‘Game Changing’ Study Finds Cause of Long Covid Brain Fog

By Pat Anson, PNN Editor

Inflamed and leaky blood vessels in the human brain appear to be the cause of brain fog and other cognitive issues in patients with Long Covid, according to a groundbreaking study by a team of Irish researchers.

The discovery that a viral infection may cause cognitive decline could help explain why memory loss, confusion and trouble concentrating is common in patients with other chronic illnesses, such as fibromyalgia, multiple sclerosis and chronic fatigue syndrome (ME/CFS).

Scientists at Trinity College Dublin and FutureNeuro used a specialized MRI to compare the brains of Long Covid patients with brain fog to those without brain fog.

The MRI images show how Long Covid can affect the brain’s delicate network of blood vessels. Patients with brain fog (right column) have significantly more inflammation and blood vessel leakage than those without brain fog (left column).

Patients with brain fog also had more elevated levels of glial fibrillary acidic protein (GFAP) in their blood, which is a sign of cerebrovascular damage often found in patients with repetitive head trauma.

The images and findings are published in the journal Nature Neuroscience.

“For the first time, we have been able to show that leaky blood vessels in the human brain, in tandem with a hyperactive immune system, may be the key drivers of brain fog associated with Long COVID,” said lead author Matthew Campbell, PhD, a Professor in Genetics and Head of Genetics at Trinity College, and Principal Investigator at FutureNeuro. 

“The concept that many other viral infections that lead to post-viral syndromes might drive blood vessel leakage in the brain is potentially game changing and is under active investigation by the team.” 

NATURE NEUROSCIENCE

About 10% of the people infected with the SARS-CoV2 virus develop Long Covid, a broad range of conditions that causes fatigue, shortness of breath, and muscle and joint pain. About half of Long Covid patients also report brain fog or some lingering neurological issue. 

“The findings will now likely change the landscape of how we understand and treat post-viral neurological conditions. It also confirms that the neurological symptoms of Long Covid are measurable with real and demonstrable metabolic and vascular changes in the brain,” said co-author Colin Doherty, Professor of Neurology and Head of the School of Medicine at Trinity, and Principal Investigator at FutureNeuro. 

In recent years, research has found that multiple sclerosis, lupus and other autoimmune conditions are triggered by the Epstein-Barr virus. The exact mechanism is unclear and proving there is a direct link between viral infections and brain fog has been challenging – until now.   

“Our findings have now set the stage for further studies examining the molecular events that lead to post-viral fatigue and brain fog. Without doubt, similar mechanisms are at play across many disparate types of viral infection and we are now tantalisingly close to understanding how and why they cause neurological dysfunction in patients,” said first author Chris Greene, PhD, a research fellow in the School of Genetics and Microbiology at Trinity.

The study was funded by Science Foundation Ireland, the European Research Council and FutureNeuro, a research center for chronic and rare neurological diseases.

DEA Urged to End ‘Red Flag’ Policy for Pharmacies

By Pat Anson, PNN Editor

A coalition of telehealth companies is urging the U.S. Drug Enforcement Administration to stop telling pharmacies to be careful about filling prescriptions for opioids and other controlled substances that originate from out-of-state.

The DEA’s “red flag” policy has had a chilling effect on doctors and patients nationwide, including those that use telehealth services. Many pain patients have found that pharmacies won’t fill opioid prescriptions written by doctors that are not near them geographically.  

In an open letter to the DEA, the American Telemedicine Association and a handful of telehealth providers said “clearer green lights” were needed from the DEA on how to safely dispense controlled substances, not more red flags.

“The DEA should provide explicit guidance to the pharmacy community that geography of a prescriber in relation to the patient or the pharmacy should not be a ‘red flag’ when a prescription is a result of a telehealth visit,” the letter states. “The distance of a telehealth prescriber from the patient alone should not give a pharmacist a signal that the prescription may be illegitimate.”

The DEA relaxed telehealth rules three years ago at the start of the Covid-19 pandemic, to allow for opioids, stimulants, sedatives and other controlled substances to be prescribed remotely via telehealth. Those temporary rules have been extended until the end of 2024, to give the DEA more time to develop permanent ones to govern telehealth.

Many pharmacies haven’t gotten the message. In a recent PNN survey, over 90% of pain patients with an opioid prescription said they had trouble getting a pharmacy to dispense their medication. Drug shortages are the primary cause, but so is the fear of some pharmacists that they could get in trouble or even lose their jobs if they filled a prescription deemed suspicious because it comes from out-of-state.

“In conversations with the pharmacy community and in our experience as prescribers, we have determined many pharmacies and pharmacists are currently considering geography as a ‘red flag.’ While red flags are not defined in statute or regulations or other official guidance, in the wake of the overprescribing and overdispensing contributing to the opioid epidemic, pharmacists have been directed to do so as a part of their corresponding responsibility, or due diligence to ensure that prescriptions are legitimate,” the letter from the telehealth coalition states.

‘An Unusual Distance’

Federal laws and regulations may not clearly define what a red flag is, but the onus is clearly put on pharmacies to catch them:

“[A] pharmacist or pharmacy may not dispense a prescription in the face of a red flag (i.e., a circumstance that does or should raise a reasonable suspicion as to the validity of a prescription) unless he or it takes steps to resolve the red flag and ensure that the prescription is valid.”

Under a 2022 opioid litigation settlement, drug distributors and big chain pharmacies agreed to tightly limit the supply of opioids and be on the lookout for suspicious orders. That includes patients with prescriptions for “highly diverted controlled substances” written by doctors from a zip code 50 miles or more from a pharmacy. Pharmacies with a high volume of those prescriptions risk having their drug supplies further restricted or cutoff.

DEA investigators and federal prosecutors have long targeted doctors and pharmacies that have out of state patients. In 2021, for example, DEA suspended the license of a Florida pharmacy that “repeatedly ignored obvious red flags of abuse or diversion,” including a high number of patients who traveled “an unusual distance” to obtain their prescriptions.

Contrary to popular belief, opioid diversion is rare. The DEA estimates that less than one percent of oxycodone (0.3%) and hydrocodone (0.42%) medications are lost, stolen or diverted.

Another example of a provider being red-flagged came in 2022, when DEA suspended the controlled substance license of Dr. David Bockoff, a California physician who treated many chronically ill patients from out of state who couldn’t find local providers.

Within days of Bockoff’s suspension, one of his patients and his wife died by suicide at their home in Georgia. A few weeks later, another patient died at her home in Arizona, apparently from complications caused by opioid withdrawal. Neither of those patients were using telehealth to see Dr. Bockoff, but their deaths highlight how red flags and heavy-handed oversight of medical providers can have serious consequences.    

“DEA must use this opportunity to make clear what their expectations are for pharmacists in filling telehealth prescriptions of controlled substances,” the letter from the telehealth coalition warns. “If DEA simply adds recordkeeping, reporting, or data requirements to the overwhelming workload pharmacies and pharmacists already face, access issues will only be exacerbated.”

Ageism: A Wake-Up Call for Baby Boomers

By Judith Graham, KFF Health News

The covid-19 pandemic would be a wake-up call for America, advocates for the elderly predicted: incontrovertible proof that the nation wasn’t doing enough to care for vulnerable older adults.

The death toll was shocking, as were reports of chaos in nursing homes and seniors suffering from isolation, depression, untreated illness, and neglect. Around 900,000 older adults have died of covid-19 to date, accounting for 3 of every 4 Americans who have perished in the pandemic.

But decisive actions that advocates had hoped for haven’t materialized. Today, most people — and government officials — appear to accept covid as a part of ordinary life.

Many seniors at high risk aren’t getting antiviral therapies for covid, and most older adults in nursing homes aren’t getting updated vaccines. Efforts to strengthen care quality in nursing homes and assisted living centers have stalled amid debate over costs and the availability of staff. And only a small percentage of people are masking or taking other precautions in public despite a new wave of covid, flu, and respiratory syncytial virus infections hospitalizing and killing seniors.

In the last week of 2023 and the first two weeks of 2024 alone, 4,810 people 65 and older lost their lives to covid — a group that would fill more than 10 large airliners — according to data provided by the CDC. But the alarm that would attend plane crashes is notably absent. (During the same period, the flu killed an additional 1,201 seniors, and RSV killed 126.)

“It boggles my mind that there isn’t more outrage,” said Alice Bonner, 66, senior adviser for aging at the Institute for Healthcare Improvement. “I’m at the point where I want to say, ‘What the heck? Why aren’t people responding and doing more for older adults?’”

It’s a good question. Do we simply not care?

I put this big-picture question, which rarely gets asked amid debates over budgets and policies, to health care professionals, researchers, and policymakers who are older themselves and have spent many years working in the aging field. Here are some of their responses.

Pandemic Made Ageism Worse

Prejudice against older adults is nothing new, but “it feels more intense, more hostile” now than previously, said Karl Pillemer, 69, a professor of psychology and gerontology at Cornell University.

“I think the pandemic helped reinforce images of older people as sick, frail, and isolated — as people who aren’t like the rest of us,” he said. “And human nature being what it is, we tend to like people who are similar to us and be less well disposed to ‘the others.’”

“A lot of us felt isolated and threatened during the pandemic. It made us sit there and think, ‘What I really care about is protecting myself, my wife, my brother, my kids, and screw everybody else,’” said W. Andrew Achenbaum, 76, the author of nine books on aging and a professor emeritus at Texas Medical Center in Houston.

In an environment of “us against them,” where everybody wants to blame somebody, Achenbaum continued, “who’s expendable? Older people who aren’t seen as productive, who consume resources believed to be in short supply. It’s really hard to give old people their due when you’re terrified about your own existence.”

Although covid continues to circulate, disproportionately affecting older adults, “people now think the crisis is over, and we have a deep desire to return to normal,” said Edwin Walker, 67, who leads the Administration on Aging at the Department of Health and Human Services. He spoke as an individual, not a government representative.

The upshot is “we didn’t learn the lessons we should have,” and the ageism that surfaced during the pandemic hasn’t abated, he observed.

“Everyone loves their own parents. But as a society, we don’t value older adults or the people who care for them,” said Robert Kramer, 74, co-founder and strategic adviser at the National Investment Center for Seniors Housing & Care.

“The message to older adults is: ‘Your time has passed, give up your seat at the table, stop consuming resources, fall in line.’”

— Anne Montgomery, Health Policy Expert

Kramer thinks boomers are reaping what they have sown. “We have chased youth and glorified youth. When you spend billions of dollars trying to stay young, look young, act young, you build in an automatic fear and prejudice of the opposite.”

Combine the fear of diminishment, decline, and death that can accompany growing older, with the trauma and fear that arose during the pandemic.

“I think covid has pushed us back in whatever progress we were making in addressing the needs of our rapidly aging society. It has further stigmatized aging,” said John Rowe, 79, professor of health policy and aging at Columbia University’s Mailman School of Public Health.

“The message to older adults is: ‘Your time has passed, give up your seat at the table, stop consuming resources, fall in line,’” said Anne Montgomery, 65, a health policy expert at the National Committee to Preserve Social Security and Medicare. She believes, however, that baby boomers can “rewrite and flip that script if we want to and if we work to change systems that embody the values of a deeply ageist society.”

Integration, Not Separation, Is Needed

The best way to overcome stigma is “to get to know the people you are stigmatizing,” said G. Allen Power, 70, a geriatrician and the chair in aging and dementia innovation at the Schlegel-University of Waterloo Research Institute for Aging in Canada. “But we separate ourselves from older people so we don’t have to think about our own aging and our own mortality.”

The solution: “We have to find ways to better integrate older adults in the community as opposed to moving them to campuses where they are apart from the rest of us,” Power said. “We need to stop seeing older people only through the lens of what services they might need and think instead of all they have to offer society.”

That point is a core precept of the National Academy of Medicine’s 2022 report Global Roadmap for Healthy Longevity. Older people are a “natural resource” who “make substantial contributions to their families and communities,” the report’s authors write in introducing their findings.

Those contributions include financial support to families, caregiving assistance, volunteering, and ongoing participation in the workforce, among other things.

“When older people thrive, all people thrive,” the report concludes.

That’s a message Kramer conveys in classes he teaches at the University of Southern California, Cornell, and other institutions.

“You have far more at stake in changing the way we approach aging than I do,” he tells his students. “You are far more likely, statistically, to live past 100 than I am. If you don’t change society’s attitudes about aging, you will be condemned to lead the last third of your life in social, economic, and cultural irrelevance.”

As for himself and the baby boom generation, Kramer thinks it’s “too late” to effect the meaningful changes he hopes the future will bring.

“I suspect things for people in my generation could get a lot worse in the years ahead,” Pillemer said. “People are greatly underestimating what the cost of caring for the older population is going to be over the next 10 to 20 years, and I think that’s going to cause increased conflict.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Long Covid Linked to Chronic Pain Conditions

By Pat Anson, PNN Editor

People with chronic pain conditions such as fibromyalgia, chronic fatigue, migraine and irritable bowel syndrome are significantly more likely to have symptoms of Long Covid after a COVID-19 infection, according to a large new analysis.

Researchers at the University of Michigan analyzed electronic health records of over two million Americans and found that the risk of having Long Covid symptoms was higher in people with a chronic overlapping pain condition (COPC).  

Over half the patients (58.6%) with a COPC and a diagnosis of COVID-19 had symptoms of Long COVID, compared to only a third (33.6%) of those without a COPC.

“We hypothesized we’d see an increase in pain and fatigue because it’s something we’ve seen in the past with other infectious diseases, like the SARS outbreak in 2002,” said lead author Rachel Bergmans, PhD, a Research Assistant Professor at U-M’s Department of Anesthesiology, Chronic Pain and Fatigue Research Center. “A big predictor of future pain is having had pain in the past.”

Findings from the retrospective cohort study, published in the journal Pain, do not establish a definitive cause that links chronic pain with Long Covid – only an association.

It’s a bit of a chicken-and-egg situation. Many of the symptoms of Long Covid mirror those of COPCs – such as brain fog, chronic fatigue, headache and body pain – so it’s not clear which condition developed first. Interestingly, Long Covid symptoms were found in 24% of patients with a COPC who were not diagnosed with COVID-19.  

That finding could be explained by a relatively new concept in pain research called neuroplasticity or nociplastic pain – chronic pain that lingers and becomes heightened in the brain and central nervous system (CNS) long after the initial injury heals. 

“With nociplastic pain, some people have what you might call a pain setting turned up in their central nervous system. There’s evidence showing that infections, trauma, and stress can be a trigger for nociplastic pain features and related symptoms,” said Bergmans.

Nociplastic pain could also explain the cognitive dysfunction and other symptoms caused by Long Covid – known technically as post-acute sequelae of SARS-CoV-2 infection (PASC). The basket of symptoms now collectively known as Long Covid may have existed before COVID-19 even came along. In 2022, the CDC estimated that 18 million American adults had Long Covid.

“The onset of long COVID features was relatively common regardless of acute COVID exposure. In addition, those with pre-existing COPCs had an increased risk of being diagnosed with long COVID features. These findings reinforce the likelihood that nociplastic pain is a key mechanism in long COVID and can inform precision medicine therapies that avoid the pitfalls of viewing long COVID exclusively in the framework of infectious disease,” researchers concluded.

“For clinicians who treat people with long COVID, it may be helpful to review the medical record and see whether someone had a pre-existing COPC diagnosis before long COVID onset.”

Bergmans and all of her co-authors are either consultants or employees of Tonix Pharmaceuticals, a company that is developing new non-opioid treatments for fibromyalgia.

New Covid Variant Leading Surge in Respiratory Illness

By Julie Appleby, KFF Health News

It’s winter, that cozy season that brings crackling fireplaces, indoor gatherings — and a wave of respiratory illness. Nearly four years since the pandemic emerged, people are growing weary of dealing with it, but the virus is not done with us.

Nationally, a sharp uptick in emergency room visits and hospitalizations for covid-19, influenza, and respiratory syncytial virus, or RSV, began in mid-December and appears to be gaining momentum.

Here are a few things to know this time around:

What’s Circulating Now?

The covid virus is continually changing, and a recent version is rapidly climbing the charts. Even though it appeared only in September, the variant known as JN.1, a descendant of omicron, is rapidly spreading, representing between 39% to half of the cases, according to pre-holiday stats from the Centers for Disease Control and Prevention.

Lab data indicates that the updated vaccines, as well as existing covid rapid tests and medical treatments, are effective with this latest iteration. More good news is that it “does not appear to pose additional risks to public health beyond that of other recent variants,” according to the CDC.

Even so, new covid hospitalizations — 34,798 for the week that ended Dec. 30 — are trending upward, although rates are still substantially lower than last December’s tally. It’s early in the season, though. Levels of virus in wastewater — one indicator of how infections are spreading — are “very high,” exceeding the levels seen this time last year.

And don’t forget, other nasty bugs are going around. More than 20,000 people were hospitalized for influenza the week ending Dec. 30, and the CDC reports that RSV remains elevated in many areas.

“The numbers so far are definitely going in the not-so-good direction,” said Ziyad Al-Aly, the chief of the research and development service at the Veterans Affairs St. Louis Healthcare System and a clinical epidemiologist at Washington University in St. Louis. “We’re likely to see a big uptick in January now that everyone is back home from the holidays.”

Milder Cases and Fewer Deaths

Certainly, compared with the first covid winter, things are better now. Far fewer people are dying or becoming seriously ill, with vaccines and prior infections providing some immunity and reducing severity of illness.

Even compared with last winter, when omicron was surging, the situation is better. New hospitalizations, for example, are about one-third of what they were around the 2022 holidays. Weekly deaths dropped slightly the last week of December to 839 and are also substantially below levels from a year ago.

“The ratio of mild disease to serious clearly has changed,” said William Schaffner, a professor of medicine in the division of infectious diseases at Vanderbilt University School of Medicine in Nashville, Tennessee.

Even so, the definition of “mild” is broad, basically referring to anything short of being sick enough to be hospitalized.

While some patients may have no more than the sniffles, others experiencing “mild” covid can be “miserable for three to five days,” Schaffner said.

How Will This Affect My Day-to-Day Life?

“Am I going to be really sick? Do I have to mask up again?” It is important to know the basics.

For starters, symptoms of the covid variants currently circulating will likely be familiar — such as a runny nose, sore throat, cough, fatigue, fever, and muscle aches.

So if you feel ill, stay home, said Marcus Plescia, chief medical officer of the Association of State and Territorial Health Officials. “It can make a big difference.”

Dust off those at-home covid test kits, check the extended expiration dates on the FDA website, and throw away the ones that have aged out. Tests can be bought at most pharmacies and, if you haven’t ordered yours yet, free test kits are still available through a federal program at covid.gov.

Test more than once, especially if your symptoms are mild. The at-home rapid tests may not detect covid infection in the first couple of days, according to the FDA, which recommends using “multiple tests over a certain time period, such as two to three days.”

With all three viruses, those most at risk include the very young, older adults, pregnant people, and those with compromised immune systems or underlying diseases, including cancer or heart problems. But those without high-risk factors can also be adversely affected.

While mask-wearing has dropped in most places, you may start to see more people wearing them in public spaces, including stores, public transit or entertainment venues.

Although a federal mask mandate is unlikely, health officials and hospitals in at least four states — California, Illinois, Massachusetts, and New York — have again told staff and patients to don masks. Such requirements were loosened last year when the public health emergency officially ended.

Such policies are advanced through county-level directives. The CDC data indicates that, nationally, about 46.7% of counties are seeing moderate to high hospital admission rates of covid.

“We are not going to see widespread mask mandates as our population will not find that acceptable,” Schaffner noted. “That said, on an individual basis, mask-wearing is a very intelligent and reasonable thing to do as an additional layer of protection.”

The N95, KN95, and KF94 masks are the most protective. Cloth and paper are not as effective.

And, finally, if you haven’t yet been vaccinated with an updated covid vaccine or gotten a flu shot, it’s not too late. There are also new vaccines and monoclonal antibodies to protect against RSV recommended for certain populations, which include older adults, pregnant people, and young children.

Generally, flu peaks in midwinter and runs into spring. Covid, while not technically seasonal, has higher rates in winter as people crowd together indoors.

“If you haven’t received vaccines,” Schaffner said, “we urge you to get them and don’t linger.”

Repeat Infections

People who have dodged covid entirely are in the minority.

At the same time, repeat infections are common. Fifteen percent of respondents to a recent Yahoo News/YouGov poll said they’d had covid two or three times. A Canadian survey released in December found 1 in 5 residents said they had gotten covid more than once as of last June.

Aside from the drag of being sick and missing work or school for days, debate continues over whether repeat infections pose smaller or larger risks of serious health effects. There are no definitive answers, although experts continue to study the issue.

Two research efforts suggest repeat infections may increase a person’s chances of developing serious illness or even long covid — which is defined various ways but generally means having one or more effects lingering for a month or more following infection. The precise percentage of cases — and underlying factors — of long covid and why people get it are among the many unanswered questions about the condition. However, there is a growing consensus among researchers that vaccination is protective.

Still, the VA’s Al-Aly said a study he co-authored that was published in November 2022 found that getting covid more than once raises an “additional risk of problems in the acute phase, be it hospitalization or even dying,” and makes a person two times as likely to experience long covid symptoms.

The Canadian survey also found a higher risk of long covid among those who self-reported two or more infections. Both studies have their limitations: Most of the 6 million in the VA database were male and older, and the data studied came from the first two years of the pandemic, so some of it reflected illnesses from before vaccines became available. The Canadian survey, although more recent, relied on self-reporting of infections and conditions, which may not be accurate.

Still, Al-Aly and other experts say taking preventive steps, such as getting vaccinated and wearing a mask in higher-risk situations, can hedge your bets.

“Even if in a prior infection you dodged the bullet of long covid,” Al-Aly said, “it doesn’t’ mean you will dodge the bullet every single time.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Evidence Should Be Updated for Covid-19 Treatment

By Dr. Lynora Saxinger, Undark Magazine

Strong science, particularly vaccine development, helped us steer our way through the Covid-19 pandemic. Now, as the pandemic recedes, it’s time to hold drug companies accountable for the treatments they’ve developed.

The evidence for these medications has not kept pace with major changes in the nature of the Covid-19 pandemic, and updated studies should be required to maintain approval for these very profitable drugs.

The Covid-19 drug development battlefield is littered with 479 failed or inactive drugs, while 358 are still in clinical or preclinical trials, according to a tracker maintained by the Biotechnology Innovation Organization, a trade group.

The only oral Covid-19 therapy approved by the U.S. Food and Drug Administration that is recommended for first line outpatient use is Pfizer’s Paxlovid (nirmatrelvir-ritonavir), a two-drug combination that stops the SARS-CoV-2 virus from replicating in the body.

Hailed as a game changer, Paxlovid is a very good antiviral drug that has saved many lives, and its incredibly rapid development was a feat of science.

The major study leading to its approval, called the EPIC-HR trial, showed that it reduced the risk of hospitalization and death by an impressive 89 percent in high-risk, unvaccinated people.

But there is a lack of high-quality research on how Paxlovid affects outcomes beyond severe Covid — such as duration of illness, how the drug affects transmission, and whether it prevents long Covid. Nevertheless, some physicians are promoting the drug for these uses based on weak, inconsistent data.

pfizer image

The stakes are high: If we fail to set a requirement for well-designed studies of Paxlovid’s impact on all concerns besides hospitalization and death, we will be setting up a slow-moving, disastrous recreation of mistakes made with drugs for other diseases such as influenza.

Early in the Covid-19 pandemic, the explosive, unorganized growth of clinical trials for treatments was intended to save lives from this fearsome new disease. But many trials were small and of low quality, with a few exceptional trials providing much of our good data. In that initial desperate push for Covid-19 treatments, experimental, everything-but-the-kitchen-sink approaches became widely used.

Ivermectin Controversy

The case of ivermectin is instructive: This antiparasitic drug was used in tremendous volumes based on poor quality and sometimes outright fraudulent data, despite advice against its use from the FDA and in formal treatment guidelines. Social media amplification of the increasingly dubious evidence base led to a near-delusional belief in its benefit — and impressive profits for some opportunistic doctors.

A few well-coordinated and well-designed trials up front would have shortened the controversy, saved costs, and avoided duplicated effort of smaller low-quality trials. Most importantly, showing it to be ineffective earlier may have prevented the ensuing social media crusade, perhaps allowing some high-risk people to accept evidence-supported treatments like Paxlovid and the intravenous antiviral remdesivir rather than requesting, or even suing hospitals, to administer ivermectin.

Covid-19’s infection outcomes changed unusually rapidly across waves of the pandemic, which meant that studies could be outdated in months if they did not reflect the current viral strains and population immune responses. Data collection in the EPIC-HR study, which still guides treatment with Paxlovid, took place in 2021 when hospitalization rates were high, many were unvaccinated (including all trial participants), the viral strains were different than today, and the main outcome of interest in many communities was “flattening the curve,” or preventing hospitalization.

Now, almost everyone has been vaccinated, infected, or both. In a recent study, 96.4 percent of U.S. blood donors had Covid-19 antibodies by September 2022. The overall risk of hospitalization and death has also decreased significantly.

A Different Disease

Essentially, we are now dealing with a different disease. We are more focused on outcomes such as time lost from work, transmission risk, and long Covid risk. Yet there is almost no direct evidence about Paxlovid’s effect on these outcomes.

Paxlovid was approved for the treatment of mild to moderate Covid-19 in adults at high risk of developing severe disease. However, physicians and pharmacists have told me, it is increasingly being prescribed off-label for lower risk patients. This contention is supported by a recent U.S.-based preprint showing that 42 percent of more than 111,000 Paxlovid recipients had no major medical comorbidities, with treatment eligibility defined by having at least one risk factor for severe Covid-19.

Some physicians are extrapolating from hamster studies and lab data to suggest it reduces Covid-19 transmission. And they’re prescribing it to reduce long Covid risk based on very weak studies that analyzed administrative databases for Covid-19 complications rather than tracking long Covid symptoms in treated and untreated patients.

This matters because Paxlovid treatment for people who are not high risk has not shown significant benefit. One still unpublished randomized trial of lower-risk patients was terminated because low rates of hospitalization overall (in treated and untreated people) made it impossible to see a benefit.

Even in higher-risk groups, a recent meta-analysis of observational studies has shown very little absolute reduction of mortality, and no benefit in such patients under age 60. At the same time, people taking Paxlovid face possible side effects, drug interactions, and volatile drug pricing. They do not know if Paxlovid is worth all of that. They don’t know if the drug will reduce transmission to others, if they are less likely to get severely ill, if they will need time off work, or if it will spare them from long Covid.

Tamiflu Questions

Infectious diseases specialists like myself are experiencing an alarming sense of déjà vu. Tamiflu (oseltamivir), a treatment for influenza, was licensed in 1999 with data showing a modest benefit in reducing illness by one day. The reviewers noted that a “more definitive demonstration of clinical or public health relevance” would require additional data.

But 24 years later, we are not farther ahead — important questions about Tamiflu remain unanswered, with longstanding debates about the benefit of the drug and a false advertising lawsuit that went on for nearly 10 years before being dropped in July. The guidelines for the use of Tamiflu in influenza vary tremendously because of varied interpretation of a poor evidence base, and newer studies call its use as an influenza treatment into question. Even so, in its first 15 years on the market, Tamiflu made $18 billion in sales.

It is hard to stop a prescribing practice once it has become the norm, despite inadequate data. This is a recognized driver of cost increases in health care.

Pharmaceutical companies play a pivotal role in the research and development of effective therapies, and their lifesaving contributions during the Covid-19 pandemic have been commendable. However, the major investments these companies make in R&D should not give them free rein to market high-cost, high-volume drugs of public health importance without continued scrutiny of their effectiveness if the initial registration studies no longer stand because of changes in the disease.

Some bold, novel options could help address this gap in evidence. In exceptional circumstances (such as pandemics), pharmaceutical companies could be required to conduct studies to reassess a drug’s effectiveness after it has entered the market if conditions have meaningfully changed since the initial trials.

Another option could require companies to put a small portion of drug profits towards funding well-designed, independent trials so that crucial, commercially successful drugs would be part of ongoing studies. The FDA and other agencies should judiciously require and support such studies that could help guide treatment decisions, while balancing the need to support appropriate research and new drug development.

The medical community has responsibility, too: Professional societies that draft treatment guidelines must take a more consistently assertive stance in advising against uses for which there is insufficient evidence, rather than leaving it open to prescriber judgment. Both prescribers and potential patients need to accept and use evidence to help sustain health care systems, and lobby for changes needed to define the best treatments for people with Covid-19.

We are at a unique juncture in the fight against Covid-19, as fear gives way to complacency — and the path forward is scientific rigor. Failing to mandate high-quality evidence for treatment choices may lead us back down the path of inadequately researched treatments, opinion-driven guidelines, and wasted resources.

Pfizer has raked in about $20 billion dollars in revenue from Paxlovid alone over the last two years. This sum is nearly half of the National Institutes of Health’s entire budget for 2022. It is not surprising that the company has not voluntarily started additional trials after approval based on the stellar results in that first, now-irrelevant trial.

In the wake of the pandemic, we have an opportunity to improve both what we are doing, and how we may address research challenges in a future crisis. Paxlovid’s price is set to increase — from $530 to $1,390 before insurance — next year, but there is no corresponding increase in our knowledge of its value. The cost of this information gap will be very high, for both individuals and health care systems.

Lynora Saxinger, MD, is a journalist, infectious disease physician, and professor at the University of Alberta who headed a Covid evidence synthesis group during the pandemic. She is currently a Fellow in Journalism and Health Impact at the Dalla Lana School for Public Health.

This article was originally published by Undark, a non-profit, editorially independent online magazine covering the complicated and often fractious intersection of science and society. You can read the original article here.

Health Misinformation Rampant on Social Media

By Dr. Monica Wang, Boston University

The global anti-vaccine movement and vaccine hesitancy that accelerated during the COVID-19 pandemic show no signs of abating.

According to a survey of U.S. adults, Americans in October 2023 were less likely to view approved vaccines as safe than they were in April 2021. As vaccine confidence falls, health misinformation continues to spread like wildfire on social media and in real life.

I am a public health expert in health misinformation, science communication and health behavior change.

In my view, we cannot underestimate the dangers of health misinformation and the need to understand why it spreads and what we can do about it. Health misinformation is defined as any health-related claim that is false based on current scientific consensus.

False Claims About Vaccines

Vaccines are the No. 1 topic of misleading health claims. Some common myths about vaccines include:

• Their supposed link with human diagnoses of autism. Multiple studies have discredited this claim, and it has been firmly refuted by the World Health Organization, the National Academies of Sciences, Engineering and Medicine, the American Academy of Pediatrics and the Centers for Disease Control and Prevention.

• Concerns with the COVID-19 vaccine leading to infertility. This connection has been debunked through a systematic review and meta-analysis, one of the most robust forms of synthesizing scientific evidence.

• Safety concerns about vaccine ingredients, such as thimerosal, aluminum and formaldehyde. Extensive studies have shown these ingredients are safe when used in the minimal amounts contained in vaccines.

• Vaccines as medically unnecessary to protect from disease. The development and dissemination of vaccines for life-threatening diseases such as smallpox, polio, measles, mumps, rubella and the flu has saved millions of lives. It also played a critical role in historic increases in average life expectancy – from 47 years in 1900 in the U.S. to 76 years in 2023.

High Cost of Misinformation

Beliefs in such myths have come at the highest cost.

An estimated 319,000 COVID-19 deaths that occurred between January 2021 and April 2022 in the U.S. could have been prevented if those individuals had been vaccinated, according to a data dashboard from the Brown University School of Public Health. Misinformation and disinformation about COVID-19 vaccines alone have cost the U.S. economy an estimated US$50 million to $300 million per day in direct costs from hospitalizations, long-term illness, lives lost and economic losses from missed work.

Though vaccine myths and misunderstandings tend to dominate conversations about health, there is an abundance of misinformation on social media surrounding diets and eating disorders, smoking or substance use, chronic diseases and medical treatments.

My team’s research and that of others show that social media platforms have become go-to sources for health information, especially among adolescents and young adults. However, many people are not equipped to maneuver the maze of health misinformation.

For example, an analysis of Instagram and TikTok posts from 2022 to 2023 by The Washington Post and the nonprofit news site The Examination found that the food, beverage and dietary supplement industries paid dozens of registered dietitian influencers to post content promoting diet soda, sugar and supplements, reaching millions of viewers. The dietitians’ relationships with the food industry were not always made clear to viewers.

Studies show that health misinformation spread on social media results in fewer people getting vaccinated and can also increase the risk of other health dangers such as disordered eating and unsafe sex practices and sexually transmitted infections. Health misinformation has even bled over into animal health, with a 2023 study finding that 53% of dog owners surveyed in a nationally representative sample report being skeptical of pet vaccines.

Declining Trust

One major reason behind the spread of health misinformation is declining trust in science and government. Rising political polarization, coupled with historical medical mistrust among communities that have experienced and continue to experience unequal health care treatment, exacerbates preexisting divides.

The lack of trust is both fueled and reinforced by the way misinformation can spread today. Social media platforms allow people to form information silos with ease; you can curate your networks and your feed by unfollowing or muting contradictory views from your own and liking and sharing content that aligns with your existing beliefs and value systems.

By tailoring content based on past interactions, social media algorithms can unintentionally limit your exposure to diverse perspectives and generate a fragmented and incomplete understanding of information. Even more concerning, a study of misinformation spread on Twitter analyzing data from 2006 to 2017 found that falsehoods were 70% more likely to be shared than the truth and spread “further, faster, deeper and more broadly than the truth” across all categories of information.

The average kindergarten student sees about 70 media messages every day. By the time they’re in high school, teens spend more than a third of their day using media.

How to Identify Misinformation

The lack of robust and standardized regulation of misinformation content on social media places the difficult task of discerning what is true or false information on individual users. We scientists and research entities can also do better in communicating our science and rebuilding trust, as my colleague and I have previously written. I also provide peer-reviewed recommendations for the important roles that parents/caregivers, policymakers and social media companies can play.

Below are some steps that consumers can take to identify and prevent health misinformation spread:

• Check the source. Determine the credibility of the health information by checking if the source is a reputable organization or agency such as the World Health Organization, the National Institutes of Health or the Centers for Disease Control and Prevention. Other credible sources include an established medical or scientific institution or a peer-reviewed study in an academic journal. Be cautious of information that comes from unknown or biased sources.

• Examine author credentials. Look for qualifications, expertise and relevant professional affiliations for the author or authors presenting the information. Be wary if author information is missing or difficult to verify.

• Pay attention to the date. Scientific knowledge by design is meant to evolve as new evidence emerges. Outdated information may not be the most accurate. Look for recent data and updates that contextualize findings within the broader field.

• Cross-reference to determine scientific consensus. Cross-reference information across multiple reliable sources. Strong consensus across experts and multiple scientific studies supports the validity of health information. If a health claim on social media contradicts widely accepted scientific consensus and stems from unknown or unreputable sources, it is likely unreliable.

• Question sensational claims. Misleading health information often uses sensational language designed to provoke strong emotions to grab attention. Phrases like “miracle cure,” “secret remedy” or “guaranteed results” may signal exaggeration. Be alert for potential conflicts of interest and sponsored content.

• Weigh scientific evidence over individual anecdotes. Prioritize information grounded in scientific studies that have undergone rigorous research methods, such as randomized controlled trials, peer review and validation. When done well with representative samples, the scientific process provides a reliable foundation for health recommendations compared to individual anecdotes. Though personal stories can be compelling, they should not be the sole basis for health decisions.

• Talk with a health care professional. If health information is confusing or contradictory, seek guidance from trusted health care providers who can offer personalized advice based on their expertise and individual health needs.

• When in doubt, don’t share. Sharing health claims without validity or verification contributes to misinformation spread and preventable harm.

All of us can play a part in responsibly consuming and sharing information so that the spread of the truth outpaces the false.

Monica Wang, ScD, is an Associate Professor of Community Health Sciences at the Boston University School of Public Health and an Adjunct Associate Professor of Health Policy and Management at the Harvard T.H. Chan School of Public Health. She receives funding from the National Institutes of Health.

This article originally appeared in The Conversation and is republished with permission.

Can Antivirals Prevent Long Covid?

By The Conversation

Evidence is continuing to accumulate on the burden and frequency of chronic effects after a COVID infection, which fall under the umbrella term “long COVID”.

At least 5%–10% of people who contract COVID experience long COVID. This can include symptoms (for example, fatigue, brain fog and breathlessness) or conditions (for example, heart conditions, neurological conditions and diabetes) after the initial infection that may be persisting, new or relapsing.

Studies show the symptoms and increased risk of chronic conditions can persist for up to two years after infection. The individual impact of long COVID can range from temporary to severely disabling, and the societal cost – for example due to reduced workforce and increased health-care costs – is enormous

The lower risk of developing long COVID with up-to-date COVID vaccinations is substantially offset by the high levels of infections and re-infections globally. As a result, the cumulative burden of long COVID has increased, including in lower and middle income countries. A conservative estimate suggests 65 million people may be currently affected globally.

So where are we at with reducing the risk of, and treating, long COVID?

Reduced Risk of Severe Disease

COVID antiviral drugs, taken orally, continue to play an important role in reducing acute severe disease after infection. In Australia and the US, they’re available to those at highest risk from COVID.

Observational research has suggested taking antivirals during a COVID infection can reduce the risk of long COVID in people with at least one risk factor for acute severe COVID.

In one study, nirmatrelvir and ritonavir, known as Paxlovid, was associated with a 26% reduced risk of developing long COVID. It was also linked to a 47% reduced risk of death and a 24% reduced risk of hospitalisation after the acute infection phase.

A similar 14% reduction in long COVID risk has been reported for molnupiravir (Lagevrio).

Ensitrelvir – a COVID antiviral available in Japan – could also reduce the risk of long COVID, preliminary analyses suggest.

More research is needed, but this data indicates antiviral medications may be a key approach to lessening the risk of long COVID.

The population most at risk of long COVID (often working-age adults) differs from those most at risk of severe disease from a COVID infection (older adults or those with chronic medical conditions). Eligibility criteria to access antivirals do not currently include consideration of long COVID.

Meanwhile, one randomised trial found metformin, a commonly prescribed diabetes medication, could also reduce long COVID risk. The study offered people with symptomatic COVID who were overweight or obese metformin for two weeks (beginning within a week of symptoms starting). This group was 41% less likely to develop long COVID compared with a placebo group that didn’t take metformin.

The way this works might involve an effect on the powerhouses of our cells, mitochondria, or directly on the virus. Whatever the precise mechanism, further research should be priortised to fast-track this potential.

Still No Treatments for Long Covid

There are no effective or approved treatments for long COVID at present. Currently about 12 clinical trials are testing potential drugs. A number of candidate treatments exist for certain components of long COVID that may be useful in subgroups of patients.

However, recently we’ve seen major advances in understanding what’s actually driving long COVID in the body. This knowledge opens up approaches for both diagnosis and treatments or interventions.

An Australian parliamentary inquiry into long COVID stressed the best way to avoid the condition is to lower the risk of getting infected with COVID in the first place (through protective behaviours such as vaccination, mask wearing and cleaner indoor air).

While these are all important measures, we would benefit from having more tools at our disposal to prevent and treat long COVID. After all, COVID is still evolving rapidly and vast numbers of people are likely to be reinfected in the months and years ahead.

Overall, the quantity and speed of clinical trials into long COVID treatments has been insufficient. And most public health policy approaches are focused on preventing severe disease from a COVID infection, rather than the long-term effects.

That said, Australia recently announced an initial A$22 million of funding and a plan for research into long COVID through the Medical Research Future Fund.

In July 2023, the White House established the Office of Long COVID Research and Practice which will coordinate the US government’s response to long COVID, as well as two randomised trials of Paxlovid.

Given what we now know about long COVID, and the additional concern of what we don’t know (for example, could organ damage reveal itself many years down the track?), we desperately need diagnostic tools, clinical care pathways coupled with health worker training, and treatments to prevent and cure long COVID.

Unaddressed, long COVID may well lead to a new and substantial health and societal burden for many years to come. The response must involve prioritisation of research, such as that which led to the fast development of COVID vaccines and antivirals.

While there are some positive signs in the policy and research space, we need to see stronger recognition of long COVID and a greater sense of urgency around finding solutions.

Authors:

Suman Majumdar, Associate Professor and Chief Health Officer - COVID and Health Emergencies, Burnet Institute

Brendan Crabb, Director and CEO, Burnet Institute

Emma Pakula, Senior Research and Policy Officer, Burnet Institute

Michelle Scoullar, Senior Research Fellow, Burnet Institute

Ziyad Al-Aly, Director Clinical Epidemiology Center, VA St. Louis Health Care System, Washington University in St Louis

The Burnet Institute is a not-for-profit independent, unaligned organisation that combines medical research in the laboratory and the field with public health action to address major health issues affecting disadvantaged communities in Australia and internationally.

This article originally appeared in The Conversation and is republished with permission.

How Do You Treat Long Covid? Patients Surveyed for Answers

By Esther Landhuis, Undark Magazine

In January 2020, Martha Eckey was working at a retail pharmacy in Champaign, Illinois, when she developed a sore throat, hacking cough, and stiff neck. A second bout of illness struck about a month later, leaving the pharmacist with a persistent fever and shortness of breath. Covid tests were unavailable at the time, but she tested positive for influenza.

The biggest challenge was “crushing, debilitating fatigue,” she told Undark. “No amount of sleep left me feeling even remotely refreshed,” she added by email. Three-and-a-half years later, Eckey has still not recovered.

Shortly after her initial illness, Eckey started reading about people with lingering post-Covid symptoms, and although she never knew for certain which virus caused her initial illness, those symptoms seemed strikingly similar to hers.

After connecting with patients navigating these conditions, Eckey wondered if she had developed myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS, a long-lasting illness that can crop up after a viral infection.

She went to see several physicians, but they “told me they were not taught about post-viral illnesses,” she recalled. “It literally wasn’t in their curriculum.” Eckey had not learned about post-viral syndromes in her four-year doctor of pharmacy training, either.

MARTHA ECKEY

Long Covid and ME/CFS are complex illnesses. Up to 2.5 million Americans live with ME/CFS, and more than 65 million people worldwide may have long Covid — though estimates vary and the dozens of symptoms across multiple body systems can make these conditions hard to define and diagnose. In some people, symptoms linger or intensify with time, but in others they occur weeks or months after recovery from the initial infection, which could be mild or undiagnosed.

In a recent analysis of 9,764 adults enrolled in the federally funded initiative RECOVER, long Covid patients fell into four subgroups based on symptoms, many overlapping with ME/CFS and other conditions. By studying biological samples from these participants, researchers hope to identify markers that can inform future trials of potential therapeutics.

Yet for now, despite an influx of research funding, there are no widely accepted treatments approved by the U.S. Food and Drug Administration to ease sufferers’ symptoms. In that void, desperate patients have turned to a range of proposed solutions — from microbiome treatments to vitamin supplements to experimental techniques like “blood washing” — to find relief. In this vast array of possible therapies, some are exorbitant and most are unproven.

Eckey quit her pharmacy job in August 2020 to search for useful patterns amid that chaos. Unlike most national initiatives and large academic research programs, Eckey is employing a bottom-up approach: She polls patients on which interventions they’ve tried and how they fared, in the hope that this crowdsourced knowledge might contain valuable insights for improving long Covid care.

While surveys like Eckey’s come with inherent limitations, some researchers think such grassroots efforts can help inform more rigorous studies.

“Large clinical trials cost millions of dollars, and it’s impossible to test hundreds of different things at once,” said Akiko Iwasaki, whose lab at the Yale School of Medicine studies the immunology of long Covid. “Knowing what has benefited the patients already provides us with insights that can be tested in future trials.”

Medications and Supplements

Late in the summer of 2022, Eckey, known to social media followers and Substack subscribers as LongCovidPharmD, created several surveys using Google Forms and shared them on Twitter (more recently rebranded as X).

One of the surveys listed about two dozen medications — including Paxlovid, statins, and beta blockers— and had respondents tick boxes for the ones they had tried. It asked them to indicate if taking the drug seemed to “moderately improve,” “vastly improve,” worsen, or have little to no effect on long Covid symptoms or quality of life. Other sections asked if they had conditions that commonly occur alongside ME/CFS or long Covid, such as dysautonomia, mast cell activation syndrome, or a history of blood clots.

Eckey also grew curious about supplements — a category that includes probiotics or enzymes, herbs, minerals, vitamins, and other over-the-counter products with suggested uses that are not regulated by the FDA. In social media posts, she noticed that people commenting on supplements would say, “‘Oh, that didn’t work at all for me,’ and then other people say, ‘oh, that cured me,’” she said.

So she created another survey, listing eight types of supplements and asking to what extent they seemed to help with fatigue, cognitive function, and other symptoms. Motivation for that survey also came from Eckey’s own frustration with being unable to get any prescribed treatments, she said: “I thought, ‘Well, I think I just have to figure out how to treat myself.’”

With more than 200 respondents, the surveys gave a sense for which types of supplements seemed most helpful. Additional surveys focused on the most promising supplements — which doses were used and for what frequency and duration, whether patients improved or felt worse, and which symptoms patients noticed seemed to be affected.

Eckey analyzed the results and started posting detailed summaries on X. Then, in late 2022, her work caught the attention of the Open Medicine Foundation, a California-based nonprofit that has raised $40 million to diagnose and treat complex, multi-system diseases including ME/CFS, long Covid, and others that have eluded doctors.

No Approved Treatments

ME/CFS and long Covid have no FDA-approved treatments, and neither has a definitive diagnostic. The situation echoes that of early days of AIDS, which, decades ago, was defined by symptoms rather than measurable changes inside the body, said Wenzhong Xiao, a computational biologist at Harvard Medical School who directs the foundation’s efforts on ME/CFS treatments.

Regulators typically validate medical treatments through a formal application that specifies the substance’s composition and how it’s made. The application also proposes further study in clinical trials, which generally won’t launch without supportive data from smaller pilot studies. When the Open Medicine Foundation came across Eckey’s work, the organization was already trying to decide which potential treatments to test in pilot studies for long Covid, and was making a registry from which to recruit patients. 

Building on her initial surveys with information gleaned from published trials, case studies, patient feedback, and her “own pharmacist intuition,” Eckey created a more comprehensive version, called “TREAT ME,” and tweeted it on Feb. 5, 2023. 

The survey — which, by Eckey’s account, took about 1,000 hours to produce — covered more than 150 medications and supplements. After collecting details about a person’s symptoms, lab tests, and medical history, the survey asked about treatments: whether they appeared to help, which symptoms improved, how long it took to see benefits, how long the benefits lasted, and whether they were outweighed by side effects. If a medication did not seem to help, the survey asked how long it was tried and at which doses.

“No one has done that deep a dive,” said Linda Tannenbaum, the CEO of the Open Medicine Foundation.

By the time the survey closed for analysis in late March, the responses had climbed to nearly 4,000.

Survey Bias

Despite the potential, surveys have unavoidable, inherent biases that can influence how data is collected and results are interpreted, said internist Lucinda Bateman, founder of the nonprofit Bateman Horne Center — a clinical care, research, and educational organization in Salt Lake City, Utah, that focuses on chronic, complex disorders including long Covid. First, there’s selection bias: Who decides to participate and why? There’s sampling bias: Who never hears about it? There’s also non-response bias: People for whom a treatment has little to no obvious effect may be less likely to participate. 

Surveys also hinge on participants’ own accounts, which aren’t typically confirmed with other sourcing. Eckey’s survey, for instance, relied on respondents to indicate whether they had an official or presumed diagnosis of long Covid or ME/CFS.

The approach also can’t typically account for the placebo effects that result from other factors besides a specific treatment or from other ongoing illnesses or treatments, which may skew the results. And beyond the difficulties with diagnosing long Covid, people may “think they got sick during the pandemic, and it’s entirely something else,” said Bateman. The uncertainty in the data is “just what happens when you do surveys,” she added.

Eckey agreed with these caveats, noting that she tried “to limit bias to the extent that I could.” For instance, to ease non-response bias, the survey instructions encouraged participants to rate treatments “even if they had no effect,” she said.

She also prompted participants to specify underlying conditions and treatments, and responses could be filtered accordingly. And Eckey included one supplement that she believed would have little to no impact on symptoms, figuring questions about it “could act as a sort of ‘placebo’ against which other treatments could be compared.” On a similar vein, she asked about several treatments that were hyped at various times and found their reported benefits to be “underwhelming” or not statistically different from related drugs.

The supplement industry is vast and largely unregulated, with many products lacking solid evidence for health benefits. Research to produce that evidence is a complex, costly process that requires FDA input, often participation from the company that produces the supplement, and approval by an independent ethics committee. What’s more, such trials must follow a company’s best guess on the right doses, optimizing the supplement’s benefit while minimizing side effects.

This approach comes with substantial risks for illnesses like long Covid, which cause a range of symptoms that differ from one person to the next, said David Putrino, director of rehabilitation innovation for the Mount Sinai Health System in New York. A single treatment won’t necessary work for all of them, Putrino, who studies and treats long Covid patients, added in an email, and “you feel like you only have ‘one shot.’”

Eckey’s survey, he said in a phone interview, “allows me to actually make data-driven decisions on what seems to be working.”

The approach is already prompting new studies. Some researchers think that certain long Covid symptoms stem from tiny blood clots; more than 60 percent of Eckey’s survey respondents said they felt better after taking supplements containing enzymes that break down fibrin, the main protein that forms the clots.

These results helped Putrino and colleagues choose one of the enzymes, called lumbrokinase, for a long Covid trial planned for early 2024.

“My desire to get better and help others in similar situations is what keeps me going.”

— Martha Eckey

The Open Medicine Foundation team is also using the survey results to inform drug trials. In a more typical trial, the group mines published scientific literature and uses machine learning to predict which medications might help. These analyses would have likely missed lumbrokinase, since it appears in relatively few academic research papers, Xiao said. Based on Eckey’s survey findings, he said, his team is “definitely thinking about doing follow-up studies.”

Beyond her dataset, Xiao added, Eckey is herself is an inspiration: “I can imagine how much effort she put, despite her own symptoms, to make this happen.”

Eckey’s lingering fatigue still keeps her mostly housebound — and, on some days, stuck in bed — but she told Undark via email that her cardiovascular symptoms have improved. On her better days, she said, she plans to volunteer at a free ME/CFS clinic that treats post-Covid patients: “My desire to get better and help others in similar situations is what keeps me going.”

Esther Landhuis (@elandhuis) is a California-based science journalist and a senior contributor to Undark. She covers biomedicine at all stages — lab discoveries, clinical trials, biotech, healthcare and its intersections with law and business. Her stories have also appeared in Scientific American, Nature, Medscape, JAMA, Science News, Quanta and other outlets.

This article was originally published by Undark, a non-profit, editorially independent online magazine covering the complicated and often fractious intersection of science and society. You can read the original article here.

Did Covid Vaccine Mandates Do More Harm Than Good?

By Dr. Rachel Gur-Arie, Arizona State University

Ending pandemics is a social decision, not scientific. Governments and organizations rely on social, cultural and political considerations to decide when to officially declare the end of a pandemic. Ideally, leaders try to minimize the social, economic and public health burden of removing emergency restrictions while maximizing potential benefits.

Vaccine policy is a particularly complicated part of pandemic decision-making, involving a variety of other complex and often contradicting interests and considerations. Although COVID-19 vaccines have saved millions of lives in the U.S., vaccine policymaking throughout the pandemic was often reactive and politicized.

A late November 2022 Kaiser Family Foundation poll found that one-third of U.S. parents believed they should be able to decide not to vaccinate their children at all. The World Health Organization and the United Nations Children’s Fund reported that between 2019 and 2021, global childhood vaccination experienced its largest drop in the past 30 years.

The Biden administration formally removed federal COVID-19 vaccination requirements for federal employees and international travelers in May 2023. Soon after, the U.S. government officially ended the COVID-19 public health emergency. But COVID-19’s burden on health systems continues globally.

I am a public health ethicist who has spent most of my academic career thinking about the ethics of vaccine policies. For as long as they’ve been around, vaccines have been a classic case study in public health and bioethics. Vaccines highlight the tensions between personal autonomy and public good, and they show how the decision of an individual can have populationwide consequences.

COVID-19 is here to stay. Reflecting on the ethical considerations surrounding the rise – and unfolding fall – of COVID-19 vaccine mandates can help society better prepare for future disease outbreaks and pandemics.

Types of Vaccine Mandates

Vaccine mandates are the most restrictive form of vaccine policy in terms of personal autonomy. Vaccine policies can be conceptualized as a spectrum, ranging from least restrictive, such as passive recommendations like informational advertisements, to most restrictive, such as a vaccine mandate that fines those who refuse to comply.

Each sort of vaccine policy also has different forms. Some recommendations offer incentives, perhaps in the form of a monetary benefit, while others are only a verbal recommendation. Some vaccine mandates are mandatory in name only, with no practical consequences, while others may trigger termination of employment upon noncompliance.

COVID-19 vaccine mandates took many forms throughout the pandemic, including but not limited to employer mandates, school mandates and vaccination certificates – often referred to as vaccine passports or immunity passports – required for travel and participation in public life.

Because of ethical considerations, vaccine mandates are typically not the first option policymakers use to maximize vaccine uptake. Vaccine mandates are paternalistic by nature because they limit freedom of choice and bodily autonomy. Additionally, because some people may see vaccine mandates as invasive, they could potentially create challenges in maintaining and garnering trust in public health. This is why mandates are usually the last resort.

However, vaccine mandates can be justified from a public health perspective on multiple grounds. They’re a powerful and effective public health intervention.

Mandates can provide lasting protection against infectious diseases in various communities, including schools and health care settings. They can provide a public good by ensuring widespread vaccination to reduce the chance of outbreaks and disease transmission overall. Subsequently, an increase in community vaccine uptake due to mandates can protect immunocompromised and vulnerable people who are at higher risk of infection.

Early in the pandemic, arguments in favor of mandating COVID-19 vaccines for adults rested primarily on evidence that COVID-19 vaccination prevented disease transmission. In 2020 and 2021, COVID-19 vaccines seemed to have a strong effect on reducing transmission, therefore justifying vaccine mandates.

COVID-19 also posed a disproportionate threat to vulnerable people, including the immunocompromised, older adults, people with chronic conditions and poorer communities. As a result, these groups would have significantly benefited from a reduction in COVID-19 outbreaks and hospitalization.

Many researchers found personal liberty and religious objections insufficient to prevent mandating COVID-19 vaccines. Additionally, decision-makers in favor of mandates appealed to the COVID-19 vaccine’s ability to reduce disease severity and therefore hospitalization rates, alleviating the pressure on overwhelmed health care facilities.

However, the emergence of even more transmissible variants of the virus dramatically changed the decision-making landscape surrounding COVID-19 vaccine mandates.

The public health intention (and ethicality) of original COVID-19 vaccine mandates became less relevant as the scientific community understood that achieving herd immunity against COVID-19 was probably impossible because of uneven vaccine uptake, and breakthrough infections among the vaccinated became more common. Many countries like England and various states in the U.S. started to roll back COVID-19 vaccine mandates.

With the rollback and removal of vaccine mandates, decision-makers are still left with important policy questions: Should vaccine mandates be dismissed, or is there still sufficient ethical and scientific justification to keep them in place?

Vaccines are lifesaving medicines that can help everyone eligible to receive them. But vaccine mandates are context-dependent tools that require considering the time, place and population they are deployed in.

Though COVID-19 vaccine mandates are less of a publicly pressing issue today, many other vaccine mandates, particularly in schools, are currently being challenged. I believe this is a reflection of decreased trust in public health authorities, institutions and researchers – resulting in part from tumultuous decision-making during the COVID-19 pandemic.

Engaging in transparent and honest conversations surrounding vaccine mandates and other health policies can help rebuild and foster trust in public health institutions and interventions.

Rachel Gur-Arie, PhD, is an assistant professor with Edson College of Nursing and Health Innovation at Arizona State University. Her expertise lies at the intersection of ethics, global health and policy. Prior to joining ASU, Rachel was a Hecht-Levi postdoctoral Fellow, focused on ethics and infectious disease, at Johns Hopkins University and the University of Oxford. She completed her doctorate in health systems management and served as a Fulbright Scholar at Ben-Gurion University of the Negev in Israel.

This article originally appeared in The Conversation and is republished with permission.

CDC Recommends New Covid Boosters

By Arthur Allen, KFF Health News

Everyone over the age of 6 months should get the latest covid-19 booster, a federal expert panel recommended Tuesday after hearing an estimate that universal vaccination could prevent 100,000 more hospitalizations each year than if only the elderly were vaccinated.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 for the motion after months of debate about whether to limit its recommendation to high-risk groups. A day earlier, the FDA approved the new booster, stating it was safe and effective at protecting against the covid variants currently circulating in the U.S.

After the last booster was released, in 2022, only 17% of the U.S. population got it — compared with the roughly half of the nation who got the first booster after it became available in fall 2021. Broader uptake was hurt by pandemic weariness and evidence the shots don’t always prevent covid infections. But those who did get the shot were far less likely to get very sick or die, according to data presented at Tuesday’s meeting.

The virus sometimes causes severe illness even in those without underlying conditions, causing more deaths in children than other vaccine-preventable diseases, as chickenpox did before vaccines against those pathogens were universally recommended.

The number of hospitalized patients with covid has ticked up modestly in recent weeks, CDC data shows, and infectious disease experts anticipate a surge in the late fall and winter.

The shots are made by Moderna and by Pfizer and its German partner, BioNTech, which have decided to charge up to $130 a shot. They have launched national marketing campaigns to encourage vaccination. The advisory committee deferred a decision on a third booster, produced by Novavax, because the FDA hasn’t yet approved it. Here’s what to know:

Who Should Get a Booster Shot?

The CDC advises that everyone over 6 months old should, for the broader benefit of all. Those at highest risk of serious disease include babies and toddlers, the elderly, pregnant women, and people with chronic health conditions including obesity. The risks are lower — though not zero — for everyone else. The vaccines, we’ve learned, tend to prevent infection in most people for only a few months. But they do a good job of preventing hospitalization and death, and by at least diminishing infections they may slow spread of the disease to the vulnerable, whose immune systems may be too weak to generate a good response to the vaccine.

Pablo Sánchez, a pediatrics professor at The Ohio State University who was the lone dissenter on the CDC panel, said he was worried the boosters hadn’t been tested enough, especially in kids. The vaccine strain in the new boosters was approved only in June, so nearly all the tests were done in mice or monkeys. However, nearly identical vaccines have been given safely to billions of people worldwide.

When Should You Get It?

The vaccine makers say they’ll begin rolling out the vaccine this week. If you’re in a high-risk group and haven’t been vaccinated or been sick with covid in the past two months, you could get it right away, says John Moore, an immunology expert at Weill Cornell Medical College. If you plan to travel this holiday season, as he does, Moore said, it would make sense to push your shot to late October or early November, to maximize the period in which protection induced by the vaccine is still high.

Who Pays For It?

When the ACIP recommends a vaccine for children, the government is legally obligated to guarantee kids free coverage, and the same holds for commercial insurance coverage of adult vaccines.

For the 25 to 30 million uninsured adults, the federal government created the Bridge Access Program. It will pay for rural and community health centers, as well as Walgreens, CVS, and some independent pharmacies, to provide covid shots for free. Manufacturers have agreed to donate some of the doses, CDC officials said.

Will New Booster Work Against Current Variants?

It should. More than 90% of currently circulating strains are closely related to the variant selected for the booster earlier this year, and studies showed the vaccines produced ample antibodies against most of them. The shots also appeared to produce a good immune response against a divergent strain that initially worried people, called BA.2.86. That strain represents fewer than 1% of cases currently. Moore calls it a “nothingburger.”

Why Are People Still Skeptical About Vaccines?

Experience with the covid vaccines has shown that their protection against hospitalization and death lasts longer than their protection against illness, which wanes relatively quickly, and this has created widespread skepticism.

Most people in the U.S. have been ill with covid and most have been vaccinated at least once, which together are generally enough to prevent grave illness, if not infection — in most people. Many doctors think the focus should be on vaccinating those truly at risk.

What About Getting Other Vaccines?

People tend to get sick in the late fall because they’re inside more and may be traveling and gathering in large family groups. This fall, for the first time, there’s a vaccine — for older adults — against respiratory syncytial virus. Kathryn Edwards, a 75-year-old Vanderbilt University pediatrician, plans to get all three shots but “probably won’t get them all together,” she said.

Covid “can have a punch” and some of the RSV vaccines and the flu shot that’s recommended for people 65 and older also can cause sore arms and, sometimes, fever or other symptoms. A hint emerged from data earlier this year that people who got flu and covid shots together might be at slightly higher risk of stroke. That linkage seems to have faded after further study, but it still might be safer not to get them together.

Pfizer and Moderna are both testing combination vaccines, with the first flu-covid shot to be available as early as next year. Although Pfizer’s shot has been approved in the European Union, Japan, and South Korea, and Moderna has won approval in Japan and Canada. Rollouts will start in the U.S. and other countries this week.

Unlike in earlier periods of the pandemic, mandates for the booster are unlikely. But “it’s important for people to have access to the vaccine if they want it,” said panel member Beth Bell, a professor of public health at the University of Washington.

“Having said that, it’s clear the risk is not equal, and the messaging needs to clarify that a lot of older people and people with underlying conditions are dying, and they really need to get a booster,” she said.

ACIP member Sarah Long, a pediatrician at Children’s Hospital of Philadelphia, voted for a universal recommendation but said she worried it was not enough. “I think we’ll recommend it and nobody will get it,” she said. “The people who need it most won’t get it.”

KFF Health News is a national newsroom that produces in-depth journalism about health issues.

Long Covid May Not Be Caused by Covid-19 Virus

By Pat Anson, PNN Editor

An immune system response to the COVID-19 virus has been suspected as a possible cause of Long Covid, a poorly understood disorder that causes chronic fatigue, brain fog, insomnia, chest pain and other symptoms long after the initial infection.  

But a small new study in the UK suggests that Long Covid may not be an inflammatory immune reaction to the SARS-CoV-2 virus. Instead, the body appears to be responding to the activation of dormant viruses many of us already have in our systems.

"Long Covid occurs in one out of 10 COVID-19 cases, but we still don't understand what causes it,” said Laura Rivino, PhD, Senior Lecturer at the University of Bristol's School of Cellular and Molecular Medicine. “Several theories proposed include whether it might be triggered by an inflammatory immune response towards the virus that is still persisting in our body, sending our immune system into overdrive or the reactivation of latent viruses such as human cytomegalovirus (CMV) and Epstein Barr virus (EBV)."

Rivino and her colleagues collected and analyzed blood samples from 63 Covid patients with mild, moderate or severe symptoms who were hospitalized at the start of the pandemic -- before vaccines were available – and tested them again 3, 8 and 12 months after their admission.  

Their findings, published in the journal eLife, show that patients with severe symptoms had significant dysfunction in their T-cell profiles after three months. T-cells are white blood cells released by the immune system to fight bacteria and viruses.

Further analysis showed there was no rapid increase in immune cells targeting SARS-CoV-2, but there was an increase in T-cells targeting CMV -- a common virus that is usually harmless but can stay in the body for life once you’re infected with it. That suggests that the prolonged T-cell activation observed at three months in severe patients may not be driven by SARS-CoV-2, but instead may be "bystander driven" by dormant viruses that were reactivated.  

"Our findings suggest that prolonged immune activation and long COVID may correlate independently with severe COVID-19. Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and non-vaccinated COVID-19 patients,” said Rivino. "Understanding whether inflammation and immune activation associate with long COVID would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition."

The good news for Covid long haulers is that after 12 months, the T-cell levels of patients with severe Covid symptoms were similar to those of patients who experienced mild and moderate symptoms – suggesting that severe cases can resolve over time.

12 Most Common Symptoms of Long Covid

By Pat Anson, PNN Editor

Since the first cases started appearing in 2020, medical experts have been baffled by Long Covid, a poorly understood disorder that causes chronic fatigue, insomnia, brain fog and dozens of other symptoms long after the initial infection with COVID-19.

The symptoms vary so much from person to person that identifying the cause is difficult. Is it Long Covid? Fibromyalgia? Chronic fatigue syndrome? Lyme disease? Or just a bad case of the flu?   

A new study led by the National Institutes of Health's RECOVER Initiative has identified the 12 most common symptoms of Long Covid, with the goal of creating a working definition of the condition to help make it easier to diagnose and treat.

"This study is an important step toward defining Long Covid beyond any one individual symptom," said lead author Leora Horwitz, MD, director of the Center for Healthcare Innovation and Delivery Science at NYU Langone Health. "This definition — which may evolve over time — will serve as a critical foundation for scientific discovery and treatment design."

Horwitz and her colleagues studied survey data from 9,764 adult volunteers from across the country. Nearly 90% had been infected with Covid. Some made complete recoveries, while others had symptoms of Long Covid – known technically as postacute sequelae of SARS-CoV-2 infection (PASC). About 23% of participants with a prior Covid infection met the working definition for Long Covid.

The study findings, published in JAMA, examined 37 symptoms across multiple body areas and organs. Researchers then applied statistical analysis to identify the 12 symptoms that someone with Long Covid is most likely to have: post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, heart palpitations, issues with sexual desire, loss of smell or taste, thirst, chronic cough, chest pain, and abnormal movements.

By assigning points to each of the 12 symptoms, researchers gave each participant a PASC score based on their combination of symptoms. Some symptoms appeared at higher rates than others, with malaise and fatigue being the most prominent, occurring in nearly 90% of cases.

Frequency of Long Covid Symptoms

SOURCE: JAMA

"Now that we're able to identify people with Long Covid, we can begin doing more in-depth studies to understand the mechanisms at play," said coauthor Andrea Foulkes, ScD, Principal Investigator of the RECOVER Data Resource Core. "These findings set the stage for identifying effective treatment strategies for people with Long Covid — understanding the biological underpinnings is going to be critical to that endeavor."

The researchers found that Long Covid was more common and severe in participants who were infected before the Omicron strain emerged in late 2021. People who were unvaccinated and those with multiple Covid infections were also more likely to have severe symptoms.

Researchers identified four subgroups of patients with different clusters of symptoms. Some clusters spanned multiple organs, such as the heart, lung and brain, suggesting that a body-wide reaction to the virus may occur in some people with Long Covid.

As of May 2023, more than 100 million Americans have been infected with COVID-19, with experts estimating that about 6 percent of those infected with the virus continue to experience Long Covid symptoms.

Long Covid May Affect Genes Involved in Pain Signaling

By Pat Anson, PNN Editor

About 16 million people in the United States have Long Covid, a poorly understood disorder that causes body aches, headaches, fatigue, insomnia, brain fog and other symptoms long after an initial infection with COVID-19. For some, the symptoms are mild, but for other they are so severe they become disabling.

Why do some people quickly recover from Covid, while about one in five have lingering symptoms?

A new animal study found that thousands of genes involved in nervous system function are affected by SARS-CoV-2, and may cause lasting damage to dorsal root ganglia, the spinal nerves that carry pain and other sensory messages to the brain. Scientists believe that genetic damage may be what causes Long Covid.

“Several studies have found that a high proportion of Long Covid patients suffer from abnormal perception of touch, pressure, temperature, pain or tingling throughout the body. Our work suggests that SARS-CoV-2 might induce lasting pain in a rather unique way, emphasizing the need for therapeutics that target molecular pathways specific to this virus,” explains co-author Venetia Zachariou, PhD, chair of pharmacology, physiology & biophysics at Boston University’s Chobanian & Avedisian School of Medicine.

Zachariou and her colleagues infected hamsters with SARS-CoV-2 and studied how it affected the animals’ sensitivity to touch, both during the initial infection and after the infection had cleared. Then they compared the effects of SARS-CoV-2 to those triggered by an influenza A virus infection, and were surprised by what they found.

In the hamsters infected with Covid, researchers observed a slow but progressive increase in sensory sensitivity over time – one that differed substantially from influenza A infections, which caused a sudden hypersensitivity that returned to normal once the initial infection ended.

Although the studies were performed on animals, researchers say they align with the acute and chronic symptoms caused by Covid in humans. They hope further studies on human genes and sensory pathways affected by the Covid virus will lead to new treatments for Long Covid and conditions such as ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome),

“We hope this study will provide new avenues for addressing somatosensory symptoms of long COVID and ME/CFS, which are only just now beginning to be addressed by mainstream medicine. While we have begun using this information by validating one promising target in this study, we believe our now publicly available data can yield insights into many new therapeutic strategies,” adds Zachariou. 

The study findings appear online in the journal Science Signaling.

The federal government’s Covid public health emergency officially ends this week, but the impact of the pandemic will likely be felt for years to come.

We Need Better Treatments for Long Covid, Fibromyalgia, Chronic Fatigue and More

By Dr. Seth Lederman

Headlines about COVID have faded, and the United States will soon turn the page on public emergency status for the pandemic. The virus no longer dominates most of our lives, yet there are still thousands of new hospitalizations daily and an estimated 15 million Americans currently suffer from Long COVID.

The deep impact of long-haul cases has contributed to a surge of patients with disabling conditions, who are often misdiagnosed or treated ineffectively. More than one in five people infected with COVID-19 develop Long COVID and its constellation of physical and neurological symptoms. The persistent pain, fatigue, sleep problems and brain fog are similar to two other post-infectious syndromes, fibromyalgia and chronic fatigue syndrome (CFS/ME).

A recent study of both conditions and Long COVID documented that the physical and cognitive impairments of Long COVID were exacerbated in people previously diagnosed with CFS/ME or fibromyalgia. These types of chronic overlapping pain conditions have long been recognized by the National Institutes of Health (NIH), and the president’s National Research Action Plan on Long COVID similarly makes the connection between CFS/ME and Long COVID.

More than 50 million people struggle with these neurological illnesses every year in our country, and the burden of their chronic diseases comes at incalculable personal harm, along with billions of dollars in healthcare costs and lost productivity. 

There is one common denominator among all these unrelenting illnesses: the human brain. Physicians like me who study infectious and neurological diseases know that getting a drug’s active ingredients into the brain is not easy. Unlike biologic drugs, which are usually administered by injection, the only medications that can cross from the bloodstream into the brain are small-molecule drugs.

But big pharmaceutical companies have largely abandoned the development of new small-molecule therapeutics, instead pursuing biologic drugs which tend to be more expensive and profitable. That is because of a complex mix of federal laws granting longer market exclusivity to biologics, patent law changes that remove economic incentives to develop new small-molecule therapeutics, and mounting Food and Drug Administration hurdles.

Yet small-molecule drugs can be highly effective and life-changing, as well as relatively cost-effective to manufacture and distribute. They are our best hope for offering real relief to people struck by cruel conditions rooted in brain function.

As we pick up the pieces from a once-in-a-generation pandemic, we cannot ignore the rise in debilitating post-infectious diseases. In a sense, the people afflicted by these illnesses are living with invisible scars from the infections that preceded their current illnesses. There is an urgent need to help them by restoring incentives for small-molecule drug development and streamlining regulatory processes for new treatments.

The government should be accelerating efforts to expand its support for new drug therapies to address fibromyalgia, CFS/ME, Long COVID, and other illnesses that originate in the brain. The untapped potential of emerging therapeutics is unacceptable, as is the fact that many patients’ symptoms are frequently misinterpreted or dismissed.

It is good news that the Advanced Research Project Agency for Health has been established within NIH to pursue biomedical breakthroughs. But our country could still be doing more on this front. Congress has the power to legislate a more level playing field for small-molecule drug development, correcting decades of bureaucratic bias.

Lawmakers should appropriate more resources to fast-track clinical trials and scale-up delivery of novel therapies for post-infectious diseases. Public-private partnerships could also go a long way towards bridging the gap between treatments that would transform patients’ lives and their current limited options.

We know from our experience with COVID that medical science is capable of swift and significant breakthroughs. Our public health system should be equipped to readily diagnose and effectively treat people with fibromyalgia, CFS/ME, Long COVID, and similar devastating illnesses.

While the symptoms of these diseases are often not visible, our responsibility to provide patients with advanced and effective care is very real. For millions of Americans and their families, the time for better treatments is now.

Seth Lederman, MD, is a physician-scientist and CEO of Tonix Pharmaceuticals, a company developing technologies to treat Long COVID, PTSD, fibromyalgia, and other diseases.