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Six-month follow-up shows continuing morbidity for COVID-19 survivors
In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.
Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.
At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.
In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.
The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.
“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.
The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO2 concentration, or needed an intravenous infusion of vasopressors.
In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.
Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.
At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.
A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).
In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.
At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.
Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.
“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.
Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).
“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.
Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.
Dr. Kashyap, who was approached for an independent comment, also pointed out that in follow-up of SARS patients, some of them recovered but went on to develop chronic fatigue syndrome which is characterized by extreme fatigue that doesn’t improve with rest. “So the scientific community is contemplating if this will be true for patients with COVID-19 infection as well,” he said. “We have already seen that some of the ‘long haulers’ continue to have symptoms such as shortness of breath, joint pain, fatigue, loss of smell and taste, and even hearing loss in extreme cases.”
Some research is also confirming what has been reported from Wuhan. “Data from Ireland, that looked at 150 survivors, showed that almost 60% said they did not feel they were back to full health, regardless of the severity of the disease,” Dr. Kashyap said. “So, aside from Wuhan, we are now getting data from other sources that is similar. But what is interesting about the data from Ireland is that not all of the patients had severe illness or were in ICU.”
He added that data continue to come in from the United States and other countries, looking at long-term effects. “More and more patients are surviving as the care is getting better,” he said. “But beyond a year, we just don’t know yet.”
There was no outside sponsor listed. Dr. Peng and Dr. Kashyap have no disclosures.
In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.
Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.
At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.
In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.
The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.
“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.
The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO2 concentration, or needed an intravenous infusion of vasopressors.
In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.
Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.
At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.
A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).
In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.
At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.
Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.
“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.
Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).
“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.
Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.
Dr. Kashyap, who was approached for an independent comment, also pointed out that in follow-up of SARS patients, some of them recovered but went on to develop chronic fatigue syndrome which is characterized by extreme fatigue that doesn’t improve with rest. “So the scientific community is contemplating if this will be true for patients with COVID-19 infection as well,” he said. “We have already seen that some of the ‘long haulers’ continue to have symptoms such as shortness of breath, joint pain, fatigue, loss of smell and taste, and even hearing loss in extreme cases.”
Some research is also confirming what has been reported from Wuhan. “Data from Ireland, that looked at 150 survivors, showed that almost 60% said they did not feel they were back to full health, regardless of the severity of the disease,” Dr. Kashyap said. “So, aside from Wuhan, we are now getting data from other sources that is similar. But what is interesting about the data from Ireland is that not all of the patients had severe illness or were in ICU.”
He added that data continue to come in from the United States and other countries, looking at long-term effects. “More and more patients are surviving as the care is getting better,” he said. “But beyond a year, we just don’t know yet.”
There was no outside sponsor listed. Dr. Peng and Dr. Kashyap have no disclosures.
In December 2019, a cluster of cases of what was first identified as a “mysterious pneumonia” was reported in the central Chinese city of Wuhan. Within a few short months, the disease had spread all over the world.
Wuhan was essentially “ground zero” for the novel coronavirus, or COVID-19, and now researchers report that many of the early survivors continue to experience a variety of lingering health issues.
At 6 months, for example, pulmonary and immune function have still not returned to normal in many of the patients who had been critically ill, said Zhiyong Peng, MD, PhD, an intensivist and medical researcher, in the department of critical care medicine, Zhonnan Hospital, Wuhan.
In addition, many are still experiencing varying degrees of psychiatric disability and physical morbidity.
The results of the report were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.
In 2020, Dr. Peng and colleagues conducted a single-center case series involving 138 patients with coronavirus pneumonia in order to describe the clinical characteristics of this new disease. Within this group, 26% of patients required admission to the intensive care unit and 4.3% died. As of Feb. 3, 2020, 26% required ICU care, 34.1% were discharged, 4.3% died, and 61.6% remained hospitalized. (JAMA. 2020 Mar 17;323[11]:1061-69) Not surprisingly, those requiring critical care experienced a higher rate of severe complications, including shock, arrythmias, acute cardiac injury and acute respiratory distress syndrome, compared with non-ICU patients.
“However, the long-term outcomes of survivors were unknown,” said Dr. Peng. Thus, the goal of the current study was to analyze the outcomes based on pulmonary function, physical morbidity, immunological status, health-related quality of life, cognitive impairment, and psychiatric disability.
The cohort included patients from four hospitals in Wuhan, who had been treated in the adult ICU and required mechanical ventilation (invasive or noninvasive), or had a high FiO2 concentration, or needed an intravenous infusion of vasopressors.
In all, 171 critically ill patients were admitted to the four designated hospitals, and of this group, 110 were discharged from ICU and 106 survived. At the 3-month follow-up, 92 patients were evaluated and at 6 months, 72 were evaluated.
Pulmonary function tests were performed, and all patients received a chest CT scan, and did the “6-minute walk test.” For immune function, lymphocyte counts and function assays were performed. The SF-36 questionnaire was used to evaluate health related quality of life, and cognitive and psychological assessments were conducted with a variety of tools including the Mini-Mental State Examination and Montreal Cognitive Assessment. Depression and anxiety were measured with Zung’s Self-Rating Anxiety Scale and the Hamilton Rating Scale.
At 3 months, 5 patients (5.4%) were seropositive for IgM and 9 (9.8%) were seronegative, while at 6 months, 9 patients (12.9%) tested seropositive for IgM and 12 (16.67%) tested seronegative.
A high proportion of patients also reported tachypnea after exercising (54%), heart palpitations (51.8%), fatigue (44.6%), and joint pain (20.5%).
In terms of lung function, survivors who had been intubated scored worse on pulmonary function tests and had a significant decrease in diffusing capacity for carbon monoxide (DLCO), compared with those who had not been intubated.
At 6 months, the DLCO remained at 76% of the predicted level, but the walking test and chest CT scan improved over time. “In multivariate analysis tracheostomy was a risk factor associated with distance walked in 6 minutes,” said Dr. Peng.
Other results showed that B cells were lower in survivors who had been intubated, compared with those who weren’t, and they were still low at 3 and 6 months, compared with normal values. T-cell subsets were also persistently low.
“Hyperfunction of T lymphocytes and hypofunction of NK cells were detected, which had not improved at 6 months,” said Dr. Peng.
Cognitive dysfunction and depression were reported in some survivors. Cognitive dysfunction at 3 months affected 12.8% of survivors, but it improved by 6 months, affecting on only 2.9% of the cohort (P = .029). However, rates of depression more than doubled from 3 to 6 months (20% vs. 47.8%, P < .001), and anxiety showed a slight increase (15.6% vs. 17.6%, P = .726).
“Further follow-up will be performed to confirm these findings,” Dr. Peng concluded.
Rahul Kashyap, MBBS, MBA, a research scientist and assistant professor of anesthesiology at the Mayo Clinic, Rochester, Minn., noted that currently the research from Wuhan is showing the follow-up for 6 months, but it takes time to gather and analyze the data. “I suspect we will be seeing results from the 1-year follow-up by June,” he said.
Dr. Kashyap, who was approached for an independent comment, also pointed out that in follow-up of SARS patients, some of them recovered but went on to develop chronic fatigue syndrome which is characterized by extreme fatigue that doesn’t improve with rest. “So the scientific community is contemplating if this will be true for patients with COVID-19 infection as well,” he said. “We have already seen that some of the ‘long haulers’ continue to have symptoms such as shortness of breath, joint pain, fatigue, loss of smell and taste, and even hearing loss in extreme cases.”
Some research is also confirming what has been reported from Wuhan. “Data from Ireland, that looked at 150 survivors, showed that almost 60% said they did not feel they were back to full health, regardless of the severity of the disease,” Dr. Kashyap said. “So, aside from Wuhan, we are now getting data from other sources that is similar. But what is interesting about the data from Ireland is that not all of the patients had severe illness or were in ICU.”
He added that data continue to come in from the United States and other countries, looking at long-term effects. “More and more patients are surviving as the care is getting better,” he said. “But beyond a year, we just don’t know yet.”
There was no outside sponsor listed. Dr. Peng and Dr. Kashyap have no disclosures.
FROM CCC50
COVID-19 vaccines: New candidates & answers to commonly asked questions
REFERENCES
- CDC. COVID-19 vaccination. Accessed February 22, 2021.
- CDC. COVID data tracker. Accessed February 22, 2021.
- Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2020;69:1922-1924. Accessed February 22, 2021.
- Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2021;69:1653-1656. Accessed February 22, 2021.
- Gee J, Marquez P, Su J, et al. First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020–January 13, 2021. MMWR Morbid Mortal Wkly Rep. ePub: February 19, 2021. Accessed February 22, 2021.
- CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:125-129. Accessed February 25, 2021.
REFERENCES
- CDC. COVID-19 vaccination. Accessed February 22, 2021.
- CDC. COVID data tracker. Accessed February 22, 2021.
- Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2020;69:1922-1924. Accessed February 22, 2021.
- Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2021;69:1653-1656. Accessed February 22, 2021.
- Gee J, Marquez P, Su J, et al. First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020–January 13, 2021. MMWR Morbid Mortal Wkly Rep. ePub: February 19, 2021. Accessed February 22, 2021.
- CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:125-129. Accessed February 25, 2021.
REFERENCES
- CDC. COVID-19 vaccination. Accessed February 22, 2021.
- CDC. COVID data tracker. Accessed February 22, 2021.
- Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2020;69:1922-1924. Accessed February 22, 2021.
- Oliver SE, Gargano JW, Marin M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for use of Moderna COVID-19 vaccine—United States, December 2020. MMWR Morbid Mortal Wkly Rep. 2021;69:1653-1656. Accessed February 22, 2021.
- Gee J, Marquez P, Su J, et al. First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020–January 13, 2021. MMWR Morbid Mortal Wkly Rep. ePub: February 19, 2021. Accessed February 22, 2021.
- CDC COVID-19 Response Team; Food and Drug Administration. Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020–January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:125-129. Accessed February 25, 2021.
Organ transplant patient dies after receiving COVID-19–infected lungs
Doctors say a woman in Michigan contracted COVID-19 and died last fall 2 months after receiving a tainted double-lung transplant from a donor who turned out to harbor the virus that causes the disease – despite showing no signs of illness and initially testing negative.
Officials at the University of Michigan Medical School suggested it may be the first proven case of COVID-19 in the U.S. in which the virus was transmitted via an organ transplant. A surgeon who handled the donor lungs was also infected with the virus and fell ill but later recovered.
The incident appears to be isolated – the only confirmed case among nearly 40,000 transplants in 2020. But it has led to calls for more thorough testing of lung transplant donors, with samples taken from deep within the donor lungs as well as the nose and throat, said Dr. Daniel Kaul, director of Michigan Medicine’s transplant infectious disease service.
“We would absolutely not have used the lungs if we’d had a positive COVID-19 test,” said Dr. Kaul, who coauthored a report about the case in the American Journal of Transplantation.
The virus was transmitted when lungs from a woman from the Upper Midwest, who died after suffering a severe brain injury in a car accident, were transplanted into a woman with chronic obstructive lung disease at University Hospital in Ann Arbor. The nose and throat samples routinely collected from both organ donors and recipients tested negative for SARS-CoV-2, the virus that causes covid.
“All the screening that we normally do and are able to do, we did,” Dr. Kaul said.
Three days after the operation, however, the recipient spiked a fever; her blood pressure fell and her breathing became labored. Imaging showed signs of lung infection.
As her condition worsened, the patient developed septic shock and heart function problems. Doctors decided to test for SARS-CoV-2, Dr. Kaul said. Samples from her new lungs came back positive.
Suspicious about the origin of the infection, doctors returned to samples from the transplant donor. A molecular test of a swab from the donor’s nose and throat, taken 48 hours after her lungs were procured, had been negative for SARS-Cov-2. The donor’s family told doctors she had no history of recent travel or COVID-19 symptoms and no known exposure to anyone with the disease.
But doctors had kept a sample of fluid washed from deep within the donor lungs. When they tested that fluid, it was positive for the virus. Four days after the transplant, the surgeon who handled the donor lungs and performed the surgery tested positive, too. Genetic screening revealed that the transplant recipient and the surgeon had been infected by the donor. Ten other members of the transplant team tested negative for the virus.
The transplant recipient deteriorated rapidly, developing multisystem organ failure. Doctors tried known treatments for COVID-19, including remdesivir, a newly approved drug, and convalescent blood plasma from people previously infected with the disease. Eventually, she was placed on the last-resort option of ECMO, or extracorporeal membrane oxygenation, to no avail. Life support was withdrawn, and she died 61 days after the transplant.
Dr. Kaul called the incident “a tragic case.”
While the Michigan case marks the first confirmed incident in the U.S. of transmission through a transplant, others have been suspected. A recent Centers for Disease Control and Prevention report reviewed eight possible cases of what’s known as donor-derived infection that occurred last spring, but concluded the most likely source of transmission of the COVID-19 virus in those cases was in a community or health care setting.
Before this incident, it was not clear whether the COVID-19 virus could be transmitted through solid organ transplants, though it’s well documented with other respiratory viruses. Donor transmission of H1N1 2009 pandemic influenza has been detected almost exclusively in lung transplant recipients, Dr. Kaul noted.
While it’s not surprising that SARS-CoV-2 can be transmitted through infected lungs, it remains uncertain whether other organs affected by COVID-19 – hearts, livers and kidneys, for instance – can transmit the virus, too.
“It seems for non-lung donors that it may be very difficult to transmit COVID-19, even if the donor has COVID-19,” Dr. Kaul said.
Organ donors have been tested routinely for SARS-CoV-2 during the pandemic, though it’s not required by the Organ Procurement and Transplantation Network, or OPTN, which oversees transplants in the U.S. But the Michigan case underscores the need for more extensive sampling before transplant, especially in areas with high rates of covid transmission, Dr. Kaul said.
When it comes to lungs, that means making sure to test samples from the donor’s lower respiratory tract, as well as from the nose and throat. Obtaining and testing such samples from donors can be difficult to carry out in a timely fashion. There’s also the risk of introducing infection into the donated lungs, Dr. Kaul said.
Because no organs other than lungs were used, the Michigan case doesn’t provide insight into testing protocols for other organs.
Overall, viral transmissions from organ donors to recipients remain rare, occurring in fewer than 1% of transplant recipients, research shows. The medical risks facing ailing patients who reject a donor organ are generally far higher, said Dr. David Klassen, chief medical officer with the United Network for Organ Sharing, the federal contractor that runs the OPTN.
“The risks of turning down transplants are catastrophic,” he said. “I don’t think patients should be afraid of the transplant process.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Doctors say a woman in Michigan contracted COVID-19 and died last fall 2 months after receiving a tainted double-lung transplant from a donor who turned out to harbor the virus that causes the disease – despite showing no signs of illness and initially testing negative.
Officials at the University of Michigan Medical School suggested it may be the first proven case of COVID-19 in the U.S. in which the virus was transmitted via an organ transplant. A surgeon who handled the donor lungs was also infected with the virus and fell ill but later recovered.
The incident appears to be isolated – the only confirmed case among nearly 40,000 transplants in 2020. But it has led to calls for more thorough testing of lung transplant donors, with samples taken from deep within the donor lungs as well as the nose and throat, said Dr. Daniel Kaul, director of Michigan Medicine’s transplant infectious disease service.
“We would absolutely not have used the lungs if we’d had a positive COVID-19 test,” said Dr. Kaul, who coauthored a report about the case in the American Journal of Transplantation.
The virus was transmitted when lungs from a woman from the Upper Midwest, who died after suffering a severe brain injury in a car accident, were transplanted into a woman with chronic obstructive lung disease at University Hospital in Ann Arbor. The nose and throat samples routinely collected from both organ donors and recipients tested negative for SARS-CoV-2, the virus that causes covid.
“All the screening that we normally do and are able to do, we did,” Dr. Kaul said.
Three days after the operation, however, the recipient spiked a fever; her blood pressure fell and her breathing became labored. Imaging showed signs of lung infection.
As her condition worsened, the patient developed septic shock and heart function problems. Doctors decided to test for SARS-CoV-2, Dr. Kaul said. Samples from her new lungs came back positive.
Suspicious about the origin of the infection, doctors returned to samples from the transplant donor. A molecular test of a swab from the donor’s nose and throat, taken 48 hours after her lungs were procured, had been negative for SARS-Cov-2. The donor’s family told doctors she had no history of recent travel or COVID-19 symptoms and no known exposure to anyone with the disease.
But doctors had kept a sample of fluid washed from deep within the donor lungs. When they tested that fluid, it was positive for the virus. Four days after the transplant, the surgeon who handled the donor lungs and performed the surgery tested positive, too. Genetic screening revealed that the transplant recipient and the surgeon had been infected by the donor. Ten other members of the transplant team tested negative for the virus.
The transplant recipient deteriorated rapidly, developing multisystem organ failure. Doctors tried known treatments for COVID-19, including remdesivir, a newly approved drug, and convalescent blood plasma from people previously infected with the disease. Eventually, she was placed on the last-resort option of ECMO, or extracorporeal membrane oxygenation, to no avail. Life support was withdrawn, and she died 61 days after the transplant.
Dr. Kaul called the incident “a tragic case.”
While the Michigan case marks the first confirmed incident in the U.S. of transmission through a transplant, others have been suspected. A recent Centers for Disease Control and Prevention report reviewed eight possible cases of what’s known as donor-derived infection that occurred last spring, but concluded the most likely source of transmission of the COVID-19 virus in those cases was in a community or health care setting.
Before this incident, it was not clear whether the COVID-19 virus could be transmitted through solid organ transplants, though it’s well documented with other respiratory viruses. Donor transmission of H1N1 2009 pandemic influenza has been detected almost exclusively in lung transplant recipients, Dr. Kaul noted.
While it’s not surprising that SARS-CoV-2 can be transmitted through infected lungs, it remains uncertain whether other organs affected by COVID-19 – hearts, livers and kidneys, for instance – can transmit the virus, too.
“It seems for non-lung donors that it may be very difficult to transmit COVID-19, even if the donor has COVID-19,” Dr. Kaul said.
Organ donors have been tested routinely for SARS-CoV-2 during the pandemic, though it’s not required by the Organ Procurement and Transplantation Network, or OPTN, which oversees transplants in the U.S. But the Michigan case underscores the need for more extensive sampling before transplant, especially in areas with high rates of covid transmission, Dr. Kaul said.
When it comes to lungs, that means making sure to test samples from the donor’s lower respiratory tract, as well as from the nose and throat. Obtaining and testing such samples from donors can be difficult to carry out in a timely fashion. There’s also the risk of introducing infection into the donated lungs, Dr. Kaul said.
Because no organs other than lungs were used, the Michigan case doesn’t provide insight into testing protocols for other organs.
Overall, viral transmissions from organ donors to recipients remain rare, occurring in fewer than 1% of transplant recipients, research shows. The medical risks facing ailing patients who reject a donor organ are generally far higher, said Dr. David Klassen, chief medical officer with the United Network for Organ Sharing, the federal contractor that runs the OPTN.
“The risks of turning down transplants are catastrophic,” he said. “I don’t think patients should be afraid of the transplant process.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Doctors say a woman in Michigan contracted COVID-19 and died last fall 2 months after receiving a tainted double-lung transplant from a donor who turned out to harbor the virus that causes the disease – despite showing no signs of illness and initially testing negative.
Officials at the University of Michigan Medical School suggested it may be the first proven case of COVID-19 in the U.S. in which the virus was transmitted via an organ transplant. A surgeon who handled the donor lungs was also infected with the virus and fell ill but later recovered.
The incident appears to be isolated – the only confirmed case among nearly 40,000 transplants in 2020. But it has led to calls for more thorough testing of lung transplant donors, with samples taken from deep within the donor lungs as well as the nose and throat, said Dr. Daniel Kaul, director of Michigan Medicine’s transplant infectious disease service.
“We would absolutely not have used the lungs if we’d had a positive COVID-19 test,” said Dr. Kaul, who coauthored a report about the case in the American Journal of Transplantation.
The virus was transmitted when lungs from a woman from the Upper Midwest, who died after suffering a severe brain injury in a car accident, were transplanted into a woman with chronic obstructive lung disease at University Hospital in Ann Arbor. The nose and throat samples routinely collected from both organ donors and recipients tested negative for SARS-CoV-2, the virus that causes covid.
“All the screening that we normally do and are able to do, we did,” Dr. Kaul said.
Three days after the operation, however, the recipient spiked a fever; her blood pressure fell and her breathing became labored. Imaging showed signs of lung infection.
As her condition worsened, the patient developed septic shock and heart function problems. Doctors decided to test for SARS-CoV-2, Dr. Kaul said. Samples from her new lungs came back positive.
Suspicious about the origin of the infection, doctors returned to samples from the transplant donor. A molecular test of a swab from the donor’s nose and throat, taken 48 hours after her lungs were procured, had been negative for SARS-Cov-2. The donor’s family told doctors she had no history of recent travel or COVID-19 symptoms and no known exposure to anyone with the disease.
But doctors had kept a sample of fluid washed from deep within the donor lungs. When they tested that fluid, it was positive for the virus. Four days after the transplant, the surgeon who handled the donor lungs and performed the surgery tested positive, too. Genetic screening revealed that the transplant recipient and the surgeon had been infected by the donor. Ten other members of the transplant team tested negative for the virus.
The transplant recipient deteriorated rapidly, developing multisystem organ failure. Doctors tried known treatments for COVID-19, including remdesivir, a newly approved drug, and convalescent blood plasma from people previously infected with the disease. Eventually, she was placed on the last-resort option of ECMO, or extracorporeal membrane oxygenation, to no avail. Life support was withdrawn, and she died 61 days after the transplant.
Dr. Kaul called the incident “a tragic case.”
While the Michigan case marks the first confirmed incident in the U.S. of transmission through a transplant, others have been suspected. A recent Centers for Disease Control and Prevention report reviewed eight possible cases of what’s known as donor-derived infection that occurred last spring, but concluded the most likely source of transmission of the COVID-19 virus in those cases was in a community or health care setting.
Before this incident, it was not clear whether the COVID-19 virus could be transmitted through solid organ transplants, though it’s well documented with other respiratory viruses. Donor transmission of H1N1 2009 pandemic influenza has been detected almost exclusively in lung transplant recipients, Dr. Kaul noted.
While it’s not surprising that SARS-CoV-2 can be transmitted through infected lungs, it remains uncertain whether other organs affected by COVID-19 – hearts, livers and kidneys, for instance – can transmit the virus, too.
“It seems for non-lung donors that it may be very difficult to transmit COVID-19, even if the donor has COVID-19,” Dr. Kaul said.
Organ donors have been tested routinely for SARS-CoV-2 during the pandemic, though it’s not required by the Organ Procurement and Transplantation Network, or OPTN, which oversees transplants in the U.S. But the Michigan case underscores the need for more extensive sampling before transplant, especially in areas with high rates of covid transmission, Dr. Kaul said.
When it comes to lungs, that means making sure to test samples from the donor’s lower respiratory tract, as well as from the nose and throat. Obtaining and testing such samples from donors can be difficult to carry out in a timely fashion. There’s also the risk of introducing infection into the donated lungs, Dr. Kaul said.
Because no organs other than lungs were used, the Michigan case doesn’t provide insight into testing protocols for other organs.
Overall, viral transmissions from organ donors to recipients remain rare, occurring in fewer than 1% of transplant recipients, research shows. The medical risks facing ailing patients who reject a donor organ are generally far higher, said Dr. David Klassen, chief medical officer with the United Network for Organ Sharing, the federal contractor that runs the OPTN.
“The risks of turning down transplants are catastrophic,” he said. “I don’t think patients should be afraid of the transplant process.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
Ivabradine knocks down heart rate, symptoms in POTS
The heart failure drug ivabradine (Corlanor) can provide relief from the elevated heart rate and often debilitating symptoms associated with postural orthostatic tachycardia syndrome (POTS), a new study suggests.
Ivabradine significantly lowered standing heart rate, compared with placebo (77.9 vs. 94.2 beats/min; P < .001). The typical surge in heart rate that occurs upon standing in these patients was also blunted, compared with baseline (13.0 vs. 21.4 beats/min; P = .001).
“There are really not a lot of great options for patients with POTS and, mechanistically, ivabradine just make sense because it’s a drug that lowers heart rate very selectively and doesn’t lower blood pressure,” lead study author Pam R. Taub, MD, told this news organization.
Surprisingly, the reduction in heart rate translated into improved physical (P = .008) and social (P = .021) functioning after just 1 month of ivabradine, without any other background POTS medications or a change in nonpharmacologic therapies, she said. “What’s really nice to see is when you tackle a really significant part of the disease, which is the elevated heart rate, just how much better they feel.”
POTS patients are mostly healthy, active young women, who after some inciting event – such as viral infection, trauma, or surgery – experience an increase in heart rate of at least 30 beats/min upon standing accompanied by a range of symptoms, including dizziness, palpitations, brain fog, and fatigue.
A COVID connection?
The study enrolled patients with hyperadrenergic POTS as the predominant subtype, but another group to keep in mind that might benefit is the post-COVID POTS patient, said Dr. Taub, from the University of California, San Diego.
“We’re seeing an incredible number of patients post COVID that meet the criteria for POTS, and a lot of these patients also have COVID fatigue,” she said. “So clinically, myself and many other cardiologists who understand ivabradine have been using it off-label for the COVID patients, as long as they meet the criteria. You don’t want to use it in every COVID patient, but if someone’s predominant complaint is that their heart rate is going up when they’re standing and they’re debilitated by it, this is a drug to consider.”
Anecdotal findings in patients with long-hauler COVID need to be translated into rigorous research protocols, but mechanistically, whether it’s POTS from COVID or from another type of infection – like Lyme disease or some other viral syndrome – it should work the same, Dr. Taub said. “POTS is POTS.”
There are no first-line drugs for POTS, and current class IIb recommendations include midodrine, which increases blood pressure and can make people feel awful, and fludrocortisone, which can cause a lot of weight gain and fluid retention, she observed. Other agents that lower heart rate, like beta-blockers, also lower blood pressure and can aggravate depression and fatigue.
Ivabradine regulates heart rate by specifically blocking the Ifunny channel of the sinoatrial node. It was approved in 2015 in the United States to reduce hospitalizations in patients with systolic heart failure, and it also has a second class IIb recommendation for inappropriate sinus tachycardia.
The present study, reported in the Feb. 23 issue of the Journal of the American College of Cardiology, is the first randomized clinical trial using ivabradine to treat POTS.
A total of 26 patients with POTS were started on ivabradine 5 mg or placebo twice daily for 1 month, then were crossed over to the other treatment for 1 month after a 1-week washout period. Six patients were started on a 2.5-mg twice-daily dose. Doses were adjusted during the study based on the patient’s heart rate response and tolerance. Patients had seven clinic visits in which norepinephrine (NE) levels were measured and head-up tilt testing conducted.
Four patients in the ivabradine arm withdrew because of adverse effects, and one withdrew during crossover.
Among the 22 patients who completed the study, exploratory analyses showed a strong trend for greater reduction in plasma NE upon standing with ivabradine (P = .056). The effect was also more profound in patients with very high baseline standing NE levels (at least 1,000 pg/mL) than in those with lower NE levels (600 to 1,000 pg/mL).
“It makes sense because that means their sympathetic nervous system is more overactive; they have a higher heart rate,” Dr. Taub said. “So it’s a potential clinical tool that people can use in their practice to determine, ‘okay, is this a patient I should be considering ivabradine on?’ ”
Although the present study had only 22 patients, “it should definitely be looked at as a step forward, both in terms of ivabradine specifically and in terms of setting the standard for the types of studies we want to see in our patients,” Satish R. Raj, MD, MSCI, University of Calgary (Alta.), said in an interview.
In a related editorial, however, Dr. Raj and coauthor Robert S. Sheldon, MD, PhD, also from the University of Calgary, point out that the standing heart rate in the placebo phase was only 94 beats/min, “suggesting that these patients may be affected only mildly by their POTS.”
Asked about the point, Dr. Taub said: “I don’t know if I agree with that.” She noted that the diagnosis of POTS was confirmed by tilt-table testing and NE levels and that patients’ symptoms vary from day to day. “The standard deviation was plus or minus 16.8, so there’s variability.”
Both Dr. Raj and Dr. Taub said they expect the results will be included in the next scientific statement for POTS, but in the meantime, it may be a struggle to get the drug covered by insurance.
“The challenge is that this is a very off-label use for this medication, and the medication’s not cheap,” Dr. Raj observed. The price for 60 tablets, which is about a 1-month supply, is $485 on GoodRx.
Another question going forward, he said, is whether ivabradine is superior to beta-blockers, which will be studied in a 20-patient crossover trial sponsored by the University of Calgary that is about to launch. The primary completion date is set for 2024.
The study was supported by a grant from Amgen. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA. Dr. Raj has received a research grant from the Canadian Institutes of Health Research and research grants from Dysautonomia International to address the pathophysiology of POTS. Dr. Sheldon has received a research grant from Dysautonomia International for a clinical trial assessing ivabradine and propranolol for the treatment of POTS.
A version of this article first appeared on Medscape.com.
The heart failure drug ivabradine (Corlanor) can provide relief from the elevated heart rate and often debilitating symptoms associated with postural orthostatic tachycardia syndrome (POTS), a new study suggests.
Ivabradine significantly lowered standing heart rate, compared with placebo (77.9 vs. 94.2 beats/min; P < .001). The typical surge in heart rate that occurs upon standing in these patients was also blunted, compared with baseline (13.0 vs. 21.4 beats/min; P = .001).
“There are really not a lot of great options for patients with POTS and, mechanistically, ivabradine just make sense because it’s a drug that lowers heart rate very selectively and doesn’t lower blood pressure,” lead study author Pam R. Taub, MD, told this news organization.
Surprisingly, the reduction in heart rate translated into improved physical (P = .008) and social (P = .021) functioning after just 1 month of ivabradine, without any other background POTS medications or a change in nonpharmacologic therapies, she said. “What’s really nice to see is when you tackle a really significant part of the disease, which is the elevated heart rate, just how much better they feel.”
POTS patients are mostly healthy, active young women, who after some inciting event – such as viral infection, trauma, or surgery – experience an increase in heart rate of at least 30 beats/min upon standing accompanied by a range of symptoms, including dizziness, palpitations, brain fog, and fatigue.
A COVID connection?
The study enrolled patients with hyperadrenergic POTS as the predominant subtype, but another group to keep in mind that might benefit is the post-COVID POTS patient, said Dr. Taub, from the University of California, San Diego.
“We’re seeing an incredible number of patients post COVID that meet the criteria for POTS, and a lot of these patients also have COVID fatigue,” she said. “So clinically, myself and many other cardiologists who understand ivabradine have been using it off-label for the COVID patients, as long as they meet the criteria. You don’t want to use it in every COVID patient, but if someone’s predominant complaint is that their heart rate is going up when they’re standing and they’re debilitated by it, this is a drug to consider.”
Anecdotal findings in patients with long-hauler COVID need to be translated into rigorous research protocols, but mechanistically, whether it’s POTS from COVID or from another type of infection – like Lyme disease or some other viral syndrome – it should work the same, Dr. Taub said. “POTS is POTS.”
There are no first-line drugs for POTS, and current class IIb recommendations include midodrine, which increases blood pressure and can make people feel awful, and fludrocortisone, which can cause a lot of weight gain and fluid retention, she observed. Other agents that lower heart rate, like beta-blockers, also lower blood pressure and can aggravate depression and fatigue.
Ivabradine regulates heart rate by specifically blocking the Ifunny channel of the sinoatrial node. It was approved in 2015 in the United States to reduce hospitalizations in patients with systolic heart failure, and it also has a second class IIb recommendation for inappropriate sinus tachycardia.
The present study, reported in the Feb. 23 issue of the Journal of the American College of Cardiology, is the first randomized clinical trial using ivabradine to treat POTS.
A total of 26 patients with POTS were started on ivabradine 5 mg or placebo twice daily for 1 month, then were crossed over to the other treatment for 1 month after a 1-week washout period. Six patients were started on a 2.5-mg twice-daily dose. Doses were adjusted during the study based on the patient’s heart rate response and tolerance. Patients had seven clinic visits in which norepinephrine (NE) levels were measured and head-up tilt testing conducted.
Four patients in the ivabradine arm withdrew because of adverse effects, and one withdrew during crossover.
Among the 22 patients who completed the study, exploratory analyses showed a strong trend for greater reduction in plasma NE upon standing with ivabradine (P = .056). The effect was also more profound in patients with very high baseline standing NE levels (at least 1,000 pg/mL) than in those with lower NE levels (600 to 1,000 pg/mL).
“It makes sense because that means their sympathetic nervous system is more overactive; they have a higher heart rate,” Dr. Taub said. “So it’s a potential clinical tool that people can use in their practice to determine, ‘okay, is this a patient I should be considering ivabradine on?’ ”
Although the present study had only 22 patients, “it should definitely be looked at as a step forward, both in terms of ivabradine specifically and in terms of setting the standard for the types of studies we want to see in our patients,” Satish R. Raj, MD, MSCI, University of Calgary (Alta.), said in an interview.
In a related editorial, however, Dr. Raj and coauthor Robert S. Sheldon, MD, PhD, also from the University of Calgary, point out that the standing heart rate in the placebo phase was only 94 beats/min, “suggesting that these patients may be affected only mildly by their POTS.”
Asked about the point, Dr. Taub said: “I don’t know if I agree with that.” She noted that the diagnosis of POTS was confirmed by tilt-table testing and NE levels and that patients’ symptoms vary from day to day. “The standard deviation was plus or minus 16.8, so there’s variability.”
Both Dr. Raj and Dr. Taub said they expect the results will be included in the next scientific statement for POTS, but in the meantime, it may be a struggle to get the drug covered by insurance.
“The challenge is that this is a very off-label use for this medication, and the medication’s not cheap,” Dr. Raj observed. The price for 60 tablets, which is about a 1-month supply, is $485 on GoodRx.
Another question going forward, he said, is whether ivabradine is superior to beta-blockers, which will be studied in a 20-patient crossover trial sponsored by the University of Calgary that is about to launch. The primary completion date is set for 2024.
The study was supported by a grant from Amgen. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA. Dr. Raj has received a research grant from the Canadian Institutes of Health Research and research grants from Dysautonomia International to address the pathophysiology of POTS. Dr. Sheldon has received a research grant from Dysautonomia International for a clinical trial assessing ivabradine and propranolol for the treatment of POTS.
A version of this article first appeared on Medscape.com.
The heart failure drug ivabradine (Corlanor) can provide relief from the elevated heart rate and often debilitating symptoms associated with postural orthostatic tachycardia syndrome (POTS), a new study suggests.
Ivabradine significantly lowered standing heart rate, compared with placebo (77.9 vs. 94.2 beats/min; P < .001). The typical surge in heart rate that occurs upon standing in these patients was also blunted, compared with baseline (13.0 vs. 21.4 beats/min; P = .001).
“There are really not a lot of great options for patients with POTS and, mechanistically, ivabradine just make sense because it’s a drug that lowers heart rate very selectively and doesn’t lower blood pressure,” lead study author Pam R. Taub, MD, told this news organization.
Surprisingly, the reduction in heart rate translated into improved physical (P = .008) and social (P = .021) functioning after just 1 month of ivabradine, without any other background POTS medications or a change in nonpharmacologic therapies, she said. “What’s really nice to see is when you tackle a really significant part of the disease, which is the elevated heart rate, just how much better they feel.”
POTS patients are mostly healthy, active young women, who after some inciting event – such as viral infection, trauma, or surgery – experience an increase in heart rate of at least 30 beats/min upon standing accompanied by a range of symptoms, including dizziness, palpitations, brain fog, and fatigue.
A COVID connection?
The study enrolled patients with hyperadrenergic POTS as the predominant subtype, but another group to keep in mind that might benefit is the post-COVID POTS patient, said Dr. Taub, from the University of California, San Diego.
“We’re seeing an incredible number of patients post COVID that meet the criteria for POTS, and a lot of these patients also have COVID fatigue,” she said. “So clinically, myself and many other cardiologists who understand ivabradine have been using it off-label for the COVID patients, as long as they meet the criteria. You don’t want to use it in every COVID patient, but if someone’s predominant complaint is that their heart rate is going up when they’re standing and they’re debilitated by it, this is a drug to consider.”
Anecdotal findings in patients with long-hauler COVID need to be translated into rigorous research protocols, but mechanistically, whether it’s POTS from COVID or from another type of infection – like Lyme disease or some other viral syndrome – it should work the same, Dr. Taub said. “POTS is POTS.”
There are no first-line drugs for POTS, and current class IIb recommendations include midodrine, which increases blood pressure and can make people feel awful, and fludrocortisone, which can cause a lot of weight gain and fluid retention, she observed. Other agents that lower heart rate, like beta-blockers, also lower blood pressure and can aggravate depression and fatigue.
Ivabradine regulates heart rate by specifically blocking the Ifunny channel of the sinoatrial node. It was approved in 2015 in the United States to reduce hospitalizations in patients with systolic heart failure, and it also has a second class IIb recommendation for inappropriate sinus tachycardia.
The present study, reported in the Feb. 23 issue of the Journal of the American College of Cardiology, is the first randomized clinical trial using ivabradine to treat POTS.
A total of 26 patients with POTS were started on ivabradine 5 mg or placebo twice daily for 1 month, then were crossed over to the other treatment for 1 month after a 1-week washout period. Six patients were started on a 2.5-mg twice-daily dose. Doses were adjusted during the study based on the patient’s heart rate response and tolerance. Patients had seven clinic visits in which norepinephrine (NE) levels were measured and head-up tilt testing conducted.
Four patients in the ivabradine arm withdrew because of adverse effects, and one withdrew during crossover.
Among the 22 patients who completed the study, exploratory analyses showed a strong trend for greater reduction in plasma NE upon standing with ivabradine (P = .056). The effect was also more profound in patients with very high baseline standing NE levels (at least 1,000 pg/mL) than in those with lower NE levels (600 to 1,000 pg/mL).
“It makes sense because that means their sympathetic nervous system is more overactive; they have a higher heart rate,” Dr. Taub said. “So it’s a potential clinical tool that people can use in their practice to determine, ‘okay, is this a patient I should be considering ivabradine on?’ ”
Although the present study had only 22 patients, “it should definitely be looked at as a step forward, both in terms of ivabradine specifically and in terms of setting the standard for the types of studies we want to see in our patients,” Satish R. Raj, MD, MSCI, University of Calgary (Alta.), said in an interview.
In a related editorial, however, Dr. Raj and coauthor Robert S. Sheldon, MD, PhD, also from the University of Calgary, point out that the standing heart rate in the placebo phase was only 94 beats/min, “suggesting that these patients may be affected only mildly by their POTS.”
Asked about the point, Dr. Taub said: “I don’t know if I agree with that.” She noted that the diagnosis of POTS was confirmed by tilt-table testing and NE levels and that patients’ symptoms vary from day to day. “The standard deviation was plus or minus 16.8, so there’s variability.”
Both Dr. Raj and Dr. Taub said they expect the results will be included in the next scientific statement for POTS, but in the meantime, it may be a struggle to get the drug covered by insurance.
“The challenge is that this is a very off-label use for this medication, and the medication’s not cheap,” Dr. Raj observed. The price for 60 tablets, which is about a 1-month supply, is $485 on GoodRx.
Another question going forward, he said, is whether ivabradine is superior to beta-blockers, which will be studied in a 20-patient crossover trial sponsored by the University of Calgary that is about to launch. The primary completion date is set for 2024.
The study was supported by a grant from Amgen. Dr. Taub has served as a consultant for Amgen, Bayer, Esperion, Boehringer Ingelheim, Novo Nordisk, and Sanofi; is a shareholder in Epirium Bio; and has received research grants from the National Institutes of Health, the American Heart Association, and the Department of Homeland Security/FEMA. Dr. Raj has received a research grant from the Canadian Institutes of Health Research and research grants from Dysautonomia International to address the pathophysiology of POTS. Dr. Sheldon has received a research grant from Dysautonomia International for a clinical trial assessing ivabradine and propranolol for the treatment of POTS.
A version of this article first appeared on Medscape.com.
Routine COVID-19 screening unnecessary for cancer outpatients
There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.
The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.
“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).
Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.
Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.
Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.
The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.
Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).
There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.
The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.
“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.
“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.
“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”
Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.
Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.
Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.
COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.
Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.
The funding source wasn’t reported. The speakers had no relevant disclosures.
There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.
The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.
“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).
Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.
Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.
Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.
The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.
Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).
There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.
The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.
“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.
“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.
“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”
Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.
Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.
Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.
COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.
Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.
The funding source wasn’t reported. The speakers had no relevant disclosures.
There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.
The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.
“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).
Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.
Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.
Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.
The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.
Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).
There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.
The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.
“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.
“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.
“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”
Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.
Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.
Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.
COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.
Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.
The funding source wasn’t reported. The speakers had no relevant disclosures.
FROM AACR: COVID-19 AND CANCER 2021
How does an emotionally drained workforce move on post pandemic?
Psychiatric community is facing ‘triple challenges’ tied to COVID
When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.
“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”
According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.
“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”
Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.
“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”
Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.
General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.
“Why is this crisis so hard for us docs?” she asked. “Because This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’
“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”
Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”
To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”
She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”
Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”
She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”
Dr. Bernstein reported having no financial disclosures.
Psychiatric community is facing ‘triple challenges’ tied to COVID
Psychiatric community is facing ‘triple challenges’ tied to COVID
When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.
“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”
According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.
“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”
Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.
“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”
Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.
General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.
“Why is this crisis so hard for us docs?” she asked. “Because This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’
“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”
Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”
To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”
She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”
Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”
She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”
Dr. Bernstein reported having no financial disclosures.
When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.
“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”
According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.
“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”
Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.
“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”
Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.
General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.
“Why is this crisis so hard for us docs?” she asked. “Because This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’
“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”
Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”
To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”
She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”
Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”
She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”
Dr. Bernstein reported having no financial disclosures.
FROM NPA 2021
CDC chief lays out attack plan for COVID variants
earlier this week.
As part of JAMA’s Q&A series with JAMA editor in chief Howard Bauchner, MD, Dr. Walensky referenced the blueprint she coathored with Anthony Fauci, MD, the nation’s top infectious disease expert, and Henry T. Walke, MD, MPH, of the CDC, which was published on Feb. 17 in JAMA.
In the viewpoint article, they explain that the Department of Health & Human Services has established the SARS-CoV-2 Interagency Group to improve coordination among the CDC, the National Institutes of Health, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Agriculture, and the Department of Defense.
Dr. Walensky said the first objective is to reinforce vigilance regarding public health mitigation strategies to decrease the amount of virus that’s circulating.
As part of that strategy, she said, the CDC strongly urges against nonessential travel.
In addition, public health leaders are working on a surveillance system to better understand the SARS-CoV-2 variants. That will take ramping up genome sequencing of the SARS-CoV-2 virus and ensuring that sampling is geographically representative.
She said the CDC is partnering with state health labs to obtain about 750 samples every week and is teaming up with commercial labs and academic centers to obtain an interim target of 6,000 samples per week.
She acknowledged the United States “is not where we need to be” with sequencing but has come a long way since January. At that time, they were sequencing 250 samples every week; they are currently sequencing thousands each week.
Data analysis is another concern: “We need to be able to understand at the basic science level what the information means,” Dr. Walensky said.
Researchers aren’t sure how the variants might affect use of convalescent plasma or monoclonal antibody treatments. It is expected that 5% of persons who are vaccinated against COVID-19 will nevertheless contract the disease. Sequencing will help answer whether such persons who have been vaccinated and who subsequently contract the virus are among those 5% or whether have been infected by a variant that evades the vaccine.
Accelerating vaccine administration globally and in the United States is essential, Dr. Walensky said.
As of Feb. 17, 56 million doses had been administered in the United States.
Top three threats
She updated the numbers on the three biggest variant threats.
Regarding B.1.1.7, which originated in the United Kingdom, she said: “So far, we’ve had over 1,200 cases in 41 states.” She noted that the variant is likely to be about 50% more transmissible and 30% to 50% more virulent.
“So far, it looks like that strain doesn’t have any real decrease in susceptibility to our vaccines,” she said.
The strain from South Africa (B.1.351) has been found in 19 cases in the United States.
The P.1. variant, which originated in Brazil, has been identified in two cases in two states.
Outlook for March and April
Dr. Bauchner asked Dr. Walensky what she envisions for March and April. He noted that public optimism is high in light of the continued reductions in COVID-19 case numbers, hospitalizations, and deaths, as well as the fact that warmer weather is coming and that more vaccinations are on the horizon.
“While I really am hopeful for what could happen in March and April,” Dr. Walensky said, “I really do know that this could go bad so fast. We saw it in November. We saw it in December.”
CDC models have projected that, by March, the more transmissible B.1.1.7 strain is likely to be the dominant strain, she reiterated.
“I worry that it will be spring, and we will all have had enough,” Dr. Walensky said. She noted that some states are already relaxing mask mandates.
“Around that time, life will look and feel a little better, and the motivation for those who might be vaccine hesitant may be diminished,” she said.
Dr. Bauchner also asked her to weigh in on whether a third vaccine, from Johnson & Johnson (J&J), may soon gain FDA emergency-use authorization – and whether its lower expected efficacy rate may result in a tiered system of vaccinations, with higher-risk populations receiving the more efficacious vaccines.
Dr. Walensky said more data are needed before that question can be answered.
“It may very well be that the data point us to the best populations in which to use this vaccine,” she said.
In phase 3 data, the J&J vaccine was shown to be 72% effective in the United States for moderate to severe disease.
Dr. Walensky said it’s important to remember that the projected efficacy for that vaccine is higher than that for the flu shot as well as many other vaccines currently in use for other diseases.
She said it also has several advantages. The vaccine has less-stringent storage requirements, requires just one dose, and protects against hospitalization and death, although it’s less efficacious in protecting against contracting the disease.
“I think many people would opt to get that one if they could get it sooner,” she said.
A version of this article first appeared on Medscape.com.
earlier this week.
As part of JAMA’s Q&A series with JAMA editor in chief Howard Bauchner, MD, Dr. Walensky referenced the blueprint she coathored with Anthony Fauci, MD, the nation’s top infectious disease expert, and Henry T. Walke, MD, MPH, of the CDC, which was published on Feb. 17 in JAMA.
In the viewpoint article, they explain that the Department of Health & Human Services has established the SARS-CoV-2 Interagency Group to improve coordination among the CDC, the National Institutes of Health, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Agriculture, and the Department of Defense.
Dr. Walensky said the first objective is to reinforce vigilance regarding public health mitigation strategies to decrease the amount of virus that’s circulating.
As part of that strategy, she said, the CDC strongly urges against nonessential travel.
In addition, public health leaders are working on a surveillance system to better understand the SARS-CoV-2 variants. That will take ramping up genome sequencing of the SARS-CoV-2 virus and ensuring that sampling is geographically representative.
She said the CDC is partnering with state health labs to obtain about 750 samples every week and is teaming up with commercial labs and academic centers to obtain an interim target of 6,000 samples per week.
She acknowledged the United States “is not where we need to be” with sequencing but has come a long way since January. At that time, they were sequencing 250 samples every week; they are currently sequencing thousands each week.
Data analysis is another concern: “We need to be able to understand at the basic science level what the information means,” Dr. Walensky said.
Researchers aren’t sure how the variants might affect use of convalescent plasma or monoclonal antibody treatments. It is expected that 5% of persons who are vaccinated against COVID-19 will nevertheless contract the disease. Sequencing will help answer whether such persons who have been vaccinated and who subsequently contract the virus are among those 5% or whether have been infected by a variant that evades the vaccine.
Accelerating vaccine administration globally and in the United States is essential, Dr. Walensky said.
As of Feb. 17, 56 million doses had been administered in the United States.
Top three threats
She updated the numbers on the three biggest variant threats.
Regarding B.1.1.7, which originated in the United Kingdom, she said: “So far, we’ve had over 1,200 cases in 41 states.” She noted that the variant is likely to be about 50% more transmissible and 30% to 50% more virulent.
“So far, it looks like that strain doesn’t have any real decrease in susceptibility to our vaccines,” she said.
The strain from South Africa (B.1.351) has been found in 19 cases in the United States.
The P.1. variant, which originated in Brazil, has been identified in two cases in two states.
Outlook for March and April
Dr. Bauchner asked Dr. Walensky what she envisions for March and April. He noted that public optimism is high in light of the continued reductions in COVID-19 case numbers, hospitalizations, and deaths, as well as the fact that warmer weather is coming and that more vaccinations are on the horizon.
“While I really am hopeful for what could happen in March and April,” Dr. Walensky said, “I really do know that this could go bad so fast. We saw it in November. We saw it in December.”
CDC models have projected that, by March, the more transmissible B.1.1.7 strain is likely to be the dominant strain, she reiterated.
“I worry that it will be spring, and we will all have had enough,” Dr. Walensky said. She noted that some states are already relaxing mask mandates.
“Around that time, life will look and feel a little better, and the motivation for those who might be vaccine hesitant may be diminished,” she said.
Dr. Bauchner also asked her to weigh in on whether a third vaccine, from Johnson & Johnson (J&J), may soon gain FDA emergency-use authorization – and whether its lower expected efficacy rate may result in a tiered system of vaccinations, with higher-risk populations receiving the more efficacious vaccines.
Dr. Walensky said more data are needed before that question can be answered.
“It may very well be that the data point us to the best populations in which to use this vaccine,” she said.
In phase 3 data, the J&J vaccine was shown to be 72% effective in the United States for moderate to severe disease.
Dr. Walensky said it’s important to remember that the projected efficacy for that vaccine is higher than that for the flu shot as well as many other vaccines currently in use for other diseases.
She said it also has several advantages. The vaccine has less-stringent storage requirements, requires just one dose, and protects against hospitalization and death, although it’s less efficacious in protecting against contracting the disease.
“I think many people would opt to get that one if they could get it sooner,” she said.
A version of this article first appeared on Medscape.com.
earlier this week.
As part of JAMA’s Q&A series with JAMA editor in chief Howard Bauchner, MD, Dr. Walensky referenced the blueprint she coathored with Anthony Fauci, MD, the nation’s top infectious disease expert, and Henry T. Walke, MD, MPH, of the CDC, which was published on Feb. 17 in JAMA.
In the viewpoint article, they explain that the Department of Health & Human Services has established the SARS-CoV-2 Interagency Group to improve coordination among the CDC, the National Institutes of Health, the Food and Drug Administration, the Biomedical Advanced Research and Development Authority, the Department of Agriculture, and the Department of Defense.
Dr. Walensky said the first objective is to reinforce vigilance regarding public health mitigation strategies to decrease the amount of virus that’s circulating.
As part of that strategy, she said, the CDC strongly urges against nonessential travel.
In addition, public health leaders are working on a surveillance system to better understand the SARS-CoV-2 variants. That will take ramping up genome sequencing of the SARS-CoV-2 virus and ensuring that sampling is geographically representative.
She said the CDC is partnering with state health labs to obtain about 750 samples every week and is teaming up with commercial labs and academic centers to obtain an interim target of 6,000 samples per week.
She acknowledged the United States “is not where we need to be” with sequencing but has come a long way since January. At that time, they were sequencing 250 samples every week; they are currently sequencing thousands each week.
Data analysis is another concern: “We need to be able to understand at the basic science level what the information means,” Dr. Walensky said.
Researchers aren’t sure how the variants might affect use of convalescent plasma or monoclonal antibody treatments. It is expected that 5% of persons who are vaccinated against COVID-19 will nevertheless contract the disease. Sequencing will help answer whether such persons who have been vaccinated and who subsequently contract the virus are among those 5% or whether have been infected by a variant that evades the vaccine.
Accelerating vaccine administration globally and in the United States is essential, Dr. Walensky said.
As of Feb. 17, 56 million doses had been administered in the United States.
Top three threats
She updated the numbers on the three biggest variant threats.
Regarding B.1.1.7, which originated in the United Kingdom, she said: “So far, we’ve had over 1,200 cases in 41 states.” She noted that the variant is likely to be about 50% more transmissible and 30% to 50% more virulent.
“So far, it looks like that strain doesn’t have any real decrease in susceptibility to our vaccines,” she said.
The strain from South Africa (B.1.351) has been found in 19 cases in the United States.
The P.1. variant, which originated in Brazil, has been identified in two cases in two states.
Outlook for March and April
Dr. Bauchner asked Dr. Walensky what she envisions for March and April. He noted that public optimism is high in light of the continued reductions in COVID-19 case numbers, hospitalizations, and deaths, as well as the fact that warmer weather is coming and that more vaccinations are on the horizon.
“While I really am hopeful for what could happen in March and April,” Dr. Walensky said, “I really do know that this could go bad so fast. We saw it in November. We saw it in December.”
CDC models have projected that, by March, the more transmissible B.1.1.7 strain is likely to be the dominant strain, she reiterated.
“I worry that it will be spring, and we will all have had enough,” Dr. Walensky said. She noted that some states are already relaxing mask mandates.
“Around that time, life will look and feel a little better, and the motivation for those who might be vaccine hesitant may be diminished,” she said.
Dr. Bauchner also asked her to weigh in on whether a third vaccine, from Johnson & Johnson (J&J), may soon gain FDA emergency-use authorization – and whether its lower expected efficacy rate may result in a tiered system of vaccinations, with higher-risk populations receiving the more efficacious vaccines.
Dr. Walensky said more data are needed before that question can be answered.
“It may very well be that the data point us to the best populations in which to use this vaccine,” she said.
In phase 3 data, the J&J vaccine was shown to be 72% effective in the United States for moderate to severe disease.
Dr. Walensky said it’s important to remember that the projected efficacy for that vaccine is higher than that for the flu shot as well as many other vaccines currently in use for other diseases.
She said it also has several advantages. The vaccine has less-stringent storage requirements, requires just one dose, and protects against hospitalization and death, although it’s less efficacious in protecting against contracting the disease.
“I think many people would opt to get that one if they could get it sooner,” she said.
A version of this article first appeared on Medscape.com.
Alien cells may explain COVID-19 brain fog
, a new report suggests.
The authors report five separate post-mortem cases from patients who died with COVID-19 in which large cells resembling megakaryocytes were identified in cortical capillaries. Immunohistochemistry subsequently confirmed their megakaryocyte identity.
They point out that the finding is of interest as – to their knowledge – megakaryocytes have not been found in the brain before.
The observations are described in a research letter published online Feb. 12 in JAMA Neurology.
Bone marrow cells in the brain
Lead author David Nauen, MD, PhD, a neuropathologist from Johns Hopkins University, Baltimore, reported that he identified these cells in the first analysis of post-mortem brain tissue from a patient who had COVID-19.
“Some other viruses cause changes in the brain such as encephalopathy, and as neurologic symptoms are often reported in COVID-19, I was curious to see if similar effects were seen in brain post-mortem samples from patients who had died with the infection,” Dr. Nauen said.
On his first analysis of the brain tissue of a patient who had COVID-19, Dr. Nauen saw no evidence of viral encephalitis, but he observed some “unusually large” cells in the brain capillaries.
“I was taken aback; I couldn’t figure out what they were. Then I realized these cells were megakaryocytes from the bone marrow. I have never seen these cells in the brain before. I asked several colleagues and none of them had either. After extensive literature searches, I could find no evidence of megakaryocytes being in the brain,” Dr. Nauen noted.
Megakaryocytes, he explained, are “very large cells, and the brain capillaries are very small – just large enough to let red blood cells and lymphocytes pass through. To see these very large cells in such vessels is extremely unusual. It looks like they are causing occlusions.”
By occluding flow through individual capillaries, these large cells could cause ischemic alteration in a distinct pattern, potentially resulting in an atypical form of neurologic impairment, the authors suggest.
“This might alter the hemodynamics and put pressure on other vessels, possibly contributing to the increased risk of stroke that has been reported in COVID-19,” Dr. Nauen said. None of the samples he examined came from patients with COVID-19 who had had a stroke, he reported.
Other than the presence of megakaryocytes in the capillaries, the brain looked normal, he said. He has now examined samples from 15 brains of patients who had COVID-19 and megakaryocytes have been found in the brain capillaries in five cases.
New neurologic complication
Classic encephalitis found with other viruses has not been reported in brain post-mortem examinations from patients who had COVID-19, Dr. Nauen noted. “The cognitive issues such as grogginess associated with COVID-19 would indicate problems with the cortex but that hasn’t been documented. This occlusion of a multitude of tiny vessels by megalokaryocytes may offer some explanation of the cognitive issues. This is a new kind of vascular insult seen on pathology, and suggests a new kind of neurologic complication,” he added.
The big question is what these megakaryocytes are doing in the brain.
“Megakaryocytes are bone marrow cells. They are not immune cells. Their job is to produce platelets to help the blood clot. They are not normally found outside the bone marrow, but they have been reported in other organs in COVID-19 patients.
“But the big puzzle associated with finding them in the brain is how they get through the very fine network of blood vessels in the lungs. The geometry just doesn’t work. We don’t know which part of the COVID inflammatory response makes this happen,” said Dr. Nauen.
The authors suggest one possibility is that altered endothelial or other signaling is recruiting megakaryocytes into the circulation and somehow permitting them to pass through the lungs.
“We need to try and understand if there is anything distinctive about these megakaryocytes – which proteins are they expressing that may explain why they are behaving in such an unusual way,” said Dr. Nauen.
Noting that many patients with severe COVID-19 have problems with clotting, and megakaryocytes are part of the clotting system, he speculated that some sort of aberrant message is being sent to these cells.
“It is notable that we found megakaryocytes in cortical capillaries in 33% of cases examined. Because the standard brain autopsy sections taken sampled at random [are] only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable,” the authors wrote.
Dr. Nauen added that to his knowledge, this is the first report of such observations, and the next step is to look for similar findings in larger sample sizes.
A version of this article first appeared on Medscape.com.
, a new report suggests.
The authors report five separate post-mortem cases from patients who died with COVID-19 in which large cells resembling megakaryocytes were identified in cortical capillaries. Immunohistochemistry subsequently confirmed their megakaryocyte identity.
They point out that the finding is of interest as – to their knowledge – megakaryocytes have not been found in the brain before.
The observations are described in a research letter published online Feb. 12 in JAMA Neurology.
Bone marrow cells in the brain
Lead author David Nauen, MD, PhD, a neuropathologist from Johns Hopkins University, Baltimore, reported that he identified these cells in the first analysis of post-mortem brain tissue from a patient who had COVID-19.
“Some other viruses cause changes in the brain such as encephalopathy, and as neurologic symptoms are often reported in COVID-19, I was curious to see if similar effects were seen in brain post-mortem samples from patients who had died with the infection,” Dr. Nauen said.
On his first analysis of the brain tissue of a patient who had COVID-19, Dr. Nauen saw no evidence of viral encephalitis, but he observed some “unusually large” cells in the brain capillaries.
“I was taken aback; I couldn’t figure out what they were. Then I realized these cells were megakaryocytes from the bone marrow. I have never seen these cells in the brain before. I asked several colleagues and none of them had either. After extensive literature searches, I could find no evidence of megakaryocytes being in the brain,” Dr. Nauen noted.
Megakaryocytes, he explained, are “very large cells, and the brain capillaries are very small – just large enough to let red blood cells and lymphocytes pass through. To see these very large cells in such vessels is extremely unusual. It looks like they are causing occlusions.”
By occluding flow through individual capillaries, these large cells could cause ischemic alteration in a distinct pattern, potentially resulting in an atypical form of neurologic impairment, the authors suggest.
“This might alter the hemodynamics and put pressure on other vessels, possibly contributing to the increased risk of stroke that has been reported in COVID-19,” Dr. Nauen said. None of the samples he examined came from patients with COVID-19 who had had a stroke, he reported.
Other than the presence of megakaryocytes in the capillaries, the brain looked normal, he said. He has now examined samples from 15 brains of patients who had COVID-19 and megakaryocytes have been found in the brain capillaries in five cases.
New neurologic complication
Classic encephalitis found with other viruses has not been reported in brain post-mortem examinations from patients who had COVID-19, Dr. Nauen noted. “The cognitive issues such as grogginess associated with COVID-19 would indicate problems with the cortex but that hasn’t been documented. This occlusion of a multitude of tiny vessels by megalokaryocytes may offer some explanation of the cognitive issues. This is a new kind of vascular insult seen on pathology, and suggests a new kind of neurologic complication,” he added.
The big question is what these megakaryocytes are doing in the brain.
“Megakaryocytes are bone marrow cells. They are not immune cells. Their job is to produce platelets to help the blood clot. They are not normally found outside the bone marrow, but they have been reported in other organs in COVID-19 patients.
“But the big puzzle associated with finding them in the brain is how they get through the very fine network of blood vessels in the lungs. The geometry just doesn’t work. We don’t know which part of the COVID inflammatory response makes this happen,” said Dr. Nauen.
The authors suggest one possibility is that altered endothelial or other signaling is recruiting megakaryocytes into the circulation and somehow permitting them to pass through the lungs.
“We need to try and understand if there is anything distinctive about these megakaryocytes – which proteins are they expressing that may explain why they are behaving in such an unusual way,” said Dr. Nauen.
Noting that many patients with severe COVID-19 have problems with clotting, and megakaryocytes are part of the clotting system, he speculated that some sort of aberrant message is being sent to these cells.
“It is notable that we found megakaryocytes in cortical capillaries in 33% of cases examined. Because the standard brain autopsy sections taken sampled at random [are] only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable,” the authors wrote.
Dr. Nauen added that to his knowledge, this is the first report of such observations, and the next step is to look for similar findings in larger sample sizes.
A version of this article first appeared on Medscape.com.
, a new report suggests.
The authors report five separate post-mortem cases from patients who died with COVID-19 in which large cells resembling megakaryocytes were identified in cortical capillaries. Immunohistochemistry subsequently confirmed their megakaryocyte identity.
They point out that the finding is of interest as – to their knowledge – megakaryocytes have not been found in the brain before.
The observations are described in a research letter published online Feb. 12 in JAMA Neurology.
Bone marrow cells in the brain
Lead author David Nauen, MD, PhD, a neuropathologist from Johns Hopkins University, Baltimore, reported that he identified these cells in the first analysis of post-mortem brain tissue from a patient who had COVID-19.
“Some other viruses cause changes in the brain such as encephalopathy, and as neurologic symptoms are often reported in COVID-19, I was curious to see if similar effects were seen in brain post-mortem samples from patients who had died with the infection,” Dr. Nauen said.
On his first analysis of the brain tissue of a patient who had COVID-19, Dr. Nauen saw no evidence of viral encephalitis, but he observed some “unusually large” cells in the brain capillaries.
“I was taken aback; I couldn’t figure out what they were. Then I realized these cells were megakaryocytes from the bone marrow. I have never seen these cells in the brain before. I asked several colleagues and none of them had either. After extensive literature searches, I could find no evidence of megakaryocytes being in the brain,” Dr. Nauen noted.
Megakaryocytes, he explained, are “very large cells, and the brain capillaries are very small – just large enough to let red blood cells and lymphocytes pass through. To see these very large cells in such vessels is extremely unusual. It looks like they are causing occlusions.”
By occluding flow through individual capillaries, these large cells could cause ischemic alteration in a distinct pattern, potentially resulting in an atypical form of neurologic impairment, the authors suggest.
“This might alter the hemodynamics and put pressure on other vessels, possibly contributing to the increased risk of stroke that has been reported in COVID-19,” Dr. Nauen said. None of the samples he examined came from patients with COVID-19 who had had a stroke, he reported.
Other than the presence of megakaryocytes in the capillaries, the brain looked normal, he said. He has now examined samples from 15 brains of patients who had COVID-19 and megakaryocytes have been found in the brain capillaries in five cases.
New neurologic complication
Classic encephalitis found with other viruses has not been reported in brain post-mortem examinations from patients who had COVID-19, Dr. Nauen noted. “The cognitive issues such as grogginess associated with COVID-19 would indicate problems with the cortex but that hasn’t been documented. This occlusion of a multitude of tiny vessels by megalokaryocytes may offer some explanation of the cognitive issues. This is a new kind of vascular insult seen on pathology, and suggests a new kind of neurologic complication,” he added.
The big question is what these megakaryocytes are doing in the brain.
“Megakaryocytes are bone marrow cells. They are not immune cells. Their job is to produce platelets to help the blood clot. They are not normally found outside the bone marrow, but they have been reported in other organs in COVID-19 patients.
“But the big puzzle associated with finding them in the brain is how they get through the very fine network of blood vessels in the lungs. The geometry just doesn’t work. We don’t know which part of the COVID inflammatory response makes this happen,” said Dr. Nauen.
The authors suggest one possibility is that altered endothelial or other signaling is recruiting megakaryocytes into the circulation and somehow permitting them to pass through the lungs.
“We need to try and understand if there is anything distinctive about these megakaryocytes – which proteins are they expressing that may explain why they are behaving in such an unusual way,” said Dr. Nauen.
Noting that many patients with severe COVID-19 have problems with clotting, and megakaryocytes are part of the clotting system, he speculated that some sort of aberrant message is being sent to these cells.
“It is notable that we found megakaryocytes in cortical capillaries in 33% of cases examined. Because the standard brain autopsy sections taken sampled at random [are] only a minute portion of the cortical volume, finding these cells suggests the total burden could be considerable,” the authors wrote.
Dr. Nauen added that to his knowledge, this is the first report of such observations, and the next step is to look for similar findings in larger sample sizes.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY
How has the pandemic affected rural and urban cancer patients?
Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.
Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).
A new survey has provided some insight into how the COVID-19 pandemic has impacted rural and urban cancer patients differently.
The survey showed that urban patients were more likely to report changes to their daily lives, thought themselves more likely to become infected with SARS-CoV-2, and were more likely to take measures to mitigate the risk of infection. However, there were no major differences between urban and rural patients with regard to changes in social interaction.
Bailee Daniels of the University of Utah in Salt Lake City, presented these results at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S04-03).
The COVID-19 and Oncology Patient Experience Consortium
Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.
At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.
The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
Assessing behaviors, attitudes, and outcomes
Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.
Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.
Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.
The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
Characteristics of urban and rural cancer patients
There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.
More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).
“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
Changes in daily life and health-related behavior during the pandemic
Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).
However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).
Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).
In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).
Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).
It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
Future directions
Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.
It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.
As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.
In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.
As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.
Ms. Daniels reported having no relevant disclosures.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.
Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).
A new survey has provided some insight into how the COVID-19 pandemic has impacted rural and urban cancer patients differently.
The survey showed that urban patients were more likely to report changes to their daily lives, thought themselves more likely to become infected with SARS-CoV-2, and were more likely to take measures to mitigate the risk of infection. However, there were no major differences between urban and rural patients with regard to changes in social interaction.
Bailee Daniels of the University of Utah in Salt Lake City, presented these results at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S04-03).
The COVID-19 and Oncology Patient Experience Consortium
Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.
At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.
The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
Assessing behaviors, attitudes, and outcomes
Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.
Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.
Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.
The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
Characteristics of urban and rural cancer patients
There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.
More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).
“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
Changes in daily life and health-related behavior during the pandemic
Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).
However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).
Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).
In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).
Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).
It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
Future directions
Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.
It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.
As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.
In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.
As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.
Ms. Daniels reported having no relevant disclosures.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.
Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).
A new survey has provided some insight into how the COVID-19 pandemic has impacted rural and urban cancer patients differently.
The survey showed that urban patients were more likely to report changes to their daily lives, thought themselves more likely to become infected with SARS-CoV-2, and were more likely to take measures to mitigate the risk of infection. However, there were no major differences between urban and rural patients with regard to changes in social interaction.
Bailee Daniels of the University of Utah in Salt Lake City, presented these results at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S04-03).
The COVID-19 and Oncology Patient Experience Consortium
Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.
At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.
The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
Assessing behaviors, attitudes, and outcomes
Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.
Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.
Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.
The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
Characteristics of urban and rural cancer patients
There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.
More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).
“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
Changes in daily life and health-related behavior during the pandemic
Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).
However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).
Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).
In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).
Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).
It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
Future directions
Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.
It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.
As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.
In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.
As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.
Ms. Daniels reported having no relevant disclosures.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
FROM AACR: COVID-19 AND CANCER 2021
New child COVID-19 cases decline as total passes 3 million
New COVID-19 cases in children continue to drop each week, but the total number of cases has now surpassed 3 million since the start of the pandemic, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
It was still enough, though, to bring the total to 3.03 million children infected with SARS-CoV-19 in the United States, the AAP and the CHA said in their weekly report.
The nation also hit a couple of other ignominious milestones. The cumulative rate of COVID-19 infection now stands at 4,030 per 100,000, so 4% of all children have been infected. Also, children represented 16.9% of all new cases for the week, which equals the highest proportion seen throughout the pandemic, based on data from health departments in 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.
There have been 241 COVID-19–related deaths in children so far, with 14 reported during the week of Feb. 5-11. Kansas just recorded its first pediatric death, which leaves 10 states that have had no fatalities. Texas, with 39 deaths, has had more than any other state, among the 43 that are reporting mortality by age, the AAP/CHA report showed.
New COVID-19 cases in children continue to drop each week, but the total number of cases has now surpassed 3 million since the start of the pandemic, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
It was still enough, though, to bring the total to 3.03 million children infected with SARS-CoV-19 in the United States, the AAP and the CHA said in their weekly report.
The nation also hit a couple of other ignominious milestones. The cumulative rate of COVID-19 infection now stands at 4,030 per 100,000, so 4% of all children have been infected. Also, children represented 16.9% of all new cases for the week, which equals the highest proportion seen throughout the pandemic, based on data from health departments in 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.
There have been 241 COVID-19–related deaths in children so far, with 14 reported during the week of Feb. 5-11. Kansas just recorded its first pediatric death, which leaves 10 states that have had no fatalities. Texas, with 39 deaths, has had more than any other state, among the 43 that are reporting mortality by age, the AAP/CHA report showed.
New COVID-19 cases in children continue to drop each week, but the total number of cases has now surpassed 3 million since the start of the pandemic, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
It was still enough, though, to bring the total to 3.03 million children infected with SARS-CoV-19 in the United States, the AAP and the CHA said in their weekly report.
The nation also hit a couple of other ignominious milestones. The cumulative rate of COVID-19 infection now stands at 4,030 per 100,000, so 4% of all children have been infected. Also, children represented 16.9% of all new cases for the week, which equals the highest proportion seen throughout the pandemic, based on data from health departments in 49 states (excluding New York), the District of Columbia, New York City, Puerto Rico, and Guam.
There have been 241 COVID-19–related deaths in children so far, with 14 reported during the week of Feb. 5-11. Kansas just recorded its first pediatric death, which leaves 10 states that have had no fatalities. Texas, with 39 deaths, has had more than any other state, among the 43 that are reporting mortality by age, the AAP/CHA report showed.