on early versions of the iPad, which were generously and widely donated by local school systems. Desperate to allow families to connect, many providers resorted to using personal devices to facilitate video visits and family meetings. And we discovered that many video visits caused more not less family angst, especially for critically ill patients. Families often required preparation and coaching on what to expect and how to interact with intubated, sedated, proned, and paralyzed loved ones.

Our hospital medicine and palliative care teams have an established strong partnership. The COVID-19 pandemic created novel communication challenges but our shared mission toward patient-centered care allowed us to effectively collaborate to bring the patients goals of care to the forefront aligning patients, families, physicians, nurses, and staff during the COVID-19 surge.

Dr. Johnston is associate professor at Dell Medical School at The University of Texas in Austin. She practices hospital medicine and inpatient palliative care at Dell Seton Medical Center. Dr. Cooremans is a resident physician at Dell Medical School. Dr. Salib is the internal medicine clerkship director and an associate professor at Dell Medical School. Dr. Nieto is an assistant professor and associate chief of the Division of Hospital Medicine at Dell Medical School. Dr. Patel is an assistant professor at Dell Medical School. This article is part of a series written by members of the Division of Hospital Medicine at Dell Medical School, exploring lessons learned from the coronavirus pandemic and outlining an approach for creating COVID-19 Centers of Excellence. The article first appeared in The Hospital Leader, the official blog of SHM.

Patients dying without their loved ones, families forced to remotely decide goals of care without the physical presence or human connection of the care team, overworked staff physically isolated from their critically ill patients, and at-risk community members with uncertain and undocumented goals for care are among the universal challenges confronted by hospitals and hospitalists during this COVID-19 pandemic. Partnerships among hospital medicine (HM) and palliative care (PC) teams at Dell Medical School/Dell Seton Medical Center thrive on mutually shared core values of patient centered care – compassion, empathy, and humanity.

A key PC-HM collaboration was adapting our multidisciplinary huddle to focus on communication effectiveness and efficiency in the medical intensive care unit (MICU). Expanded interprofessional and cross-specialty collaboration promoted streamlined, succinct, and standardized communication with patients’ families while their loved ones were critically ill with COVID-19. The PC team attended daily MICU multidisciplinary huddles, attentive to both the medical and psychosocial updates for each patient. During huddles, residents or HM providers were asked to end their presentation with a clinical status “headline” and solicited feedback from the multidisciplinary team before messaging to the family. The PC team then communicated with families a succinct and cohesive medical update and continuously explored goals of care. This allowed the HM team, often overwhelmed with admissions, co-managing intensive care patients, and facilitating safe discharges, to focus on urgent issues while PC provided continuity and personalized support for patients and families. PC’s ability to synthesize and summarize clinical information from multiple teams and then provide cohesive updates in patient-friendly language modeled important communication skills for learners and simultaneously benefited HM providers.

Our chaplains, too, were central to facilitating timely, proactive conversations and documentation of Medical Power of Attorney (MPOA) for patients with COVID-19 admitted to our hospital. HM prioritized early admission conversations with patients to counsel them on severity of illness, prognosis based on risk factors, to elucidate wishes for intubation or resuscitation, and to capture their desired medical decision maker. HM was notified of all COVID and PUI admissions, allowing us to speak with even critically ill patients in the ER or ICU prior to intubation in order to quickly and accurately capture patients’ wishes for treatment and delegate decision makers. Our chaplains supported and supplemented these efforts by diligently and dutifully soliciting, hearing, and documenting patient MPOA delegates, with over 50% MPOA completion by 24 hours of hospitalization.

Another early PC-HM project, “Meet My Loved One,” was adapted from the University of Alabama at Birmingham Palliative and Comfort Unit. The absence of families visiting the ICU and sharing pictures, stories, anecdotes of our patients left a deeply felt, dehumanizing void in the halls and rooms of our hospital. To fill this space with life and humanity, furloughed medical students on their “transition of care” electives contacted family members of their “continuity” patients focusing primarily on those patients expected to have prolonged ICU or hospital stays and solicited personal, humanizing information about our patients. Questions included: “What is your loved one’s preferred name or nickname?” and “What are three things we should know to take better care of your loved one?” With family permission, we posted this information on the door outside the patient’s room. Nursing staff, in particular, appreciated getting to know their patients more personally and families appreciated the staff’s desire to know their loved one as an individual.

It is also important to acknowledge setbacks. Early efforts to engage technology proved more foe than friend. We continue to struggle with using our iPads for video visits. Most of our families prefer “WhatsApp” for video communication, which is not compatible with operating systems on early versions of the iPad, which were generously and widely donated by local school systems. Desperate to allow families to connect, many providers resorted to using personal devices to facilitate video visits and family meetings. And we discovered that many video visits caused more not less family angst, especially for critically ill patients. Families often required preparation and coaching on what to expect and how to interact with intubated, sedated, proned, and paralyzed loved ones.

Our hospital medicine and palliative care teams have an established strong partnership. The COVID-19 pandemic created novel communication challenges but our shared mission toward patient-centered care allowed us to effectively collaborate to bring the patients goals of care to the forefront aligning patients, families, physicians, nurses, and staff during the COVID-19 surge.

Dr. Johnston is associate professor at Dell Medical School at The University of Texas in Austin. She practices hospital medicine and inpatient palliative care at Dell Seton Medical Center. Dr. Cooremans is a resident physician at Dell Medical School. Dr. Salib is the internal medicine clerkship director and an associate professor at Dell Medical School. Dr. Nieto is an assistant professor and associate chief of the Division of Hospital Medicine at Dell Medical School. Dr. Patel is an assistant professor at Dell Medical School. This article is part of a series written by members of the Division of Hospital Medicine at Dell Medical School, exploring lessons learned from the coronavirus pandemic and outlining an approach for creating COVID-19 Centers of Excellence. The article first appeared in The Hospital Leader, the official blog of SHM.