Covid ICYMI

It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so. – Josh Billings
 

Some patients believe COVID-19 is a hoax. Many think there’s truth to the rumor that Bill Gates is behind it all and intends to use COVID vaccinations as a devious way to implant microchips in us. He will then, of course, use the new 5G towers to track us all (although what Gates will do with the information that I was shopping at a Trader Joe’s yesterday is yet unknown).

It’s easy to dismiss patients with these beliefs as nuts or dumb or both. They’re neither, they’re just human. Conspiracy theories have been shared from the first time two humans met. They are, after all, simply hypotheses to explain an experience that’s difficult to understand. Making up a story to explain things feels safer than living with the unknown, and so we do. Our natural tendency to be suspicious makes conspiracy hypotheses more salient and more likely to spread. The pandemic itself is exacerbating this problem: People are alone and afraid, and dependent on social media for connection. Add a compelling story about a nefarious robber baron plotting to exploit us and you’ve got the conditions for conspiracy theories to explode like wind-driven wildfires. Astonishingly, a Pew Research poll showed 36% of Americans surveyed who have heard something about it say the Bill Gates cabal theory is “probably” or “definitely” true.

That many patients fervently believe conspiracy theories poses several problems for us. First, when a vaccine does become available, some patients will refuse to be vaccinated. The consequences to their health and the health of the community are grave. Secondly, whenever patients have cause to distrust doctors, it makes our jobs more challenging. If they don’t trust us on vaccines, it can spread to not trusting us about wearing masks or sunscreens or taking statins. Lastly, it’s near impossible to have a friendly conversation with a patient carrying forth on why Bill Gates is not in jail or how I’m part of the medical-industrial complex enabling him. Sheesh.

It isn’t their fault. The underpinning of these beliefs can be understood as a cognitive bias. In this case, an idea that is easy to imagine or recall is believed to be true more than an idea that is complex and difficult. Understanding viral replication and R0 numbers or viral vectors and protein subunit vaccines is hard. Imagining a chip being injected into your arm is easy. And, as behavioral economist Daniel Kahneman opined, we humans possess an almost unlimited ability to ignore our ignorance. We physicians can help in a way that friends and family members can’t. Here are ways you can help patients who believe in conspiracy theories:

Approach this problem like any other infirmity, with compassion. No one wants to drink too much and knock out their teeth falling off a bike. It was a mistake. Similarly, when people are steeped in self-delusion, it’s not a misdeed, it’s a lapse. Be kind and respectful.

Meet them where they are. It might be helpful to state with sincerity: So you feel that there is a government plot to use COVID to track us? Have you considered that might not be true?

Have the conversation in private. Harder even than being wrong is being publicly wrong.

Try the Socratic method. (We’re pretty good at this from teaching students and residents.) Conspiracy-believing patients have the illusion of knowledge, yet, like students, it’s often easy to show them their gaps. Do so gently by leading them to discover for themselves.

Stop when you stall. You cannot change someone’s mind by dint of force. However, you surely can damage your relationship if you keep pushing them.

Don’t worry if you fail to break through; you might yet have moved them a bit. This might make it possible for them to discover the truth later. Or, you could simply switch to explain what holds up the ground we walk upon. There’s rumor we’re supported on the backs of turtles, all the way down. Maybe Bill Gates is feeding them.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so. – Josh Billings
 

Some patients believe COVID-19 is a hoax. Many think there’s truth to the rumor that Bill Gates is behind it all and intends to use COVID vaccinations as a devious way to implant microchips in us. He will then, of course, use the new 5G towers to track us all (although what Gates will do with the information that I was shopping at a Trader Joe’s yesterday is yet unknown).

It’s easy to dismiss patients with these beliefs as nuts or dumb or both. They’re neither, they’re just human. Conspiracy theories have been shared from the first time two humans met. They are, after all, simply hypotheses to explain an experience that’s difficult to understand. Making up a story to explain things feels safer than living with the unknown, and so we do. Our natural tendency to be suspicious makes conspiracy hypotheses more salient and more likely to spread. The pandemic itself is exacerbating this problem: People are alone and afraid, and dependent on social media for connection. Add a compelling story about a nefarious robber baron plotting to exploit us and you’ve got the conditions for conspiracy theories to explode like wind-driven wildfires. Astonishingly, a Pew Research poll showed 36% of Americans surveyed who have heard something about it say the Bill Gates cabal theory is “probably” or “definitely” true.

That many patients fervently believe conspiracy theories poses several problems for us. First, when a vaccine does become available, some patients will refuse to be vaccinated. The consequences to their health and the health of the community are grave. Secondly, whenever patients have cause to distrust doctors, it makes our jobs more challenging. If they don’t trust us on vaccines, it can spread to not trusting us about wearing masks or sunscreens or taking statins. Lastly, it’s near impossible to have a friendly conversation with a patient carrying forth on why Bill Gates is not in jail or how I’m part of the medical-industrial complex enabling him. Sheesh.

It isn’t their fault. The underpinning of these beliefs can be understood as a cognitive bias. In this case, an idea that is easy to imagine or recall is believed to be true more than an idea that is complex and difficult. Understanding viral replication and R0 numbers or viral vectors and protein subunit vaccines is hard. Imagining a chip being injected into your arm is easy. And, as behavioral economist Daniel Kahneman opined, we humans possess an almost unlimited ability to ignore our ignorance. We physicians can help in a way that friends and family members can’t. Here are ways you can help patients who believe in conspiracy theories:

Approach this problem like any other infirmity, with compassion. No one wants to drink too much and knock out their teeth falling off a bike. It was a mistake. Similarly, when people are steeped in self-delusion, it’s not a misdeed, it’s a lapse. Be kind and respectful.

Meet them where they are. It might be helpful to state with sincerity: So you feel that there is a government plot to use COVID to track us? Have you considered that might not be true?

Have the conversation in private. Harder even than being wrong is being publicly wrong.

Try the Socratic method. (We’re pretty good at this from teaching students and residents.) Conspiracy-believing patients have the illusion of knowledge, yet, like students, it’s often easy to show them their gaps. Do so gently by leading them to discover for themselves.

Stop when you stall. You cannot change someone’s mind by dint of force. However, you surely can damage your relationship if you keep pushing them.

Don’t worry if you fail to break through; you might yet have moved them a bit. This might make it possible for them to discover the truth later. Or, you could simply switch to explain what holds up the ground we walk upon. There’s rumor we’re supported on the backs of turtles, all the way down. Maybe Bill Gates is feeding them.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so. – Josh Billings
 

Some patients believe COVID-19 is a hoax. Many think there’s truth to the rumor that Bill Gates is behind it all and intends to use COVID vaccinations as a devious way to implant microchips in us. He will then, of course, use the new 5G towers to track us all (although what Gates will do with the information that I was shopping at a Trader Joe’s yesterday is yet unknown).

It’s easy to dismiss patients with these beliefs as nuts or dumb or both. They’re neither, they’re just human. Conspiracy theories have been shared from the first time two humans met. They are, after all, simply hypotheses to explain an experience that’s difficult to understand. Making up a story to explain things feels safer than living with the unknown, and so we do. Our natural tendency to be suspicious makes conspiracy hypotheses more salient and more likely to spread. The pandemic itself is exacerbating this problem: People are alone and afraid, and dependent on social media for connection. Add a compelling story about a nefarious robber baron plotting to exploit us and you’ve got the conditions for conspiracy theories to explode like wind-driven wildfires. Astonishingly, a Pew Research poll showed 36% of Americans surveyed who have heard something about it say the Bill Gates cabal theory is “probably” or “definitely” true.

That many patients fervently believe conspiracy theories poses several problems for us. First, when a vaccine does become available, some patients will refuse to be vaccinated. The consequences to their health and the health of the community are grave. Secondly, whenever patients have cause to distrust doctors, it makes our jobs more challenging. If they don’t trust us on vaccines, it can spread to not trusting us about wearing masks or sunscreens or taking statins. Lastly, it’s near impossible to have a friendly conversation with a patient carrying forth on why Bill Gates is not in jail or how I’m part of the medical-industrial complex enabling him. Sheesh.

It isn’t their fault. The underpinning of these beliefs can be understood as a cognitive bias. In this case, an idea that is easy to imagine or recall is believed to be true more than an idea that is complex and difficult. Understanding viral replication and R0 numbers or viral vectors and protein subunit vaccines is hard. Imagining a chip being injected into your arm is easy. And, as behavioral economist Daniel Kahneman opined, we humans possess an almost unlimited ability to ignore our ignorance. We physicians can help in a way that friends and family members can’t. Here are ways you can help patients who believe in conspiracy theories:

Approach this problem like any other infirmity, with compassion. No one wants to drink too much and knock out their teeth falling off a bike. It was a mistake. Similarly, when people are steeped in self-delusion, it’s not a misdeed, it’s a lapse. Be kind and respectful.

Meet them where they are. It might be helpful to state with sincerity: So you feel that there is a government plot to use COVID to track us? Have you considered that might not be true?

Have the conversation in private. Harder even than being wrong is being publicly wrong.

Try the Socratic method. (We’re pretty good at this from teaching students and residents.) Conspiracy-believing patients have the illusion of knowledge, yet, like students, it’s often easy to show them their gaps. Do so gently by leading them to discover for themselves.

Stop when you stall. You cannot change someone’s mind by dint of force. However, you surely can damage your relationship if you keep pushing them.

Don’t worry if you fail to break through; you might yet have moved them a bit. This might make it possible for them to discover the truth later. Or, you could simply switch to explain what holds up the ground we walk upon. There’s rumor we’re supported on the backs of turtles, all the way down. Maybe Bill Gates is feeding them.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

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.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

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.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

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.

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Intimate partner violence (IPV) has not increased during the COVID-19 pandemic, at least during the early stages of the pandemic, new research suggests.

In April 2020, investigators surveyed over 1,750 individuals in intimate partner relationships. The survey was drawn from social media and email distribution lists. The researchers found that, of the roughly one-fifth who screened positive for IPV, half stated that the degree of victimization had remained the same since the COVID-19 outbreak; 17% reported that it had worsened; and one third reported that it had gotten better.

Those who reported worsening victimization said that sexual and physical violence, in particular, were exacerbated early in the pandemic’s course.

‘Shadow pandemic?’

The World Health Organization called upon health care organizations to be prepared to curb a potential IPV “shadow pandemic” during the COVID-19 pandemic.

However, no study has specifically evaluated whether self-reported victimization, particularly with regard to the severity and type of abuse, changed during the early period after COVID-19 social distancing polices were mandated.

“We scrambled right away when the pandemic hit because it was a unique opportunity to examine how behaviors change due to early stay-at-home policies; and, as a violence and injury epidemiologist, I am always curious about IPV, and this was a small subanalysis of that larger question,” Dr. Jetelina said.

The researchers recruited participants through their university and private social media accounts as well as professional distribution lists. Of those who completed the survey, 1,759 (mean age, 42 years) reported that they currently had an intimate partner. These participants were included in the study.

IPV was determined using the five-item Extended Hurt, Insulted, Threatened, and Scream (E-HITS) construct. Respondents were asked how often their partner physically hurt them, insulted them, threatened them with harm, screamed or cursed at them, or forced them to engage in sexual activities.

Each item was answered using a 5-point Likert scale. Scores ranged from 1, indicating never, to 5, indicating frequently. Participants who scored ≥7 were considered IPV positive.

Participants were also asked whether IPV severity had gotten much/somewhat better, had remained the same, or had gotten somewhat/much worse.
 

First peek

Of the total sample, 18% screened positive for IPV. Of these, 54% reported that the victimization had remained the same, 17% reported that it had worsened, and 30% said it had improved.

The majority of IPV victims experienced being insulted (97%) or being screamed at (86%).

Among those who reported worsening of IPV, the risk for physical violence was 4.38 times higher than the risk for nonphysical victimization. The risk for sexual victimization was 2.31 times higher than the risk for nonsexual victimization.

Among those who reported that IPV had gotten better, the improvement was 3.47 times higher with regard to physical victimization, compared with nonphysical victimization. Dr. Jetelina acknowledged that the findings cannot be generalized to the broader population.

“This was a convenience sample, but it is the first peek into what is happening behind closed doors and a first step to hearing collecting data from the victims themselves to better understand this ‘shadow pandemic’ and inform creative efforts to create better services for them while they are in isolation,” she said.
 

Lethality indicators

Commenting on the study, Peter Cronholm, MD, MSCE, associate professor of family medicine and community health at the Hospital of the University of Pennsylvania, Philadelphia, questioned the use of a score of 7 on the E-HITS screen to determine the presence of IPV.

“I think there are other thresholds that might be important, and even low levels of sexual violence may be different than higher levels of emotional violence,” said Dr. Cronholm, who was not involved with the study.

“Someone may have been sexually assaulted frequently but not cross the threshold, so I think it would have been helpful for the researchers to look at different types of violence,” he said.

Also commenting on the study, Jessica Palardy, LSW, program supervisor at STOP Intimate Partner Violence, Philadelphia, said, the findings “solidify a trend we sensed was happening but couldn’t confirm.”

She said her agency’s clients “have had a wide variety of experiences, in terms of increases or decreases in victimization.”

Some clients were able to use the quarantine as an excuse to stay with family or friends and so could avoid seeing their partners. “Others indicated that because their partners were distracted by figuring out a new method of work, the tension shifted away from the victim,” said Ms. Palardy, who was not involved in the research.

“For those who saw an increase in victimization, we noticed that this increase also came with an increase in lethality indicators, such as strangulation, physical violence, use of weapons and substances, etc,” she said.

She emphasized that it is critical to screen people for IPV to ensure their safety.

“The goal is to connect people with resources before they are in a more lethal situation so that they can increase their safety and know their options,” Ms. Palardy said.

The National Domestic Violence Hotline and the Crisis Text Line are two sources of support for IPV victims.

Dr. Jetelina and coauthors, Dr. Cronholm, and Ms. Palardy reported no relevant financial relationships.

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

Intimate partner violence (IPV) has not increased during the COVID-19 pandemic, at least during the early stages of the pandemic, new research suggests.

In April 2020, investigators surveyed over 1,750 individuals in intimate partner relationships. The survey was drawn from social media and email distribution lists. The researchers found that, of the roughly one-fifth who screened positive for IPV, half stated that the degree of victimization had remained the same since the COVID-19 outbreak; 17% reported that it had worsened; and one third reported that it had gotten better.

Those who reported worsening victimization said that sexual and physical violence, in particular, were exacerbated early in the pandemic’s course.

‘Shadow pandemic?’

The World Health Organization called upon health care organizations to be prepared to curb a potential IPV “shadow pandemic” during the COVID-19 pandemic.

However, no study has specifically evaluated whether self-reported victimization, particularly with regard to the severity and type of abuse, changed during the early period after COVID-19 social distancing polices were mandated.

“We scrambled right away when the pandemic hit because it was a unique opportunity to examine how behaviors change due to early stay-at-home policies; and, as a violence and injury epidemiologist, I am always curious about IPV, and this was a small subanalysis of that larger question,” Dr. Jetelina said.

The researchers recruited participants through their university and private social media accounts as well as professional distribution lists. Of those who completed the survey, 1,759 (mean age, 42 years) reported that they currently had an intimate partner. These participants were included in the study.

IPV was determined using the five-item Extended Hurt, Insulted, Threatened, and Scream (E-HITS) construct. Respondents were asked how often their partner physically hurt them, insulted them, threatened them with harm, screamed or cursed at them, or forced them to engage in sexual activities.

Each item was answered using a 5-point Likert scale. Scores ranged from 1, indicating never, to 5, indicating frequently. Participants who scored ≥7 were considered IPV positive.

Participants were also asked whether IPV severity had gotten much/somewhat better, had remained the same, or had gotten somewhat/much worse.
 

First peek

Of the total sample, 18% screened positive for IPV. Of these, 54% reported that the victimization had remained the same, 17% reported that it had worsened, and 30% said it had improved.

The majority of IPV victims experienced being insulted (97%) or being screamed at (86%).

Among those who reported worsening of IPV, the risk for physical violence was 4.38 times higher than the risk for nonphysical victimization. The risk for sexual victimization was 2.31 times higher than the risk for nonsexual victimization.

Among those who reported that IPV had gotten better, the improvement was 3.47 times higher with regard to physical victimization, compared with nonphysical victimization. Dr. Jetelina acknowledged that the findings cannot be generalized to the broader population.

“This was a convenience sample, but it is the first peek into what is happening behind closed doors and a first step to hearing collecting data from the victims themselves to better understand this ‘shadow pandemic’ and inform creative efforts to create better services for them while they are in isolation,” she said.
 

Lethality indicators

Commenting on the study, Peter Cronholm, MD, MSCE, associate professor of family medicine and community health at the Hospital of the University of Pennsylvania, Philadelphia, questioned the use of a score of 7 on the E-HITS screen to determine the presence of IPV.

“I think there are other thresholds that might be important, and even low levels of sexual violence may be different than higher levels of emotional violence,” said Dr. Cronholm, who was not involved with the study.

“Someone may have been sexually assaulted frequently but not cross the threshold, so I think it would have been helpful for the researchers to look at different types of violence,” he said.

Also commenting on the study, Jessica Palardy, LSW, program supervisor at STOP Intimate Partner Violence, Philadelphia, said, the findings “solidify a trend we sensed was happening but couldn’t confirm.”

She said her agency’s clients “have had a wide variety of experiences, in terms of increases or decreases in victimization.”

Some clients were able to use the quarantine as an excuse to stay with family or friends and so could avoid seeing their partners. “Others indicated that because their partners were distracted by figuring out a new method of work, the tension shifted away from the victim,” said Ms. Palardy, who was not involved in the research.

“For those who saw an increase in victimization, we noticed that this increase also came with an increase in lethality indicators, such as strangulation, physical violence, use of weapons and substances, etc,” she said.

She emphasized that it is critical to screen people for IPV to ensure their safety.

“The goal is to connect people with resources before they are in a more lethal situation so that they can increase their safety and know their options,” Ms. Palardy said.

The National Domestic Violence Hotline and the Crisis Text Line are two sources of support for IPV victims.

Dr. Jetelina and coauthors, Dr. Cronholm, and Ms. Palardy reported no relevant financial relationships.

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

Intimate partner violence (IPV) has not increased during the COVID-19 pandemic, at least during the early stages of the pandemic, new research suggests.

In April 2020, investigators surveyed over 1,750 individuals in intimate partner relationships. The survey was drawn from social media and email distribution lists. The researchers found that, of the roughly one-fifth who screened positive for IPV, half stated that the degree of victimization had remained the same since the COVID-19 outbreak; 17% reported that it had worsened; and one third reported that it had gotten better.

Those who reported worsening victimization said that sexual and physical violence, in particular, were exacerbated early in the pandemic’s course.

‘Shadow pandemic?’

The World Health Organization called upon health care organizations to be prepared to curb a potential IPV “shadow pandemic” during the COVID-19 pandemic.

However, no study has specifically evaluated whether self-reported victimization, particularly with regard to the severity and type of abuse, changed during the early period after COVID-19 social distancing polices were mandated.

“We scrambled right away when the pandemic hit because it was a unique opportunity to examine how behaviors change due to early stay-at-home policies; and, as a violence and injury epidemiologist, I am always curious about IPV, and this was a small subanalysis of that larger question,” Dr. Jetelina said.

The researchers recruited participants through their university and private social media accounts as well as professional distribution lists. Of those who completed the survey, 1,759 (mean age, 42 years) reported that they currently had an intimate partner. These participants were included in the study.

IPV was determined using the five-item Extended Hurt, Insulted, Threatened, and Scream (E-HITS) construct. Respondents were asked how often their partner physically hurt them, insulted them, threatened them with harm, screamed or cursed at them, or forced them to engage in sexual activities.

Each item was answered using a 5-point Likert scale. Scores ranged from 1, indicating never, to 5, indicating frequently. Participants who scored ≥7 were considered IPV positive.

Participants were also asked whether IPV severity had gotten much/somewhat better, had remained the same, or had gotten somewhat/much worse.
 

First peek

Of the total sample, 18% screened positive for IPV. Of these, 54% reported that the victimization had remained the same, 17% reported that it had worsened, and 30% said it had improved.

The majority of IPV victims experienced being insulted (97%) or being screamed at (86%).

Among those who reported worsening of IPV, the risk for physical violence was 4.38 times higher than the risk for nonphysical victimization. The risk for sexual victimization was 2.31 times higher than the risk for nonsexual victimization.

Among those who reported that IPV had gotten better, the improvement was 3.47 times higher with regard to physical victimization, compared with nonphysical victimization. Dr. Jetelina acknowledged that the findings cannot be generalized to the broader population.

“This was a convenience sample, but it is the first peek into what is happening behind closed doors and a first step to hearing collecting data from the victims themselves to better understand this ‘shadow pandemic’ and inform creative efforts to create better services for them while they are in isolation,” she said.
 

Lethality indicators

Commenting on the study, Peter Cronholm, MD, MSCE, associate professor of family medicine and community health at the Hospital of the University of Pennsylvania, Philadelphia, questioned the use of a score of 7 on the E-HITS screen to determine the presence of IPV.

“I think there are other thresholds that might be important, and even low levels of sexual violence may be different than higher levels of emotional violence,” said Dr. Cronholm, who was not involved with the study.

“Someone may have been sexually assaulted frequently but not cross the threshold, so I think it would have been helpful for the researchers to look at different types of violence,” he said.

Also commenting on the study, Jessica Palardy, LSW, program supervisor at STOP Intimate Partner Violence, Philadelphia, said, the findings “solidify a trend we sensed was happening but couldn’t confirm.”

She said her agency’s clients “have had a wide variety of experiences, in terms of increases or decreases in victimization.”

Some clients were able to use the quarantine as an excuse to stay with family or friends and so could avoid seeing their partners. “Others indicated that because their partners were distracted by figuring out a new method of work, the tension shifted away from the victim,” said Ms. Palardy, who was not involved in the research.

“For those who saw an increase in victimization, we noticed that this increase also came with an increase in lethality indicators, such as strangulation, physical violence, use of weapons and substances, etc,” she said.

She emphasized that it is critical to screen people for IPV to ensure their safety.

“The goal is to connect people with resources before they are in a more lethal situation so that they can increase their safety and know their options,” Ms. Palardy said.

The National Domestic Violence Hotline and the Crisis Text Line are two sources of support for IPV victims.

Dr. Jetelina and coauthors, Dr. Cronholm, and Ms. Palardy reported no relevant financial relationships.

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

Abnormal coagulation is a hallmark of COVID-19. Now, as we’re learning more about the high risk of thrombosis, physicians need to prescribe prophylaxis routinely in the hospital, stay alert, and act immediately when signs of trouble appear. “We must have a low suspicion for diagnosis and treatment of thrombosis,” said hematologist-oncologist Thomas DeLoughery, MD, professor of medicine at Oregon Health & Science University in Portland in a presentation at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Still, research is sparse, and there are disagreements about the best strategies to protect patients, said DeLoughery. Physicians recognized coagulation problems early on during the course of the COVID-19 pandemic, he said, and they’re very common. According to DeLoughery, most patients have abnormal coagulation, very high D-dimer test results, and very high fibrinogen levels—even to the extraordinary level of 1,500 mg/dL, he said. And unlike in typical patients with septic shock, patients with thrombosis have a higher risk than bleeding.

A high D-dimer level is a major prognostic indicator of thrombosis and bad outcomes. “It’s representative of widespread coagulation activation, and it can be a sign of pulmonary thrombosis and local thrombosis happening at the site of the COVID infection,” he said.

DeLoughery highlighted an April 2020 study that found that “patients with D‐dimer levels ≥ 2.0 µg/mL had a higher incidence of mortality when compared with those who with D‐dimer levels < 2.0 µg/mL (12/67 vs 1/267; P < .001; hazard ratio, 51.5; 95% CI, 12.9‐206.7).”

Research also suggests that “there's something about getting COVID and going to the intensive care unit (ICU) that dramatically raises the risk of thrombosis,” he said, and the risk goes up over time in the ICU. Venous thrombosis isn’t the only risk. Relatively young patients with COVID have suffered from arterial thrombosis, even though they have minimal to no respiratory symptoms and no cardiovascular risk factors.

As for treatments, DeLoughery noted that thrombosis can occur despite standard prophylaxis, and patients may show resistance to heparin and, therefore, need massive doses. Still, there’s consensus that every patient with COVID-19 in the hospital should get thromboprophylaxis with low-molecular-weight heparin (LMWH), he said, and unfractionated heparin is appropriate for those with renal failure.

“The problem is everything else is controversial,” he said. For example, hematologists are split evenly on whether heparin dosing should be increased beyond standard protocol for patients in the ICU with 1.5 to 3 times normal D-dimers levels. He agreed with this approach but notes that some centers set their D-dimer triggers higher—at 3 to 6 times the normal level.

“The problem is that there’s limited data,” he said. “We have lots of observational studies suggesting benefits from higher doses, but we have no randomized trial data, and the observational studies are not uniform in their recommendations.”

What about outpatient prophylaxis? It appears that risk of thrombosis is < 1% percent when patients are out of the hospital, he said. “This is very reassuring that once the patient gets better, their prothrombotic drive goes away.”

Dr. DeLoughery highlighted the protocol at Oregon Health & Science University:

• Prophylaxis. Everyone with COVID-19 admitted to the hospital receives enoxaparin 40 mg daily. If the patient’s body mass index > 40, it should be increased to twice daily. For patients with renal failure, use unfractionated heparin 5000 u twice daily or enoxaparin 30 mg daily.
• In the ICU. Screen for deep vein thrombosis at admission and every 4 to 5 days thereafter. Increase enoxaparin to 40 mg twice daily, and to 1 mg/kg twice daily if signs of thrombosis develop, such as sudden deterioration, respiratory failure, the patient is too unstable to get a computed tomography, or with D-dimer > 3.0 µg/mL. “People’s thresholds for initiating empiric therapy differ, but this is an option,” he said.

For outpatient patients who are likely to be immobile for a month, 40 mg enoxaparin or 10 mg rivaroxaban are appropriate. “We’re not as aggressive as we used to be about outpatient prophylaxis,” he said.

Moving forward, he said, “this is an area where we really need clinical trials. There's just so much uncertainty.”

DeLoughery reported no disclosures.

Abnormal coagulation is a hallmark of COVID-19. Now, as we’re learning more about the high risk of thrombosis, physicians need to prescribe prophylaxis routinely in the hospital, stay alert, and act immediately when signs of trouble appear. “We must have a low suspicion for diagnosis and treatment of thrombosis,” said hematologist-oncologist Thomas DeLoughery, MD, professor of medicine at Oregon Health & Science University in Portland in a presentation at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Still, research is sparse, and there are disagreements about the best strategies to protect patients, said DeLoughery. Physicians recognized coagulation problems early on during the course of the COVID-19 pandemic, he said, and they’re very common. According to DeLoughery, most patients have abnormal coagulation, very high D-dimer test results, and very high fibrinogen levels—even to the extraordinary level of 1,500 mg/dL, he said. And unlike in typical patients with septic shock, patients with thrombosis have a higher risk than bleeding.

A high D-dimer level is a major prognostic indicator of thrombosis and bad outcomes. “It’s representative of widespread coagulation activation, and it can be a sign of pulmonary thrombosis and local thrombosis happening at the site of the COVID infection,” he said.

DeLoughery highlighted an April 2020 study that found that “patients with D‐dimer levels ≥ 2.0 µg/mL had a higher incidence of mortality when compared with those who with D‐dimer levels < 2.0 µg/mL (12/67 vs 1/267; P < .001; hazard ratio, 51.5; 95% CI, 12.9‐206.7).”

Research also suggests that “there's something about getting COVID and going to the intensive care unit (ICU) that dramatically raises the risk of thrombosis,” he said, and the risk goes up over time in the ICU. Venous thrombosis isn’t the only risk. Relatively young patients with COVID have suffered from arterial thrombosis, even though they have minimal to no respiratory symptoms and no cardiovascular risk factors.

As for treatments, DeLoughery noted that thrombosis can occur despite standard prophylaxis, and patients may show resistance to heparin and, therefore, need massive doses. Still, there’s consensus that every patient with COVID-19 in the hospital should get thromboprophylaxis with low-molecular-weight heparin (LMWH), he said, and unfractionated heparin is appropriate for those with renal failure.

“The problem is everything else is controversial,” he said. For example, hematologists are split evenly on whether heparin dosing should be increased beyond standard protocol for patients in the ICU with 1.5 to 3 times normal D-dimers levels. He agreed with this approach but notes that some centers set their D-dimer triggers higher—at 3 to 6 times the normal level.

“The problem is that there’s limited data,” he said. “We have lots of observational studies suggesting benefits from higher doses, but we have no randomized trial data, and the observational studies are not uniform in their recommendations.”

What about outpatient prophylaxis? It appears that risk of thrombosis is < 1% percent when patients are out of the hospital, he said. “This is very reassuring that once the patient gets better, their prothrombotic drive goes away.”

Dr. DeLoughery highlighted the protocol at Oregon Health & Science University:

• Prophylaxis. Everyone with COVID-19 admitted to the hospital receives enoxaparin 40 mg daily. If the patient’s body mass index > 40, it should be increased to twice daily. For patients with renal failure, use unfractionated heparin 5000 u twice daily or enoxaparin 30 mg daily.
• In the ICU. Screen for deep vein thrombosis at admission and every 4 to 5 days thereafter. Increase enoxaparin to 40 mg twice daily, and to 1 mg/kg twice daily if signs of thrombosis develop, such as sudden deterioration, respiratory failure, the patient is too unstable to get a computed tomography, or with D-dimer > 3.0 µg/mL. “People’s thresholds for initiating empiric therapy differ, but this is an option,” he said.

For outpatient patients who are likely to be immobile for a month, 40 mg enoxaparin or 10 mg rivaroxaban are appropriate. “We’re not as aggressive as we used to be about outpatient prophylaxis,” he said.

Moving forward, he said, “this is an area where we really need clinical trials. There's just so much uncertainty.”

DeLoughery reported no disclosures.

Abnormal coagulation is a hallmark of COVID-19. Now, as we’re learning more about the high risk of thrombosis, physicians need to prescribe prophylaxis routinely in the hospital, stay alert, and act immediately when signs of trouble appear. “We must have a low suspicion for diagnosis and treatment of thrombosis,” said hematologist-oncologist Thomas DeLoughery, MD, professor of medicine at Oregon Health & Science University in Portland in a presentation at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Still, research is sparse, and there are disagreements about the best strategies to protect patients, said DeLoughery. Physicians recognized coagulation problems early on during the course of the COVID-19 pandemic, he said, and they’re very common. According to DeLoughery, most patients have abnormal coagulation, very high D-dimer test results, and very high fibrinogen levels—even to the extraordinary level of 1,500 mg/dL, he said. And unlike in typical patients with septic shock, patients with thrombosis have a higher risk than bleeding.

A high D-dimer level is a major prognostic indicator of thrombosis and bad outcomes. “It’s representative of widespread coagulation activation, and it can be a sign of pulmonary thrombosis and local thrombosis happening at the site of the COVID infection,” he said.

DeLoughery highlighted an April 2020 study that found that “patients with D‐dimer levels ≥ 2.0 µg/mL had a higher incidence of mortality when compared with those who with D‐dimer levels < 2.0 µg/mL (12/67 vs 1/267; P < .001; hazard ratio, 51.5; 95% CI, 12.9‐206.7).”

Research also suggests that “there's something about getting COVID and going to the intensive care unit (ICU) that dramatically raises the risk of thrombosis,” he said, and the risk goes up over time in the ICU. Venous thrombosis isn’t the only risk. Relatively young patients with COVID have suffered from arterial thrombosis, even though they have minimal to no respiratory symptoms and no cardiovascular risk factors.

As for treatments, DeLoughery noted that thrombosis can occur despite standard prophylaxis, and patients may show resistance to heparin and, therefore, need massive doses. Still, there’s consensus that every patient with COVID-19 in the hospital should get thromboprophylaxis with low-molecular-weight heparin (LMWH), he said, and unfractionated heparin is appropriate for those with renal failure.

“The problem is everything else is controversial,” he said. For example, hematologists are split evenly on whether heparin dosing should be increased beyond standard protocol for patients in the ICU with 1.5 to 3 times normal D-dimers levels. He agreed with this approach but notes that some centers set their D-dimer triggers higher—at 3 to 6 times the normal level.

“The problem is that there’s limited data,” he said. “We have lots of observational studies suggesting benefits from higher doses, but we have no randomized trial data, and the observational studies are not uniform in their recommendations.”

What about outpatient prophylaxis? It appears that risk of thrombosis is < 1% percent when patients are out of the hospital, he said. “This is very reassuring that once the patient gets better, their prothrombotic drive goes away.”

Dr. DeLoughery highlighted the protocol at Oregon Health & Science University:

• Prophylaxis. Everyone with COVID-19 admitted to the hospital receives enoxaparin 40 mg daily. If the patient’s body mass index > 40, it should be increased to twice daily. For patients with renal failure, use unfractionated heparin 5000 u twice daily or enoxaparin 30 mg daily.
• In the ICU. Screen for deep vein thrombosis at admission and every 4 to 5 days thereafter. Increase enoxaparin to 40 mg twice daily, and to 1 mg/kg twice daily if signs of thrombosis develop, such as sudden deterioration, respiratory failure, the patient is too unstable to get a computed tomography, or with D-dimer > 3.0 µg/mL. “People’s thresholds for initiating empiric therapy differ, but this is an option,” he said.

For outpatient patients who are likely to be immobile for a month, 40 mg enoxaparin or 10 mg rivaroxaban are appropriate. “We’re not as aggressive as we used to be about outpatient prophylaxis,” he said.

Moving forward, he said, “this is an area where we really need clinical trials. There's just so much uncertainty.”

DeLoughery reported no disclosures.

Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”¹

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.²

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.³ (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.⁴

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
 

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.⁵ Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.^5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
 

Behavioral manifestations and psychosocial health

As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.⁷ Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.

We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.⁸

An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”⁹

The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.

Strategies aimed at supporting mental health

Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.

In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
 

Employing assessment scales

To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.¹⁰

As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.¹⁰ As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
 

Moving forward: The next step in COVID-19 preparedness

As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.

For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.

It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.¹¹ There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.¹²

References

1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.

2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.

3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.

4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.

5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.

6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.

7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.

8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.

9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.

10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.

11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.

12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.

Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.

Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”¹

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.²

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.³ (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.⁴

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
 

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.⁵ Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.^5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
 

Behavioral manifestations and psychosocial health

As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.⁷ Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.

We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.⁸

An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”⁹

The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.

Strategies aimed at supporting mental health

Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.

In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
 

Employing assessment scales

To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.¹⁰

As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.¹⁰ As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
 

Moving forward: The next step in COVID-19 preparedness

As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.

For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.

It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.¹¹ There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.¹²

References

1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.

2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.

3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.

4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.

5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.

6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.

7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.

8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.

9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.

10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.

11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.

12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.

Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.

Psychological First Aid is an innovative program launched by the American Red Cross with the goal of addressing issues of concern such as those stemming from COVID-19–related stress. According to Red Cross mental health volunteer representative Deb Butman-Perkins, the program provides “a general overview of what does stress look like, how do we feel it, how do we recognize it in our bodies ... physical, emotional, spiritual, physiological, where does all that stress occur?”¹

The program brings a spotlight to the interdisciplinary nature of the stress response, especially with respect to the importance of developing the necessary coping skills during an ongoing crisis. However, to effectively evaluate and manage the overall stress response for psychiatric patients during quarantine conditions, as well as those who are formally diagnosed with COVID-19, clinicians also will need to revisit what we’ve learned about the hypothalamic-pituitary-adrenal (HPA) axis.

We know that the stress response – which varies somewhat across the spectrum – is necessary to ensure homeostatic regulation. A feedback loop is initiated at the receptor level, involving a myriad of hormones and chemical signals that bring forth the body’s “flight-or-fight” response. Hormones such as epinephrine/norepinephrine and cortisol are secreted by the HPA axis in reaction to the stress response, resulting in a spike in heart rate, blood pressure, and transient hyperglycemia, respectively. In particular, hyperglycemia provides immediate energy to muscles during a perceived crisis.²

In addition, prolonged exposure to living in quarantine can lead to feelings of isolation and estrangement – and excessive anxiety. Combined, those conditions may exert an indelible effect on the HPA axis – leading to a warped pattern of cortisol secretion with respect to baseline.³ (It has been noted in the literature that serum cortisol plays a protective role in thwarting off the effects of PTSD development. Consistent with this line of thinking, military personnel have been preemptively treated with high-dose cortisol during acute exposure.)

Prolonged exposure to psychosocial stressors also increases the overall risk of developing medical comorbidities. Patients who adopt maladaptive responses to traumatic events, for example, may experience dysregulation in eating behaviors and/or disordered sleep.⁴

In light of those realities, clinicians should explore the role of steroid therapy as a means of treating mental health patients experiencing psychological stress formation tied to ongoing quarantine conditions.
 

Challenges of neuroendocrine medications for COVID-19

COVID-19, caused by exposure to SARS-CoV-2, adeptly leverages the ACE2 receptor of the lungs as an entry point to evade the host’s defenses. It should be noted that the ACE2 protein is expressed on the cells of multiple organs of the body, including the adrenals, which are largely responsible for coordinating the stress response of the HPA axis.

Postmortem analysis from severe acute respiratory syndrome (SARS-CoV is also from the Coronaviridae family) patients indicates the presence of necrotic adrenal cells, further solidifying the association of the HPA axis to the COVID-19 disease state and pathophysiological course.⁵ Molecular mimicry of the adrenocorticotropic hormone allows SARS-CoV the ability to infiltrate the host’s defenses, in particular, the ability to mount a clinically apt cortisol stress response (e.g., hypocortisolism).As for those who survived the 2003 SARS outbreak, less than half of the patients have been observed to develop symptoms of frank hypocortisolism within a few months after exposure.

The World Health Organization recently endorsed the use of steroid therapy for critically ill COVID-19 patients, and an ongoing clinical trial is evaluating the safety and efficacy parameters of corticosteroids in COVID-19–exposed patients.

In addition, there is reason to believe that application of prophylactic steroids might affect the overall clinical course of COVID-19, thereby reducing mortality and morbidity rates in patients with severe presentation, such as septic shock. The rationale for this line of thought is based on the ability of glucocorticoids to suppress an ensuing cytokine storm by the virus in question.^5,6 In clinical practice, steroids have been used to treat a host of viral diseases, including influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus.

Aside from the selective use of corticosteroids, the medication regimen may incorporate ACE inhibitors and/or angiotensin receptor blockers (ARBs) because of COVID-19’s ability to activate the renin-angiotensin-aldosterone system with respect to the physiological stress response.

The interplay of the HPA axis with the sympathoadrenal system is responsible for adaptive behaviors in the individual. Disrupted feedback loops from prolonged activation are associated with numerous stress-based conditions in mental illness, namely, PTSD, anxiety, and mood disorders. We are concerned about frontline health care workers, who are particularly prone to chronic stress and burnout because of the cumbersome patient load and equipment shortage that have characterized the coronavirus crisis.

Timely administration of corticosteroids on a case-by-case basis would keep the cytokines at bay by precluding their undue activation of the HPA axis and corresponding cascade stress response. Steroids are also known to restore disrupted feedback loops at the level of the immune cells. However, because of conflicting reports concerning viral clearance in some SARS and COVID-19 studies, treatment with steroids may be limited to select patient populations with the necessary dose adjustments. Ongoing clinical trials will further elucidate upon the applicability of steroids as well as the role of other neuroendocrine agents, such as ACE inhibitors or ARBs, in the treatment of COVID-19.
 

Behavioral manifestations and psychosocial health

As far as the stress response is concerned, an analysis performed by researchers in China after the COVID-19 outbreak found gender disparities in symptom expression. In the study (n = 1,210) the researchers found in female citizens a greater frequency of behavioral manifestations, including acute stress reaction, and symptoms of anxiety and mood disorders – namely, depression.⁷ Patient perception and awareness of the perils of coronavirus typically varied across the spectrum; some individuals reportedly undermined and devalued their risk of contracting COVID-19 – these patients may benefit from therapeutic modalities, such as cognitive-behavioral therapy (CBT), as a means of challenging their firmly entrenched cognitive distortions. CBT is an effective tool in addressing maladaptive coping responses, because these strategies tend to correspond with poor prognosis with respect to overall mental health. Aside from CBT, the clinician may advise other behavioral techniques, such as relaxation training, with the aim of controlling the symptoms of mood and anxiety disorders.

We often take for granted general pandemic safety precautions, such as maintaining physical distancing coupled with engaging in regular hand hygiene and wearing masks, but these actions also are known to alleviate mental anguish. Access to accurate and easy-to-consume health information regarding COVID-19 is also associated with psychological well-being during the quarantine.⁸

An intriguing “phenomenon” has emerged in the form of “panic buying.”However, researchers reported in the peer-reviewed journal Nature Human Behaviour that this pattern of behaviors is not typical for those under distress and represents an overstated misnomer of sorts. According to Jay J. Van Bavel, PhD, and associates, prevailing reports from news outlets have skewed the features of a panic. “News stories that employ the language of panic often create the very phenomena that they purport to condemn,” Dr. Van Bavel and associates wrote. “They can foster the very individualism and competitiveness that turn sensible preparations into dysfunctional stockpiling and undermine the sense of collective purpose which facilitates people supporting one another during an emergency.”⁹

The researchers proceeded to highlight the scope of effective crisis leadership with respect to establishing a sense of communal “self-efficacy and hope.” The influence of organized leadership serves to solidify the structure of the community as a whole, allowing group members the opportunity to address the stressors of interest. Such leadership may mitigate the stress response by fostering a necessary, healthy set for stress management.

Strategies aimed at supporting mental health

Coping and stress management strategies may include the process of building virtual networks (e.g., social media platforms) because physical distancing may contribute toward further isolation and social estrangement. However, it should be noted that ideally social media consumption should be centered upon interactive enrichment activities that provide a suitable substitute for the absence of physical support systems. The goal is to facilitate meaningful relationships and enduring communications that produce healthy and resilient mindsets.

In particular, individuals who possess adaptive mindsets with a realistic view of ongoing psychosocial stressors, be it from the impact of the pandemic or other influential events, are more likely to benefit when moving forward with life. In other words, the individual in question leverages these experiences as a means of “stress-related growth,” thereby enhancing the overall quality of relationships. Tentative studies in stress management have yielded promising support for interventions that aim to modulate mindsets (as a function of the stress response) by proper appraisal of the stress stimuli, according to Dr. Van Bavel and associates.
 

Employing assessment scales

To mitigate the stress response, clinicians need to use the relevant stress scales for assessing the full impact of distress brought on by COVID-19 and optimizing therapeutic modalities for those who need them most. Again, the stress response would vary, depending on the patient, and may include paranoia, xenophobia, compulsive ritualistic behavior, as well as full-fledged symptoms of acute stress disorder/PTSD.Steven Taylor, PhD, RPsych, and associates, part of a research team funded by the Canadian Institutes of Health Research and the University of Regina (Sask.), formulated their proprietary COVID Stress Scales (CSS) based on 36 items pertaining to individual anxiety and/or stress responses.¹⁰

As general purpose pandemic scales, the assessment tools will be transferable to similar outbreaks, and have been examined for validity and reliability. Additional validation scales include the Patient Health Questionnaire–4 for anxiety and depression, the Short Health Anxiety Inventory for anxiety (irrespective of physical condition), and the Marlowe-Crowne Social Desirability Scale–Short Form for psychological well-being based on the presence (or the lack thereof) of desirable characteristics.¹⁰ As a composite scale and predictive tool (especially with respect to future pandemics), the CSS allows clinicians a means of identifying the people who are most compliant with safety procedures, social distancing, hygiene expectations, and vaccine protocols – when applicable – reported Dr. Taylor and associates.
 

Moving forward: The next step in COVID-19 preparedness

As clinicians continue to develop guidelines that are befitting of COVID-19’s “new normal,” a holistic psychosocial framework will need to integrate the various psychometrics gathered from assessment scales, as well as understanding trauma, especially with respect to the HPA axis.

For starters, there is a certain element of “anticipatory anxiety” for those experiencing distress from COVID-19. A highly uncertain future with no immediate cure in the future, isolation and social estrangement, as well as financial setbacks, compound the situation. Moreover, the DSM fails to acknowledge other sources of traumatic experiences that are systemic in nature, such as discriminatory practices, injustice, and/or persecution.

It has also been noted that some distressed individuals experience a hypervigilant state that is comparable with PTSD.¹¹ There may be a push to incorporate machine learning and other modalities to better identify those at risk (for example, health care professionals who perform their duties with limited resources, thereby inducing sleep dysregulation, anxiety, and hopelessness) for mental health deterioration. Interventions may need to be coordinated in a timely manner to disrupt the progression of acute stress disorder to PTSD. Peer support programs and resiliency training – successful therapeutic approaches for PTSD – may prove to have considerable utility for mitigating the overall stress response of COVID-19.¹²

References

1. “Red Cross offering online course to manage crisis-related stress.” ABC 6 News. kaaltv.com, 2020 Aug 29.

2. Islam FA, Choudhry C. J Psychiatry Psychiatric Disord 2017;1(5): 290-3.

3. Faravelli C et al. World J Psychiatry. 2012 Feb 22;2(1):13-25.

4. Carmassi C et al. Psychiatry Res. 2015 Jan 30;225(1-2):64-9.

5. Pal R. Endocrine. 2020 Apr 28. doi: 10.1007/s12020-020-02325-1.

6. Steenblock C et al. Mol Psychiatry. 2020 May. doi: 10.1038/s41380-020-0758-9.

7. Wang C et al. Int J Environ Res Public Health. 2020 Jan;17(5):1729.

8. Ho CS et al. Ann Acad Med Singap. 2020 Mar 16;49(3):155-60.

9. Van Bavel JJ et al. Nat Hum Behav. 2020 Apr 30. doi: 10.1038/s41562-020-0884-z.

10. Taylor S et al. J Anxiety Disord. 2020 May 4;72:102232.

11. Horesh D, Brown AD. Psychol Trauma. 2020 May;12(4):331-5.

12. Clark H et al. National Health Library and Knowledge Service/Evidence Team. Summary of Evidence: COVID-19, 2020 May 22. Version 2.0.

Dr. Faisal A. Islam is a medical adviser for the International Maternal and Child Health Foundation, Montreal, and is based in New York. He also is a postdoctoral fellow, psychopharmacologist, and a board-certified medical affairs specialist. Dr. Mohammed S. Islam is a research physician and extern at Interfaith Medical Center, New York. Dr. Choudhry is the chief scientific officer and head of the department of mental health and clinical research at the International Maternal and Child Health Foundation. Dr. Jolayemi is an attending psychiatrist at Interfaith Medical Center. No disclosures were reported.

The patients walk into Dr. Melissa Marshall’s community clinics in Northern California with the telltale symptoms. They’re having trouble breathing. It may even hurt to inhale. They’ve got a cough, and the sore throat is definitely there.

A straight case of COVID-19? Not so fast. This is wildfire country.

Up and down the West Coast, hospitals and health facilities are reporting an influx of patients with problems most likely related to smoke inhalation. As fires rage largely uncontrolled amid dry heat and high winds, smoke and ash are billowing and settling on coastal areas like San Francisco and cities and towns hundreds of miles inland as well, turning the sky orange or gray and making even ordinary breathing difficult.

But that, Marshall said, is only part of the challenge. Facilities already strapped for testing supplies and personal protective equipment must first rule out COVID-19 in these patients, because many of the symptoms they present with are the same as those caused by the virus.

“Obviously, there’s overlap in the symptoms,” said Marshall, the CEO of CommuniCare, a collection of six clinics in Yolo County, near Sacramento, that treats mostly underinsured and uninsured patients. “Any time someone comes in with even some of those symptoms, we ask ourselves, ‘Is it COVID?’ At the end of the day, clinically speaking, I still want to rule out the virus.”

The protocol is to treat the symptoms, whatever their cause, while recommending that the patient quarantine until test results for the virus come back, she said.

It is a scene playing out in numerous hospitals. Administrators and physicians, finely attuned to COVID-19’s ability to spread quickly and wreak havoc, simply won’t take a chance when they recognize symptoms that could emanate from the virus.

“We’ve seen an increase in patients presenting to the emergency department with respiratory distress,” said Dr. Nanette Mickiewicz, president and CEO of Dominican Hospital in Santa Cruz. “As this can also be a symptom of COVID-19, we’re treating these patients as we would any person under investigation for coronavirus until we can rule them out through our screening process.” During the workup, symptoms that are more specific to COVID-19, like fever, would become apparent.

For the workers at Dominican, the issue moved to the top of the list quickly. Santa Cruz and San Mateo counties have borne the brunt of the CZU Lightning Complex fires, which as of Sept. 10 had burned more than 86,000 acres, destroying 1,100 structures and threatening more than 7,600 others. Nearly a month after they began, the fires were approximately 84% contained, but thousands of people remained evacuated.

Dominican, a Dignity Health hospital, is “open, safe and providing care,” Mickiewicz said. Multiple tents erected outside the building serve as an extension of its ER waiting room. They also are used to perform what has come to be understood as an essential role: separating those with symptoms of COVID-19 from those without.

At the two Solano County hospitals operated by NorthBay Healthcare, the path of some of the wildfires prompted officials to review their evacuation procedures, said spokesperson Steve Huddleston. They ultimately avoided the need to evacuate patients, and new ones arrived with COVID-like symptoms that may actually have been from smoke inhalation.

Huddleston said NorthBay’s intake process “calls for anyone with COVID characteristics to be handled as [a] patient under investigation for COVID, which means they’re separated, screened and managed by staff in special PPE.” At the two hospitals, which have handled nearly 200 COVID cases so far, the protocol is well established.

Hospitals in California, though not under siege in most cases, are dealing with multiple issues they might typically face only sporadically. In Napa County, Adventist Health St. Helena Hospital evacuated 51 patients on a single August night as a fire approached, moving them to 10 other facilities according to their needs and bed space. After a 10-day closure, the hospital was allowed to reopen as evacuation orders were lifted, the fire having been contained some distance away.

The wildfires are also taking a personal toll on health care workers. CommuniCare’s Marshall lost her family’s home in rural Winters, along with 20 acres of olive trees and other plantings that surrounded it, in the Aug. 19 fires that swept through Solano County.

“They called it a ‘firenado,’ ” Marshall said. An apparent confluence of three fires raged out of control, demolishing thousands of acres. With her family safely accounted for and temporary housing arranged by a friend, she returned to work. “Our clinics interact with a very vulnerable population,” she said, “and this is a critical time for them.”

While she pondered how her family would rebuild, the CEO was faced with another immediate crisis: the clinic’s shortage of supplies. Last month, CommuniCare got down to 19 COVID test kits on hand, and ran so low on swabs “that we were literally turning to our veterinary friends for reinforcements,” the doctor said. The clinic’s COVID test results, meanwhile, were taking nearly two weeks to be returned from an overwhelmed outside lab, rendering contact tracing almost useless.

Those situations have been addressed, at least temporarily, Marshall said. But although the West Coast is in the most dangerous time of year for wildfires, generally September to December, another complication for health providers lies on the horizon: flu season.

The Southern Hemisphere, whose influenza trends during our summer months typically predict what’s to come for the U.S., has had very little of the disease this year, presumably because of restricted travel, social distancing and face masks. But it’s too early to be sure what the U.S. flu season will entail.

“You can start to see some cases of the flu in late October,” said Marshall, “and the reality is that it’s going to carry a number of characteristics that could also be symptomatic of COVID. And nothing changes: You have to rule it out, just to eliminate the risk.”

KHN (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. This KHN story first published on California Healthline, a service of the California Health Care Foundation.

The patients walk into Dr. Melissa Marshall’s community clinics in Northern California with the telltale symptoms. They’re having trouble breathing. It may even hurt to inhale. They’ve got a cough, and the sore throat is definitely there.

A straight case of COVID-19? Not so fast. This is wildfire country.

Up and down the West Coast, hospitals and health facilities are reporting an influx of patients with problems most likely related to smoke inhalation. As fires rage largely uncontrolled amid dry heat and high winds, smoke and ash are billowing and settling on coastal areas like San Francisco and cities and towns hundreds of miles inland as well, turning the sky orange or gray and making even ordinary breathing difficult.

But that, Marshall said, is only part of the challenge. Facilities already strapped for testing supplies and personal protective equipment must first rule out COVID-19 in these patients, because many of the symptoms they present with are the same as those caused by the virus.

“Obviously, there’s overlap in the symptoms,” said Marshall, the CEO of CommuniCare, a collection of six clinics in Yolo County, near Sacramento, that treats mostly underinsured and uninsured patients. “Any time someone comes in with even some of those symptoms, we ask ourselves, ‘Is it COVID?’ At the end of the day, clinically speaking, I still want to rule out the virus.”

The protocol is to treat the symptoms, whatever their cause, while recommending that the patient quarantine until test results for the virus come back, she said.

It is a scene playing out in numerous hospitals. Administrators and physicians, finely attuned to COVID-19’s ability to spread quickly and wreak havoc, simply won’t take a chance when they recognize symptoms that could emanate from the virus.

“We’ve seen an increase in patients presenting to the emergency department with respiratory distress,” said Dr. Nanette Mickiewicz, president and CEO of Dominican Hospital in Santa Cruz. “As this can also be a symptom of COVID-19, we’re treating these patients as we would any person under investigation for coronavirus until we can rule them out through our screening process.” During the workup, symptoms that are more specific to COVID-19, like fever, would become apparent.

For the workers at Dominican, the issue moved to the top of the list quickly. Santa Cruz and San Mateo counties have borne the brunt of the CZU Lightning Complex fires, which as of Sept. 10 had burned more than 86,000 acres, destroying 1,100 structures and threatening more than 7,600 others. Nearly a month after they began, the fires were approximately 84% contained, but thousands of people remained evacuated.

Dominican, a Dignity Health hospital, is “open, safe and providing care,” Mickiewicz said. Multiple tents erected outside the building serve as an extension of its ER waiting room. They also are used to perform what has come to be understood as an essential role: separating those with symptoms of COVID-19 from those without.

At the two Solano County hospitals operated by NorthBay Healthcare, the path of some of the wildfires prompted officials to review their evacuation procedures, said spokesperson Steve Huddleston. They ultimately avoided the need to evacuate patients, and new ones arrived with COVID-like symptoms that may actually have been from smoke inhalation.

Huddleston said NorthBay’s intake process “calls for anyone with COVID characteristics to be handled as [a] patient under investigation for COVID, which means they’re separated, screened and managed by staff in special PPE.” At the two hospitals, which have handled nearly 200 COVID cases so far, the protocol is well established.

Hospitals in California, though not under siege in most cases, are dealing with multiple issues they might typically face only sporadically. In Napa County, Adventist Health St. Helena Hospital evacuated 51 patients on a single August night as a fire approached, moving them to 10 other facilities according to their needs and bed space. After a 10-day closure, the hospital was allowed to reopen as evacuation orders were lifted, the fire having been contained some distance away.

The wildfires are also taking a personal toll on health care workers. CommuniCare’s Marshall lost her family’s home in rural Winters, along with 20 acres of olive trees and other plantings that surrounded it, in the Aug. 19 fires that swept through Solano County.

“They called it a ‘firenado,’ ” Marshall said. An apparent confluence of three fires raged out of control, demolishing thousands of acres. With her family safely accounted for and temporary housing arranged by a friend, she returned to work. “Our clinics interact with a very vulnerable population,” she said, “and this is a critical time for them.”

While she pondered how her family would rebuild, the CEO was faced with another immediate crisis: the clinic’s shortage of supplies. Last month, CommuniCare got down to 19 COVID test kits on hand, and ran so low on swabs “that we were literally turning to our veterinary friends for reinforcements,” the doctor said. The clinic’s COVID test results, meanwhile, were taking nearly two weeks to be returned from an overwhelmed outside lab, rendering contact tracing almost useless.

Those situations have been addressed, at least temporarily, Marshall said. But although the West Coast is in the most dangerous time of year for wildfires, generally September to December, another complication for health providers lies on the horizon: flu season.

The Southern Hemisphere, whose influenza trends during our summer months typically predict what’s to come for the U.S., has had very little of the disease this year, presumably because of restricted travel, social distancing and face masks. But it’s too early to be sure what the U.S. flu season will entail.

“You can start to see some cases of the flu in late October,” said Marshall, “and the reality is that it’s going to carry a number of characteristics that could also be symptomatic of COVID. And nothing changes: You have to rule it out, just to eliminate the risk.”

KHN (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. This KHN story first published on California Healthline, a service of the California Health Care Foundation.

The patients walk into Dr. Melissa Marshall’s community clinics in Northern California with the telltale symptoms. They’re having trouble breathing. It may even hurt to inhale. They’ve got a cough, and the sore throat is definitely there.

A straight case of COVID-19? Not so fast. This is wildfire country.

Up and down the West Coast, hospitals and health facilities are reporting an influx of patients with problems most likely related to smoke inhalation. As fires rage largely uncontrolled amid dry heat and high winds, smoke and ash are billowing and settling on coastal areas like San Francisco and cities and towns hundreds of miles inland as well, turning the sky orange or gray and making even ordinary breathing difficult.

But that, Marshall said, is only part of the challenge. Facilities already strapped for testing supplies and personal protective equipment must first rule out COVID-19 in these patients, because many of the symptoms they present with are the same as those caused by the virus.

“Obviously, there’s overlap in the symptoms,” said Marshall, the CEO of CommuniCare, a collection of six clinics in Yolo County, near Sacramento, that treats mostly underinsured and uninsured patients. “Any time someone comes in with even some of those symptoms, we ask ourselves, ‘Is it COVID?’ At the end of the day, clinically speaking, I still want to rule out the virus.”

The protocol is to treat the symptoms, whatever their cause, while recommending that the patient quarantine until test results for the virus come back, she said.

It is a scene playing out in numerous hospitals. Administrators and physicians, finely attuned to COVID-19’s ability to spread quickly and wreak havoc, simply won’t take a chance when they recognize symptoms that could emanate from the virus.

“We’ve seen an increase in patients presenting to the emergency department with respiratory distress,” said Dr. Nanette Mickiewicz, president and CEO of Dominican Hospital in Santa Cruz. “As this can also be a symptom of COVID-19, we’re treating these patients as we would any person under investigation for coronavirus until we can rule them out through our screening process.” During the workup, symptoms that are more specific to COVID-19, like fever, would become apparent.

For the workers at Dominican, the issue moved to the top of the list quickly. Santa Cruz and San Mateo counties have borne the brunt of the CZU Lightning Complex fires, which as of Sept. 10 had burned more than 86,000 acres, destroying 1,100 structures and threatening more than 7,600 others. Nearly a month after they began, the fires were approximately 84% contained, but thousands of people remained evacuated.

Dominican, a Dignity Health hospital, is “open, safe and providing care,” Mickiewicz said. Multiple tents erected outside the building serve as an extension of its ER waiting room. They also are used to perform what has come to be understood as an essential role: separating those with symptoms of COVID-19 from those without.

At the two Solano County hospitals operated by NorthBay Healthcare, the path of some of the wildfires prompted officials to review their evacuation procedures, said spokesperson Steve Huddleston. They ultimately avoided the need to evacuate patients, and new ones arrived with COVID-like symptoms that may actually have been from smoke inhalation.

Huddleston said NorthBay’s intake process “calls for anyone with COVID characteristics to be handled as [a] patient under investigation for COVID, which means they’re separated, screened and managed by staff in special PPE.” At the two hospitals, which have handled nearly 200 COVID cases so far, the protocol is well established.

Hospitals in California, though not under siege in most cases, are dealing with multiple issues they might typically face only sporadically. In Napa County, Adventist Health St. Helena Hospital evacuated 51 patients on a single August night as a fire approached, moving them to 10 other facilities according to their needs and bed space. After a 10-day closure, the hospital was allowed to reopen as evacuation orders were lifted, the fire having been contained some distance away.

The wildfires are also taking a personal toll on health care workers. CommuniCare’s Marshall lost her family’s home in rural Winters, along with 20 acres of olive trees and other plantings that surrounded it, in the Aug. 19 fires that swept through Solano County.

“They called it a ‘firenado,’ ” Marshall said. An apparent confluence of three fires raged out of control, demolishing thousands of acres. With her family safely accounted for and temporary housing arranged by a friend, she returned to work. “Our clinics interact with a very vulnerable population,” she said, “and this is a critical time for them.”

While she pondered how her family would rebuild, the CEO was faced with another immediate crisis: the clinic’s shortage of supplies. Last month, CommuniCare got down to 19 COVID test kits on hand, and ran so low on swabs “that we were literally turning to our veterinary friends for reinforcements,” the doctor said. The clinic’s COVID test results, meanwhile, were taking nearly two weeks to be returned from an overwhelmed outside lab, rendering contact tracing almost useless.

Those situations have been addressed, at least temporarily, Marshall said. But although the West Coast is in the most dangerous time of year for wildfires, generally September to December, another complication for health providers lies on the horizon: flu season.

The Southern Hemisphere, whose influenza trends during our summer months typically predict what’s to come for the U.S., has had very little of the disease this year, presumably because of restricted travel, social distancing and face masks. But it’s too early to be sure what the U.S. flu season will entail.

“You can start to see some cases of the flu in late October,” said Marshall, “and the reality is that it’s going to carry a number of characteristics that could also be symptomatic of COVID. And nothing changes: You have to rule it out, just to eliminate the risk.”

KHN (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. This KHN story first published on California Healthline, a service of the California Health Care Foundation.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Continued use of tumor necrosis factor inhibitors or methotrexate is acceptable in most patients who acquire COVID-19, results of a recent cohort study suggest.

Among patients on tumor necrosis factor inhibitors (TNFi) or methotrexate who developed COVID-19, death and hospitalization rates were similar to matched COVID-19 patients not on those medications, according to authors of the multicenter research network study.

Reassuringly, likelihood of hospitalization and mortality were not significantly different between 214 patients with COVID-19 taking TNFi or methotrexate and 31,862 matched COVID-19 patients not on those medications, according to the investigators, whose findings were published recently in the Journal of the American Academy of Dermatology.

Zachary Zinn, MD, corresponding author on the study, said in an interview that the findings suggest these medicines can be safely continued in the majority of patients taking them during the COVID-19 pandemic.

“If you’re a prescribing physician who’s giving patients TNF inhibitors or methotrexate or both, I think you can comfortably tell your patients there is good data that these do not lead to worse outcomes if you get COVID-19,” said Dr. Zinn, associate professor in the department of dermatology at West Virginia University, Morgantown.

The findings from these researchers corroborate a growing body of evidence suggesting that immunosuppressive treatments can be continued in patients with dermatologic and rheumatic conditions.

In recent guidance from the National Psoriasis Foundation, released Sept. 4, an expert consensus panel cited 15 studies that they said suggested that treatments for psoriasis or psoriatic arthritis “do not meaningfully alter the risk of acquiring SARS-CoV-2 infection or having worse COVID-19 outcomes.”

That said, the data to date are mainly from small case series and registry studies based on spontaneously reported COVID-19 cases, which suggests a continued need for shared decision making. In addition, chronic systemic corticosteroids should be avoided for management of psoriatic arthritis, the guidance states, based on rheumatology and gastroenterology literature suggesting this treatment is linked to worse COVID-19 outcomes.

In the interview, Dr. Zinn noted that some previous studies of immunosuppressive treatments in patients who acquire COVID-19 have aggregated data on numerous classes of biologic medications, lessening the strength of data for each specific medication.

“By focusing specifically on TNF inhibitors and methotrexate, this study gives better guidance to prescribers of these medications,” he said.

To see whether TNFi or methotrexate increased risk of worsened COVID-19 outcomes, Dr. Zinn and coinvestigators evaluated data from TriNetX, a research network that includes approximately 53 million unique patient records, predominantly in the United States.

They identified 32,076 adult patients with COVID-19, of whom 214 had recent exposure to TNFi or methotrexate. The patients in the TNFi/methotrexate group were similar in age to those without exposure to those drugs, at 55.1 versus 53.2 years, respectively. However, patients in the drug exposure group were more frequently White, female, and had substantially more comorbidities, including diabetes and obesity, according to the investigators.

Nevertheless, the likelihood of hospitalization was not statistically different in the TNFi/methotrexate group versus the non-TNFi/methotrexate group, with a risk ratio of 0.91 (95% confidence interval, 0.68-1.22; P = .5260).

Likewise, the likelihood of death was not different between groups, with a RR of 0.87 (95% CI, 0.42-1.78; P = .6958). Looking at subgroups of patients exposed to TNFi or methotrexate only didn’t change the results, the investigators added.

Taken together, the findings argue against interruption of these treatments because of the fear of the possibly worse COVID-19 outcomes, the investigators concluded, although they emphasized the need for more research.

“Because the COVID-19 pandemic is ongoing, there is a desperate need for evidence-based data on biologic and immunomodulator exposure in the setting of COVID-19 infection,” they wrote.

Dr. Zinn and coauthors reported no conflicts of interest and no funding sources related to the study.

SOURCE: Zinn Z et al. J Am Acad Dermatol. 2020 Sep 11. doi: 10.1016/j.jaad.2020.09.009.

Pique-Regi R, Romero R, Tarca AL, et al. Does the human placenta express the canonical cell entry mediators for SARS CoV-2? eLife. 2020;9:e58716. 

EXPERT COMMENTARY

Maternal infection with the novel SARS-CoV-2 virus has been associated with severe maternal morbidity and mortality causing adverse pregnancy outcomes, such as preterm birth and, potentially, stillbirth, with vertical transmission of the virus to the fetus possible.^1,2 

Uniquely, maternal physiology supports both pro- and anti-inflammatory states within pregnancy—a system that not only must protect the mother but also must tolerate a semi-allogenic fetus. Studies demonstrate that the first and third trimesters are pro-inflammatory, while the second trimester is thought to be anti-inflammatory.³ Since the discovery of the SARS-CoV-2 virus, the question surrounding vertical transmission (infectivity from mother to fetus via the placenta) has occupied the imagination of physicians, scientists, and pregnant women. Importantly, the virus is transmitted to human cells via the ACE2 (angiotensin-converting enzyme 2) receptor, which aids in viral cell attachment. ACE2 receptors are expressed in placental stromal cells, perivascular cells of decidua, cytotrophoblast and syncytiotrophoblast,⁴ as well as blood vessel endothelium and vascular smooth muscle from both primary and secondary villi. 

Details of the study 

In their recent study, Pique-Regi and colleagues used single-cell RNA sequencing data to investigate whether the receptors responsible for SARS-CoV-2 infection are expressed in the human placenta.⁵ Their findings suggest that TMPRSS2 is present in insufficient quantity in the placenta to make vertical transmission possible and/or clinically relevant. Thus, despite the presence of ACE2 receptors in placental tissue, without the enzymatic assistance of a helper protein like TMPRSS2 (transmembrane protease, serine 2), vertical transmission is highly unlikely. The researchers found that there was negligible co-transcription for ACE2 and TMPRSS2 in the placenta and that placental tissue lacks the mRNA necessary to produce the enzyme; they concluded that the likelihood of vertical transmission to the fetus was therefore unlikely. 

As a caveat to their research, the authors noted that: 

1. transcription levels do not always correlate with protein expression 
2. it is possible that a noncanonical cell-entry mediator facilitates entry 
3. individuals with complications related to the renin-angiotensin-aldosterone system (such as hypertensive disease) may have alterations to the expression of ACE2. 

Study strengths and limitations 

Methods for this study reveal that the researchers examined 32 placentas, all taken in the third trimester (32.9-39.1 weeks), with a median gestational age of 36.9 weeks. Notably, 81.3% of placentas were from Black women, 6.2% from White women, and 12.5% from Other women. The median maternal age was 25 years, median body mass index was 27.8 kg/m², and 84.4% of women were multiparous. While this sample was not representative of race, gestational age, or parity, it is difficult to know whether those selection biases would have changed the researchers' findings. 

The question regarding vertical transmission is one not answered solely on the basis of RNA sequencing data. Clinically, we know that neonates of mothers infected with SARS-CoV-2 have been born with immunoglobulin M antibodies, indicating antenatal exposure to the virus.^6,7 In addition, infants have tested positive immediately after birth for coronavirus disease 2019 (COVID-19) via nasopharyngeal swab and amniotic fluid, and there are ample cases of histologic and polymerase chain reaction evidence of placental infection.^8,9 We also know that inflammatory damage to the placenta could possibly break down the placental barrier.¹⁰ 

The destruction that SARS-CoV-2 often leaves in its wake is devastating for the maternal-fetal dyad. The effects of maternal infection on the placenta—where additional research is needed—can be profound, causing profuse endothelial damage, vascular malperfusion, thrombi, and infarcts, all of which can be lethal to some developing fetuses. 

Pique-Regi R, Romero R, Tarca AL, et al. Does the human placenta express the canonical cell entry mediators for SARS CoV-2? eLife. 2020;9:e58716. 

EXPERT COMMENTARY

Maternal infection with the novel SARS-CoV-2 virus has been associated with severe maternal morbidity and mortality causing adverse pregnancy outcomes, such as preterm birth and, potentially, stillbirth, with vertical transmission of the virus to the fetus possible.^1,2 

Uniquely, maternal physiology supports both pro- and anti-inflammatory states within pregnancy—a system that not only must protect the mother but also must tolerate a semi-allogenic fetus. Studies demonstrate that the first and third trimesters are pro-inflammatory, while the second trimester is thought to be anti-inflammatory.³ Since the discovery of the SARS-CoV-2 virus, the question surrounding vertical transmission (infectivity from mother to fetus via the placenta) has occupied the imagination of physicians, scientists, and pregnant women. Importantly, the virus is transmitted to human cells via the ACE2 (angiotensin-converting enzyme 2) receptor, which aids in viral cell attachment. ACE2 receptors are expressed in placental stromal cells, perivascular cells of decidua, cytotrophoblast and syncytiotrophoblast,⁴ as well as blood vessel endothelium and vascular smooth muscle from both primary and secondary villi. 

Details of the study 

In their recent study, Pique-Regi and colleagues used single-cell RNA sequencing data to investigate whether the receptors responsible for SARS-CoV-2 infection are expressed in the human placenta.⁵ Their findings suggest that TMPRSS2 is present in insufficient quantity in the placenta to make vertical transmission possible and/or clinically relevant. Thus, despite the presence of ACE2 receptors in placental tissue, without the enzymatic assistance of a helper protein like TMPRSS2 (transmembrane protease, serine 2), vertical transmission is highly unlikely. The researchers found that there was negligible co-transcription for ACE2 and TMPRSS2 in the placenta and that placental tissue lacks the mRNA necessary to produce the enzyme; they concluded that the likelihood of vertical transmission to the fetus was therefore unlikely. 

As a caveat to their research, the authors noted that: 

1. transcription levels do not always correlate with protein expression 
2. it is possible that a noncanonical cell-entry mediator facilitates entry 
3. individuals with complications related to the renin-angiotensin-aldosterone system (such as hypertensive disease) may have alterations to the expression of ACE2. 

Study strengths and limitations 

Methods for this study reveal that the researchers examined 32 placentas, all taken in the third trimester (32.9-39.1 weeks), with a median gestational age of 36.9 weeks. Notably, 81.3% of placentas were from Black women, 6.2% from White women, and 12.5% from Other women. The median maternal age was 25 years, median body mass index was 27.8 kg/m², and 84.4% of women were multiparous. While this sample was not representative of race, gestational age, or parity, it is difficult to know whether those selection biases would have changed the researchers' findings. 

The question regarding vertical transmission is one not answered solely on the basis of RNA sequencing data. Clinically, we know that neonates of mothers infected with SARS-CoV-2 have been born with immunoglobulin M antibodies, indicating antenatal exposure to the virus.^6,7 In addition, infants have tested positive immediately after birth for coronavirus disease 2019 (COVID-19) via nasopharyngeal swab and amniotic fluid, and there are ample cases of histologic and polymerase chain reaction evidence of placental infection.^8,9 We also know that inflammatory damage to the placenta could possibly break down the placental barrier.¹⁰ 

The destruction that SARS-CoV-2 often leaves in its wake is devastating for the maternal-fetal dyad. The effects of maternal infection on the placenta—where additional research is needed—can be profound, causing profuse endothelial damage, vascular malperfusion, thrombi, and infarcts, all of which can be lethal to some developing fetuses. 

Pique-Regi R, Romero R, Tarca AL, et al. Does the human placenta express the canonical cell entry mediators for SARS CoV-2? eLife. 2020;9:e58716. 

EXPERT COMMENTARY

Maternal infection with the novel SARS-CoV-2 virus has been associated with severe maternal morbidity and mortality causing adverse pregnancy outcomes, such as preterm birth and, potentially, stillbirth, with vertical transmission of the virus to the fetus possible.^1,2 

Uniquely, maternal physiology supports both pro- and anti-inflammatory states within pregnancy—a system that not only must protect the mother but also must tolerate a semi-allogenic fetus. Studies demonstrate that the first and third trimesters are pro-inflammatory, while the second trimester is thought to be anti-inflammatory.³ Since the discovery of the SARS-CoV-2 virus, the question surrounding vertical transmission (infectivity from mother to fetus via the placenta) has occupied the imagination of physicians, scientists, and pregnant women. Importantly, the virus is transmitted to human cells via the ACE2 (angiotensin-converting enzyme 2) receptor, which aids in viral cell attachment. ACE2 receptors are expressed in placental stromal cells, perivascular cells of decidua, cytotrophoblast and syncytiotrophoblast,⁴ as well as blood vessel endothelium and vascular smooth muscle from both primary and secondary villi. 

Details of the study 

In their recent study, Pique-Regi and colleagues used single-cell RNA sequencing data to investigate whether the receptors responsible for SARS-CoV-2 infection are expressed in the human placenta.⁵ Their findings suggest that TMPRSS2 is present in insufficient quantity in the placenta to make vertical transmission possible and/or clinically relevant. Thus, despite the presence of ACE2 receptors in placental tissue, without the enzymatic assistance of a helper protein like TMPRSS2 (transmembrane protease, serine 2), vertical transmission is highly unlikely. The researchers found that there was negligible co-transcription for ACE2 and TMPRSS2 in the placenta and that placental tissue lacks the mRNA necessary to produce the enzyme; they concluded that the likelihood of vertical transmission to the fetus was therefore unlikely. 

As a caveat to their research, the authors noted that: 

1. transcription levels do not always correlate with protein expression 
2. it is possible that a noncanonical cell-entry mediator facilitates entry 
3. individuals with complications related to the renin-angiotensin-aldosterone system (such as hypertensive disease) may have alterations to the expression of ACE2. 

Study strengths and limitations 

Methods for this study reveal that the researchers examined 32 placentas, all taken in the third trimester (32.9-39.1 weeks), with a median gestational age of 36.9 weeks. Notably, 81.3% of placentas were from Black women, 6.2% from White women, and 12.5% from Other women. The median maternal age was 25 years, median body mass index was 27.8 kg/m², and 84.4% of women were multiparous. While this sample was not representative of race, gestational age, or parity, it is difficult to know whether those selection biases would have changed the researchers' findings. 

The question regarding vertical transmission is one not answered solely on the basis of RNA sequencing data. Clinically, we know that neonates of mothers infected with SARS-CoV-2 have been born with immunoglobulin M antibodies, indicating antenatal exposure to the virus.^6,7 In addition, infants have tested positive immediately after birth for coronavirus disease 2019 (COVID-19) via nasopharyngeal swab and amniotic fluid, and there are ample cases of histologic and polymerase chain reaction evidence of placental infection.^8,9 We also know that inflammatory damage to the placenta could possibly break down the placental barrier.¹⁰ 

The destruction that SARS-CoV-2 often leaves in its wake is devastating for the maternal-fetal dyad. The effects of maternal infection on the placenta—where additional research is needed—can be profound, causing profuse endothelial damage, vascular malperfusion, thrombi, and infarcts, all of which can be lethal to some developing fetuses. 

Responses from physicians in eight countries show profound effects from COVID-19 on their personal and professional lives, according to the results of a Medscape survey.

More than 7,500 physicians – nearly 5,000 in the United States, and others in Brazil, France, Germany, Mexico, Portugal, Spain, and the United Kingdom – responded to questions about their struggles to save patients and how the pandemic has changed their income and their lives at home and at work.

The pain was evident in this response from an emergency medicine physician in Spain: “It has been the worst time in my life ever, in both my personal and professional life.”

Conversely, some reported positive effects.

An internist in Brazil wrote: “I feel more proud of my career than ever before.”
 

One quarter of U.S. physicians considering earlier retirement

Physicians in the United States were asked what career changes, if any, they were considering in light of their experience with COVID-19. Although a little more than half (51%) said they were not planning any changes, 25% answered, “retiring earlier than previously planned,” and 12% answered, “a career change away from medicine.”

The number of physicians reporting an income drop was highest in Brazil (63% reported a drop), followed by the United States (62%), Mexico (56%), Portugal (49%), Germany (42%), France (41%), and Spain (31%). The question was not asked in the United Kingdom survey.

In the United States, the size of the drop has been substantial: 9% lost 76%-100% of their income; 14% lost 51%-75%; 28% lost 26%-50%; 33% lost 11%-25%; and 15% lost 1%-10%.

The U.S. specialists with the largest drop in income were ophthalmologists, who lost 51%, followed by allergists (46%), plastic surgeons (46%), and otolaryngologists (45%).

“I’m looking for a new profession due to economic impact,” an otolaryngologist in the United States said. “We are at risk while essentially using our private savings to keep our practice solvent.”

More than half of U.S. physicians (54%) have personally treated patients with COVID-19. Percentages were higher in France, Spain, and the United Kingdom (percentages ranged from 60%-68%).

The United States led all eight countries in treating patients with COVID-19 via telemedicine, at 26%. Germany had the lowest telemedicine percentage, at 10%.
 

Burnout intensifies

About two thirds of US physicians (64%) said that burnout had intensified during the crisis (70% of female physicians and 61% of male physicians said it had).

Many factors are feeding the burnout.

A critical care physician in the United States responded, “It is terrible to see people arriving at their rooms and assuming they were going to die soon; to see people saying goodbye to their families before dying or before being intubated.”

In all eight countries, a substantial percentage of physicians reported they “sometimes, often or always” treated patients with COVID-19 without the proper personal protective equipment. Spain had by far the largest percentage who answered that way (67%), followed by France (45%), Mexico (40%), the United Kingdom (34%), Brazil and Germany (28% each); and the United States and Portugal (23% each).

A U.S. rheumatologist wrote: “The fact that we were sent to take care of infectious patients without proper protection equipment made me feel we were betrayed in this fight.”

Sense of duty to volunteer to treat COVID-19 patients varied substantially among countries, from 69% who felt that way in Spain to 40% in Brazil. Half (50%) in the United States felt that way.

“Altruism must take second place where a real and present threat exists to my own personal existence,” one U.S. internist wrote.
 

Numbers personally infected

One fifth of physicians in Spain and the United Kingdom had personally been infected with the virus. Brazil, France, and Mexico had the next highest numbers, with 13%-15% of physicians infected; 5%-6% in the United States, Germany, and Portugal said they had been infected.

The percentage of physicians who reported that immediate family members had been infected ranged from 25% in Spain to 6% in Portugal. Among US physicians, 9% reported that family members had been diagnosed with COVID-19.

In the United States, 44% of respondents who had family living with them at home during the pandemic reported that relationships at home were more stressed because of stay-at-home guidelines and social distancing. Almost half (47%) said there had been no change, and 9% said relationships were less stressed.
 

Eating is coping mechanism of choice

Physicians were asked what they were doing more of during the pandemic, and food seemed to be the top source of comfort in all eight countries.

Loneliness reports differ across globe

Portugal had the highest percentage (51%) of physicians reporting increased loneliness. Next were Brazil (48%), the United States (46%), the United Kingdom (42%), France (41%), Spain and Mexico (40% each), and Germany (32%).

All eight countries lacked workplace activities to help physicians with grief. More than half (55%) of U.K. physicians reported having such activities available at their workplace, whereas only 25% of physicians in Germany did; 12%-24% of respondents across the countries were unsure about the offerings.

This article first appeared on Medscape.com.

Responses from physicians in eight countries show profound effects from COVID-19 on their personal and professional lives, according to the results of a Medscape survey.

More than 7,500 physicians – nearly 5,000 in the United States, and others in Brazil, France, Germany, Mexico, Portugal, Spain, and the United Kingdom – responded to questions about their struggles to save patients and how the pandemic has changed their income and their lives at home and at work.

The pain was evident in this response from an emergency medicine physician in Spain: “It has been the worst time in my life ever, in both my personal and professional life.”

Conversely, some reported positive effects.

An internist in Brazil wrote: “I feel more proud of my career than ever before.”
 

One quarter of U.S. physicians considering earlier retirement

Physicians in the United States were asked what career changes, if any, they were considering in light of their experience with COVID-19. Although a little more than half (51%) said they were not planning any changes, 25% answered, “retiring earlier than previously planned,” and 12% answered, “a career change away from medicine.”

The number of physicians reporting an income drop was highest in Brazil (63% reported a drop), followed by the United States (62%), Mexico (56%), Portugal (49%), Germany (42%), France (41%), and Spain (31%). The question was not asked in the United Kingdom survey.

In the United States, the size of the drop has been substantial: 9% lost 76%-100% of their income; 14% lost 51%-75%; 28% lost 26%-50%; 33% lost 11%-25%; and 15% lost 1%-10%.

The U.S. specialists with the largest drop in income were ophthalmologists, who lost 51%, followed by allergists (46%), plastic surgeons (46%), and otolaryngologists (45%).

“I’m looking for a new profession due to economic impact,” an otolaryngologist in the United States said. “We are at risk while essentially using our private savings to keep our practice solvent.”

More than half of U.S. physicians (54%) have personally treated patients with COVID-19. Percentages were higher in France, Spain, and the United Kingdom (percentages ranged from 60%-68%).

The United States led all eight countries in treating patients with COVID-19 via telemedicine, at 26%. Germany had the lowest telemedicine percentage, at 10%.
 

Burnout intensifies

About two thirds of US physicians (64%) said that burnout had intensified during the crisis (70% of female physicians and 61% of male physicians said it had).

Many factors are feeding the burnout.

A critical care physician in the United States responded, “It is terrible to see people arriving at their rooms and assuming they were going to die soon; to see people saying goodbye to their families before dying or before being intubated.”

In all eight countries, a substantial percentage of physicians reported they “sometimes, often or always” treated patients with COVID-19 without the proper personal protective equipment. Spain had by far the largest percentage who answered that way (67%), followed by France (45%), Mexico (40%), the United Kingdom (34%), Brazil and Germany (28% each); and the United States and Portugal (23% each).

A U.S. rheumatologist wrote: “The fact that we were sent to take care of infectious patients without proper protection equipment made me feel we were betrayed in this fight.”

Sense of duty to volunteer to treat COVID-19 patients varied substantially among countries, from 69% who felt that way in Spain to 40% in Brazil. Half (50%) in the United States felt that way.

“Altruism must take second place where a real and present threat exists to my own personal existence,” one U.S. internist wrote.
 

Numbers personally infected

One fifth of physicians in Spain and the United Kingdom had personally been infected with the virus. Brazil, France, and Mexico had the next highest numbers, with 13%-15% of physicians infected; 5%-6% in the United States, Germany, and Portugal said they had been infected.

The percentage of physicians who reported that immediate family members had been infected ranged from 25% in Spain to 6% in Portugal. Among US physicians, 9% reported that family members had been diagnosed with COVID-19.

In the United States, 44% of respondents who had family living with them at home during the pandemic reported that relationships at home were more stressed because of stay-at-home guidelines and social distancing. Almost half (47%) said there had been no change, and 9% said relationships were less stressed.
 

Eating is coping mechanism of choice

Physicians were asked what they were doing more of during the pandemic, and food seemed to be the top source of comfort in all eight countries.

Loneliness reports differ across globe

Portugal had the highest percentage (51%) of physicians reporting increased loneliness. Next were Brazil (48%), the United States (46%), the United Kingdom (42%), France (41%), Spain and Mexico (40% each), and Germany (32%).

All eight countries lacked workplace activities to help physicians with grief. More than half (55%) of U.K. physicians reported having such activities available at their workplace, whereas only 25% of physicians in Germany did; 12%-24% of respondents across the countries were unsure about the offerings.

This article first appeared on Medscape.com.

Responses from physicians in eight countries show profound effects from COVID-19 on their personal and professional lives, according to the results of a Medscape survey.

More than 7,500 physicians – nearly 5,000 in the United States, and others in Brazil, France, Germany, Mexico, Portugal, Spain, and the United Kingdom – responded to questions about their struggles to save patients and how the pandemic has changed their income and their lives at home and at work.

The pain was evident in this response from an emergency medicine physician in Spain: “It has been the worst time in my life ever, in both my personal and professional life.”

Conversely, some reported positive effects.

An internist in Brazil wrote: “I feel more proud of my career than ever before.”
 

One quarter of U.S. physicians considering earlier retirement

Physicians in the United States were asked what career changes, if any, they were considering in light of their experience with COVID-19. Although a little more than half (51%) said they were not planning any changes, 25% answered, “retiring earlier than previously planned,” and 12% answered, “a career change away from medicine.”

The number of physicians reporting an income drop was highest in Brazil (63% reported a drop), followed by the United States (62%), Mexico (56%), Portugal (49%), Germany (42%), France (41%), and Spain (31%). The question was not asked in the United Kingdom survey.

In the United States, the size of the drop has been substantial: 9% lost 76%-100% of their income; 14% lost 51%-75%; 28% lost 26%-50%; 33% lost 11%-25%; and 15% lost 1%-10%.

The U.S. specialists with the largest drop in income were ophthalmologists, who lost 51%, followed by allergists (46%), plastic surgeons (46%), and otolaryngologists (45%).

“I’m looking for a new profession due to economic impact,” an otolaryngologist in the United States said. “We are at risk while essentially using our private savings to keep our practice solvent.”

More than half of U.S. physicians (54%) have personally treated patients with COVID-19. Percentages were higher in France, Spain, and the United Kingdom (percentages ranged from 60%-68%).

The United States led all eight countries in treating patients with COVID-19 via telemedicine, at 26%. Germany had the lowest telemedicine percentage, at 10%.
 

Burnout intensifies

About two thirds of US physicians (64%) said that burnout had intensified during the crisis (70% of female physicians and 61% of male physicians said it had).

Many factors are feeding the burnout.

A critical care physician in the United States responded, “It is terrible to see people arriving at their rooms and assuming they were going to die soon; to see people saying goodbye to their families before dying or before being intubated.”

In all eight countries, a substantial percentage of physicians reported they “sometimes, often or always” treated patients with COVID-19 without the proper personal protective equipment. Spain had by far the largest percentage who answered that way (67%), followed by France (45%), Mexico (40%), the United Kingdom (34%), Brazil and Germany (28% each); and the United States and Portugal (23% each).

A U.S. rheumatologist wrote: “The fact that we were sent to take care of infectious patients without proper protection equipment made me feel we were betrayed in this fight.”

Sense of duty to volunteer to treat COVID-19 patients varied substantially among countries, from 69% who felt that way in Spain to 40% in Brazil. Half (50%) in the United States felt that way.

“Altruism must take second place where a real and present threat exists to my own personal existence,” one U.S. internist wrote.
 

Numbers personally infected

One fifth of physicians in Spain and the United Kingdom had personally been infected with the virus. Brazil, France, and Mexico had the next highest numbers, with 13%-15% of physicians infected; 5%-6% in the United States, Germany, and Portugal said they had been infected.

The percentage of physicians who reported that immediate family members had been infected ranged from 25% in Spain to 6% in Portugal. Among US physicians, 9% reported that family members had been diagnosed with COVID-19.

In the United States, 44% of respondents who had family living with them at home during the pandemic reported that relationships at home were more stressed because of stay-at-home guidelines and social distancing. Almost half (47%) said there had been no change, and 9% said relationships were less stressed.
 

Eating is coping mechanism of choice

Physicians were asked what they were doing more of during the pandemic, and food seemed to be the top source of comfort in all eight countries.

Loneliness reports differ across globe

Portugal had the highest percentage (51%) of physicians reporting increased loneliness. Next were Brazil (48%), the United States (46%), the United Kingdom (42%), France (41%), Spain and Mexico (40% each), and Germany (32%).

All eight countries lacked workplace activities to help physicians with grief. More than half (55%) of U.K. physicians reported having such activities available at their workplace, whereas only 25% of physicians in Germany did; 12%-24% of respondents across the countries were unsure about the offerings.

This article first appeared on Medscape.com.

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in 7 of the 15 participants tested in one of two hospitals in Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.
 

Ramping up COVID-19 testing

As a follow-up to these and other findings – including the testing of more than 2,000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 – the same investigators are establishing a CUHK Coronavirus Testing Center.

As of Aug. 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2,000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a Sept. 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.
 

Active infection detected in stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22-71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in 7 of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.
 

Microbiome matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity versus participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The U.S. Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis K.L. Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV-2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.
 

Novel finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling – in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Va.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.
 

This article first appeared on Medscape.com.

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in 7 of the 15 participants tested in one of two hospitals in Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.
 

Ramping up COVID-19 testing

As a follow-up to these and other findings – including the testing of more than 2,000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 – the same investigators are establishing a CUHK Coronavirus Testing Center.

As of Aug. 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2,000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a Sept. 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.
 

Active infection detected in stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22-71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in 7 of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.
 

Microbiome matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity versus participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The U.S. Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis K.L. Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV-2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.
 

Novel finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling – in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Va.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.
 

This article first appeared on Medscape.com.

For the first time, researchers detected active and prolonged infection of SARS-CoV-2 virus in the gastrointestinal (GI) tracts of people with confirmed COVID-19. Stool tests were positive among people with no GI symptoms, and in some cases up to 6 days after nasopharyngeal swabs yielded negative results.

The small pilot study suggests a quiescent but active infection in the gut. Stool testing revealed genomic evidence of active infection in 7 of the 15 participants tested in one of two hospitals in Hong Kong.

“We found active and prolonged SARS-CoV-2 infection in the stool of patients with COVID-19, even after recovery, suggesting that coronavirus could remain in the gut of asymptomatic carriers,” senior author Siew C. Ng, MBBS, PhD, told Medscape Medical News.

“Due to the potential threat of fecal-oral transmission, it is important to maintain long-term coronavirus and health surveillance,” said Ng, Associate Director of the Centre for Gut Microbiota Research at the Chinese University of Hong Kong (CUHK).

“Discharged patients and their caretakers should remain vigilant and observe strict personal and toileting hygiene,” she added.

The prospective, observational study was published online July 20 in Gut.
 

Ramping up COVID-19 testing

As a follow-up to these and other findings – including the testing of more than 2,000 stool samples in children and the needy arriving at Hong Kong airports starting March 29 – the same investigators are establishing a CUHK Coronavirus Testing Center.

As of Aug. 31, the detection rate in tested children was 0.28%. The Center plans to offer as many as 2,000 COVID-19 tests daily going forward to help identify asymptomatic carriers, the investigators announced in a Sept. 7 news release.

In contrast to nasopharyngeal sampling, stool specimens are “more convenient, safe and non-invasive to collect in the pediatric population,” professor Paul Chan, chairman of the Department of Microbiology, CU Medicine, said in the release. “This makes the stool test a better option for COVID-19 screening in babies, young children and those whose respiratory samples are difficult to collect.”

Even though previous researchers identified SARS-CoV-2 in the stool, the activity and infectivity of the virus in the gastrointestinal tract during and after COVID-19 respiratory positivity remained largely unknown.
 

Active infection detected in stool

This prospective study involved 15 people hospitalized with COVID-19 in March and April. Participants were a median 55 years old (range, 22-71 years) and all presented with respiratory symptoms. Only one patient had concurrent GI symptoms at admission. Median length of stay was 21 days.

Investigators collected fecal samples serially until discharge. They extracted viral DNA to test for transcriptional genetic evidence of active infection, which they detected in 7 of 15 patients. The patient with GI symptoms was not in this positive group.

The findings suggest a “quiescent but active GI infection,” the researchers note.

Three of the seven patients continued to test positive for active infection in their stool up to 6 days after respiratory clearance of SARS-CoV-2.
 

Microbiome matters

The investigators also extracted, amplified, and sequenced DNA from the stool samples. Their “metagenomic” profile revealed the type and amounts of bacterial strains in each patient’s gut microbiome.

Interestingly, bacterial strains differed between people with high SARS-CoV-2 infectivity versus participants with low to no evidence of active infection.

“Stool with high viral activity had higher abundance of pathogenic bacteria,” Ng said. In contrast, people with low or no infectivity had more beneficial bacterial strains, including bacteria that play critical roles in boosting host immunity.

Each patient’s microbiome composition changed during the course of the study. Whether the microbiome alters the course of COVID-19 or COVID-19 alters the composition of the microbiome requires further study, the authors note.

The U.S. Food and Drug Administration and officials in other countries have contacted the Hong Kong investigators for more details on their stool testing strategy, professor Francis K.L. Chan, dean of the faculty of medicine and director of the Centre for Gut Microbiota Research at CUHK, stated in the news release.

Further research into revealing the infectivity and pathogenesis of SARS-CoV-2 in the GI tract is warranted. The value of modulating the human gut microbiome in this patient population could be worthwhile to investigate as well, the researchers said.
 

Novel finding

“Some of it is not-so-new news and some is new,” David A. Johnson, MD, told Medscape Medical News when asked to comment on the study.

For example, previous researchers have detected SARS-CoV-2 virus in the stool. However, this study takes it a step further and shows that the virus present in stool can remain infectious on the basis of metagenomic signatures.

Furthermore, the virus can remain infectious in the gut even after a patient tests negative for COVID-19 through nasopharyngeal sampling – in this report up to 6 days later, said Johnson, professor of medicine, chief of gastroenterology, Eastern Virginia Medical School in Norfolk, Va.

The study carries important implications for people who currently test negative following active COVID-19 infection, he added. Centers for Disease Control and Prevention criteria clear a person as negative after two nasopharyngeal swabs at least 24 hours apart.

People in this category could believe they are no longer infectious and might return to a setting where they could infect others, Johnson said.

One potential means for spreading SARS-CoV-2 from the gut is from a toilet plume, as Johnson previously highlighted in a video report for Medscape Medical News.

The study authors disclosed no relevant financial relationships. Johnson serves as an adviser to WebMD/Medscape.
 

This article first appeared on Medscape.com.