February 2023 Coronavirus Updates

[missy]

Good morning and happy belated Groundhog's Day.
Here is our February 2023 coronavirus thread for updates

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The latest​

President Biden will end the national emergencies to combat the pandemic on May 11, my colleagues Tyler Pager and Lena H. Sun report.

The move kicks off a massive effort to unwind a sprawling set of changes put in place during the earliest days of the crisis to give the government greater flexibility to respond. Since then, most Americans have been fully vaccinated against the virus and life has largely returned to normal. Still, an average of more than 500 Americans are dying every day from covid-19.

Among the most significant effects of ending the emergencies are that many Americans could have to start paying for coronavirus testing and treatments, depending on their insurance coverage and where they live. Another would be the termination of Title 42, a public health measure put in place by the Trump administration that limited the inflow of migrants at the border. In addition, health-care providers who have come to rely on flexibility around hospital bed capacity and billing procedures will be affected.

The administration announced its decision as it criticized House Republican plans to vote on bills that would immediately end the emergency declarations, saying such a move “would create wide-ranging chaos and uncertainty throughout the health care system.”

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The full extent of criminal activity targeting the U.S. government’s roughly $5 trillion in coronavirus aid may not be known for “years to come,” an investigative official warned Congress Wednesday, as he and others pleaded for new laws and money to combat waste, fraud and abuse, The Washington Post’s Tony Romm writes.

Appearing before the House Oversight and Accountability Committee, three federal officials pointed to the staggering amount of money stolen from federal aid programs since 2020. They called on lawmakers to enhance their powers to collect and monitor data on pandemic aid spending, bring civil and criminal charges, and recover taxpayer money.

The requests offered an early test for House Republicans, who havepromised to aggressively investigate Biden — even though much of the trouble that plagues pandemic spending dates back to the Trump administration. Check out The Post’s year-long investigation, “The covid money trail,” to learn more.

Other important news​

Children lost out on more than one-third of a school year’s worth of learning when in-person instruction was halted during the coronavirus pandemic, according to a sweeping global studypublished this week in the journal Nature Human Behavior. Two years later, they still haven’t overcome those deficits, according to the study.

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Resentment over pandemic public health measures is still running deep among activist Republicans, The Washington Post’s Yasmeen Abutaleb, Rachel Roubein and Isaac Arnsdorf report. The issue is emerging as a cornerstone of the party’s messaging even though many Americans have put the virus behind them.

Pharmaceutical companies are refusing to refund $1.4 billion in advance payments for coronavirus vaccines doses that were supposed to go toward immunizations in lower-income nations but have since been canceled due to plummeting demand for the shots, Stephanie Nolen and Rebecca Robbins report for the New York Times.

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[missy]

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Positive Test No Longer Required to Get COVID Antivirals​

Lisa O'Mary
February 02, 2023

People no longer need a positive COVID-19 test to be prescribed the antiviral medications Paxlovid or Lagevrio.
The FDA announced the changes Wednesday in letters sent to the drugs' manufacturers, Pfizer and Merck.
Both medications are approved to treat mild to moderate COVID-19 in people with a high risk of developing severe disease, such as being older or having certain health conditions. Paxlovid remains approved for patients ages 12 and up; Lagevrio remains approved for patients ages 18 and older.

Antivirals can stop the replication of the virus in the body, thereby reducing a person's overall viral load. This reduces the chances of the illness having more serious symptoms and possibly requiring hospitalization.
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[missy]

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Italy Eases Anti-COVID Measures for Travelers From China​

February 01, 2023

MILAN (Reuters) - Italy will loosen its anti-COVID controls for travellers arriving from China, making swabs random rather than mandatory at its airports, a document seen by Reuters on Tuesday showed.
Under a new order signed by Health Minister Orazio Schillaci, Italy will require those flying from China to test negative within 48 hours of departure and may carry out additional swabs "on a random basis" upon arrival at the airport.
On Dec. 28, Italy imposed mandatory COVID tests and virus sequencing for passengers coming from China.
Tuesday's order will come into force on Wednesday and will be valid until the end of February.

Italy's stance contrasts with that of France which on Saturday extended mandatory COVID tests for travellers from China until Feb. 15.





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[missy]

Fauci interview

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When he was a young boy growing up in Brooklyn, Anthony Fauci loved playing sports. As captain of his high school basketball team, he wanted to be an athlete, but at 5-foot-7, he says it wasn't in the cards. So, he decided to become a doctor instead.

Fauci, who turned 82 in December, stepped down as the head of the National Institute of Allergy and Infectious Diseases that same month, leaving behind a high-profile career in government spanning more than half a century, during which he counseled seven presidents, including Joe Biden. Fauci worked at the National Institutes of Health for 54 years and served as director of the National Institute of Allergy and Infectious Diseases for 38 years. In an interview last week, he spoke to WebMD about his career and his plans for the future.

This interview has been edited and condensed.


It's only been a few weeks since your official "retirement," but what's next for you?


Looking back over your career, what were some of the highs and lows, or turning points?
I first became involved in the personal care and research on persons with HIV, literally in the fall of 1981. [That was] weeks to months after the first cases were recognized. My colleagues and I spent the next few years taking care of desperately ill patients, and we did not have effective therapies because the first couple of years, we did not even know what the ideologic agent was. Even after it was recognized after 1983 and 1984, it took several years before effective therapies were developed, so there was a period of time where we were in a very difficult situation. We were essentially putting Band-Aids on hemorrhages, metaphorically, because no matter what we did, our patients continued to decline. That was a low and dark period of our lives, inspired only by the bravery and the resilience of our patients. A very high period was in [the late 1990s] and into the next century [with the development] of drugs that were highly effective in prolonged and effective suppression of viral loads to the point where people who were living with HIV, if they had access to therapy, could essentially lead a normal lifespan.
We put together the President's Emergency Plan for AIDS Relief program known as PEPFAR, which now, celebrating its 20th anniversary, has resulted in saving 20-25 million lives. So, I would say that is … the highest point in my experience as a physician and a scientist, to have been an important part in the development of that program.
Do you feel like there's any unfinished business? Anything you would change?
Certainly, there's unfinished business. One of the goals I would have liked to have achieved, but that is going to have to wait another few years, is the development of a safe and effective vaccine for HIV. A lot of very elegant science has been done in that regard, but we're not there yet, it's a very challenging scientific problem.
The other unfinished business is some of the other diseases that cause a considerable amount of morbidity and mortality globally, diseases like malariaand tuberculosis. We've made extraordinary progress over the 38 years that I've been director of the institute We have a vaccine, though it isn't a perfect vaccine [for malaria]; we have monoclonal antibodies that are now highly effective in preventing malaria; we have newer drugs, better drugs for tuberculosis, but we don't have an effective vaccine for tuberculosis. So, malaria vaccines, tuberculosis vaccines, those are all unfinished business. I believe we will get there.
These new COVID-19 variants keep getting more and more contagious. Do you see the potential for a serious new variant that could plunge us back into some level of public restrictions?
Anything is possible. One cannot predict, exactly, what the likelihood of getting yet again another variant that's so different that it eludes the protection that we have from the vaccines and from prior infection. Again, I can't give a number on that. I don't think it's highly likely that will happen.

Ever since Omicron came well over a year ago, we have had sublineages of Omicron that progressively seem to elude the immune response that's been developed. But the one thing that's good and has been sustained is that protection against severity of disease seems to hold out pretty well. I don't think that we should be talking about restrictions in the sense of draconian methods of shutting things down; I mean, that was only done for a very brief period of time when our hospitals were being overrun. I don't anticipate that that is going to be something in the future, but you've got to be prepared for it. There are some things that have been highly successful, and that is the vaccines that were developed in less than 1 year. And now, our challenge is to get more people to get their updated boosters.

There's already been criticism of the FDA's discussion of an annual COVID-19 vaccine. One criticism is that the COVID vaccines' effectiveness appears to wane after several months, so it would not offer protection for much of the year. Is that a legitimate criticism?
There's no perfect solution to keeping the country optimally protected. I believe that it gets down to, "It's not perfect, but don't let the perfect be the enemy of the good." We want to get into some regular cadence to get people updated with a booster that is hopefully managed reasonably well to what the circulating variant is. There are certainly going to be people – perhaps the elderly, some of the immune-compromised, and perhaps children – who will need a shot more than once per year, but the FDA's leaning towards getting a shot that is [timed] with the flu shot, would at least bring some degree of order and stability to the process of people getting into the regular routine of keeping themselves updated and protected to the best extent possible.

Do you think we need to move on from mRNA vaccines to something that hopefully has longer-lasting protection?
Yes, we certainly want next-generation vaccines – both vaccines that have a greater degree of breadth, namely covering multiple variants, as well as a greater degree of duration. So, the real question is, "Is it the mRNA vaccine platform that is inducing a response that is not durable, or is the response against coronaviruses not a durable response?" That's still uncertain. Yes, we need to do better with a better platform, or an improvement on the platform; that could mean adding adjuvants, that could mean a [nasal] vaccine in addition to a systemic vaccine.
Do you always wear a mask when you go out into the world? How do you evaluate the relative risk of situations when you go out in public?
I've been vaccinated, doubly boosted, I've gotten infected, and I've gotten the bivalent boost. So, I evaluate things depending upon what the level of viral activity is in the particular location where I'm at. If I'm going to go on a plane, for example, I have no idea where these people are coming from, I generally wear a mask on a plane. I don't really go to congregate settings often. Many of the events I do go to are situations where a requirement for [attending] is to get a test that's negative that day.

When you're in a situation like that, even if it's a crowded congregant setting, I don't have any problem not wearing a mask. But when I'm unsure of what the status is and I might be in an area where there is a considerable degree of viral activity, I would wear a mask. I think you just have to use [your] judgment, depending on the circumstances that you find yourself in.

Doctors and health care professionals have been through hell during COVID. Do you think this might bring a permanent change to how doctors perceive their jobs?

Health care providers have been under a considerable amount of stress because this is a totally unprecedented situation that we find ourselves in. This is the likes of which we have not seen in well over 100 years. I hope this is not something that is going to be permanent, I don't think it is, I think that we are ultimately going to get to a point where the level of virus is low enough that it's not going to disrupt either society or the health care system or the economy.


We're not totally there yet. We're still having about 500 deaths per day, which is much, much better than the 3,000 to 4,000 deaths that we were seeing over a year ago, but it is still not low enough to be able to feel comfortable.


As a scientist, even a semi-retired one, what scares you? What wakes you up at night with worry?


The same thing I have been concerned about for, you know, 40 years: the appearance of a highly transmissible respiratory virus that has a degree of morbidity and mortality that could really be very disruptive of us in this country and globally. Unfortunately, we're in the middle of that situation now, finishing our third year and going into year 4. So what worries me is yet another pandemic. Now that could be a year from now, 5 years from now, 50 years from now. Remember, the last time a pandemic of this magnitude occurred was well over 100 years ago. My concern is that we stay prepared. [We may] not necessarily prevent the emergence of a new infection, but hopefully we can prevent it from becoming a pandemic.
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[missy]

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The Future of At-Home Testing: Flu, RSV Rapid Tests Are Coming​

Lisa O'Mary
February 02, 2023




It's easy these days to take an at-home COVID test when you have symptoms like a fever and sore throat. But when the test is negative, the next step toward diagnosis usually means leaving the comforts of home.
But that could soon change. The FDA says it is confident that at-home rapid tests like those for COVID-19 are forthcoming for the flu and respiratory syncytial virus, or RSV.
The division of the National Institutes of Health that helped create rapid COVID tests confirmed it is partnering with developers on combination tests that can look for multiple respiratory illnesses.
Combination tests that can look for the markers of more than one disease are called multianalyte. Europe and Australia already have over-the-counter tests that look for flu and RSV along with COVID-19.

"We will be authorizing at-home flu and/or RSV tests that are multianalyte with COVID," an FDA official told WebMD. "I can't tell you exactly when that would happen, but we are eager to do that."


"The public's expectations for medical testing are clearly being shaped differently due to the convenience, privacy, and speed of obtaining these results at home, which is a good thing," Shannon Haymond, PhD, president of the American Association for Clinical Chemistry, wrote in an email. She is also the director of clinical mass spectrometry at the Ann & Robert H. Lurie Children's Hospital of Chicago and an associate professor of pathology at Northwestern University Feinberg School of Medicine.


With pandemic culture propelling demand for at-home testing, many are recalling the 1970s era known as the sexual revolution, which centered on women's autonomy over their own bodies. During that time, pregnancy testing moved from the clinical setting to the privacy of women's homes.


"I really liked the term from, I think it was an EPT ad, from the '70s that it was 'a private little revolution,'" says historian Sarah Leavitt, PhD, a former historian at the NIH whose pregnancy test timeline, "The Thin Blue Line," is one of the NIH's most popular historical publications. "It brings the pregnancy test into your own private sphere, you have power over it again, and it's your story and your body, and you can tell people when you want to."


Fifty years ago, the thin blue line wasn't a 15-minute wait, which is about the time it takes these days to see the result of a pregnancy test or COVID test.


"One big difference is that, when the first at-home pregnancy test hit the market in the 1970s, testing technology was a lot less advanced than it is today," explained Haymond. "This means that the first home pregnancy test was very complicated to perform — it involved 10 steps and equipment like test tubes, and users had to keep the test tubes in a place free from vibrations for two hours. The easy-to-use stick tests that we're familiar with today weren't developed until 1988."


"The public's expectations for medical testing are clearly being shaped differently due to the convenience, privacy, and speed of obtaining these results at home, which is a good thing," Shannon Haymond, PhD, president of the American Association for Clinical Chemistry, wrote in an email. She is also the director of clinical mass spectrometry at the Ann & Robert H. Lurie Children's Hospital of Chicago and an associate professor of pathology at Northwestern University Feinberg School of Medicine.


With pandemic culture propelling demand for at-home testing, many are recalling the 1970s era known as the sexual revolution, which centered on women's autonomy over their own bodies. During that time, pregnancy testing moved from the clinical setting to the privacy of women's homes.


"I really liked the term from, I think it was an EPT ad, from the '70s that it was 'a private little revolution,'" says historian Sarah Leavitt, PhD, a former historian at the NIH whose pregnancy test timeline, "The Thin Blue Line," is one of the NIH's most popular historical publications. "It brings the pregnancy test into your own private sphere, you have power over it again, and it's your story and your body, and you can tell people when you want to."


Fifty years ago, the thin blue line wasn't a 15-minute wait, which is about the time it takes these days to see the result of a pregnancy test or COVID test.


"One big difference is that, when the first at-home pregnancy test hit the market in the 1970s, testing technology was a lot less advanced than it is today," explained Haymond. "This means that the first home pregnancy test was very complicated to perform — it involved 10 steps and equipment like test tubes, and users had to keep the test tubes in a place free from vibrations for two hours. The easy-to-use stick tests that we're familiar with today weren't developed until 1988."



Both at-home COVID and pregnancy tests drew early concern from the medical community regarding test accuracy and potential for user error.


"In retrospect, these concerns might seem overly cautious, but this push-pull between innovation and caution is integral to ensuring that medical advancements are made with patient safety foremost in mind," Haymond said.


The best approach is one that leverages the benefits of home testing with the expertise available from healthcare providers, who can advise when to test, how to interpret results, and determine if any extra medical care is needed, she said.

The Future of At-Home Diagnostics​

Television can be a mirror for how science finds its place in our culture, Leavitt says.


"I was trying to envision when COVID tests will show up as a cultural marker in television shows," she says, noting that beyond pregnancy tests, HIV tests and paternity tests have found their way into plots. "I don't know what the plot point would be — maybe the test that's found in the garbage and whose test was it?"


By the time COVID tests show up in television, the pace of technology may have already brought a new forefront for at-home testing. Haymond foresees artificial intelligence on the horizon for at-home diagnostics.


"Of course, like almost all areas of healthcare, we in laboratory medicine are anticipating data analytics as another major area of innovation and transformation," she said. "This involves using technology such as artificial intelligence to find patterns and trends in healthcare datasets, and then using these findings to identify vulnerable patients before they become ill, better personalize testing and treatments, and augment human workflows in clinical testing and result interpretation."


In the more near-term, Tromberg at the National Institute of Biomedical Imaging and Bioengineering can envision a program that would help people in rural areas — sometimes called "healthcare deserts" — test at home and then easily be connected to care. The institute is already helping pilot such a program involving at-home COVID testing and connection to treatment in Pennsylvania. He could see a program like that easily using at-home flu and RSV tests.


"People clearly would like to test at home if they could," Tromberg says. "It's not such a stretch, given that many people are already having telemedicine visits anyway."

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[missy]

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WHO Maintains Highest Alert Over COVID, but Sees Hope Ahead​

(Reuters) -The World Health Organization (WHO) said on Monday that COVID-19 continues to constitute a public health emergency of international concern, its highest form of alert.
The pandemic was likely in a "transition point" that continues to need careful management to "mitigate the potential negative consequences", the agency added in a statement.
It is three years since the WHO first declared that COVID represented a global health emergency. More than 6.8 million people have died during the outbreak, which has touched every country on Earth, ravaging communities and economies.
However, the advent of vaccines and treatments has changed the pandemic situation considerably since 2020, and WHO Director-General Tedros Adhanom Ghebreyesus has said he hopes to see an end to the emergency this year, particularly if access to the counter-measures can be improved globally.

"We remain hopeful that in the coming year, the world will transition to a new phase in which we reduce (COVID) hospitalisations and deaths to their lowest possible level,” Tedros told a separate WHO meeting on Monday.


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Inflammation and Immunity Troubles Top Long COVID Suspect List​

Solarina Ho
February 01, 2023


Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it's growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

"I think that it's a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it's probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue," says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University School of Medicine, who also runs a long COVID clinic.

Long COVID, post-COVID-19 condition, and post-acute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10% to 30% of people infected with COVID-19. Symptoms — as many as 200 — can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.


So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes — including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus — could be the culprit, a theory also supported by a comprehensive and in-depth review of long COVID studies published in January in the journal Nature Reviews Microbiology.


"One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms," says Peluso.

A small Harvard University study published in September, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they're first diagnosed.

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines — small proteins that tell the body's immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled "self-fueled hyperinflammation" during the early COVID-19 infection can become continued immune cell disruption that drives long COVID symptoms.

"Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we're seeing are a side effect of that," says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.


Australian researchers also found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

"Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That's very easily an infection or some other insult to the body. So that's the generalized hypothesis as to why insults to the body may worsen the symptoms," says Truong.

An Autoimmune Condition?​

But inflammation alone does not fully explain post-COVID-19 problems.

Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he co-founded more than two years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs, known as NSAIDs — including ibuprofen — and prednisone were prescribed to long COVID patients.

"It didn't make a difference at all for any of these folks," he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person's immune system doesn't tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal Science Translational Medicine in December found that among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well — findings that researchers said resembled some kind of "autoimmune-like process."

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.

Immune System Problems​

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.


Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multi-organ damage. These traps are net-like structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.


Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York City, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatological diseases, he says.

Biomarkers and Blood Clots​

Scientists are homing in on biomarkers, or detectable and measurable traits — in this case, molecular indicators — that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.


In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study published in December by Charney and his team at Mount Sinai.


Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots — undetectable via regular pathology tests — may be cutting off oxygen flow to tissue by blocking capillaries — billions of tiny, delicate blood vessels throughout the body — and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with others. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don't detect many of the signs seen in long COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

"People are suffering now, and they want answers now...it's not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear — we need a vaccine," says Charney.

"It's going to be a long haul to figure out what is going on."

Sources:

Alexander Truong, MD, pulmonologist, assistant professor, Emory University School of Medicine, Atlanta.

Alexander Charney, MD, PhD, lead principal investigator, RECOVER adult cohort, associate professor of psychiatry, genetics and genomic sciences, neuroscience, and neurosurgery, Icahn School of Medicine at Mount Sinai, New York.

Michael Peluso, MD, assistant professor of medicine, infectious diseases doctor, University of California, San Francisco.

Rainu Kaushal, MD, senior associate dean for clinical research, Weill Cornell Medicine, New York.

The Lancet eClinicalMedicine: "Characterizing long COVID in an international cohort: 7 months of symptoms and their impact."

Nature Reviews Microbiology: "Long COVID: major findings, mechanisms and recommendations."

Immunity, Inflammation and Disease: "COVID-19 associated EBV reactivation and effects of ganciclovir treatment."

Clinical Infectious Diseases: "Persistent Circulating Severe Acute Respiratory Syndrome Coronavirus 2 Spike Is Associated With Post-acute Coronavirus Disease 2019 Sequelae."

Cell Reports Medicine: "The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19."

Nature Medicine: "Data-driven identification of post-acute SARS-CoV-2 infection subphenotypes," "Molecular states during acute COVID-19 reveal distinct etiologies of long-term sequelae."

Nature Immunology: "Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection."

Science Translational Medicine: "Persistent post—COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium."

European Respiratory Journal: "Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms."

Journal of Medical Virology: "Persistence of neutrophil extracellular traps and anticardiolipin auto-antibodies in post-acute phase COVID-19 patients."

Johns Hopkins Medicine: "What are common symptoms of autoimmune disease?"

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Positive Test No Longer Required to Get COVID Antivirals​

Lisa O'Mary
February 02, 2023

People no longer need a positive COVID-19 test to be prescribed the antiviral medications Paxlovid or Lagevrio.
The FDA announced the changes Wednesday in letters sent to the drugs' manufacturers, Pfizer and Merck.
Both medications are approved to treat mild to moderate COVID-19 in people with a high risk of developing severe disease, such as being older or having certain health conditions. Paxlovid remains approved for patients ages 12 and up; Lagevrio remains approved for patients ages 18 and older.

Antivirals can stop the replication of the virus in the body, thereby reducing a person's overall viral load. This reduces the chances of the illness having more serious symptoms and possibly requiring hospitalization.


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Booster Doses Linked With Reduced COVID-Related Mortality in Patients With Multimorbidity​

Carolyn Crist
February 03, 2023




A regimen of three doses of COVID-19 vaccine, compared with two doses, is associated with a greater than 90% decrease in COVID-19-related deaths among patients with multiple chronic conditions, data suggest.
Booster vaccination can play a crucial role in protecting vulnerable groups as the pandemic continues to evolve, the study authors write.

"People with multimorbidity are known to be at increased risk of SARS-CoV-2 infection and severe complications and thus are one of the most vulnerable populations amid the pandemic," senior author Esther Wai Yin Chan, PhD, an associate professor of pharmacology and pharmacy with the Centre for Safe Medication Practice and Research in the Li Ka Shing Faculty of Medicine at the University of Hong Kong, told Medscape Medical News.


"Given the newly emerging viral strains and waning protection from the priming doses, it is important to investigate and demonstrate the effectiveness of a timely booster shot among this high-risk population," she said.

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The researchers included 120,724 patients who received the BNT162b2 mRNA vaccine from Fosun-BioNTech (equivalent to Pfizer-BioNTech outside of China), including 87,289 who received a booster dose and 127,318 patients who received Sinovac's CoronaVac shot. Of the latter patients, 94,977 received a booster. In general, those who received a booster dose were slightly older. There were more COVID-19-related deaths among CoronaVac recipients.

Overall, the risk for mortality was lower among those who received a third dose of either vaccine. Among BNT162b2 recipients, there were five COVID-19-related deaths among booster-vaccinated patients and 34 COVID-19-related deaths among two-dose recipients, yielding incidence rates per million person-days of 1.3 and 23.4, respectively. Among CoronaVac recipients, there were 26 COVID-19-related deaths among booster-vaccinated patients and 88 COVID-19-related deaths among two-dose recipients, yielding incidence rates per million person-days of 5.3 and 53.1, respectively.

For both vaccines, a booster dose was associated with a more than 90% decrease in mortality rate amid the Omicron wave, the authors write. Subgroup and sensitivity analyses yielded similar results for booster vaccination.


"We were slightly surprised at the drastic differences," said Chan. "We did expect great effectiveness before the analyses, but 90% is an incredible finding, particularly as this was a real-world study and not a controlled clinical trial with strict patient inclusion criteria — it is often in controlled trials where we see comparatively higher effectiveness."


Chan and colleagues are continuing to conduct research on COVID-19 vaccines and antivirals in vulnerable groups to understand how public health measures can reduce complications as the pandemic continues. They also plan to analyze how COVID-19 sequelae may increase the incidence of multimorbidity among those with ongoing symptoms.

Chan attributes the notable mortality differences between groups in this study to a higher baseline COVID-19-related mortality risk among patients with multimorbidity, as well as the long duration since the second dose. Many two-dose recipients received their last shot more than 6 months before the Omicron wave, which likely led to waning protection, she noted.

Vaccination Saves Lives​

Commenting on the study for Medscape, Antonios Diab, PhD, a postdoctoral fellow with the Canadian Society of Pharmacology and Therapeutics and Dalhousie University's College of Pharmacy in Halifax, Nova Scotia, said, "It is becoming increasingly clear that vaccination against COVID-19 saves lives and that booster doses are needed. What remains to be addressed is how long after a booster dose does an individual remain protected, and how does this change between populations? Do those with multimorbidity need more frequent vaccination?"


Diab, who wasn't involved with this study, has researched COVID-19 pathophysiology and pharmacology in clinical vaccine and drug trials authorized by Health Canada. He and his colleagues are assessing best practices and gaps in trial design in ordewr to create guidelines for future trials.

"Unfortunately, in many jurisdictions, as public health measures wane, so does active monitoring of the virus, and this increases the uncertainty of the risk of infection," he said. "The ideal situation, including with the XBB.1.5 variant, would be timing booster doses with periods of increased risk — defined as the convergence of waning immunity, increased chance of exposure, and preexisting health conditions, such as multimorbidity. However, we need the proper research, monitoring, and data to be able to assess risk."

The study was funded by a research grant from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region through the Health and Medical Research Fund Research on COVID-19. Chan has received grants from the Research Grants Council of Hong Kong, the Research Fund Secretariat of the Food and Health Bureau of Hong Kong, the National Natural Science Fund of China, the Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and the Narcotics Division of the Security Bureau of Hong Kong outside of the current study. She has also received an honorarium from the Hong Kong Hospital Authority. Diab has disclosed no relevant financial relationships.

CMAJ. Published January 30, 2023. Full text

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.

"

​

 

[dk168]

Flew out to Arizona on 28 January 2023 and American Airline required proof of up to date Covid vaccinations prior to acceptance for departure.

While in Tucson and Phoenix, mask wearing was still being practiced by a small number of people.

The hospitality industry has been hit hard and has yet to recover, as could been seen by the closure of 3 big restaurants in an entertainment complex with a 24-screen cinema in downtown Phoenix, very sad to see.

DK

 

[missy]

"

A New (Old) Drug Joins the COVID Fray, and Guess What? It Works​

F. Perry Wilson, MD, MSCE
February 08, 2023

This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.
With SARS-CoV-2 sidestepping monoclonal antibodies faster than a Texas square dance, the need for new therapeutic options to treat — not prevent — COVID-19 is becoming more and more dire.

At this point, with the monoclonals found to be essentially useless, we are left with remdesivir with its modest efficacy and Paxlovid, which, for some reason, people don't seem to be taking.


Part of the reason the monoclonals have failed lately is because of their specificity; they are homogeneous antibodies targeted toward a very specific epitope that may change from variant to variant. We need a broader therapeutic, one that has activity across all variants — maybe even one that has activity against all viruses? We've got one. Interferon.

The first mention of interferon as a potential COVID therapy was at the very start of the pandemic, so I'm sort of surprised that the first large, randomized trial is only being reported now in The New England Journal of Medicine.

Before we dig into the results, let's talk mechanism. This is a trial of interferon-lambda, also known as interleukin-29.

The lambda interferons were only discovered in 2003. They differ from the more familiar interferons only in their cellular receptors; the downstream effects seem quite similar. As opposed to the cellular receptors for interferon alfa, which are widely expressed, the receptors for lambda are restricted to epithelial tissues. This makes it a good choice as a COVID treatment, since the virus also preferentially targets those epithelial cells.

In this study, 1951 participants from Brazil and Canada, but mostly Brazil, with new COVID infections who were not yet hospitalized were randomized to receive 180 µg of interferon lambda or placebo.

This was a relatively current COVID trial, as you can see from the participant characteristics. The majority had been vaccinated, and nearly half of the infections were during the Omicron phase of the pandemic.


If you just want to cut to the chase, interferon worked.


The primary outcome — hospitalization or a prolonged emergency room visit for COVID — was 50% lower in the interferon group.

Key secondary outcomes, including death from COVID, were lower in the interferon group as well. These effects persisted across most of the subgroups I was looking out for.

Putting it all together, the state of play for interferons in COVID may be changing. To date, the FDA has not recommended the use of interferon alfa or -beta for COVID-19, citing some data that they are ineffective or even harmful in hospitalized patients with COVID. Interferon lambda is not FDA approved and thus not even available in the United States. But the reason it has not been approved is that there has not been a large, well-conducted interferon lambda trial. Now there is. Will this study be enough to prompt an emergency use authorization? The elephant in the room, of course, is Paxlovid, which at this point has a longer safety track record and, importantly, is oral. I'd love to see a head-to-head trial. Short of that, I tend to be in favor of having more options on the table.


For Medscape, I'm Perry Wilson.

"

 

[missy]

"

Booster Doses Linked With Reduced COVID-Related Mortality in Patients With Multimorbidity​

Carolyn Crist
February 03, 2023

A regimen of three doses of COVID-19 vaccine, compared with two doses, is associated with a greater than 90% decrease in COVID-19-related deaths among patients with multiple chronic conditions, data suggest.

Booster vaccination can play a crucial role in protecting vulnerable groups as the pandemic continues to evolve, the study authors write.

"People with multimorbidity are known to be at increased risk of SARS-CoV-2 infection and severe complications and thus are one of the most vulnerable populations amid the pandemic," senior author Esther Wai Yin Chan, PhD, an associate professor of pharmacology and pharmacy with the Centre for Safe Medication Practice and Research in the Li Ka Shing Faculty of Medicine at the University of Hong Kong, told Medscape Medical News.



"Given the newly emerging viral strains and waning protection from the priming doses, it is important to investigate and demonstrate the effectiveness of a timely booster shot among this high-risk population," she said.

In a territory-wide retrospective cohort study, the researchers analyzed routine clinical records from public health facilities in Hong Kong. They compared the risk for COVID-19-related death between adults with two or more chronic conditions who received a third dose between November 2021 and March 2022 and those who received only two doses. Multimorbidity included 30 conditions, such as high blood pressure, diabetes, and chronic kidney disease.

The researchers included 120,724 patients who received the BNT162b2 mRNA vaccine from Fosun-BioNTech (equivalent to Pfizer-BioNTech outside of China), including 87,289 who received a booster dose and 127,318 patients who received Sinovac's CoronaVac shot. Of the latter patients, 94,977 received a booster. In general, those who received a booster dose were slightly older. There were more COVID-19-related deaths among CoronaVac recipients.

Overall, the risk for mortality was lower among those who received a third dose of either vaccine. Among BNT162b2 recipients, there were five COVID-19-related deaths among booster-vaccinated patients and 34 COVID-19-related deaths among two-dose recipients, yielding incidence rates per million person-days of 1.3 and 23.4, respectively. Among CoronaVac recipients, there were 26 COVID-19-related deaths among booster-vaccinated patients and 88 COVID-19-related deaths among two-dose recipients, yielding incidence rates per million person-days of 5.3 and 53.1, respectively.

For both vaccines, a booster dose was associated with a more than 90% decrease in mortality rate amid the Omicron wave, the authors write. Subgroup and sensitivity analyses yielded similar results for booster vaccination.


"We were slightly surprised at the drastic differences," said Chan. "We did expect great effectiveness before the analyses, but 90% is an incredible finding, particularly as this was a real-world study and not a controlled clinical trial with strict patient inclusion criteria — it is often in controlled trials where we see comparatively higher effectiveness."


Chan and colleagues are continuing to conduct research on COVID-19 vaccines and antivirals in vulnerable groups to understand how public health measures can reduce complications as the pandemic continues. They also plan to analyze how COVID-19 sequelae may increase the incidence of multimorbidity among those with ongoing symptoms.

​

Diab, who wasn't involved with this study, has researched COVID-19 pathophysiology and pharmacology in clinical vaccine and drug trials authorized by Health Canada. He and his colleagues are assessing best practices and gaps in trial design in ordewr to create guidelines for future trials.


"Unfortunately, in many jurisdictions, as public health measures wane, so does active monitoring of the virus, and this increases the uncertainty of the risk of infection," he said. "The ideal situation, including with the XBB.1.5 variant, would be timing booster doses with periods of increased risk — defined as the convergence of waning immunity, increased chance of exposure, and preexisting health conditions, such as multimorbidity. However, we need the proper research, monitoring, and data to be able to assess risk."


The study was funded by a research grant from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region through the Health and Medical Research Fund Research on COVID-19. Chan has received grants from the Research Grants Council of Hong Kong, the Research Fund Secretariat of the Food and Health Bureau of Hong Kong, the National Natural Science Fund of China, the Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and the Narcotics Division of the Security Bureau of Hong Kong outside of the current study. She has also received an honorarium from the Hong Kong Hospital Authority. Diab has disclosed no relevant financial relationships.
"

​

 

[missy]

"

The latest​

No new coronavirus variants emerged in Beijing in the first weeks after China ended its “zero-covid” policies, according to a Chinese study. Its authors said the findings “could be considered a snapshot” of the country, but others cast doubt on applying the findings so broadly.​

Chinese researchers analyzed over 400 randomly selected infections in Beijing between Nov. 14 and Dec. 20 and found that more than 90 percent of the cases were caused by the previous omicron subvariants BA.5.2 and BF.7.

Key context: China began relaxing its strict virus mitigation measures late last year after thousands of residents protested the regulations. The changes sparked a massive surge of infections and deaths, stoking fears around the globe that the outbreak could spawn new variants of concern.

The Chinese-funded study, published in the Lancet, drew mixed reactions from outside experts, who cautioned against drawing broad conclusions since the sampling covered a short period early in the outbreak and was limited to Beijing. However, its findings are in line with reports from other countries that have tested infected people arriving from China, Wolfgang Preiser and Tongai Maponga, virologists at South Africa’s Stellenbosch University, noted in a comment piece.

Half of students nationwide started the academic year below grade level in at least one subject, my colleague Donna St. George reports.​

The finding, estimated by school leaders nationwide, was virtually unchanged from a year earlier and 13 percentage points worse than the typical year before the coronavirus, according to newly released survey data from the National Center for Education Statistics. Among school officials who reported students below grade level, nearly all said at least some students were lagging in reading and math. Eighty percent cited shortfalls in science and about 70 percent, social studies.

The results add to a growing body of research that suggests many students face a steep climb to get back to grade level. School leaders are looking to familiar strategies to help them catch up, including offering tutoring, spending more time on targeted subjects, extending the school day and hiring more teachers to provide small-group instruction. “It just means we’ve got a long road ahead of us,” said Rachel Hansen, director of the center’s survey project.

Other important news​

Early in the pandemic, before the advent of coronavirus vaccines, 622 more U.S. physicians died than would have been expected. However, no excess deaths occurred after April 2021, once the shots were broadly available, Stanford University researchers concluded in a research letter published this week in JAMA Internal Medicine.

The U.S. government may have paid out $191 billion in improper pandemic unemployment benefits, the Labor Department’s watchdog told Congress this week as Washington continues its probe into waste, fraud and abuse targeting covid aid. The new estimate is a substantial increase from the $163 billion in questionable payments that the office identified last year, a significant portion of which officials said is attributable to fraud.

New York City, which once had some of the nation’s strictest coronavirus vaccination rules, will no longer require the shots for municipal employees starting Feb. 10, Mayor Eric Adams (D) announced this week.



"

 

[mellowyellowgirl]

A little light hearted fun about the crazy two years we lived through!

View this content on Instagram

View this content on Instagram

I remember letting packages sit at the back for a few days during Delta.

Never did break out the spray cans or wipes though. My greenie self couldn't live with the guilt of generating all that extra waste.

 

[missy]

"

New variants haven’t emerged in China​

China’s reopening has been marked by a conspicuous dearth of new Covid variants. The country went almost overnight from the strictest control measures to the most lax at the end of last year, after China abruptly dropped its zero tolerance approach and allowed the virus to rip. The pathogen followed. The country’s chief epidemiologist estimated 80% of the population, more than 1.1 billion people, were infected in just a few weeks. Millions then returned to their hometowns for the Lunar New Year holiday, sparking fear that new variants from the massive outbreak could spread to every corner of the country. The US and many European countries required negative Covid tests for travelers from China to keep out theoretical new mutations. But none have materialized. Health officials from 28 regions across China — including every major city — have been sending genetic information on recent infections to GISAID, a consortium tracking the pandemic. None deviate from the variants that were circulating widely in the rest of the world in the second half of 2022. All are various flavors of omicron, the most common variant of concern. The same is true for the rest of the world, where there hasn’t been a significant new variant to challenge omicron in more than a year. That doesn’t mean there won’t be future surges of infection. Officials remain concerned that mutations within the omicron family may eventually cause havoc, by evading existing immunity or triggering more severe disease. The World Health Organization is tracking four omicron lineages closely because of the potential risk, including signals they may be more fit or transmit more easily. The biggest targets at the moment are recombinant variants, when two earlier strains come together. The most common is XBB.1.5, which an evolutionary professor dubbed Kraken on Twitter. The WHO has issued two rapid risk assessments of it in recent weeks, concluding that it’s likely to spur an increase in cases globally in the coming weeks. Fortunately, there’s no evidence that it’s more dangerous than older versions of the virus. It’s not coming from China, however. The US is the epicenter for XBB.1.5, where it accounted for nearly 75% of all infections last week. China will continue to monitor for new variants, said George Gao, a professor at the Institute for Microbiology at the Chinese Academy of Sciences and the former head of the Chinese Center for Disease Control and Prevention. He led a study, published in The Lancet, that found most Covid cases circulating in Beijing — and likely all of China — are the older BA5.2 and BF.7 variants. That doesn’t mean China is out of the woods. While the findings are reassuring, it’s possible that humans in other parts of the country could transmit the virus to animals, two experts from South Africa wrote in a commentary that accompanied the article. That’s a particularly dangerous event if it “spills back” into people in a further evolved version, they said. Of course, that could happen anywhere. —Michelle Fay Cortez "

 

[missy]

"

Should Future COVID Boosters Include the Ancestral Strain?​

— We need a new approach to formulating and rolling out the vaccines​

by John P. Moore, PhD, and Céline Gounder, MD, ScM February 8, 2023

The current COVID-19 mRNA vaccine boosters are bivalent, meaning they contain equal amounts of spike protein mRNA for the original Wuhan virus sequence and for the BA.4/5 Omicron variants that emerged in mid-2022. How well does this type of bivalent booster perform?
The question is relevant because FDA's recent Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting discussed COVID-19 vaccine composition ahead of key decisions to be made later this year. For now, the FDA advisors voted to harmonize vaccine formulations; the same bivalent vaccineopens in a new tab or windowcurrently authorized will be used for both primary and booster vaccinations. But should any new vaccine continue to include the ancestral strain's sequence? Or should it be based only on an Omicron lineage variant?

A Review of the Latest Evidence
We now have better data from a large, randomized, controlled trialopens in a new tab or window conducted in the U.K. in early 2022 during the first BA.1 Omicron wave. Early in the trial, study participants were given a BA.1 monovalent booster or the original monovalent booster. But over the course of the trial, the virus continued to mutate in the real world and new Omicron subvariants emerged. It was hypothesized that a bivalent booster targeting BA.1 and the ancestral strain would elicit better cross-protection to the subvariants, and thus in the second half of the trial, study participants were given a BA.1 bivalent booster or the original monovalent booster.

Credit: FDA Vaccines and Related Biological Products Advisory Committee presentation, January 26, 2023

Although the monovalent and bivalent COVID vaccines studied in this trial were targeted at the BA.1 Omicron variant, not the later BA.4/5 Omicron variant, the results are highly relevant. Note that although the total dose in bivalent vaccines is identical to that of the monovalent vaccines, the current formulations deliver only half a dose of vaccine against the Omicron subvariants.

The main clinical outcome, a secondary endpoint in the study, was COVID-19 as defined in the COVE trial. The BA.1 monovalent vaccine appeared to be the most effective booster of the three, followed by the BA.1 bivalent booster, and then the original monovalent booster. However, the differences were small. Relative vaccine effectiveness with the BA.1 bivalent booster was a non-significant 11.4% (95% CI -10.2 to 28.7) when compared with the original monovalent vaccine. Immunological data paralleled the clinical data. The monovalent BA.1 booster elicited marginally higher neutralizing antibody (NAb) titers against the BA.1 subvariant than did the bivalent booster, as did the BA.1 bivalent booster as compared toopens in a new tab or window the original monovalent booster.
This randomized controlled trial demonstrated that the BA.1 bivalent booster is only marginally better at preventing COVID than the original monovalent booster, and that the best performer, although not by much, was the monovalent BA.1 Omicron booster. These findings are in line with what we suggested last year. Furthermore, the BA.1 bivalent booster elicited only a 1.5 times higher NAb titer than did the original monovalent booster, which is concordant with a body of literature on bivalent boosters that we previously summarizedopens in a new tab or window, as well as with twoopens in a new tab or window recent papersopens in a new tab or window on the performance of the BA.4/5 bivalent booster. NAbs are the principal correlate of protection for prevention of infectionopens in a new tab or window. Consistent with the predictions of an influential modelopens in a new tab or window, slightly higher NAb titers had limited impact on the clinical endpoint.

We do not have comparable randomized trial data on the BA.4/5 bivalent boosters, so we may never know with certainty the extent to which they were an "upgrade" over the original monovalent booster. However, in recent months, federal officialsopens in a new tab or windowand othersopens in a new tab or window have claimed that the bivalent boosters are "better" than the original monovalent booster. These statements are based on the results of clinical or laboratory studies performed under non-comparable conditions and not from a randomized controlled trial.
In observational studies, the clinical performance of the BA.4/5 bivalent booster has been assessed and compared with historic data on the original monovalent booster. What these studies show is the beneficial impact of the bivalent booster at reducing the incidence of a clinical endpoint. However, comparisons of how different boosters performed at different intervals since last vaccination or infection are inexactopens in a new tab or window. Longer intervalsopens in a new tab or window between booster doses allow for greater time-dependent affinity maturationopens in a new tab or window of NAbs and thus higher NAb titer boosts with an additional dose of vaccine. Such differences in intervals since last vaccination do not arise when the serum samples are collected in a randomized controlled trial, as in the phase III trialopens in a new tab or window of monovalent and bivalent boosters in the U.K., or when factored into the study design. Observationalopens in a new tab or window studiesopens in a new tab or window may also be confounded by COVID-cautiousnessopens in a new tab or window and other behavioral differences between those who do or don't get boosted. People who get boosted are more likely to make use of other mitigation measures like masking or testing to further reduce the risk of COVID. For example, a recent studyopens in a new tab or window from Israel demonstrated instantaneous protection from getting a bivalent vaccine booster over no booster, but we know it takes a few daysopens in a new tab or windowbefore one could plausibly expectopens in a new tab or window to see an immunological responseopens in a new tab or window.

Putting the Evidence Into Practice
Boosting is useful for improving protection against infection, which is particularly important for people at serious risk of severe COVID-19 due to age or underlying medical conditions. The current BA.4/5 bivalent booster performs adequately for this purpose. To the general public, it is a moot point how much "better" the bivalent booster is compared to a monovalent vaccine they can no longer obtain. However, moving forward, we need to understand how well the bivalent boosters work because the FDA will soon be discussing further changes to booster compositionopens in a new tab or window.
We argue, again, that there is no value to continuing with bivalent boosters -- a monovalent Omicron-based vaccine is currently a better option. We also suggest that switching in a few months from targeting the BA.4/5 Omicron subvariant to a new, yet-to-emerge Omicron subvariant would yield only a small incremental improvement in either NAb titers or clinical performance. Another Omicron vaccine boost, of any composition, would act as a "dose twoopens in a new tab or window" for people who have received the BA.4/5 bivalent vaccine, and thereby induceopens in a new tab or window broadly active, affinity-matured NAbs to Omicron-specific epitopes (the bivalent vaccine has already done this in people who were also Omicron virus-infected last year).

"Better" can mean what people want it to mean. A 6-foot 6-inch-tall basketball player may be 2 inches taller than one who is merely 6-foot 4-inches tall, but does the extra 2 inches make him a better player worth a more lucrative contract? There is more to the sport than height, and there is more to vaccine performance than a marginal -- and often inappropriately exaggerated -- increase in NAb titers. Vaccine composition changes are very expensive. At a time when federal resources for COVID-19 are becoming increasingly stretched, the FDA needs to give serious thought to using the available funds most wisely.
John P. Moore, PhD, is a professor of microbiology and immunology at Weill Cornell Medicine in New York City. Céline Gounder, MD, ScM, is an internist, infectious disease specialist, and epidemiologist; a senior fellow and editor-at-large for public health at the Kaiser Family Foundation and Kaiser Health News; and host of the "American Diagnosisopens in a new tab or window" and "Epidemicopens in a new tab or window" podcasts.
"

 

[missy]

"

Phase 3 Trial Reports Promising Results for New COVID Treatment​

Lisa O'Mary
February 09, 2023


Results from a phase III trial of a new COVID-19 treatment showed it reduced the risk of hospitalization or long ER visits by half.

"The data look quite promising and other treatments have now fallen by the wayside," Paul Sax, MD, of Brigham and Women's Hospital in Boston, told USA Today. Sax was not involved in the research.

Most treatments for COVID-19 have become ineffective as the virus has evolved, leaving just a few antivirals such as Paxlovid as the remaining available treatments.


The new treatment is called pegylated interferon lambda and is made by California-based Eiger BioPharmaceutical. It is given as a single injection.



The study was published today in The New England Journal of Medicine. Researchers evaluated the treatment compared to placebo in 1,949 adults in Canada and Brazil who were at high risk of severe COVID-19. Those in the treatment group got the shot within 7 days of symptom onset.

The treatment worked best when taken within 3 days of symptoms appearing. Results also showed it was effective for both vaccinated and unvaccinated individuals, as well as against varying COVID variants.

"Peginterferon lambda has tremendous therapeutic potential, and we continue to see the emergence of aggressive variants of the virus spreading around the globe which are less sensitive to both vaccines and treatment with antibodies," said researcher Jordan Feld, MD, MPH, associate professor of medicine at the University of Toronto, in a news release. "Resistance due to variants or new strains of the virus could be an issue with some therapies, but this may not be a concern with peginterferon lambda due to its mechanism of action that involves activation of multiple virus-killing pathways."

Eiger BioPharmaceutical said it has 100,000 doses available and the capability to manufacture 10 million more.

The New York Times reported that the company may seek authorization for the treatment to be used outside the U.S. because of hurdles with the FDA.

"Regulators at the Food and Drug Administration late last year told the drug's maker, Eiger Biopharmaceuticals, that they were not prepared to authorize it for emergency use," the Times reported. "Eiger executives said part of the problem seemed to be that the clinical trial did not include an American site, but rather only sites in Brazil and Canada, and that it was initiated and run by academic researchers, rather than the company itself."

Sources:


The New England Journal of Medicine: "Early Treatment with Pegylated Interferon Lambda for Covid-19."


USA Today: "An experimental COVID treatment could be a promising alternative to Paxlovid, study finds."


Eiger BioPharmaceutical: "New England Journal of Medicine Publishes Positive Phase 3 TOGETHER Results with Peginterferon Lambda in COVID-19."


The New York Times: "Why the Odds Are Stacked Against a Promising New Covid Drug."

"

 

[missy]

"

My Initial Impressions of a New COVID Treatment: Pegylated Interferon Lambda​

— A major study offered encouraging results, but some barriers to treatment exist​

by Jeremy Faust, MD February 14, 2023

Earlier this week, a new studyopens in a new tab or window published in the New England Journal of Medicinefound thatopens in a new tab or window patients who received one injection of pegylated interferon lambda did better than those who received placebo. Interferons like this one work by helping cells keep viruses from invading and taking up shop.
The new study compared outcomes in mostly vaccinated participants across several periods, including Omicron. Interferon recipients had lower rates of the study's "primary outcome" of interest; Participants were deemed as having experienced the primary outcome if either a COVID-related hospitalization or an emergency department (ED) stay longer than 6 hours occurred.

I'll need to spend more time with this paper before I finalize my thinking on this. But there are some interesting things to say now, which I'll share.
In favor of the drug, not only did the trial succeed in lowering rates of its primary outcome by about half but also in a slew of secondary outcomes. When everything agrees, bending in the same direction, that can be a sign that a drug is working.
Here, both components of the primary outcome -- COVID-related hospitalizations and ED stays of longer than 6 hours -- were statistically lower in the interferon recipients.
That said, some key secondary outcomes were not as impressive. For example, COVID-19 deaths, all-cause deaths, and all-cause hospitalizations were not statistically loweropens in a new tab or window than that of the placebo group, even though the numerical rates were lower (that is, the raw rates of these events were lower, but the findings were not statistically significant). Now, that could be because the drug doesn't work as well as billed, or it could be simply because the study was not designed to have enough patients to be able to make such determinations. That said, even for secondary outcomes not reaching statistical significance, it's conspicuous and impressive how many had non-statistically significant decreases in outcomes like death. That gives me hope that this thing works.

The skeptic in me notes that a few findings were less impressive than the headline. For example, when researchers measured all-cause death or COVID-related hospitalization (factoring out longer ED stays), about half of that signal of benefit vanished (i.e., there was a 25% reduction in those outcomes as opposed to a 51% reduction in the primary outcome). When researchers measured all-cause ED visits, hospitalizations, or deaths, the signal of benefit almost vanished altogether; there was just a 6% reduction in these outcomes combined, a finding that was not distinguishable from noise/chance. This matters. As a patient, I don't really care whether I die of COVID or something else. If a drug lowers my COVID death rate, but not my overall death rate, I sort of lose interest. The point is to live, not to die in the same time window but not have the word "COVID-19" on my death certificate.

Nevertheless, as I mentioned, a bunch of secondary outcomes found either a statistically significant sign of benefit or had promising results that did not clear statistical thresholds. So, this all looks encouraging for interferon. And if this works even a fraction as well as these data suggest, it would still be good news. What's more, there's no reason this treatment should only work on COVID-19. So, this might have broader applications.
And yet, as the New York Timesopens in a new tab or window reported, the FDA is unlikely to authorize this drug for use in the U.S. The reasons for this are actually kind of silly. First, the study was done in Brazil and Canada -- and the FDA likes U.S. data. It seems to me that in a pandemic, science is science, regardless of its locale. What matters is the quality of the endeavor, not the country code where it took place. Japan made a mistake by not accepting U.S. data on mRNA vaccines back in 2021, which meant that it was slow to get its vaccination campaign up and running. We should not make the same mistake on therapeutics. Second, the FDA doesn't like that the study was conducted by academics, rather than the pharmaceutical company that makes the drug. This is downright bizarre. If anything, industry-run studies are more likely to have been designed to detect a benefit than studies done by academic researchers. (That said, the company that makes the drug donated the drug to the study, so it's not as if this study was truly independent anyway.) Punishing the study for not being substantially biased by virtue of being run by the company that makes the drug seems backwards.

Something I hear few people discussing is how expensive this drug is. I can't quite figure out what the drug costs per dose, but it seems like it's many thousands of dollars. Considering that hundreds of patients would need to get the drug to save one life, scaling this drug up may not be feasible in many places. In a global pandemic, we're looking for drugs that are both effective and affordable.
It will be interesting to see if these findings are replicated. I'm also looking for other experts (skeptics in particular) to chime in. If these data are too good to be true, it would be great to know that before we start spending billions of dollars on this particular interferon.
Jeremy Faust, MD, is editor-in-chief of MedPage Today, and an emergency medicine physician at Brigham and Women's Hospital. This post originally appeared in Inside Medicineopens in a new tab or window.
"

 

[missy]

"

Guiding New York City Through COVID-19​

— Former N.Y.C. Health Commissioner on leading the public through the pandemic​

by Henry Bair and Tyler Johnson, MD February 14, 2023

In the first half of 2020, New York City quickly became the American epicenter of the COVID-19 pandemic, with over 200,000 cases reported in the first few months. The city came to a standstill as thousands of people died alone in hospitals and bodies piled up in freezer trucks that could not transport them away fast enough.



In August 2020, amid this cataclysm, Dave Chokshi, MDopens in a new tab or window, of New York University Grossman School of Medicine, assumed position as New York City's Health Commissioner and began the arduous task of repairing a broken city and restoring public trust among its residents. Prior to this work, Chokshi was chief population health officer for N.Y.C. opens in a new tab or windowHealth and Hospitalsopens in a new tab or window and was a White House fellow at the Department of Veterans Affairs.

In this episode, Chokshi joins Henry Bair and Tyler Johnson, MD, to share the core values that drive his public health work and how he navigated the challenges of leading New York City through COVID-19.

In this episode, you will hear about:

• 3:52 How Chokshi, early in his life, came to understand the association between health and opportunity
• 7:40 A discussion of how privilege impacts the opportunities available to individuals and how this recognition impacts Chokshi's medical work
• 15:48 How Hurricane Katrina revealed to Chokshi the flaws in our existing health system
• 19:34 Chokshi's involvement with Universities Allied for Essential Medicines
• 24:31 An account of Chokshi's tenure as New York City Health Commissioner during the height of the COVID-19 pandemic
• 32:31 Chokshi's principles of effective leadership
• 37:15 Reflections on the first wave of the COVID-19 pandemic and how indebted society is to nurses and hospital house staff
• 53:48 Chokshi's personal philosophy on maintaining a balanced sense of humility
• 57:38 Five lessons for medical trainees and clinicians on staying connected to what makes medicine meaningful

Following is a partial transcript (note errors are possible):

Johnson: So, Dave, can you begin by telling us, how did you end up being a doctor? What brought you into medicine?

Chokshi: Yeah, well, I was not one of those kids with the Fisher-Price stethoscope, I guess, is how I'll begin. I was the first doctor in my family, and that meant that I didn't really have role models for what it meant to practice medicine. I didn't know the day to day of taking care of patients in that way. But what I did know and sort of observed through my childhood and young adulthood was all of the ways in which health was connected to opportunity.

You know, I experienced this personally as a kid growing up with asthma, watching how the diagnosis of diabetes affected my father and his life, and then having some early formative experiences that showed me just how tightly linked health and opportunity were. There's one that comes to mind. It was a summer that I spent as a college student in Mumbai. Actually, all of my extended family lives in Mumbai, India. It's where my parents grew up and I had the chance to work for a nonprofit organization called Committed Communities Development Trust in Kamathipura, which is one of the red light districts in Mumbai. And this was around the turn of the century, about 2000. And the organization was providing child care for the children of commercial sex workers in Mumbai, many of whom had been infected with HIV as a result of being a sex worker and many of whom had transmitted that infection to their children.



I thought about the lot of the kids that we were taking care of, and I thought about how little separated their life and the opportunity that they would have in their lives from mine. You know, if things had just been slightly different with respect to my family and their path, I could have very easily been in the shoes of the children that we were trying to take care of.

And I saw everywhere from that experience, from a few others that I had early in my career, that it's not just a connection between health and opportunity, but it's often a cycle. What I think of as either a vicious cycle or a virtuous cycle. Ways in which illness can beget other problems, often economic problems, sometimes poverty, but also the ways in which good health can beget opportunity in a positive way as well. So it's all to say, you know, I was sort of propelled to a career in medicine because I cared about health and I found it so fundamental to people's life prospects, whether it was in a red light district in Mumbai or where I grew up in Baton Rouge, Louisiana.



Johnson: Can I just ask, Dave, as an aside -- we talk a lot on this podcast about deeper philosophical, metaphysical questions, and I feel like since we were in med school together, a term that has become very popular in the lay press and even in politics is "privilege." And part of what I hear you saying is that it really is so striking to think about the differences in inherent privilege with which a person is born, depending on their zip code, their parentage, their social capital, their family situation, and on and on and on.

And there have been many studies recently demonstrating, for example, that one of the most determinative forces in a person's life -- in the United States, anyway -- is the zip code in which they're born. Right? Which makes sense when you think about the schools to which a person has access and on and on and on. But I guess from a philosophical perspective, that relatively early recognition that you had been endowed with enormous privilege because of where you had been born and what your parents did and educational opportunities and all the rest, that was so much greater than so many other people in the world. What do you do with that philosophically and/or how does that help to shape how you practice as a doctor?



Chokshi: Yeah, that's a really thoughtful question. And first, Tyler, I have to say, I remember our conversations in med school so well. I actually remember we would sometimes have coffee in the bookstore on Penn's campus and try to puzzle through some of these questions together. And I'll just pick up on one of the words that you used, which is "endowed." And I think that, just as you pointed out, many of us are endowed in a positive direction. We have the advantages that you described in terms of family and education and sometimes health as well.

But I think the realization that that endowment is not equally distributed and that so much of life circumstances are in some cases random and other cases represent the intergenerational transmission of things like illness or poverty, it makes me assess endowment in a different way as well, which is that it generates, it endows us with some responsibility to recognize the structural forces that we've talked about, but then ultimately to try to close some of the gaps that we see in our world.



One of the ways that I think about this is the difference between inequity and inequality. And the distinction that I always keep in mind is that inequity is a difference that is avoidable and unfair. And when we see inequity in that way, those of us who have the privilege to occupy spaces like we do in medicine or in other sectors, it's our responsibility to take up those inequities and actually change the trajectory, change the direction in which those inequities cause illness and cause lack of opportunity.

For the full transcript, visit The Doctor's Artopens in a new tab or window.

Copyright © The Doctor's Art Podcast 2023.
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Does COVID Vaccine Blunt Elevated Diabetes Risk After Infection?​

— Unvaccinated had a 78% higher risk for new-onset diabetes; no link seen among the vaccinated​

by Kristen Monaco, Staff Writer, MedPage Today February 14, 2023

New evidence further supports the link between COVID-19 infection and new-onset diabetes, but also suggests that vaccination may mostly mitigate this risk, researchers reported.
In a cohort of nearly 24,000 adults at a large California health system, adjusted models showed that having a history of a treated COVID infection was tied with a 58% higher likelihood of developing new-onset diabetes compared with a new diagnosis of a benchmark condition (OR 1.58, 95% CI 1.24-2.02, P<0.001), according to Alan Kwan, MD, MSc, of Cedars-Sinai Health System in Los Angeles, and colleagues.

However, this risk appeared to be mostly driven by unvaccinated individuals, the group detailed in JAMA Network Openopens in a new tab or window.
Unvaccinated individuals saw a 78% increased chance of developing diabetes within 90 days of infection (OR 1.78, 95% CI 1.35-2.37, P<0.001), while no significant association was observed in vaccinated individuals (OR 1.07, 95% CI 0.64-1.77).
Kwan's group noted, however, that although the diabetes risk was higher among the unvaccinated individuals, "suggesting a benefit of vaccination," the interaction term between vaccination status and diabetes diagnosis didn't reach statistical significance (OR 0.59, 95% CI 0.34-1.06, P=0.0. No interaction was observed for age, sex, or preexisting cardiovascular risk factors, including hypertension or hyperlipidemia.
"Our results validate early findings revealing a risk of developing type 2 diabetes after a COVID-19 infection and indicate that this risk has, unfortunately, persisted through the Omicron era," said Kwan in a statement. "These results suggest that COVID-19 vaccination prior to infection may provide a protective effect against diabetes risk."

"Although further studies are needed to validate this hypothesis, we remain steadfast in our belief that COVID-19 vaccination remains an important tool in protecting against COVID-19 and the still-uncertain risks that people may experience during the post-infection period," he added.
To account for temporal confounders stemming from disruptions in healthcare use during the pandemic, the researchers used a new benchmark diagnosis -- such as urinary tract infection and gastroesophageal reflux -- as the comparator to represent a marker of healthcare engagement unrelated to COVID-19. Models were adjusted for sex, timing of index infection, and pre-infection vaccination status.
COVID-19 infection didn't appear to increase the risk for other cardiometabolic conditions compared with a benchmark diagnosis, however, specifically in regards to new-onset hypertension (OR 1.06, 95% CI 0.88-1.2 and hyperlipidemia (OR 0.91, 95% CI 0.73-1.15), the team said.
"Mechanisms contributing to postinfection diabetes risk remain unclear, although persistent inflammation contributing to insulin resistance is a proposed pathway," the researchers explained. "Our results suggest that this risk persisted as the Omicron variant became predominant, and the association remained even after accounting for temporal confounders."

This wasn't the first study to draw a line between COVID and diabetes risk either. Kwan's group referred to a meta-analysisopens in a new tab or window published in November 2022 that found a 48-70% higher relative risk of type 1 and type 2 diabetes in people with a history of COVID. One of the studiesopens in a new tab or window included in this meta-analysis found that people who survived the post-acute phase of a COVID-19 infection (i.e., the first 30 days) had an 85% higher risk of needing a new antihyperglycemic medication.
The current study included 23,709 adult patients (54% of whom were female) with at least one COVID-19 infection treated within the Cedars-Sinai Health System between the beginning of the pandemic through June 2022. The average age was 47 years and diagnostic data were pulled from ICD-9 and ICD-10 codes. A total of 14,856 patients were unvaccinated prior to infection and 8,853 were vaccinated.
During the study time frame, incidence of new-onset type 2 diabetes was 2.1% overall: 2.7% of the unvaccinated group and 1% of the vaccinated group.
Kwan and co-authors suggested that future studies are needed "to understand cardiometabolic sequelae of COVID-19 and whether COVID-19 vaccination attenuates risk of cardiometabolic disease."

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  Kristen Monaco is a staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures
The study was funded by the Erika J. Glazer Family Foundation, the Doris Duke Charitable Foundation, and NIH grants.
Kwan and co-authors reported relationships with the Doris Duke Charitable Foundation, NIH, Cardurion, Corvia, Cytokinetics, Intellia, Novartis, and Zogenix.
Primary Source
JAMA Network Open
Source Reference: opens in a new tab or windowKwan AC, et al "Association of COVID-19 vaccination with risk for incident diabetes after COVID-19 infection" JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2022.55965.
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Long COVID or Functional Neurological Disorder?​

— Neurologic symptoms in long COVID insufficiently studied, systematic review suggests​

by Judy George, Deputy Managing Editor, MedPage Today February 14, 2023

The hypothesis that long COVID might be related to a functional neurological disorder (FND) remains untested, a systematic review showed.

Across 102 long COVID studies, neurologic symptoms were insufficiently characterized to support or refute a diagnosis of FND, reported Tiago Teodoro, MD, PhD, of St. George's Hospital in London, and colleagues.

Given the characteristics of the disorder, some people with FND might be inappropriately considered to be long COVID patients, which could delay diagnosis and treatment and affect prognosis, the researchers wrote in the European Journal of Neurologyopens in a new tab or window.



"We remain struck by the similarities between some manifestations of long COVID and functional disorders triggered by acute illnesses," Teodoro told MedPage Today.

"Our systematic review shows that the possibility that some people labeled as having long COVID might in fact be experiencing a form of functional neurological disorder has, so far, been largely overlooked in the medical literature," he said.

"This is a major problem for understanding long COVID but primarily for patient management, as this is a condition with specific diagnostic criteria and for which effective treatments are available," he added.

FND refers to disorders caused by an abnormality in brain signalingopens in a new tab or window with no significant structural damage in the brain. It occurs in an estimated four to 12 people per 100,000opens in a new tab or window per year.

"These are common neurological conditions caused by malfunctioning of the brain but not directly related with structural damage," Teodoro noted.

"We have previously seen many patients developing functional neurological symptoms following an acute event such as an injury, an invasive medical procedure, or an infection, among many others," he said.



"These factors do not directly cause the functional neurological symptoms, but are best understood as triggers, which precipitate this condition in people with a pre-existing predisposition," Teodoro continued. "In some cases, these functional neurological symptoms might become persistent."

The analysis by Teodoro and co-authors "seems to be well done, which is not surprising given that the authors are well-known, respected academics," observed Mark Hallett, MD, emeritus investigator and former chief of medical neurology at the National Institute of Neurological Disorders and Stroke (NINDS), who wasn't involved with the study.

"Their major conclusion is that it is not known how frequently functional neurological disorder plays a role in long COVID, if at all, largely because data have not been collected in sufficient detail and the diagnosis has not generally even been considered," Hallett told MedPage Today.

"However, it is likely that some long COVID patients do have FND, or FND together with some other pathology," he noted.



"The most important issue is that FND requires its own treatment and that such treatment can be successful," Hallett said. "Physicians should know that FND is a possibility, that it can be diagnosed based on positive features, and that appropriate therapy, as always, depends on making the right diagnosis."

A diagnosis of functional neurologic symptoms is positive and not just based on ruling out other conditions, Teodoro and co-authors emphasized. "A key feature is inconsistency over time, which means that symptoms often occur intermittently and/or with fluctuating severity," they wrote.

Teodoro and colleagues reviewed 102 studies spanning 412,726 who had COVID-19. Of these, 31 studies recruited participants who had long COVID (11,860 patients). The remaining studies looked at people with acute COVID screened for ongoing long COVID symptoms.

Overall, 51 studies were prospective, 33 were cross-sectional, and 12 were retrospective; 18 included a control group. Most (89 studies) defined long COVID as symptoms persisting for 4 weeks or more.



Mean or median age in most studies was between 40 and 59, and the proportions of male and female participants were similar.

Neurologic symptoms reported most consistently were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms, and ageusia or anosmia.

"Overall, we found no evidence that any authors had systematically looked for positive features of FND," Teodoro and colleagues wrote. "An exception were three studies describing temporal inconsistency."

"Moreover, only 13 studies specifically focused on long COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated," they added.

"There are a growing number of case reports of FNDopens in a new tab or window triggered by COVID-19 infection (and vaccination)," Teodoro and co-authors pointed out. "This is in line with our expectations and makes the absence of patients with FND in the long COVID cohorts we reviewed or that FND was not generally considered by authors as a differential diagnosis even more surprising."



Researchers and clinicians need to appreciate the likely complexity and heterogeneity of the mechanisms for long COVID symptoms, the researchers noted.

"This includes ensuring that neuropsychiatric and functional explanations for symptoms are considered alongside other explanations without the prejudice that such explanations make symptoms less genuine or disabling, or are less 'real' than more traditional biological explanations for symptoms," Teodoro and co-authors wrote.

"It is also likely that patients may have more than one diagnosis accounting for their multiple symptoms -- something which runs the risk of being hidden through the use of a syndromic label such as long COVID," they added. "Without understanding these issues, it is likely that patients will not be able to access suitable treatment, and development of novel treatments and services will be delayed."

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Cardiac Issues Twice as Likely With COVID Plus High Troponin​

Marilynn Larkin
February 13, 2023


Hospitalized COVID-19 patients with high troponin levels are twice as likely to have cardiac abnormalities than those with normal troponin, with or without COVID-19, a multicenter UK study suggests.
The causes were diverse, myocarditis prevalence was lower than previously reported, and myocardial scar emerged as an independent risk factor for adverse cardiovascular outcomes at 12 months.
"We know that multiorgan involvement in hospitalized patients with COVID-19 is common...and may result in acute myocardial injury, detected by an increase in cardiac troponin concentrations," John P. Greenwood, PhD, of the University of Leeds in England, told theheart.org | Medscape Cardiology. "Elevated cardiac troponin is associated with a worse prognosis."

"Multiple mechanisms of myocardial injury have been proposed and...mitigation or prevention strategies likely depend on the underpinning mechanisms," he said. "The sequelae of scar may predispose to late events."


The study, published online January 27 in Circulation, also identified a new pattern of microinfarction on cardiac magnetic resonance (CMR) imaging, highlighting the pro-thrombotic nature of SARS-CoV-2, Greenwood said.

Injury Patterns Different​

Three hundred and forty-two patients with COVID-19 and elevated troponin levels (COVID+/troponin+) across 25 centers were enrolled between June 2020 and March 2021 in COVID-HEART, deemed an "urgent public health study" in the UK. The aim was to characterize myocardial injury and its associations and sequelae in convalescent patients after hospitalization with COVID-19.

Enrollment took place during the Wuhan and Alpha waves of COVID-19, before vaccination, and when dexamethasone and anticoagulant protocols were emerging. All participants underwent CMR at a median of 21 days after discharge.
Two prospective control groups also were recruited: 64 patients with COVID-19 and normal troponin levels (COVID+/troponin−) and 113 without COVID-19 or elevated troponin matched by age and cardiovascular comorbidities (COVID−/comorbidity+).
Overall, participants' median age was 61 years and 69% were men. Common comorbidities included hypertension (47%), obesity (43%), and diabetes (25%).
The frequency of any heart abnormality — eg, left or right ventricular impairment, scar, or pericardial disease — was twice as great (61%) in COVID+/troponin+ cases compared with controls (36% for COVID+/troponin− patients vs 31% for COVID−/comorbidity+ patients).

Specifically, more cases than controls had ventricular impairment (17.2% vs 3.1% and 7.1%) or scar (42% vs 7% and 23%).

The myocardial injury pattern differed between cases and controls, with cases more likely to have infarction (13% vs 2% and 7%) or microinfarction (9% vs 0% and 1%).

However, there was no between-group difference in nonischemic scar (13% vs 5% and 14%).

The prevalence of probable recent myocarditis was 6.7% in cases compared with 1.7% in controls without COVID-19 — "much lower" than in previous studies, Greenwood noted.

During follow-up, four COVID+/troponin+ patients (1.2%) died and 34 (10%) experienced a subsequent major adverse cardiovascular event (MACE; 10.2%), which was similar to controls (6.1%).

Myocardial scar, but not previous COVID-19 infection or troponin level, was an independent predictor of MACE (odds ratio, 2.25).

"These findings suggest that macroangiopathic and microangiopathic thrombosis may be the key pathologic process for myocardial injury in COVID-19 survivors," the authors conclude.

Greenwood added, "We are currently analyzing the 6-month follow-up CMR scans, the quality-of-life questionnaires and the 6-minute walk tests. These will give us great understanding of how the heart repairs after acute myocardial injury associated with COVID-19. It will also allow us to assess the impact on patient quality of life and functional capacity."

"Tour de Force"​

Commenting on the study for theheart.org | Medscape Cardiology, James A. de Lemos, MD, co-chair of the American Heart Association's COVID-19 CVD Registry Steering Committee and a professor of medicine at the University of Texas Southwestern Medical Center in Dallas, said, "This is a tour de force collaboration — obtaining this many MRIs across multiple centers in the pandemic is quite remarkable. The study highlights the multiple different processes that lead to cardiac injury in COVID patients, complements autopsy studies and prior smaller MRI studies [and] also provides the best data on the rate of myocarditis to date among the subset of COVID patients with cardiac injury."


Overall, he said, the findings "do support closer follow-up for patients who had COVID and elevated troponins. We need to see follow-up MRI results in this cohort, as well as longer term outcomes. We also need studies on newer, more benign variants that are likely to have lower rates of cardiac injury and even fewer MRI abnormalities."


Matthias Stuber, PhD, and Aaron L. Baggish, MD, both of Lausanne University Hospital and University of Lausanne in Switzerland, noted in a related editorial, "We are also reminded that the clinical severity of COVID-19 is most often dictated by the presence of pre-existing comorbidity, with antecedent ischemic scar now added to the long list of bad actors. Although not the primary focus of the COVID-HEART study, the question of whether cardiac troponin levels should be checked routinely and universally during the index admission for COVID-19 remains unresolved," they noted.


"In general, we are most effective as clinicians when we use tests to confirm or rule out the specific disease processes suspected by careful basic clinical assessment rather than in a shotgun manner among undifferentiated all-comers," they conclude.


No commercial funding or relevant financial relationships were reported
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Paxlovid Doesn’t Increase Risk for Rebound COVID Infection: Study​

Lisa O'Mary
February 15, 2023

People who took the antiviral Paxlovid to treat COVID-19 infections were not more likely to get back-to-back bouts of the virus, a new study shows.
The findings offer clarity amid concerns that the use of Paxlovid, which works by stopping the spread of the virus in the body, increased the risk of COVID-19 rebound.
"Rebound is a re-emergence of symptoms and an uptick in viral load after a period of recovery," the Center for Infectious Disease Research and Policy explained in a summary of the study.

Researchers found that patients who received Paxlovid, another antiviral called Lagevrio, or no antiviral medication had rebounds at similar rates, ranging from 4.5% to 6.6%.

The study was published Monday in the journal The Lancet Infectious Diseases and included 4,592 people in Hong Kong who were hospitalized within 3 days of a COVID diagnosis. The study period was from Feb. 26, 2022, to July 3, 2022, which is the time that the Omicron subvariant BA.2.2 was predominant.

The study further found that the risk of rebound was tied to being 18 to 65 years old (compared to older patients), having chronic medical conditions, and receiving steroid treatment. Another finding, which the authors noted was important, was that it appeared Paxlovid did not make rebounds more severe. People who got Paxlovid and had a rebound infection were not more likely to be admitted to the intensive care unit, need a ventilator to help them breathe, or die.

In a commentary published alongside the study, infectious disease expert Nicola Petrosillo, MD, noted that an unexpected finding was the relationship between vaccination status and rebound.


"Surprisingly, the odds of viral burden rebound in patients receiving [Paxlovid] were significantly reduced in individuals who were not fully vaccinated," he noted.

Petrosillo, who treated some of the earliest COVID cases in Rome, said the takeaway from the study is the importance of continuing to offer antivirals to people at high risk of developing severe COVID.

Sources:

Center for Infectious Disease Research and Policy: "COVID antivirals not tied to rebound or worse outcomes."


The Lancet Infectious Diseases: "Viral burden rebound in hospitalised patients with COVID-19 receiving oral antivirals in Hong Kong: a population-wide retrospective cohort study," "SARS-CoV-2 rebound with and without antivirals."


ContagionLive: "Fighting C Difficile Infection during the COVID-19 Pandemic."




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Moderna will provide free coronavirus vaccines for millions of uninsured and underinsured individuals, the company announced this week, pledging to ensure continued access to the shots once the government ends its public health emergency on May 11.​

“Everyone in the United States will have access to Moderna’s coronavirus vaccine regardless of their ability to pay,” the company said in a statement.

The vaccine maker faced blowback last month after CEO Stephane Bancel told The Wall Street Journal that the company could chargebetween $110 and $130 per dose when it shifts from government contracts for the shots to commercial distribution. That’s more thanquadruple the price the Biden administration paid for a bulk purchase of updated coronavirus boosters last summer, at about $26 per dose.

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Among the critics of Modern’s proposed price hike is Sen. Bernie Sanders (I-Vt.), who called the increase “outrageous” in a letter to Bancel last month. Sanders, the new chairman of the Senate’s health committee, plans to publicly grill Bancel about the pricing proposal in a hearing next month. Sanders said he would underscore the nearly $2 billion in federal funding the company received to develop the vaccine.

Many adults hospitalized for covid-19 continue to experience lingering symptoms, physical limitations and financial challenges months after being discharged, a new study confirms.​

The study, partly funded by the National Institutes of Health and published this week in the journal JAMA Network Open, looked at more than 800 adults who were treated for the virus between August 2020 and July 2021. It found that at the six-month mark, more than 70 percent of the participants reported continuing symptoms, such as coughing, rapid or irregular heartbeat and breathlessness.

Notably, the study also found that many covid long-haulers develop additional health challenges as time goes on. Patients reported higher rates of heart and lung problems six months after coming home from the hospital, highlighting that new symptoms can develop long after the initial infection.

In addition, researchers found that more than half of patients experience financial challenges up to six months after being discharged, with Hispanic and Black participants most likely to be affected. Among this group, about 30 percent said their family finances were moderately, severely, or extremely drained as a result of their hospitalization.

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Other important news​

The National Institutes of Health is launching a clinical trial to test whether an oral antiviral drug developed by Hokkaido University and Shionogi & Co. in Japan can benefit adult patients hospitalized with covid-19, as the number of effective treatments continues to decline as the virus mutates.

China’s recent coronavirus surge may have killed between a million and 1.5 million people, according to new estimates that far exceed Beijing’s official count of 83,150 deaths, the New York Times reports.

Coronavirus survivors are about 58 percent more likely to be diagnosed with new-onset diabetes compared to those who haven’t contracted the virus, according to a new study by Penn State College of Medicine that adds to the growing mountain of evidence that covid patients are at an increased risk for metabolic and cardiovascular problems after infection.

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What makes a pandemic a pandemic?​

When will the Covid pandemic no longer be considered a pandemic? Does it get downgraded to epidemic at some point? JB, Fullerton, California Today’s Q&A is a lesson in the vocabulary of epidemiology, with some assistance from our regular expert on the subject, Katrine Wallaceat University of Illinois at Chicago. “Pandemic, epidemic and endemic are all terms used to describe level of disease spread,” Wallace says. A disease reaches epidemic status when there are more cases of it over time than you’d normally expect in a given location. When there are epidemics in multiple places — potentially impacting large swaths of the global population — that’s a pandemic. ”A pandemic is typically caused by a situation where we have little or no immunity and a rapidly spreading disease,” Wallace says. That could be a new disease (like Covid), or one that has mutated to become more contagious. It could also be a disease that’s made a comeback after a period of control. Endemic diseases are those that stick around. “An epidemic disease level could be downgraded to an endemic level in a population if the number of new cases becomes consistently present, as expected in the population without significant fluctuations,” Wallace says. The real question, then, is whether — or when — Covid will be considered endemic. Though fewer people are getting sick than a year ago, there’s still a significant amount of Covid transmission. The virus also hasn’t established a clear seasonal pattern, like we see with influenza. “These things make it difficult to know exactly what that ‘expected’ level of disease will eventually be,” Wallace says. “Also, the risk of (sometimes serious) post-viral complications exists with Covid, and we don’t have that risk with other respiratory viruses.” When Covid establishes a more predictable rhythm, health officials can better prepare for outbreaks because they’ll know when to distribute vaccinations and take other measures. Recently President Joe Biden announced we’re moving toward a single annual Covid booster, though we’re still getting a sense of whether that matches the behavior of the disease. “It definitely remains to be seen what additional tricks the virus has in store for us,” Wallace says. — Kristen V. Brown "

 

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Research identifies potential long COVID racial disparities
Published February 17, 2023 | Originally published on MedicalXpress Breaking News-and-Events

Black and Hispanic Americans appear to experience more symptoms and health problems related to long COVID, a lay term that captures an array of symptoms and health problems, than white people, but are not as likely to be diagnosed with the condition, according to new research. The findings—from two different studies by NIH's Researching COVID to Enhance Recovery (RECOVER) Initiative—add to a growing body of research aimed to better understand the complex symptoms and other issues associated with long COVID that millions have experienced.

"This new evidence suggests that there may be important differences in how long COVID manifests in different racial and ethnic groups," said Mitchell S.V. Elkind, M.D., a professor of neurology and epidemiology at Columbia University, New York City, and chief clinical science officer for the American Heart Association. "However, further research is needed to better understand the mechanisms for these differences in symptoms and access to care, and also if diagnostic codes assigned by clinicians may play a role."

In one analysis, published in the Journal of General Internal Medicine, researchers looked at the health records of 62,339 adults who received a positive COVID-19 test at one of five academic health centers in New York City, all between March 2020 and October 2021. They tracked the patients' health for one to six months after the positive test and compared the findings to 247,881 adults who never had COVID.

Among 13,106 adults who had severe COVID that required hospital care, the researchers found Black and Hispanic adults were disproportionately represented. Of those who had these severe cases, for example, 1 in 4 were Black adults, 1 in 4 were Hispanic adults, and 1 in 7 were white adults.

In the months following infection, Black adults with severe disease were more likely than white adults to be diagnosed with diabetes and experience headaches, chest pain and joint pain, but less likely to have sleep disorders, cognitive problems, or fatigue. Similarly, Hispanic adults who required hospital care were more likely than white adults to have headaches, shortness of breath, joint paint, and chest pain, but less likely to have sleep disorders, cognitive problems, or fatigue.

Similar patterns emerged among people with mild to moderate disease. Among patients who were not hospitalized, Black adults were more likely to have blood clots in their lungs, chest pain, joint pain, anemia, or be malnourished. Hispanic adults were more likely than white adults to have dementia, headaches, anemia, chest pain, and diabetes. Conversely, white adults were most likely to have conditions such as cognitive impairment (sometimes referred to as "brain fog") and fatigue.

The researchers also found that in comparison to people who did not have COVID, those who did were more likely to experience conditions affecting their nervous system, respiratory function, and circulation, and more likely to feel fatigued or have joint pain.

"It's not clear what's behind these symptom variations," said Dhruv Khullar, M.D., a study author and physician and assistant professor of health policy and economics at Weill Cornell Medicine, New York City. "We hope this work draws attention to possible differences across racial and ethnic groups, stimulates research into the potential mechanisms, and sparks discussion among patients, clinicians, and policymakers."

In the second study, which published in BMC Medicine, researchers analyzed data from the electronic health records of 33,782 adults and children who received a diagnosis for long COVID between October 2021 and May 2022 at one of 34 U.S. medical centers. All had been given a diagnosis—Post COVID-19 condition, unspecified—the code for the condition first introduced in U.S. health care systems in October 2021.

In studying the profile of these patients and their symptoms, the researchers found multiple patterns. Among the more striking: most of the patients were white, female, non-Hispanic, and likely to live in areas with low poverty and greater access to health care.

Given what researchers already knew about the disproportionate impact of COVID on people of color and economically disadvantaged populations, the findings stood out. Emily Pfaff, Ph.D., a study author and assistant professor in the Division of Endocrinology and Metabolism at the University of North Carolina, Chapel Hill, said the pattern suggested that not all patients who have long COVID are being diagnosed.

The reasons vary. In addition to long-documented health disparities based on race and other factors, she said, women are more likely than men to seek health care in general, and patients with the time and resources to access health care tend to be disproportionally represented in clinical data.

"You can see all the different ways these diagnostic codes can provide insight, but they can also skew the whole story," Pfaff said.

Still, she added, the insights help. She and her team found, for example, that most of the patients with long COVID had just mild to moderate, not severe, symptoms of acute infection. They also discovered that long-term symptoms could be grouped into common clusters—cardiopulmonary, neurological, gastrointestinal, and coexisting conditions—as well as by age.

Children and teens were more likely to experience gastrointestinal and upper respiratory problems, including stomach aches and coughing. Adults ages 21-45 commonly experienced neurological problems, such as brain fog and fatigue. Adults ages 66 and older were more likely to have coexisting conditions, such as heart problems and diabetes, which the authors suspect is more likely present because of age than long COVID.

The authors of both papers said additional studies are needed to confirm and further categorize these trends.

"This research contributes to our understanding of symptom clusters in long COVID that may be differentiated by race, ethnicity, and influenced by social determinants of health," said Gary H. Gibbons, M.D., director of the National Heart, Lung, and Blood Institute. "It also provides vital insights into the utility, as well as the constraints, of the diagnostic code now in use for long COVID."

This article was originally published on MedicalXpress Breaking News-and-Events.

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[missy]

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Do masks work?​

KATELYN JETELINA AND KRISTEN PANTHAGANI, MD, PHD FEB 21

​

On my way back from Turkey, and there’s nothing quite like international travel to help put things into perspective. There are much bigger problems in this world right now than the mask debate.
Still, it would be tragic if people left the emergency thinking one of two extremes: “masks don’t work” or “any mask works.” Another pandemic will come, and we will need to be better and smarter. Hell, every winter, we could be smarter.
This post is to provide a sober perspective on the “story arc” of the science around masks—an attempt to communicate important nuances and provide clarity to a story that is not yet done.

The question​

Everyone wants a one word answer to this question: Do masks work? But these three words strung together beg several loaded questions: What does “work” mean? What kind of mask? During what period of transmission? During what disease? In what social context?
All these questions and the answers are getting jumbled together for the public. This may be intentional (to make a point) or unintentional because people really want a simple answer to a complicated question.
Science has been moving at a lightning speed, and we’ve been discovering answers as we go.

Where did we start?​

At the beginning of the pandemic, public health faced a decision: Do we recommend people wear masks? It’s hard to remember how limited information was at the time:

• We had no data on masks and SARS-CoV-2. We relied on data for other viruses—influenza, and a handful of studies from SARS and MERS outbreaks. Some of these found no benefit, while others did find benefit.
• We had no evidence—yet—of asymptomatic transmission. So recommendations said asymptomatic individuals should not wear masks, while people with COVID symptoms or those at high risk of exposure (health care workers) should wear masks.
• We had critical shortage of PPE for healthcare.

Then, as the pandemic progressed, a few things changed:

• We learned that even “healthy” people could transmit the virus (i.e., asymptomatic or pre-symptomatic transmission).
• COVID spread like wildfire. Cases became much more common. Thus, those at risk of exposure eventually became “everyone.”
• PPE supply was growing.
• Scientists indicated concern about aerosol transmission.

COVID wasn’t going away. Social distancing indefinitely was not a viable option, and vaccines were months (years?) out. Masks represented a way to slow the spread as people started to resume (semi) normal lives.
People started wearing masks, countries and spaces started mandating, and scientists started studying specific questions.

Do masks work against SARS-CoV-2 in a lab?​

The first scientific question that needed to be answered was: For the mask wearer, can masks physically stop droplets and aerosols coming in or going out?
This is a physics question. To answer it, scientists placed test subjects in very tightly controlled environments with equipment that precisely measured the number of particles that were released or inhaled with whispering, coughing, laughing, etc., while wearing different masks. The lab set up looked like something below:

​

Multiple studies showed that masks help protect the wearer against SARS-CoV-2 (i.e., reduce the number of particles inhaled by someone).
Also, masks reduced the number of particles emitted by a person. One study found that “surgical masks and KN95 reduce outward particle emission rates by 90% and 74%.”
The details mattered, though:

• Filter (i.e. type of mask)
• Size of infectious disease particles
• Fit

For example, surgical masks work best against droplets. They can have aerosol impact but leak a lot. Cloth masks work for droplets too, but really don’t do much for aerosols. N95s are best, curbing spread via droplets and aerosols.
We still have a lot of unanswered questions, like: If surgical masks leak, can they still help reduce the viral load, and thus lead to less severe disease?

Do masks work on an individual level?​

If masks work in a lab, they must prevent infections among individuals in the real world, right? Not necessarily. Tightly controlled environments are different from the real world. We’ve seen this in several studies during the pandemic:

• People don’t wear them, even if recommended.
• People wear them at different frequencies. The more someone wears a mask, the less likely they are to get an infection. (And, vice versa).
• People adapt masks. Using two surgical masks worked better than one mask. Tying the strings on a surgical mask increased effectiveness.

Do masks work on a population level?​

If masks work in a lab and sometimes on individuals, then if hundreds/thousands of people wear them perfectly and imperfectly at one time, will they reduce transmission during a pandemic?
Viral transmission in a population is exponential. Even if masks only reduce the risk of transmission for each individual by a small fraction, when a community masks, those small effects compound exponentially across a population, making a big dent in cases. Just like compounding interest—a small change in the percentage makes a big difference down the road.

​

Image by Kristen Panthagani
But how much do masks reduce transmission? Studies have attempted to answer this:

• Mask wearing corresponded to a 19% decrease in the R(0) in one study. In other words, masks helped reduce transmission.
• In Bangladesh villages were randomized to be provided free masks. Villages that got the intervention had more than double the mask usage than villages that didn’t (13% vs. 42%). This resulted in a 9% reduction in cases in the mask-wearing villages.
• In the U.S., a 10% increase in mask wearing was associated with greater control of transmission.
• In Germany, mask mandates reduced spread by 45%.

These studies found a huge range (9%-45%) and reflect vastly different settings and cultures. We need more studies. Many unanswered questions also remain: At what R(0) do masks not help? How many people have to wear them well to help reduce transmission (i.e. compliance)? How does social pressure or fear impact usage?

What are the policy options?​

If masks help the individual and reduce transmission in the population, then what is the best “policy” during a pandemic?
Public health ethics suggests interventions must be designed around certain criteria: effectiveness (i.e., masks will achieve the public health goal), necessity (i.e., timing during a pandemic), proportionality (do benefits outweigh risks and moral norms), least infringement (least restrictive and least intrusive), impartiality, etc. Who carries the burden and when?
As the public health ethics “Intervention Ladder” outlines, we have many options ranging from least to most intrusive.

​

Image designed by Katelyn Jetelina, Framework from Bernheim RG et al. Essentials Of Public Health Ethics. 1st ed. Essential Public Health. Jones & Bartlett Learning; 2013
The effectiveness of some, but not all, of these strategies was tested throughout the pandemic:

• Enable choice: Recommend masks. One randomized study in Denmark found this was weak and didn’t impact infections.
• Guide choice by incentives: Hand masks out for free. This worked in Bangladesh.
• Restrict choice: Mandate in certain spaces. Mandating masks in schools was shown to be highly effective in Boston. Other studies show effectiveness in healthcare settings (here, here, here).
• Eliminate choice: Mandate everywhere. Some studies showed that mandates worked, especially in the early days of the pandemic (here, here, here, here). Other studies showed considerable weak evidence of mandates and subsequent wearing (here, here).

We have more work to do to understand what does and does not work when weighing social, moral, cultural, and epidemiological factors during an emergency.

Then, the Cochrane review was published and took social media by storm​

Cochrane reviews are meta-analyses; they aren’t new studies, but rather attempts to pool studies to find an overall “answer.” Importantly, there have to be enough studies asking the same question, with the same intervention, and measuring the same outcome for this to be useful. This is why we don’t have meta-analyses for every scientific question. If done correctly, Cochrane reviews are incredibly powerful and typically respected in the scientific field.
This specific review included studies on non-pharmaceutical interventions, including masks. If we just look at the mask studies, the Cochrane review included 12 studies. But the details matter, as these studies:

• Only included randomized control trials (RCTs). This is typical for meta-analyses as RCTs are the “gold standard” for scientific questions. But these RCTs had a number of problems and, given the limited number of RCTs on COVID-19, do not represent the totality of evidence (i.e., see all studies above).
• Combined different viruses. When a virus is less contagious, an effect is harder to detect. Many of the RCTs evaluated influenza, which is far less contagious than COVID-19. This means that if we combine them, the impact of masks may be underestimated. (Another scientist, separate from this review, removed the flu studies and reran the meta-analysis. He found masks protected against SARS-CoV-2.)

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Source: @gidmk

• Combined settings. Studies ranged from suburban schools to hospital wards in high‐income countries, crowded inner city settings in low‐income countries, and an immigrant neighborhood in a high‐income country.
• Only asked one question. Does wearing a mask protect me? This ignores other important questions.

The authors of the review ultimately concluded there was no evidence of masks making a difference. On top of the limitations described above, keep in mind that “no evidence of a difference” is different from “evidence of no difference.” Don’t use an inconclusive Cochrane review to reject the value of masks, or any other intervention for that matter.

Where are we going?​

All of the aforementioned studies have limitations. Every single one. No study is perfect. This is normal. Because of that, we have holes in our knowledge and, as we fill them, evidence will continue to evolve.
We now have the time, data, and energy (maybe?) to understand why, where, and how well masks work, so we can be better and smarter next time.

Bottom line​

The scientific “arc” of mask discovery is ongoing. Science is always evolving. Do not let anyone convince you of a one word answer to the question: Do masks work? It depends.


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[missy]

https://www.washingtonpost.com/opinions/2023/02/16/cochrane-study-masks-covid-pandemic/

Snip…
“ The science hasn’t changed: Well-fitting N95, KN95 or KF94 masks protect their wearers against covid and other respiratory diseases. John and others who are elderly, immunocompromised or otherwise want to avoid covid should continue wearing them in indoor crowded spaces.”

 

[missy]

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Higher Dose of Ivermectin, and for Longer, Still No Help Against COVID​

— Losing streak continues for controversial antiparasitic​

by Ed Susman, Contributing Writer, MedPage Today February 23, 2023


SEATTLE -- A higher dose of ivermectin given for a longer duration still failed to offer any benefit in mild to moderate COVID-19, data from a large randomized U.S. trial showed.
In the ACTIV-6 trial of more than 1,200 largely vaccinated outpatients, the median time to sustained recovery was an identical 11 days with either 6 days of ivermectin at a targeted daily dose of 600 μg/kg or placebo (P=0.6, reported Susanna Naggie, MD, MHS, of the Duke University School of Medicine in Durham, North Carolina.

And no difference was seen for the secondary endpoint of hospitalization, urgent or emergency department care visits, or death, at 5.7% with ivermectin compared with 6% with placebo (P=0.53), according to findings detailed at the Conference on Retroviruses and Opportunistic Infectionsopens in a new tab or window annual meeting.
"These findings do not support the use of ivermectin in outpatients with COVID-19," said Naggie.
One death and four hospitalizations occurred in the ivermectin group versus no deaths and two hospitalizations in the placebo group. Overall, adverse events (AEs) were uncommon in both arms.
Results of the trial were published simultaneously in JAMAopens in a new tab or window.
In an accompanying editor's noteopens in a new tab or window, JAMA Editor-in-Chief Kirsten Bibbins-Domingo, MD, PhD, and Preeti Malani, MD, MSJ, the journal's deputy editor, pointed out that a 2022 Cochrane meta-analysisopens in a new tab or window of 11 eligible studies showed no benefit with ivermectin for COVID-19, and that three randomized trials since then have all reached the same conclusion.
Yet the negative trials failed to silence proponents of the controversial antiparasitic, with criticism often lobbed at the dosage selected or duration of treatment used in trials.

"Today JAMA publishes a new trial of ivermectin treatment for mild to moderate COVID-19 that addresses the possibility that the existing literature may have missed the efficacy of ivermectin because the previously tested dose -- approximately 400 μg/kg daily for 3 daysopens in a new tab or window -- was insufficient," they wrote. "At a higher treatment dose -- 600 μg/kg daily and longer treatment duration of 6 days, Naggie and colleagues again conclude that ivermectin is not beneficial for the treatment of COVID-19."
Although AEs were not significantly different between the ivermectin and placebo groups, Bibbins-Domingo and Malani cautioned that ivermectin treatment for COVID-19 could still be harmful, particularly if it delays the use of other proven interventions.
Naggie's group said a strength of the current study was that 83.5% had received at least two doses of vaccine, "thus representing a highly relevant study population," noting that past ivermectin trials had excluded vaccinated participants. No different effect by vaccination status was seen for the primary endpoint of time to sustained recovery, which was defined as at least 3 consecutive days without symptoms.

In an accompanying editorialopens in a new tab or window, Alex John London, PhD, of Carnegie Mellon University in Pittsburgh, and Christopher Seymour, MD, of the University of Pittsburgh, highlighted that despite all the evidence against it thus far, ivermectin studies continued, perhaps at the expense of other more fruitful endeavors.
"Decisions about what investigations to undertake must be responsive to the relative social value of continuing to reduce uncertainty around one intervention, and stakeholders must consider whether scarce time, resources, and participant effort could be better invested examining other questions," they wrote.
The current arm of the ACTIV-6 platform trial recruited from February 2022 to July 2022 at 93 sites in the U.S., and ultimately included 1,206 participants with confirmed COVID-19. Participants were randomized to ivermectin at a daily targeted maximum dose of 600 μg/kg for 6 days (n=602) or placebo (n=604).
Participants had a median age of 48 years, about 60% were women, and three-fourths were white. About a quarter of the individuals had hypertension, 13-16% had asthma, and 9% had diabetes.

Participants had to have at least two COVID-19 symptoms for no longer than 7 days before enrollment. From symptom onset, the median time to enrollment was 3 and 60% received treatment within 5 days. Exclusion criteria included hospitalization, ivermectin use within the past 14 days, and known allergy or contraindication to the study drug.
Concurrent use of standard therapies for COVID-19 was allowed. Here, 2.5% of patients on the ivermectin arm received nirmatrelvir-ritonavir (Paxlovid) versus 4.3% of placebo patients. Other treatments included the use of monoclonal antibodies in 4.2% and 3.6%, respectively, and molnupiravir in 0.2% and 0.8%.

• 
  
  Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.
  "

 

[missy]

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Today's ACIP meeting Cliff notes​

KATELYN JETELINA FEB 24

This week ACIP—CDC’s external advisory group of scientists—met to discuss all vaccines. This was part of their regularly scheduled meeting (i.e., these happen with or without a pandemic). This morning they focused on COVID-19 vaccines.

This discussion was much anticipated because it follows the VRBPAC meeting in which the FDA discussed the future of boosters in the U.S. We had a lot of unanswered questions following that meeting.

Overall, I was pleasantly surprised on the range and depth of data presented today. There were a lot of golden nuggets.

Here are your Cliff notes.

Vaccines continue to be safe​

Reassuring data on the safety of COVID-19 vaccines was presented. I won’t go through all of it because there was a lot, but I will highlight one thing: temporal scan results. I hadn’t seen this before, and it’s pretty cool.

The CDC looks at real-time adverse events and maps them over time. They have a system that finds abnormal clusters. This helps because random events happen all the time. These clusters are designed to be very sensitive; they cast a wide net to find the smallest of signals. This comes with a trade-off, though—we may see things that happen by chance alone.

This is what may have happened with the stroke signal found after bivalent vaccine among those over 65 years. They saw a cluster, but then the cluster receded. The other monitoring systems didn’t find anything.

​

This is just another example of how many people and how much data go into ensuring these vaccines are safe.

Vast majority of COVID hospitalizations are “for” COVID-19, still​

Critical data on hospitalizations “for” (primary reason) and “with” (coincidental) COVID-19, by age and over time and chronic conditions, were presented. I also hadn’t seen this data before. The vast majority of COVID-19 hospitalizations (80-90%) for those under age 5 years or over 50 years are “for” COVID-19. This hasn’t changed over time. So, yes, COVID-19 is still a problem.

​

(Slide from CDC)
Among adults hospitalized for COVID-19, 96% had at least one underlying condition. Among kids hospitalized, 49% had no underlying health conditions. Among those with underlying health conditions, the driving force differed by age: prematurity for those under 2 years and asthma for those 2-17 years old.

Risk-benefit for adolescents still favorable, but getting tighter​

There has been a LOT of chatter around whether the benefits of COVID-19 vaccines still outweigh the risks for adolescents, in whom myocarditis is a rare but real risk. The CDC ran a risk-benefit analysis on bivalent boosters. I’ve been waiting on this for a long time. It didn’t disappoint.

Per 1 million bivalent vaccines given to 12-17 year olds:

• Benefits: 17-75 hospitalizations “for” COVID-19; 5-22 ICU admissions “for” COVID-19; and 0-1 deaths prevented
• Risks: 0 cases of myocarditis

So benefits still outweigh risks, but it’s getting tighter compared to the primary series.

​

(CDC slide)
Look at the small print in the slide above. No data is perfect, so the “true” number of myocarditis cases could range from 0-122 (males=62 and females=60). This means 122 myocarditis events per 1 million doses is a worst case scenario. This means there could be future scenarios in which risks outweigh benefits for adolescents.

BUT, keep in mind two things:

1. These data are based on a snapshot in time. Specifically, the numbers above are based on what we saw this winter, which was a relatively quiet time for adolescents and COVID-19. If we see a future surge, on the other hand, the benefits would immediately increase. Increased time between doses also increases benefits. We can see that in the slide below.
   

   ​

   (CDC slide)
2. The benefits described above are limited to severe disease; other benefits may include prevented infections, long COVID-19, days of work missed, reduced transmission, etc.

The CDC conducted risk-benefit analyses for all other ages, too. There is no question that vaccines still greatly outweigh risks for adults, especially for those over 65 years.

​

(CDC slide)

Everyone gets one shot per year​

Older adults who were vaccinated in September are coming up on 6 months post-vaccine. Do they need another vaccine? Or do they wait until fall like everyone else?

Data on protection against infection by age was presented. It’s clear that this protection wanes and more so among older adults.

​

(Slide from CDC)
But bivalent vaccines continue to be very protective against hospitalizations. (There has not been enough time to see waning).

​

CDC further clarified the goal of the vaccine program: Prevention of severe disease.

Because of this, ACIP decided there was “insufficient evidence” to suggest older adults need another bivalent dose at this time. They did say this could change in the future based on three things:

1. Hospitalization rates among those who got the bivalent start to increase
2. Other signals of waning vaccine effectiveness of bivalent vaccines
3. SARS-CoV-2 significantly mutates

They did a similar evaluation for immunocompromised. And came to the same conclusion.

So, as of now, everyone will be eligible for one shot a year. We will need to be flexible, as this may change. Is this the right call? Time will tell.

Bottom line​

Today’s meeting was super helpful. But we have to find a way to get data and analyze it more quickly in the U.S. It will help combat misinformation, improve confidence in vaccines, and improve confidence in public health overall. This should be our number one priority.

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