Covid ICYMI

People whose treatment for cancer is delayed by even 1 month have a 6%-13% higher risk of dying, suggests research published online in the BMJ.

In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.

Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.

The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).

For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).

Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.

A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.

The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.

This article originally appeared on Univadis, part of the Medscape Professional Network.

People whose treatment for cancer is delayed by even 1 month have a 6%-13% higher risk of dying, suggests research published online in the BMJ.

In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.

Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.

The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).

For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).

Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.

A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.

The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.

This article originally appeared on Univadis, part of the Medscape Professional Network.

People whose treatment for cancer is delayed by even 1 month have a 6%-13% higher risk of dying, suggests research published online in the BMJ.

In light of the treatment delays resulting from the pandemic, Canadian and U.K. researchers carried out a review and analysis of relevant studies published between January 2000 and April 2020.

Included studies examined data on surgical interventions, systemic therapy, or radiotherapy for seven forms of cancer – bladder, breast, colon, rectum, lung, cervix, and head and neck. Delays were measured from diagnosis to the first treatment or from the completion of one treatment to the start of the next.

The search identified 34 suitable studies for 17 indications, with data from more than 1.2 million patients. The analysis identified a significant association between delay and increased mortality for 13 of the 17 indications (P < .05).

For surgery, there was a 6%-8% increase in the risk of death for every 4-week treatment delay. Estimates for systemic treatment varied (hazard ratio range, 1.01-1.28). Four-week delays in radiotherapy were for radical radiotherapy for head and neck cancer (HR, 1.09; 95% confidence interval, 1.05-1.14), adjuvant radiotherapy after breast-conserving surgery (HR, 0.98; 95% CI, 0.88-1.09), and cervical cancer adjuvant radiotherapy (HR, 1.23; 95% CI, 1.00-1.50).

Delays of up to 8 and 12 weeks further increased mortality. An 8-week delay in breast cancer surgery was linked to a 17% increased mortality, and a 12-week delay would increase mortality by 26%.

A surgical delay of 12 weeks for patients with breast cancer continuing for 1 year – which is likely to be the case as the pandemic continues – would lead to 1,400 excess deaths in the United Kingdom.

The authors said the results of this study could be used to guide policy making on the organization of cancer services, particularly as the pandemic continues and further delays are expected.

This article originally appeared on Univadis, part of the Medscape Professional Network.

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

New data document the global fallout for rheumatology patients when hydroxychloroquine (HCQ) supplies were being diverted to hospitals for COVID-19 patients.

Demand for HCQ soared on evidence-lacking claims that the drug was effective in treating and preventing SARS-CoV-2 infection. Further research has since shown HCQ to be ineffective for COVID-19 and potentially harmful to patients.

But during the height of the COVID-19-related hype, patients worldwide with autoimmune diseases, particularly lupus and rheumatoid arthritis, had trouble getting the pills at all or couldn’t get as many as they needed for their chronic conditions.

Emily Sirotich, MSc, a PhD student at McMaster University in Hamilton, Ont., presented data at the virtual annual meeting of the American College of Rheumatology demonstrating that the severity of shortages differed widely.

Whereas 26.7% of rheumatology patients in Africa and 21.4% in southeast Asia said their pharmacy ran short of HCQ – which was originally developed as an antimalarial drug but has been found effective in treating some rheumatic diseases – only 6.8% of patients in the Americas and 2.1% in European regions reported the shortages.

“There are large regional disparities in access to antimalarials whether they were caused by the COVID-19 pandemic or already existed,” she said in an interview.

Global survey polled patient experience

Ms. Sirotich’s team analyzed data from the Global Rheumatology Alliance Patient Experience Survey.

They found that from 9,393 respondents (average age 46.1 years and 90% female), 3,872 (41.2%) were taking antimalarials. Of these, 230 (6.2% globally) were unable to keep taking the drugs because their pharmacy ran out.

Researchers evaluated the effect of drug shortages on disease activity, mental health, and physical health by comparing mean values with two-sided independent t-tests to identify significant differences.

They found that patients who were unable to obtain antimalarials had significantly higher levels of rheumatic disease activity as well as poorer mental and physical health (all P < .001).

The survey was distributed online through patient support groups and on social media. Patients with rheumatic diseases or their parents anonymously entered data including their rheumatic disease diagnosis, medications, COVID-19 status, and disease outcomes.

Ms. Sirotich said they are currently gathering new data to see if the gaps in access to HCQ persist and whether the physical and mental consequences of not having the medications continue.

Hospitals stockpiled HCQ in the U.S.

Michael Ganio, PharmD, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), said in an interview that hospitals in the United States received large amounts of HCQ in late spring and early summer, donated by pharmaceutical companies for COVID-19 before the lack of evidence for efficacy became clear.

Hospitals found themselves sitting on large quantities of HCQ they couldn’t use while prescriptions for rheumatology outpatients were going unfilled.

It is only in recent months that the U.S. Department of Health and Human Services has given clear direction to hospitals on how to redistribute those supplies, Dr. Ganio said.

“There’s no good real good way to move a product from a hospital to a [drug store] down the street,” he said.

The Food and Drug Administration now lists the HCQ shortages as resolved.
 

Declined prescriptions have frustrated physicians

Brett Smith, DO, a pediatric and adult rheumatologist in Alcoa, Tenn., said he was frustrated by pharmacies declining his prescriptions for HCQ for patients with rheumatoid arthritis.

“I got notes from pharmacies that I should consider alternative agents,” he said in an interview. But the safety profiles of the alternatives were not as good, he said.

“Hydroxychloroquine has no risk of infection and no risk of malignancy, and they were proposing alternative agents that carry those risks,” he said.

“I had some people with RA who couldn’t get [HCQ] who had a substantial increase in swollen joints and pain without it,” he said.

Dr. Smith said some patients who use HCQ for off-label uses such as certain skin disorders still aren’t getting the drug, as off-label use has been discouraged to make sure those with lupus and RA have enough, he said.

Saira Sheikh, MD, director of the University of North Carolina Rheumatology Lupus Clinic in Chapel Hill, said in an interview that during the summer months pharmacists required additional documentation of the diagnosis of autoimmune disease, resulting in unnecessary delays even when patients had been on the medication for many years.

She said emerging research has found patient-reported barriers to filling prescriptions, interruptions in HCQ treatment, and reported emotional stress and anxiety related to medication access during the COVID-19 pandemic.

“This experience with HCQ during the COVID-19 pandemic teaches us that while swift action and progress to address the immediate threats of the pandemic should be commended, it is important that we move forward in a conscious manner, guided by an evidence base that comes from high-quality research, not from rushed judgments based on preliminary studies, or pressure from political leaders,” Dr. Sheikh said.

Ms. Sirotich, Dr. Smith, Dr. Sheikh, and Dr. Ganio have disclosed no relevant financial relationships.

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

To the Editor: Normally I would skip the editorial; however, the title “The Other Pandemic: Addiction” caught my eye (Fed Pract. 2020;37[10]:440-441). This will, of course, require me going in for eye care in the next couple of days, but my concerns are low. After all, the hook you used wasn’t that big.

Bravo! Your choice to focus on the effects of isolation was a masterful touch. I started skimming with the assumption that you would say something along the lines of ‘COVID bad, everybody depressed, blah, blah.’ But you cut into the abscess of the issue cleanly, exposing the core—isolation “amplifies negative thoughts, dysphoria, and fearful emotions.” A deadly combination for our patients and ourselves.

I have been a physician assistant in the US Army, and as a civilian at Brooke Army Medical Center and US Department of Veterans Affairs (VA) Puget Sound Health Care System. One thing I have seen throughout that time was the effects of isolation on the active duty enlisted young, and even more so on retired older warriors. Throughout the time of our military service, we transfer to many places and make a lot of friends, but more so, we lose track of them over time.

I have cared for many older warriors who cannot get something as simple as a colonoscopy because they do not have someone to drive them home after they have been sedated. Family and friends were scattered over the country, or the world. At the VA, many older warriors come not just for an appointment, but also as a time to socialize and ‘BS’ with those who understand them.

One goal I set for myself many years ago was to have the warrior laughing before they left my office. If I did that, I knew I had made a difference. Thank you for your editorial.

Anthony J Passaniti, PA, USA (ret) [email protected]

To the Editor: Normally I would skip the editorial; however, the title “The Other Pandemic: Addiction” caught my eye (Fed Pract. 2020;37[10]:440-441). This will, of course, require me going in for eye care in the next couple of days, but my concerns are low. After all, the hook you used wasn’t that big.

Bravo! Your choice to focus on the effects of isolation was a masterful touch. I started skimming with the assumption that you would say something along the lines of ‘COVID bad, everybody depressed, blah, blah.’ But you cut into the abscess of the issue cleanly, exposing the core—isolation “amplifies negative thoughts, dysphoria, and fearful emotions.” A deadly combination for our patients and ourselves.

I have been a physician assistant in the US Army, and as a civilian at Brooke Army Medical Center and US Department of Veterans Affairs (VA) Puget Sound Health Care System. One thing I have seen throughout that time was the effects of isolation on the active duty enlisted young, and even more so on retired older warriors. Throughout the time of our military service, we transfer to many places and make a lot of friends, but more so, we lose track of them over time.

I have cared for many older warriors who cannot get something as simple as a colonoscopy because they do not have someone to drive them home after they have been sedated. Family and friends were scattered over the country, or the world. At the VA, many older warriors come not just for an appointment, but also as a time to socialize and ‘BS’ with those who understand them.

One goal I set for myself many years ago was to have the warrior laughing before they left my office. If I did that, I knew I had made a difference. Thank you for your editorial.

Anthony J Passaniti, PA, USA (ret) [email protected]

To the Editor: Normally I would skip the editorial; however, the title “The Other Pandemic: Addiction” caught my eye (Fed Pract. 2020;37[10]:440-441). This will, of course, require me going in for eye care in the next couple of days, but my concerns are low. After all, the hook you used wasn’t that big.

Bravo! Your choice to focus on the effects of isolation was a masterful touch. I started skimming with the assumption that you would say something along the lines of ‘COVID bad, everybody depressed, blah, blah.’ But you cut into the abscess of the issue cleanly, exposing the core—isolation “amplifies negative thoughts, dysphoria, and fearful emotions.” A deadly combination for our patients and ourselves.

I have been a physician assistant in the US Army, and as a civilian at Brooke Army Medical Center and US Department of Veterans Affairs (VA) Puget Sound Health Care System. One thing I have seen throughout that time was the effects of isolation on the active duty enlisted young, and even more so on retired older warriors. Throughout the time of our military service, we transfer to many places and make a lot of friends, but more so, we lose track of them over time.

I have cared for many older warriors who cannot get something as simple as a colonoscopy because they do not have someone to drive them home after they have been sedated. Family and friends were scattered over the country, or the world. At the VA, many older warriors come not just for an appointment, but also as a time to socialize and ‘BS’ with those who understand them.

One goal I set for myself many years ago was to have the warrior laughing before they left my office. If I did that, I knew I had made a difference. Thank you for your editorial.

Anthony J Passaniti, PA, USA (ret) [email protected]

Using principles of psychoanalysis to craft public health messaging may be a novel and effective way of increasing adherence to public health advice during the COVID-19 pandemic, experts say.

In a letter published online Oct. 19 in The Lancet, coauthors Austin Ratner, MD, and Nisarg Gandhi, believe that, as expert communicators, psychoanalysts should be part of the public health care team to help battle the pandemic.

“The idea of using psychoanalysis in a public health setting is relatively unheard of,” Ratner, the author of a book titled “The Psychoanalyst’s Aversion to Proof,” told Medscape Medical News. Ratner earned his MD at John Hopkins School of Medicine but left medicine to become an author. Gandhi is a clinical research intern at Saint Barnabas Medical Center in Livingston, New Jersey.

Psychoanalysis postulates that defense mechanisms, such as denial, may play an important role in nonadherence to public health guidance regarding the pandemic, Ratner said.

“Denial is a Freudian concept and we can see how it is rearing its ugly head in a number of prominent ways all around us, including nonadherence to medical advice regarding COVID-19, as well as climate change and politics.

“By understanding that fear and anxiety underpin a lot of denial, the psychoanalytic viewpoint can help influence public health officials in recognizing the fear and anxiety, how to talk about the threat [of the pandemic], and what can be done about it,” he added.
 

“A new partnership”

“Psychoanalysts have historically resisted collaboration with disciplines such as social and experimental psychology,” Ratner said. This “insularity” results in “lost opportunities on the path for psychoanalysis to become part of the conversation regarding mass denial and mass nonadherence to medical advice.”

He noted that change is afoot in the psychoanalytic community. The American Psychoanalytic Association (APsaA) has begun to “empower constituents” who seek greater “integration with experimental science and greater involvement with public health.”

To that end, Ratner suggests a “new partnership” between three fields that have until now been disparate: experimental psychology, public health, and psychoanalysis.

Cognitive scientists have studied and documented denial, attributing it to “anxiety’s power to compromise rational thought,” but their approach has not focused on the psychoanalytic model of denial as a defense mechanism, Ratner observed.

Mark Smaller, PhD, past president of APsaA and board member of the International Psychoanalytical Association, elaborated.

“From a psychoanalytic perspective, I am interested in how a defense mechanism functions for individuals and groups,” Smaller told Medscape Medical News.

Denial as a defense mechanism often arises, whether in individuals or groups, from a sense of helplessness, explained Smaller, who is also the chair of the department of public advocacy at APsaA.

“People can only tolerate a certain amount of helplessness – in fact, I would suggest as an analyst that helplessness is the most difficult feeling for humans to come to terms with,” he said.

Helplessness can contribute to trauma and “I think we have a mass case of traumatic helplessness in our country right now because of the pandemic.”

Some people respond to a sense of helplessness with depression or hopelessness, while others “try to integrate the impact of the pandemic by focusing on things over which they have control, like wearing a mask, social distancing, and avoiding places with large numbers of people where the virus can be easily transmitted,” said Smaller.

However, “what seems to have occurred in our country is that, although many people have focused on what we do have control of, a large segment of our population are acting as if COVID-19 doesn’t exist, and we have leadership supporting this denial,” he added.
 

Is “denial” evidence-based?

Commenting for Medscape Medical News, Richard McAnulty, PhD, associate professor of psychology at the University of North Carolina at Charlotte expressed skepticism about the psychoanalytic view of denial, and its potential role in addressing the pandemic.

“A key criticism of psychoanalytic and psychodynamic viewpoints is that many – including the concept of a subconscious mind – are theoretical, not open to empirical research, and not measurable; and one of the most fundamental requirements in science is that all your constructs are measurable.”

For this reason, this approach is “limited in usefulness, although it might be an interesting source of speculation,” said McAnulty.

Ratner disagreed, noting that there is research corroborating the existence of an unconscious mind. Noted analyst Carl Jung, Ratner pointed out, conducted “some great experiments to prove some of the central tenets of psychoanalysis using word associations.”

Jung found that, if individuals were challenged with words that evoked painful associations, it took them longer to arrive at the answer to the test. They also made more mistakes.

Jung’s research “goes back to a core idea of psychoanalysis, which is that painful or difficult thoughts and feelings get distorted, pushed out of consciousness, forgotten, delayed, or suppressed,” Ratner said. These responses might account for “what we’re seeing the U.S. that people are resorting to irrational thinking without being aware of it.”

McAnulty suggested that the psychodynamic idea of denial as a defense mechanism is not relevant to mass nonadherence to pandemic-related medical advice.

Rather, the denial stems from “schemas and belief systems about the world, how people should operate and behave, and the role of government and the medical establishment,” he said.

“When certain recommendations are discrepant with the world view, it creates dissonance or a mismatch and the person will try to reconcile the mismatch,” McAnulty continued. “One way to do that is to say that these recommendations are invalid because they violate the individual’s political beliefs, world view, or religious ideas.”

Ultimately, “it depends on how we define denial,” said McAnulty. “If it means dismissing information that doesn’t fit an existing belief system, that’s denial, but the psychodynamic meaning of ‘denial’ is much deeper than that.”

Smaller, the past president of APsaA, emphasized the importance of empathy when addressing the public. “Psychoanalysts bring empathy to irrationality. Having a psychoanalyst as a team member can help public health officials to communicate better and craft the understanding of anxiety and fear into their message.”

Ratner said he is “not proposing a simplistic silver bullet as an answer to a very complex, multifaceted problem of nonadherence to medical advice.”

Instead, he is “proposing something that hasn’t happened yet, which is more research and more conversation, with psychoanalysis as part of the conversation, because the notion of denial is so relevant, despite how many other factors are involved.”

Ratner, Gandhi, Smaller, and McAnulty have disclosed no relevant financial relationships. Ratner is the author of The Psychoanalyst’s Aversion to Proof and the medical textbook Concepts in Medical Physiology.

This article first appeared on Medscape.com.

Using principles of psychoanalysis to craft public health messaging may be a novel and effective way of increasing adherence to public health advice during the COVID-19 pandemic, experts say.

In a letter published online Oct. 19 in The Lancet, coauthors Austin Ratner, MD, and Nisarg Gandhi, believe that, as expert communicators, psychoanalysts should be part of the public health care team to help battle the pandemic.

“The idea of using psychoanalysis in a public health setting is relatively unheard of,” Ratner, the author of a book titled “The Psychoanalyst’s Aversion to Proof,” told Medscape Medical News. Ratner earned his MD at John Hopkins School of Medicine but left medicine to become an author. Gandhi is a clinical research intern at Saint Barnabas Medical Center in Livingston, New Jersey.

Psychoanalysis postulates that defense mechanisms, such as denial, may play an important role in nonadherence to public health guidance regarding the pandemic, Ratner said.

“Denial is a Freudian concept and we can see how it is rearing its ugly head in a number of prominent ways all around us, including nonadherence to medical advice regarding COVID-19, as well as climate change and politics.

“By understanding that fear and anxiety underpin a lot of denial, the psychoanalytic viewpoint can help influence public health officials in recognizing the fear and anxiety, how to talk about the threat [of the pandemic], and what can be done about it,” he added.
 

“A new partnership”

“Psychoanalysts have historically resisted collaboration with disciplines such as social and experimental psychology,” Ratner said. This “insularity” results in “lost opportunities on the path for psychoanalysis to become part of the conversation regarding mass denial and mass nonadherence to medical advice.”

He noted that change is afoot in the psychoanalytic community. The American Psychoanalytic Association (APsaA) has begun to “empower constituents” who seek greater “integration with experimental science and greater involvement with public health.”

To that end, Ratner suggests a “new partnership” between three fields that have until now been disparate: experimental psychology, public health, and psychoanalysis.

Cognitive scientists have studied and documented denial, attributing it to “anxiety’s power to compromise rational thought,” but their approach has not focused on the psychoanalytic model of denial as a defense mechanism, Ratner observed.

Mark Smaller, PhD, past president of APsaA and board member of the International Psychoanalytical Association, elaborated.

“From a psychoanalytic perspective, I am interested in how a defense mechanism functions for individuals and groups,” Smaller told Medscape Medical News.

Denial as a defense mechanism often arises, whether in individuals or groups, from a sense of helplessness, explained Smaller, who is also the chair of the department of public advocacy at APsaA.

“People can only tolerate a certain amount of helplessness – in fact, I would suggest as an analyst that helplessness is the most difficult feeling for humans to come to terms with,” he said.

Helplessness can contribute to trauma and “I think we have a mass case of traumatic helplessness in our country right now because of the pandemic.”

Some people respond to a sense of helplessness with depression or hopelessness, while others “try to integrate the impact of the pandemic by focusing on things over which they have control, like wearing a mask, social distancing, and avoiding places with large numbers of people where the virus can be easily transmitted,” said Smaller.

However, “what seems to have occurred in our country is that, although many people have focused on what we do have control of, a large segment of our population are acting as if COVID-19 doesn’t exist, and we have leadership supporting this denial,” he added.
 

Is “denial” evidence-based?

Commenting for Medscape Medical News, Richard McAnulty, PhD, associate professor of psychology at the University of North Carolina at Charlotte expressed skepticism about the psychoanalytic view of denial, and its potential role in addressing the pandemic.

“A key criticism of psychoanalytic and psychodynamic viewpoints is that many – including the concept of a subconscious mind – are theoretical, not open to empirical research, and not measurable; and one of the most fundamental requirements in science is that all your constructs are measurable.”

For this reason, this approach is “limited in usefulness, although it might be an interesting source of speculation,” said McAnulty.

Ratner disagreed, noting that there is research corroborating the existence of an unconscious mind. Noted analyst Carl Jung, Ratner pointed out, conducted “some great experiments to prove some of the central tenets of psychoanalysis using word associations.”

Jung found that, if individuals were challenged with words that evoked painful associations, it took them longer to arrive at the answer to the test. They also made more mistakes.

Jung’s research “goes back to a core idea of psychoanalysis, which is that painful or difficult thoughts and feelings get distorted, pushed out of consciousness, forgotten, delayed, or suppressed,” Ratner said. These responses might account for “what we’re seeing the U.S. that people are resorting to irrational thinking without being aware of it.”

McAnulty suggested that the psychodynamic idea of denial as a defense mechanism is not relevant to mass nonadherence to pandemic-related medical advice.

Rather, the denial stems from “schemas and belief systems about the world, how people should operate and behave, and the role of government and the medical establishment,” he said.

“When certain recommendations are discrepant with the world view, it creates dissonance or a mismatch and the person will try to reconcile the mismatch,” McAnulty continued. “One way to do that is to say that these recommendations are invalid because they violate the individual’s political beliefs, world view, or religious ideas.”

Ultimately, “it depends on how we define denial,” said McAnulty. “If it means dismissing information that doesn’t fit an existing belief system, that’s denial, but the psychodynamic meaning of ‘denial’ is much deeper than that.”

Smaller, the past president of APsaA, emphasized the importance of empathy when addressing the public. “Psychoanalysts bring empathy to irrationality. Having a psychoanalyst as a team member can help public health officials to communicate better and craft the understanding of anxiety and fear into their message.”

Ratner said he is “not proposing a simplistic silver bullet as an answer to a very complex, multifaceted problem of nonadherence to medical advice.”

Instead, he is “proposing something that hasn’t happened yet, which is more research and more conversation, with psychoanalysis as part of the conversation, because the notion of denial is so relevant, despite how many other factors are involved.”

Ratner, Gandhi, Smaller, and McAnulty have disclosed no relevant financial relationships. Ratner is the author of The Psychoanalyst’s Aversion to Proof and the medical textbook Concepts in Medical Physiology.

This article first appeared on Medscape.com.

Using principles of psychoanalysis to craft public health messaging may be a novel and effective way of increasing adherence to public health advice during the COVID-19 pandemic, experts say.

In a letter published online Oct. 19 in The Lancet, coauthors Austin Ratner, MD, and Nisarg Gandhi, believe that, as expert communicators, psychoanalysts should be part of the public health care team to help battle the pandemic.

“The idea of using psychoanalysis in a public health setting is relatively unheard of,” Ratner, the author of a book titled “The Psychoanalyst’s Aversion to Proof,” told Medscape Medical News. Ratner earned his MD at John Hopkins School of Medicine but left medicine to become an author. Gandhi is a clinical research intern at Saint Barnabas Medical Center in Livingston, New Jersey.

Psychoanalysis postulates that defense mechanisms, such as denial, may play an important role in nonadherence to public health guidance regarding the pandemic, Ratner said.

“Denial is a Freudian concept and we can see how it is rearing its ugly head in a number of prominent ways all around us, including nonadherence to medical advice regarding COVID-19, as well as climate change and politics.

“By understanding that fear and anxiety underpin a lot of denial, the psychoanalytic viewpoint can help influence public health officials in recognizing the fear and anxiety, how to talk about the threat [of the pandemic], and what can be done about it,” he added.
 

“A new partnership”

“Psychoanalysts have historically resisted collaboration with disciplines such as social and experimental psychology,” Ratner said. This “insularity” results in “lost opportunities on the path for psychoanalysis to become part of the conversation regarding mass denial and mass nonadherence to medical advice.”

He noted that change is afoot in the psychoanalytic community. The American Psychoanalytic Association (APsaA) has begun to “empower constituents” who seek greater “integration with experimental science and greater involvement with public health.”

To that end, Ratner suggests a “new partnership” between three fields that have until now been disparate: experimental psychology, public health, and psychoanalysis.

Cognitive scientists have studied and documented denial, attributing it to “anxiety’s power to compromise rational thought,” but their approach has not focused on the psychoanalytic model of denial as a defense mechanism, Ratner observed.

Mark Smaller, PhD, past president of APsaA and board member of the International Psychoanalytical Association, elaborated.

“From a psychoanalytic perspective, I am interested in how a defense mechanism functions for individuals and groups,” Smaller told Medscape Medical News.

Denial as a defense mechanism often arises, whether in individuals or groups, from a sense of helplessness, explained Smaller, who is also the chair of the department of public advocacy at APsaA.

“People can only tolerate a certain amount of helplessness – in fact, I would suggest as an analyst that helplessness is the most difficult feeling for humans to come to terms with,” he said.

Helplessness can contribute to trauma and “I think we have a mass case of traumatic helplessness in our country right now because of the pandemic.”

Some people respond to a sense of helplessness with depression or hopelessness, while others “try to integrate the impact of the pandemic by focusing on things over which they have control, like wearing a mask, social distancing, and avoiding places with large numbers of people where the virus can be easily transmitted,” said Smaller.

However, “what seems to have occurred in our country is that, although many people have focused on what we do have control of, a large segment of our population are acting as if COVID-19 doesn’t exist, and we have leadership supporting this denial,” he added.
 

Is “denial” evidence-based?

Commenting for Medscape Medical News, Richard McAnulty, PhD, associate professor of psychology at the University of North Carolina at Charlotte expressed skepticism about the psychoanalytic view of denial, and its potential role in addressing the pandemic.

“A key criticism of psychoanalytic and psychodynamic viewpoints is that many – including the concept of a subconscious mind – are theoretical, not open to empirical research, and not measurable; and one of the most fundamental requirements in science is that all your constructs are measurable.”

For this reason, this approach is “limited in usefulness, although it might be an interesting source of speculation,” said McAnulty.

Ratner disagreed, noting that there is research corroborating the existence of an unconscious mind. Noted analyst Carl Jung, Ratner pointed out, conducted “some great experiments to prove some of the central tenets of psychoanalysis using word associations.”

Jung found that, if individuals were challenged with words that evoked painful associations, it took them longer to arrive at the answer to the test. They also made more mistakes.

Jung’s research “goes back to a core idea of psychoanalysis, which is that painful or difficult thoughts and feelings get distorted, pushed out of consciousness, forgotten, delayed, or suppressed,” Ratner said. These responses might account for “what we’re seeing the U.S. that people are resorting to irrational thinking without being aware of it.”

McAnulty suggested that the psychodynamic idea of denial as a defense mechanism is not relevant to mass nonadherence to pandemic-related medical advice.

Rather, the denial stems from “schemas and belief systems about the world, how people should operate and behave, and the role of government and the medical establishment,” he said.

“When certain recommendations are discrepant with the world view, it creates dissonance or a mismatch and the person will try to reconcile the mismatch,” McAnulty continued. “One way to do that is to say that these recommendations are invalid because they violate the individual’s political beliefs, world view, or religious ideas.”

Ultimately, “it depends on how we define denial,” said McAnulty. “If it means dismissing information that doesn’t fit an existing belief system, that’s denial, but the psychodynamic meaning of ‘denial’ is much deeper than that.”

Smaller, the past president of APsaA, emphasized the importance of empathy when addressing the public. “Psychoanalysts bring empathy to irrationality. Having a psychoanalyst as a team member can help public health officials to communicate better and craft the understanding of anxiety and fear into their message.”

Ratner said he is “not proposing a simplistic silver bullet as an answer to a very complex, multifaceted problem of nonadherence to medical advice.”

Instead, he is “proposing something that hasn’t happened yet, which is more research and more conversation, with psychoanalysis as part of the conversation, because the notion of denial is so relevant, despite how many other factors are involved.”

Ratner, Gandhi, Smaller, and McAnulty have disclosed no relevant financial relationships. Ratner is the author of The Psychoanalyst’s Aversion to Proof and the medical textbook Concepts in Medical Physiology.

This article first appeared on Medscape.com.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

SARS-CoV-2 infection posed increased risk for pregnant women in terms of severe disease and poor pregnancy outcomes including preterm birth, based on data from two studies published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report.

In a study of birth and infant outcomes, rates of preterm birth (less than 37 weeks’ gestational age) were higher among women with confirmed SARS-CoV-2 infections compared with the national average (12.9% vs. 10.2%) wrote Kate R. Woodworth, MD, and colleagues of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team.

The researchers collected information on pregnancy and infant outcomes from 16 jurisdictions through the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET). The study included 5,252 women with laboratory-confirmed SARS-CoV-2 infection reported during March 29–Oct. 14, 2020.

Overall, 12.9% of the 3,912 live births with known gestational age were preterm. A total of 610 infants were tested for SARS-CoV-2, and 2.6% were positive. Most of these perinatal infections (85%) occurred among infants born to women with SARS-CoV-2 infection within 1 week of delivery.

Half of the infants with positive test results were preterm, possibly reflecting higher screening rates in the ICU, the researchers said. “These findings also support the growing evidence that although severe COVID-19 does occur in neonates the majority of term neonates experience asymptomatic infection or mild disease; however, information on long term outcomes among exposed infants is unknown.”

Address disparities that amplify risk

The study findings were limited by several factors including inconsistent symptom reporting, overrepresentation of Hispanic women, and incomplete information on pregnancy loss, Dr. Woodworth and associates noted. However, the results add to the knowledge about the impact of COVID-19 disease on pregnancy by providing a large, population-based cohort with completed pregnancy outcomes as well as infant testing.

“SET-NET will continue to follow pregnancies affected by SARS-CoV-2 through completion of pregnancy and infants until age 6 months to guide clinical and public health practice,” the researchers noted. “Longer-term investigation into solutions to alleviate underlying inequities in social determinants of health associated with disparities in maternal morbidity, mortality, and adverse pregnancy outcomes, and effectively addressing these inequities, could reduce the prevalence of conditions and experiences that might amplify risks from COVID-19,” they added.

Severe disease and death increased in pregnant women

In a second study published in the MMWR, Laura D. Zambrano, PhD, and colleagues, also of the CDC COVID-19 Response Pregnancy and Linked Outcomes Team, compared data on 23,434 reportedly pregnant and 386,028 nonpregnant women of reproductive age (15-44 years) with confirmed and symptomatic SARS-CoV-2 infections reported to the CDC between Jan. 22, 2020, and Oct. 3, 2020.

After adjustment for age, race, and underlying medical conditions, pregnant women with COVID-19 disease were significantly more likely than were nonpregnant women to be admitted to intensive care (10.5 per 1,000 cases vs. 3.9 per 1,000 cases), to receive invasive ventilation (2.9 vs. 1.1), receive extracorporeal membrane oxygenation (0.7 vs. 0.3) and to die (1.5 vs. 1.2).

“Irrespective of pregnancy status, ICU admissions, receipt of invasive ventilation, and death occurred more often among women aged 35-44 years than among those aged 15-24 years,” Dr. Zambrano and associates noted. In addition, non-Hispanic Black and Black women comprised 14.1% of the study population but accounted for 36.6% of deaths overall (9 in pregnant women and 167 in nonpregnant women).

The findings in the study of characteristics were limited by several factors including the voluntary reporting of COVID-19 cases, potential reporting bias, and inadequate time to assess severe cases, the researchers noted. However, “data from previous influenza pandemics, including 2009 H1N1, have shown that pregnant women are at increased risk for severe outcomes including death and the absolute risks for severe outcomes were higher than in this study of COVID-19 during pregnancy.”

“Pregnant women should be informed of their risk for severe COVID-19–associated illness and the warning signs of severe COVID-19,” Dr. Zambrano and associates said. “Providers who care for pregnant women should be familiar with guidelines for medical management of COVID-19, including considerations for management of COVID-19 in pregnancy.”

More data needed for informed counseling

“It is important to conduct research trials involving pregnant women so that we have reliable data regarding outcomes with which to counsel women,” Angela Bianco, MD, a maternal fetal medicine specialist at Mount Sinai Hospital in New York, said in an interview.

“Often pregnant women are excluded from research trials, but the impact of the current public health crisis affects all persons regardless of pregnancy status,” she said.

Dr. Bianco said that she was not surprised by the findings of either study. “In fact, our own research produced similar results.”

“These recent publications found that age-matched pregnant versus nonpregnant women had more severe manifestations of COVID-19, and specifically that pregnant women had a higher risk of requiring ventilation and intensive care admission, as well as higher risk of death,” she said. “Previous studies examining the effect of other SARS viruses have demonstrated that pregnancy is associated with worse outcomes; these findings are likely attributable to the relative state of immunosuppression in pregnancy.” Also, “one of these trials found a greater risk of premature birth in women with COVID-19; this may largely be attributable to iatrogenic delivery due to maternal illness as opposed to spontaneous preterm birth,” Dr. Bianco explained.

“Data are emerging regarding the impact of SARS-CoV-2 on pregnancy outcomes, however information remains limited,” Dr. Bianco noted. “Clinicians need to make patients aware that SARS-CoV-2 infection during pregnancy is associated with a greater risk of severe illness requiring intensive care and/or ventilatory support and even death; however, the precise rates remain unknown. “COVID-19 during pregnancy may result in a preterm birth, but at this time the rate of fetal infection remains unknown,” she said. “Clinicians need to reinforce the importance of physical distancing, mask use, and proper hand hygiene, particularly in this vulnerable population.”

Dr. Bianco emphasized: “Longitudinal studies assessing the impact of SARS-CoV-2 infection at various gestational age periods are needed, as at this time most of the available data includes women with SARS-CoV-2 infection around the time of delivery. Long-term infant outcomes are needed, as well as studies assessing the risk of fetal infection.”

The studies were supported by the Centers for Disease Control and Prevention. The researchers had no financial conflicts to disclose. Dr. Bianco had no relevant financial disclosures.

SOURCE: Woodworth KR et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e2; Zambrano LD et al. MMWR. 2020 Nov 2. doi: 10.15585/mmwr.mm6944e3.

A new report of mother-to-fetus transmission of SARS-CoV-2 through umbilical cord blood adds to a small but growing body of evidence that the virus can be transmitted in utero.

Further, this case suggests such infections may not be easily detectable in neonates until days after birth.
 

The data

In a report published in the Journal of The Pediatric Infectious Diseases Society, Isabelle Von Kohorn, MD, PhD, of Holy Cross Health in Silver Spring, Md., and colleagues, described a case of neonatal infection with SARS-CoV-2 in a boy delivered by C-section at 34 weeks to a mother diagnosed with COVID-19 some 14 hours before. The newborn was immediately removed to a neonatal ICU and reunited with his mother a week later, once the mother had recovered.

Dr. Von Kohorn and colleagues reported that, while the infant’s nasopharyngeal swab test for SARS-CoV-2 was negative at 24 hours after birth, repeat molecular tests (using different assays) from 49 hours on were positive and indicated an increasing viral burden, although the infant never developed symptoms of COVID-19. In addition to being found in the nasopharynx, viral RNA also was detected in cord blood and in urine. No viral RNA was found in the placenta.

The circumstances of the birth, and the care taken to keep mother and her infant at a safe distance along with masking of the mother, made it “extremely unlikely” that the infant acquired his infection by the respiratory route, Dr. Von Kohorn and colleagues wrote.

“While we cannot rule out microscopic maternal blood contamination of cord blood in this or any other delivery, cord blood collection procedures are designed to avoid gross contamination with maternal blood. Microscopic contamination would not explain the RNA levels observed in our patient’s cord blood,” they wrote.

Clinicians should note that a neonate born to a mother with COVID-19 may take time to test positive for SARS-CoV-2 , the investigators argued, though the current recommendation of the American Academy of Pediatrics is to test nasopharyngeal secretions of well newborns at 24 and 48 hours but not again in the absence of symptoms. “This case suggests that some cases of SARS-CoV-2 in newborns may be detectable only after 48 hours of life.”

The authors hypothesized that virus transmitted by cord blood “seeded the nasopharynx and required 2 days for incubation and replication sufficient for detection.”
 

Some perspective

In an interview, Andrea Edlow, MD, A maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, called the findings provocative if not definitive in establishing in utero or vertical transmission of SARS-CoV-2 in the same way that a Nature Communications case report did in July 2020. In that case, of a baby born to a mother with COVID-19, virus was seen at high levels in the placenta.

With the current case, “the absence of detectable virus in the placenta is certainly inconsistent/confusing if the authors claim hematogenous spread from mother to baby,” Dr. Edlow commented, “but the authors do offer plausible explanations, such as examination of limited areas within the placenta (when we know infection is likely to be patchy) and possible degradation of RNA prior to attempting to measure placental viral presence.”

Dr. Von Kohorn and colleagues’ study was funded by the National Institutes of Health, and the investigators disclosed no financial conflicts of interest. Dr. Edlow had no relevant financial disclosures.

SOURCE: Von Kohorn I et al. J Pediat Inf Dis Soc. 2020 Oct 22. doi: 10.1093/jpids/piaa127

A new report of mother-to-fetus transmission of SARS-CoV-2 through umbilical cord blood adds to a small but growing body of evidence that the virus can be transmitted in utero.

Further, this case suggests such infections may not be easily detectable in neonates until days after birth.
 

The data

In a report published in the Journal of The Pediatric Infectious Diseases Society, Isabelle Von Kohorn, MD, PhD, of Holy Cross Health in Silver Spring, Md., and colleagues, described a case of neonatal infection with SARS-CoV-2 in a boy delivered by C-section at 34 weeks to a mother diagnosed with COVID-19 some 14 hours before. The newborn was immediately removed to a neonatal ICU and reunited with his mother a week later, once the mother had recovered.

Dr. Von Kohorn and colleagues reported that, while the infant’s nasopharyngeal swab test for SARS-CoV-2 was negative at 24 hours after birth, repeat molecular tests (using different assays) from 49 hours on were positive and indicated an increasing viral burden, although the infant never developed symptoms of COVID-19. In addition to being found in the nasopharynx, viral RNA also was detected in cord blood and in urine. No viral RNA was found in the placenta.

The circumstances of the birth, and the care taken to keep mother and her infant at a safe distance along with masking of the mother, made it “extremely unlikely” that the infant acquired his infection by the respiratory route, Dr. Von Kohorn and colleagues wrote.

“While we cannot rule out microscopic maternal blood contamination of cord blood in this or any other delivery, cord blood collection procedures are designed to avoid gross contamination with maternal blood. Microscopic contamination would not explain the RNA levels observed in our patient’s cord blood,” they wrote.

Clinicians should note that a neonate born to a mother with COVID-19 may take time to test positive for SARS-CoV-2 , the investigators argued, though the current recommendation of the American Academy of Pediatrics is to test nasopharyngeal secretions of well newborns at 24 and 48 hours but not again in the absence of symptoms. “This case suggests that some cases of SARS-CoV-2 in newborns may be detectable only after 48 hours of life.”

The authors hypothesized that virus transmitted by cord blood “seeded the nasopharynx and required 2 days for incubation and replication sufficient for detection.”
 

Some perspective

In an interview, Andrea Edlow, MD, A maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, called the findings provocative if not definitive in establishing in utero or vertical transmission of SARS-CoV-2 in the same way that a Nature Communications case report did in July 2020. In that case, of a baby born to a mother with COVID-19, virus was seen at high levels in the placenta.

With the current case, “the absence of detectable virus in the placenta is certainly inconsistent/confusing if the authors claim hematogenous spread from mother to baby,” Dr. Edlow commented, “but the authors do offer plausible explanations, such as examination of limited areas within the placenta (when we know infection is likely to be patchy) and possible degradation of RNA prior to attempting to measure placental viral presence.”

Dr. Von Kohorn and colleagues’ study was funded by the National Institutes of Health, and the investigators disclosed no financial conflicts of interest. Dr. Edlow had no relevant financial disclosures.

SOURCE: Von Kohorn I et al. J Pediat Inf Dis Soc. 2020 Oct 22. doi: 10.1093/jpids/piaa127

A new report of mother-to-fetus transmission of SARS-CoV-2 through umbilical cord blood adds to a small but growing body of evidence that the virus can be transmitted in utero.

Further, this case suggests such infections may not be easily detectable in neonates until days after birth.
 

The data

In a report published in the Journal of The Pediatric Infectious Diseases Society, Isabelle Von Kohorn, MD, PhD, of Holy Cross Health in Silver Spring, Md., and colleagues, described a case of neonatal infection with SARS-CoV-2 in a boy delivered by C-section at 34 weeks to a mother diagnosed with COVID-19 some 14 hours before. The newborn was immediately removed to a neonatal ICU and reunited with his mother a week later, once the mother had recovered.

Dr. Von Kohorn and colleagues reported that, while the infant’s nasopharyngeal swab test for SARS-CoV-2 was negative at 24 hours after birth, repeat molecular tests (using different assays) from 49 hours on were positive and indicated an increasing viral burden, although the infant never developed symptoms of COVID-19. In addition to being found in the nasopharynx, viral RNA also was detected in cord blood and in urine. No viral RNA was found in the placenta.

The circumstances of the birth, and the care taken to keep mother and her infant at a safe distance along with masking of the mother, made it “extremely unlikely” that the infant acquired his infection by the respiratory route, Dr. Von Kohorn and colleagues wrote.

“While we cannot rule out microscopic maternal blood contamination of cord blood in this or any other delivery, cord blood collection procedures are designed to avoid gross contamination with maternal blood. Microscopic contamination would not explain the RNA levels observed in our patient’s cord blood,” they wrote.

Clinicians should note that a neonate born to a mother with COVID-19 may take time to test positive for SARS-CoV-2 , the investigators argued, though the current recommendation of the American Academy of Pediatrics is to test nasopharyngeal secretions of well newborns at 24 and 48 hours but not again in the absence of symptoms. “This case suggests that some cases of SARS-CoV-2 in newborns may be detectable only after 48 hours of life.”

The authors hypothesized that virus transmitted by cord blood “seeded the nasopharynx and required 2 days for incubation and replication sufficient for detection.”
 

Some perspective

In an interview, Andrea Edlow, MD, A maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, called the findings provocative if not definitive in establishing in utero or vertical transmission of SARS-CoV-2 in the same way that a Nature Communications case report did in July 2020. In that case, of a baby born to a mother with COVID-19, virus was seen at high levels in the placenta.

With the current case, “the absence of detectable virus in the placenta is certainly inconsistent/confusing if the authors claim hematogenous spread from mother to baby,” Dr. Edlow commented, “but the authors do offer plausible explanations, such as examination of limited areas within the placenta (when we know infection is likely to be patchy) and possible degradation of RNA prior to attempting to measure placental viral presence.”

Dr. Von Kohorn and colleagues’ study was funded by the National Institutes of Health, and the investigators disclosed no financial conflicts of interest. Dr. Edlow had no relevant financial disclosures.

SOURCE: Von Kohorn I et al. J Pediat Inf Dis Soc. 2020 Oct 22. doi: 10.1093/jpids/piaa127

As COVID-19 cases surge in the United States, one Texas veterinarian has been quietly tracking the spread of the disease – not in people, but in their pets.

Since June, Dr. Sarah Hamer and her team at Texas A&M University have tested hundreds of animals from area households where humans contracted COVID-19. They’ve swabbed dogs and cats, sure, but also pet hamsters and guinea pigs, looking for signs of infection. “We’re open to all of it,” said Dr. Hamer, a professor of epidemiology, who has found at least 19 cases of infection.

One pet that tested positive was Phoenix, a 7-year-old part Siamese cat owned by Kaitlyn Romoser, who works in a university lab. Ms. Romoser, 23, was confirmed to have COVID-19 twice, once in March and again in September. The second time she was much sicker, she said, and Phoenix was her constant companion.

“If I would have known animals were just getting it everywhere, I would have tried to distance myself, but he will not distance himself from me,” Ms. Romoser said. “He sleeps in my bed with me. There was absolutely no social distancing.”

Across the country, veterinarians and other researchers are scouring the animal kingdom for signs of the virus that causes COVID-19. At least 2,000 animals in the U.S. have been tested for the coronavirus since the pandemic began, according to federal records. Cats and dogs that were exposed to sick owners represent most of the animals tested and 80% of the positive cases found.

But scientists have cast a wide net investigating other animals that could be at risk. In states from California to Florida, researchers have tested species ranging from farmed minks and zoo cats to unexpected critters like dolphins, armadillos, and anteaters.

The U.S. Department of Agriculture keeps an official tally of confirmed animal COVID cases that stands at several dozen. But that list is a vast undercount of actual infections. In Utah and Wisconsin, for instance, more than 14,000 minks died in recent weeks after contracting COVID infections initially spread by humans.

So far, there’s limited evidence that animals are transmitting the virus to people. Veterinarians emphasize that pet owners appear to be in no danger from their animal companions and should continue to love and care for them. But scientists say continued testing is one way to remain vigilant in the face of a previously unknown pathogen.

“We just know that coronaviruses, as a family, infect a lot of species, mostly mammals,” said Dr. Peter Rabinowitz, a professor of environmental and occupational health sciences and the director of the University of Washington Center for One Health Research in Seattle. “It makes sense to take a species-spanning approach and look at a wide spectrum.”

Much of the testing has been rooted in scientific curiosity. Since the pandemic began, a major puzzle has been how the virus, which likely originated in bats, spread to humans. A leading theory is that it jumped to an intermediate species, still unknown, and then to people.

In April, a 4-year-old Malayan tiger at the Bronx Zoo tested positive for COVID-19 in a first-of-its-kind case after seven big cats showed signs of respiratory illness. The tiger, Nadia, contracted the virus from a caretaker, federal health officials said. Four other tigers and three African lions were also confirmed to be infected.

In Washington state, the site of the first U.S. outbreak in humans, scientists rushed to design a COVID test for animals in March, said Charlie Powell, a spokesperson for the Washington State University College of Veterinary Medicine, Pullman. “We knew with warm-blooded animals, housed together, there’s going to be some cross-infection,” he said. Tests for animals use different reagent compounds than those used for tests in people, so they don’t deplete the human supply, Mr. Powell added.

Since spring, the Washington Animal Disease Diagnostic Laboratory has tested nearly 80 animals, including 38 dogs, 29 cats, 2 ferrets, a camel, and 2 tamanduas, a type of anteater. The lab also tested six minks from the outbreak in Utah, five of which accounted for the lab’s only positive tests.

All told, nearly 1,400 animals have been tested for COVID-19 through the National Animal Health Laboratory Network or private labs, said Lyndsay Cole, a spokesperson for the USDA’s Animal and Plant Health Inspection Service. More than 400 animals have been tested through the National Veterinary Services Laboratories. At least 250 more have been tested through academic research projects.

Most of the tests have been in household cats and dogs with suspicious respiratory symptoms. In June, the USDA reported that a dog in New York was the first pet dog to test positive for the coronavirus after falling ill and struggling to breathe. The dog, a 7-year-old German shepherd named Buddy, later died. Officials determined he’d contracted the virus from his owner.

Neither the Centers for Disease Control and Prevention nor the USDA recommends routine testing for house pets or other animals – but that hasn’t stopped owners from asking, said Dr. Douglas Kratt, president of the American Veterinary Medical Association.

“The questions have become a little more consistent at my practice,” he said. “People do want to know about COVID-19 and their pets. Can their pet pick it up at a clinic or boarding or in doggie day care?”

The answer, so far, is that humans are the primary source of infection in pets. In September, a small, unpublished study from the University of Guelph in Canada found that companion cats and dogs appeared to be infected by their sick owners, judging by antibodies to the coronavirus detected in their blood.

In Texas, Dr. Hamer started testing animals from households where someone had contracted COVID-19 to learn more about transmission pathways. “Right now, we’re very much trying to describe what’s happening in nature,” she said.

So far, most of the animals – including Phoenix, Ms. Romoser’s cat – have shown no signs of illness or disease. That’s true so far for many species of animals tested for COVID-19, veterinarians said. Most nonhuman creatures appear to weather COVID infection with mild symptoms like sniffles and lethargy, if any.

Still, owners should apply best practices for avoiding COVID infection to pets, too, Dr. Kratt said. Don’t let pets come into contact with unfamiliar animals, he suggested. Owners should wash their hands frequently and avoid nuzzling and other very close contact, if possible.

Cats appear to be more susceptible to COVID-19 than dogs, researchers said. And minks, which are farmed in the U.S. and elsewhere for their fur, appear quite vulnerable.

In the meantime, the list of creatures tested for COVID-19 – whether for illness or science – is growing. In Florida, 22 animals had been tested as of early October, including 3 wild dolphins, 2 civets, 2 clouded leopards, a gorilla, an orangutan, an alpaca, and a bush baby, state officials said.

In California, 29 animals had been tested by the end of September, including a meerkat, a monkey, and a coatimundi, a member of the raccoon family.

In Seattle, a plan to test orcas, or killer whales, in Puget Sound was called off at the last minute after a member of the scientific team was exposed to COVID-19 and had to quarantine, said Dr. Joe Gaydos, a senior wildlife veterinarian and science director for the SeaDoc Society, a conservation program at the University of California-Davis. The group missed its September window to locate the animals and obtain breath and fecal samples for analysis.

No one thinks marine animals will play a big role in the pandemic decimating the human population, Dr. Gaydos said. But testing many creatures on both land and sea is vital.

“We don’t know what this virus is going to do or can do,” Dr. Gaydos said.

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.

As COVID-19 cases surge in the United States, one Texas veterinarian has been quietly tracking the spread of the disease – not in people, but in their pets.

Since June, Dr. Sarah Hamer and her team at Texas A&M University have tested hundreds of animals from area households where humans contracted COVID-19. They’ve swabbed dogs and cats, sure, but also pet hamsters and guinea pigs, looking for signs of infection. “We’re open to all of it,” said Dr. Hamer, a professor of epidemiology, who has found at least 19 cases of infection.

One pet that tested positive was Phoenix, a 7-year-old part Siamese cat owned by Kaitlyn Romoser, who works in a university lab. Ms. Romoser, 23, was confirmed to have COVID-19 twice, once in March and again in September. The second time she was much sicker, she said, and Phoenix was her constant companion.

“If I would have known animals were just getting it everywhere, I would have tried to distance myself, but he will not distance himself from me,” Ms. Romoser said. “He sleeps in my bed with me. There was absolutely no social distancing.”

Across the country, veterinarians and other researchers are scouring the animal kingdom for signs of the virus that causes COVID-19. At least 2,000 animals in the U.S. have been tested for the coronavirus since the pandemic began, according to federal records. Cats and dogs that were exposed to sick owners represent most of the animals tested and 80% of the positive cases found.

But scientists have cast a wide net investigating other animals that could be at risk. In states from California to Florida, researchers have tested species ranging from farmed minks and zoo cats to unexpected critters like dolphins, armadillos, and anteaters.

The U.S. Department of Agriculture keeps an official tally of confirmed animal COVID cases that stands at several dozen. But that list is a vast undercount of actual infections. In Utah and Wisconsin, for instance, more than 14,000 minks died in recent weeks after contracting COVID infections initially spread by humans.

So far, there’s limited evidence that animals are transmitting the virus to people. Veterinarians emphasize that pet owners appear to be in no danger from their animal companions and should continue to love and care for them. But scientists say continued testing is one way to remain vigilant in the face of a previously unknown pathogen.

“We just know that coronaviruses, as a family, infect a lot of species, mostly mammals,” said Dr. Peter Rabinowitz, a professor of environmental and occupational health sciences and the director of the University of Washington Center for One Health Research in Seattle. “It makes sense to take a species-spanning approach and look at a wide spectrum.”

Much of the testing has been rooted in scientific curiosity. Since the pandemic began, a major puzzle has been how the virus, which likely originated in bats, spread to humans. A leading theory is that it jumped to an intermediate species, still unknown, and then to people.

In April, a 4-year-old Malayan tiger at the Bronx Zoo tested positive for COVID-19 in a first-of-its-kind case after seven big cats showed signs of respiratory illness. The tiger, Nadia, contracted the virus from a caretaker, federal health officials said. Four other tigers and three African lions were also confirmed to be infected.

In Washington state, the site of the first U.S. outbreak in humans, scientists rushed to design a COVID test for animals in March, said Charlie Powell, a spokesperson for the Washington State University College of Veterinary Medicine, Pullman. “We knew with warm-blooded animals, housed together, there’s going to be some cross-infection,” he said. Tests for animals use different reagent compounds than those used for tests in people, so they don’t deplete the human supply, Mr. Powell added.

Since spring, the Washington Animal Disease Diagnostic Laboratory has tested nearly 80 animals, including 38 dogs, 29 cats, 2 ferrets, a camel, and 2 tamanduas, a type of anteater. The lab also tested six minks from the outbreak in Utah, five of which accounted for the lab’s only positive tests.

All told, nearly 1,400 animals have been tested for COVID-19 through the National Animal Health Laboratory Network or private labs, said Lyndsay Cole, a spokesperson for the USDA’s Animal and Plant Health Inspection Service. More than 400 animals have been tested through the National Veterinary Services Laboratories. At least 250 more have been tested through academic research projects.

Most of the tests have been in household cats and dogs with suspicious respiratory symptoms. In June, the USDA reported that a dog in New York was the first pet dog to test positive for the coronavirus after falling ill and struggling to breathe. The dog, a 7-year-old German shepherd named Buddy, later died. Officials determined he’d contracted the virus from his owner.

Neither the Centers for Disease Control and Prevention nor the USDA recommends routine testing for house pets or other animals – but that hasn’t stopped owners from asking, said Dr. Douglas Kratt, president of the American Veterinary Medical Association.

“The questions have become a little more consistent at my practice,” he said. “People do want to know about COVID-19 and their pets. Can their pet pick it up at a clinic or boarding or in doggie day care?”

The answer, so far, is that humans are the primary source of infection in pets. In September, a small, unpublished study from the University of Guelph in Canada found that companion cats and dogs appeared to be infected by their sick owners, judging by antibodies to the coronavirus detected in their blood.

In Texas, Dr. Hamer started testing animals from households where someone had contracted COVID-19 to learn more about transmission pathways. “Right now, we’re very much trying to describe what’s happening in nature,” she said.

So far, most of the animals – including Phoenix, Ms. Romoser’s cat – have shown no signs of illness or disease. That’s true so far for many species of animals tested for COVID-19, veterinarians said. Most nonhuman creatures appear to weather COVID infection with mild symptoms like sniffles and lethargy, if any.

Still, owners should apply best practices for avoiding COVID infection to pets, too, Dr. Kratt said. Don’t let pets come into contact with unfamiliar animals, he suggested. Owners should wash their hands frequently and avoid nuzzling and other very close contact, if possible.

Cats appear to be more susceptible to COVID-19 than dogs, researchers said. And minks, which are farmed in the U.S. and elsewhere for their fur, appear quite vulnerable.

In the meantime, the list of creatures tested for COVID-19 – whether for illness or science – is growing. In Florida, 22 animals had been tested as of early October, including 3 wild dolphins, 2 civets, 2 clouded leopards, a gorilla, an orangutan, an alpaca, and a bush baby, state officials said.

In California, 29 animals had been tested by the end of September, including a meerkat, a monkey, and a coatimundi, a member of the raccoon family.

In Seattle, a plan to test orcas, or killer whales, in Puget Sound was called off at the last minute after a member of the scientific team was exposed to COVID-19 and had to quarantine, said Dr. Joe Gaydos, a senior wildlife veterinarian and science director for the SeaDoc Society, a conservation program at the University of California-Davis. The group missed its September window to locate the animals and obtain breath and fecal samples for analysis.

No one thinks marine animals will play a big role in the pandemic decimating the human population, Dr. Gaydos said. But testing many creatures on both land and sea is vital.

“We don’t know what this virus is going to do or can do,” Dr. Gaydos said.

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.

As COVID-19 cases surge in the United States, one Texas veterinarian has been quietly tracking the spread of the disease – not in people, but in their pets.

Since June, Dr. Sarah Hamer and her team at Texas A&M University have tested hundreds of animals from area households where humans contracted COVID-19. They’ve swabbed dogs and cats, sure, but also pet hamsters and guinea pigs, looking for signs of infection. “We’re open to all of it,” said Dr. Hamer, a professor of epidemiology, who has found at least 19 cases of infection.

One pet that tested positive was Phoenix, a 7-year-old part Siamese cat owned by Kaitlyn Romoser, who works in a university lab. Ms. Romoser, 23, was confirmed to have COVID-19 twice, once in March and again in September. The second time she was much sicker, she said, and Phoenix was her constant companion.

“If I would have known animals were just getting it everywhere, I would have tried to distance myself, but he will not distance himself from me,” Ms. Romoser said. “He sleeps in my bed with me. There was absolutely no social distancing.”

Across the country, veterinarians and other researchers are scouring the animal kingdom for signs of the virus that causes COVID-19. At least 2,000 animals in the U.S. have been tested for the coronavirus since the pandemic began, according to federal records. Cats and dogs that were exposed to sick owners represent most of the animals tested and 80% of the positive cases found.

But scientists have cast a wide net investigating other animals that could be at risk. In states from California to Florida, researchers have tested species ranging from farmed minks and zoo cats to unexpected critters like dolphins, armadillos, and anteaters.

The U.S. Department of Agriculture keeps an official tally of confirmed animal COVID cases that stands at several dozen. But that list is a vast undercount of actual infections. In Utah and Wisconsin, for instance, more than 14,000 minks died in recent weeks after contracting COVID infections initially spread by humans.

So far, there’s limited evidence that animals are transmitting the virus to people. Veterinarians emphasize that pet owners appear to be in no danger from their animal companions and should continue to love and care for them. But scientists say continued testing is one way to remain vigilant in the face of a previously unknown pathogen.

“We just know that coronaviruses, as a family, infect a lot of species, mostly mammals,” said Dr. Peter Rabinowitz, a professor of environmental and occupational health sciences and the director of the University of Washington Center for One Health Research in Seattle. “It makes sense to take a species-spanning approach and look at a wide spectrum.”

Much of the testing has been rooted in scientific curiosity. Since the pandemic began, a major puzzle has been how the virus, which likely originated in bats, spread to humans. A leading theory is that it jumped to an intermediate species, still unknown, and then to people.

In April, a 4-year-old Malayan tiger at the Bronx Zoo tested positive for COVID-19 in a first-of-its-kind case after seven big cats showed signs of respiratory illness. The tiger, Nadia, contracted the virus from a caretaker, federal health officials said. Four other tigers and three African lions were also confirmed to be infected.

In Washington state, the site of the first U.S. outbreak in humans, scientists rushed to design a COVID test for animals in March, said Charlie Powell, a spokesperson for the Washington State University College of Veterinary Medicine, Pullman. “We knew with warm-blooded animals, housed together, there’s going to be some cross-infection,” he said. Tests for animals use different reagent compounds than those used for tests in people, so they don’t deplete the human supply, Mr. Powell added.

Since spring, the Washington Animal Disease Diagnostic Laboratory has tested nearly 80 animals, including 38 dogs, 29 cats, 2 ferrets, a camel, and 2 tamanduas, a type of anteater. The lab also tested six minks from the outbreak in Utah, five of which accounted for the lab’s only positive tests.

All told, nearly 1,400 animals have been tested for COVID-19 through the National Animal Health Laboratory Network or private labs, said Lyndsay Cole, a spokesperson for the USDA’s Animal and Plant Health Inspection Service. More than 400 animals have been tested through the National Veterinary Services Laboratories. At least 250 more have been tested through academic research projects.

Most of the tests have been in household cats and dogs with suspicious respiratory symptoms. In June, the USDA reported that a dog in New York was the first pet dog to test positive for the coronavirus after falling ill and struggling to breathe. The dog, a 7-year-old German shepherd named Buddy, later died. Officials determined he’d contracted the virus from his owner.

Neither the Centers for Disease Control and Prevention nor the USDA recommends routine testing for house pets or other animals – but that hasn’t stopped owners from asking, said Dr. Douglas Kratt, president of the American Veterinary Medical Association.

“The questions have become a little more consistent at my practice,” he said. “People do want to know about COVID-19 and their pets. Can their pet pick it up at a clinic or boarding or in doggie day care?”

The answer, so far, is that humans are the primary source of infection in pets. In September, a small, unpublished study from the University of Guelph in Canada found that companion cats and dogs appeared to be infected by their sick owners, judging by antibodies to the coronavirus detected in their blood.

In Texas, Dr. Hamer started testing animals from households where someone had contracted COVID-19 to learn more about transmission pathways. “Right now, we’re very much trying to describe what’s happening in nature,” she said.

So far, most of the animals – including Phoenix, Ms. Romoser’s cat – have shown no signs of illness or disease. That’s true so far for many species of animals tested for COVID-19, veterinarians said. Most nonhuman creatures appear to weather COVID infection with mild symptoms like sniffles and lethargy, if any.

Still, owners should apply best practices for avoiding COVID infection to pets, too, Dr. Kratt said. Don’t let pets come into contact with unfamiliar animals, he suggested. Owners should wash their hands frequently and avoid nuzzling and other very close contact, if possible.

Cats appear to be more susceptible to COVID-19 than dogs, researchers said. And minks, which are farmed in the U.S. and elsewhere for their fur, appear quite vulnerable.

In the meantime, the list of creatures tested for COVID-19 – whether for illness or science – is growing. In Florida, 22 animals had been tested as of early October, including 3 wild dolphins, 2 civets, 2 clouded leopards, a gorilla, an orangutan, an alpaca, and a bush baby, state officials said.

In California, 29 animals had been tested by the end of September, including a meerkat, a monkey, and a coatimundi, a member of the raccoon family.

In Seattle, a plan to test orcas, or killer whales, in Puget Sound was called off at the last minute after a member of the scientific team was exposed to COVID-19 and had to quarantine, said Dr. Joe Gaydos, a senior wildlife veterinarian and science director for the SeaDoc Society, a conservation program at the University of California-Davis. The group missed its September window to locate the animals and obtain breath and fecal samples for analysis.

No one thinks marine animals will play a big role in the pandemic decimating the human population, Dr. Gaydos said. But testing many creatures on both land and sea is vital.

“We don’t know what this virus is going to do or can do,” Dr. Gaydos said.

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.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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