Emergence of a Deadly Coronavirus

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Key Facts:
COVID-related cognitive decline equals about 20 years of normal aging.
Brain scans show reduced volume and injury in key areas after COVID-19.
Both neurological and non-neurological patients experienced cognitive deficits.
Source: University of Liverpool

New steps have been taken towards a better understanding of the immediate and long-term impact of COVID-19 on the brain in the UK’s largest study to date.

Published in Nature Medicine, the study from researchers led by the University of Liverpool alongside King’s College London and the University of Cambridge as part of the COVID-CNS Consortium shows that 12-18 months after hospitalisation due to COVID-19, patients have worse cognitive function than matched control participants.

Importantly, these findings correlate with reduced brain volume in key areas on MRI scans as well as evidence of abnormally high levels of brain injury proteins in the blood.

Strikingly, the post-COVID cognitive deficits seen in this study were equivalent to twenty years of normal ageing. It is important to emphasise that these were patients who had experienced COVID, requiring hospitalisation, and these results shouldn’t be too widely generalised to all people with lived experience of COVID.

However, the scale of deficit in all the cognitive skills tested, and the links to brain injury in the brain scans and blood tests, provide the clearest evidence to date that COVID can have significant impacts on brain and mind health long after recovery from respiratory problems.

The work forms part of the University of Liverpool’s COVID-19 Clinical Neuroscience Study (COVID-CNS), which addresses the critical need to understand the biological causes and long-term outcomes of neurological and neuropsychiatric complications in hospitalised COVID-19 patients.

Study author Dr Greta Wood from the University of Liverpool said: “After hospitalisation with COVID-19 many people report ongoing cognitive symptoms often termed ‘brain fog’.

“However, it has been unclear as to whether there is objective evidence of cognitive impairment and, if so, is there any biological evidence of brain injury; and most importantly if patients recover over time.

“In this latest research, we studied 351 COVID-19 patients who required hospitalisation with and without new neurological complications.

“We found that both those with and without acute neurological complications of COVID-19 had worse cognition than would be expected for their age, sex and level of education, based on 3,000 control subjects.”

Corresponding author Professor Benedict Michael, Professor of Neuroscience at the University of Liverpool said: “COVID-19 is not a condition simply of the lung. Often those patients who are most severely affected are the ones who have brain complications.

“These findings indicate that hospitalisation with COVID-19 can lead to global, objectively measurable cognitive deficits that can be identified even 12-18 months after hospitalisation.

“These persistent cognitive deficits were present in those hospitalised both with and without clinical neurological complications, indicating that COVID-19 alone can cause cognitive impairment without a neurological diagnosis having been made.

“The association with brain cell injury biomarkers in blood and reduced volume of brain regions on MRI indicates that there may be measurable biological mechanisms underpinning this.

“Now our group is working to understand whether the mechanisms that we have identified in COVID-19 may also be responsible for similar findings in other severe infections, such as influenza.”

Professor Gerome Breen from King’s College London said: “Long term research is now vital to determine how these patients recover or who might worsen and to establish if this in unique to COVID-19 or a common brain injury with other infections.

“Significantly our work can help guide the development of both similar studies in those with Long-COVID who often have much milder respiratory symptoms and also report cognitive symptoms such as ‘brain fog’ and also to develop therapeutic strategies.”

As cases of a new COVID-19 variant tick upward across the U.S., the federal government is again offering Americans free at-home COVID-19 test kits. Individuals and households can begin ordering the test kits later this month, on the heels of a summer wave of COVID-19 cases.

The Biden administration restarted the same program last fall, too, after a brief pause to conserve test supplies. The U.S. Department of Health and Human Services, which oversees the program, has not yet said when it will start taking orders again for the at-home COVID-19 tests through the COVIDTests.gov website. It only instructs visitors to "come back to place your order in late September 2024."

Once an order is placed, U.S. Postal Service ships the test kits directly to peoples' homes.

When the site reopens, U.S. households will be permitted to order as many as four test kits each. The over-the-counter kits detect current COVID-19 variants and can be used through the end of the year, according to HHS. The tests are expected to arrive in homes ahead of the holiday season, when families often travel to gather for Thanksgiving, Christmas and other celebrations.

The program's website encourages people to check test expiration dates against the FDA's updated guidance on tests' shelf life. Some test kits with expiration dates printed on them that are in the past, may in fact still deliver accurate results.

HHS encourages testing for COVID-19, so that individuals who contract the virus can seek treatment and self-isolate or take other steps, like wear a mask, so as not to infect others. To date, the federal program has distributed more than 900 million tests to American households.

The tests can be costly when purchased over-the-counter at drugstores across the U.S., making them unaffordable for many families. For example, a pack of two BinaxNow COVID-19 antigen self-tests from Abbott costs $18.99 at CVS.com.

Other government efforts aimed at stemming the virus' spread include a renewed vaccination initiative. The government encourages residents to get an updated COVID-19 booster shot to prepare for the fall and winter respiratory virus season.

When you reach for a COVID-19 test, it’s probably because you’ve got a scratchy throat, runny nose, or cough. But those are far from the only symptoms that make Dr. Rohit Jain, an internal medicine doctor at PennState Health, suspect the virus.

These days, when someone complains of nausea, diarrhea, or vomiting, “I always get a COVID test on that patient,” Jain says.

Why? Despite its reputation as a respiratory virus, SARS-CoV-2 can also have a profound impact on the gut. Although most people don’t realize it, “COVID-19 really is a GI-tract disease” as well as a respiratory illness, says Dr. Mark Rupp, chief of infectious diseases at the University of Nebraska Medical Center.

Here’s what to know about the gastrointestinal symptoms of COVID-19.

What are the GI symptoms of COVID-19?
While some people experience no gastrointestinal symptoms or mild ones, a subset of COVID-19 patients have experienced significant digestive symptoms since the early days of the pandemic.
Loss of appetite, nausea, vomiting, diarrhea, and stomach pain are common GI symptoms of COVID-19, according to Jain’s research. Some people experience these issues as their first signs of infection, he says, while others initially experience cold-like symptoms and develop gastrointestinal issues as their illness progresses.

It’s not entirely clear why the same virus can affect people so differently, but it’s good to be aware that SARS-CoV-2 can result in a wide range of symptoms, Rupp says.

How long do GI symptoms of COVID-19 last?
Some patients recover in a matter of days, Jain says, while others may suffer from diarrhea and other symptoms for weeks.

Still others may be sick for even longer. Gastrointestinal problems are a common manifestation of Long COVID, the name for chronic symptoms that follow a case of COVID-19 and can last indefinitely.

One recent study in Clinical Gastroenterology and Hepatology found that, among a small group of adults who were hospitalized when they had acute COVID-19, more than 40% who originally experienced GI problems such as stomach pain, nausea, vomiting, or diarrhea still had at least one a year or more later. Overall, whether they were hospitalized or not, adults who have had COVID-19 are about 36% more likely than uninfected people to develop gastrointestinal disorders including ulcers, pancreatitis, IBS, and acid reflux, according to a 2023 study published in Nature Communications.

GI problems are also common among kids with Long COVID. Stomach pain, nausea, and vomiting are telltale signs of the condition among children younger than 12, according to 2024 research published in JAMA.

Why a respiratory virus affects the gut?
How can the same virus cause both a runny nose and the runs?

Once SARS-CoV-2 gets into your body, it infects cells by binding to a protein called ACE2, which is found throughout the body. ACE2 is prevalent in the lungs, which helps explain COVID-19’s respiratory symptoms—but it’s also found in high concentrations in the gastrointestinal tract, “so it makes sense that the GI tract would be a target for the virus,” Rupp says. It’s in part because SARS-CoV-2 collects in the gut that wastewater surveillance is a useful tool for tracking the virus’ spread, Rupp adds.

Studies have shown that the virus can hide out in the “nooks and crannies” of the digestive system for months or even years, says Ziyad Al-Aly, a clinical epidemiologist at the Washington University School of Medicine in St. Louis who co-authored the Nature Communications study on chronic post-COVID GI symptoms. This may explain why gut-related symptoms can long outlast an acute infection, Al-Aly says—but there are many potential hypotheses in play, and researchers don’t know for sure which one or ones are correct.

For example, many researchers also think the virus is capable of causing widespread and sometimes long-lasting inflammation, potentially affecting organs throughout the body. This inflammatory response may have trickle-down effects on the gut microbiome, the colony of bacteria and other microbes that live in the GI tract, Rupp says. “We’re just scratching the surface as to what happens there,” Rupp says, but studies have already shown that SARS-CoV-2 can change the composition of the gut microbiome both during an acute infection and chronically.
There’s also a complex relationship between the gut and the brain, adds Dr. Badih Joseph Elmunzer, a gastroenterologist at the Medical University of South Carolina and co-author of the Clinical Gastroenterology and Hepatology study on prolonged post-COVID GI symptoms. His research suggests people are particularly likely to suffer long-term GI problems if they also have signs of PTSD from their acute illness or hospitalization.

That’s not to say GI symptoms are all in patients’ heads; on the contrary, Elmunzer says, they are very real. But, he says, there’s a lot left to learn about the microbiome, the gut, and the myriad ways they interact with other bodily systems.

Levels of the virus that causes COVID-19 remain high across the U.S. despite recent decreases in positive case reports across the country. However, viral activity varies significantly across different states, new data from the U.S. Centers for Disease Control and Prevention (CDC) shows.

As of September 21, the overall viral activity level in wastewater across the country has been demoted from "very high" to just "high," although "very high" levels are still being detected in 13 states. These are particularly concentrated in the Midwest. Twenty-one states now exhibit "high" levels of wastewater activity, and nine are classed as "moderate."

Meanwhile, "low" levels have been detected in six states, with "minimal" levels, the lowest classification, seen in New York.

After a surge in COVID-19 cases this summer, infection rates seem to be on the decline. Positive tests now account for 11.6 percent of all COVID tests (excluding at-home testing) in the U.S., down 1.8 percent from the previous week. Coronavirus levels do remain high in certain states, especially those in the Central U.S.

Recent spikes in COVID-19 cases have been largely driven by a new class of subvariants nicknamed FLiRT after the position of the mutations on the virus' spike proteins, the projections that allow them to enter our cells.

These proteins are also used as targets by immune systems and vaccinations, so changes in their structure can allow the virus to bypass the body's defenses more easily. However, existing vaccines are likely to provide at least some form of protection against more severe symptoms and long COVID.

As of September 28, the now dominant subvariant, KP.3.1.1, accounted for more than 59 percent of all U.S. COVID-19 cases over the previous two weeks, according to the CDC, with the FLiRT variants accounting for more than 80 percent of cases in total.

However, while the U.S. has seen a steady rise in infections over the summer, hospitalizations and deaths have remained relatively low. It appears that the new FLiRT variants, while more infectious, do not generally cause such severe symptoms.

The symptoms include the following, according to the CDC:

Fever or chills
Cough
Shortness of breath
Fatigue
Muscle or body aches
Headache
Loss of taste or smell
Sore throat
Runny nose
Nausea or vomiting
Diarrhea

More vulnerable individuals may still be at risk of severe illness, so it is important to self-isolate if you receive a positive COVID test.

There’s a new COVID-19 variant on the rise in Canada.

The XEC strain, first identified in Germany in June, made up an estimated 12.9 per cent of cases nation-wide last week, according to Health Canada. Provincially, the prevalence of XEC’s parent lineage nearly tripled in the last week of September, the most recently available data shared by Public Health Ontario showed.

But despite its imposing name and encroaching numbers, XEC — an Omicron subvariant — is unlikely to be significantly different from other strains, according to Isaac Bogoch, an infectious diseases specialist at Toronto General Hospital.

“This is rinse, wash, repeat,” he said. “We did this with BA.1, then BA.2, then BA.4, then BA.5, then JN.1, then XBB, then XEC. This is more of the same.”

Here’s what we know about XEC, its symptoms and how to protect yourself

COVID XEC symptoms
The XEC variant likely has the same symptoms as existing COVID-19 variants, with the potential for some subtle differences, Bogoch said, also an associate professor at the University of Toronto.

According to Health Canada, typical COVID-19 symptoms include:

Sore throat
Runny nose and/or sneezing
New or worsening cough
Shortness of breath or difficulty breathing
Fever
Muscle or body aches
Headache
The severity of XEC — and how to slow its transmission — is likely the same, too, according to Bogoch.

Do vaccines still work against XEC?
The COVID-19 vaccine is periodically updated to target new variants and a new set of vaccines from Moderna and Novavax were approved last month by Health Canada.

These vaccines were developed before XEC emerged — but they will still be effective against the new variant, according to Bogoch.

“Even though it’s not a perfect match, it never will be,” Bogoch said. “At every point in the pandemic, any vaccine that we’ve had available in Canada, regardless of the circulating variant, has done a remarkable job.”

What can I do to protect myself against XEC?
The public health advice for XEC remains the same.

The U.S. Food and Drug Administration has put on hold a trial of Novavax's (NVAX.O), opens new tab COVID-influenza and its standalone flu vaccines after a participant who took the combination shot reported nerve damage, the company said on Wednesday.

Its shares plunged as much as 24%, and if losses hold, it would wipe off nearly $400 million from the vaccine maker's market capitalization.

The stock drop also reflect concerns on whether the hold would impact Novavax's partnership with French drugmaker Sanofi (SASY.PA), opens new tab, according to one analyst.

Novavax said a participant enrolled in a mid-stage study of the combination vaccine last month reported symptoms of motor neuropathy, or damage to the nerve cells that control muscles or movement. The person was given the vaccine in January last year.

The company said it was not yet established that the vaccine had caused the safety event and it was working with the FDA to resolve the pause.

"Our goal is to successfully resolve this matter and to start our Phase 3 trial as soon as possible," Chief Medical Officer Robert Walker said.

At least two analysts said it was too early to draw a conclusion. Jefferies analyst Roger Song said motor neuropathy was not a side effect seen in any older trials of Novavax's shots.

Still, the pause fueled investor worries over the company's growth as its COVID-19 shot, Novavax's only approved product, faces low demand after a late entry into the U.S. market.

The company in May had signed a deal worth at least $1.2 billion with Sanofi to co-sell Novavax's vaccine in most countries and use the COVID shot along with its own flu vaccines to develop a combination shot.

Sanofi said the clinical hold has "nothing to do with" its partnership with Novavax. Outside of the agreement, the companies can individually develop their own flu-COVID vaccines and other products, it said in an e-mailed statement.
"Fundamentally this doesn't seem to have a direct impact on Novavax's partnership with Sanofi," TD Cowen analyst Brendan Smith said.

Conservative political analyst Tucker Carlson and Canadian psychologist Jordan Peterson were among those who were funded by the Russian state-owned news outlet RT to boost anti-vax claims in 2022, Canadian Prime Minister Justin Trudeau claimed while under oath during testimony delivered Wednesday at the Foreign Interference Commission.

"Justin Trudeau Testifies That Russia Funded Tucker Carlson and Jordan Peterson in Support of Their Anti-Vax Covid Claims"


I don't know if this is credible...but it is incredible!

Viruses don’t often come with silver linings, and infections don’t generally lead to positive health effects. But during the pandemic, some doctors anecdotally began noticing that some people with cancer who got very sick with COVID-19 saw their tumors shrink or grow more slowly.

“We didn’t know if it was real, because these patients were so sick,” says Dr. Ankit Bharat, chief of thoracic surgery at Northwestern University. “Was it because the immune system was so triggered by COVID-19 that it also started to kill cancer cells? What was it?”

Bharat and his team decided conduct a study to find out if the seeming “benefit” of COVID-19 for these cancer patients could teach them anything about a potential new way to fight cancer—or if it was simply a red herring. They published their findings Nov. 15 in the Journal of Clinical Investigation.

Using a combination of human cells and animal models, Bharat and his team found that in the presence of SARS-CoV-2, immune cells called monocytes act differently than they normally do. Typically, monocytes, as part of the immune system, cruise the bloodstream and alert other immune cells to the presence of foreign cells or pathogens; some monocytes can attract cancer-killing immune cells to tumors, but others aren't as effective in doing so. That's because in some cases, cancer cells can co-opt monocytes —“like a demon summoning forces,” says Bharat—and form an immune wall protecting the tumor from being discovered and attacked by additional immune defenses.

But during a COVID-19 infection, SARS-CoV-2 attaches itself to these monocytes, and by doing so reverts them back to doing their original job: defending the body against cancer. “They look the same, and are still recruited to the tumor sites, but instead of protecting the cancer cells, they start to bring specific natural killer cells—which are the body’s main cells that kill cancer—to these tumor sites,” says Bharat. “So where before the cancer was brainwashing the monocytes into protecting the cancer, the virus now helps them to attack cancer.”

t’s a potentially powerful turnabout that—if confirmed by human studies—could represent a new way to control cancer. By analyzing the receptor on the monocytes that the COVID-19 virus attached to, Bharat found a compound that currently isn’t used to treat any disease but is a close mimic of the COVID-19 virus in the way that it binds to the monocyte to induce the cell’s transformation into a cancer-fighting cell. “We can use a drug to cause the same effect that the RNA of the COVID-19 virus was doing,” he says. “By manipulating that pathway through the drug, we might be able to help patients with many different types of cancers, particularly those with stage 4 cancers.”

In animal tests, the compound—called muramyl dipeptide (MDP)—reduced tumors by 60% to 70% in mice with human cancers including breast, colon, lung, and melanoma.

More studies are needed to confirm whether the cells have the same cancer-fighting effect in people, but there are promising hints. These transformed, cancer-flagging monocytes, called inducible non-classical monocytes, are rare compared to other types of monocytes, but tend to proliferate when inflammation occurs, such as during a COVID-19 infection. Transplant surgeons have previously identified them in people who have had lung and spleen transplants, and Bharat is conducting additional research to understand why the transplant process and COVID-19 infections—both of which activate the immune system—trigger the specific change in the monocytes. Interestingly, the transformation doesn’t occur with all RNA-based viruses; Bharat tested influenza and parainfluenza, which are also RNA viruses, and failed to see the same population of cancer-fighting monocytes emerge.

Another intriguing part of the equation, says Bharat, is that this pathway is independent of the T cell immune treatments that are becoming a big part of cancer therapy now, in which doctors boost the population of T cells that can recognize and attack cancer cells. They can be effective, but generally only work for a while, since cancers quickly find ways to circumvent the T cells and become resistant to the therapies.

The virus-induced changes in the monocytes, in contrast, aren’t dependent on T cells. Bharat tested the approach in mice genetically bred to lack T cells and still saw a strong effect on tumors in these animals from the monocytes. That means that the monocytes may help shore up the body's response to immunotherapy—and its ability to fight tumors.

There are certain phrases that Wachuka Gichohi finds difficult to hear after enduring four years of living with long COVID, marked by debilitating fatigue, pain, panic attacks and other symptoms so severe she feared she would die overnight.

Among them are normally innocuous statements such as, "Feel better soon" or "Wishing you a quick recovery," the Kenyan businesswoman said, shaking her head.

Gichohi, 41, knows such phrases are well-intentioned. "I think you have to accept, for me, it’s not going to happen."

Recent scientific studies shed new light on the experience of millions of patients like Gichohi. They suggest the longer someone is sick, the lower their chances of making a full recovery.

The best window for recovery is in the first six months after getting COVID-19, with better odds for people whose initial illness was less severe, as well as those who are vaccinated, researchers in the United Kingdom and the United States found. People whose symptoms last between six months and two years are less likely to fully recover.

For patients who have been struggling for more than two years, the chance of a full recovery "is going to be very slim," said Manoj Sivan, a professor of rehabilitation medicine at the University of Leeds and one of the authors of the findings published in The Lancet.

Sivan said this should be termed "persistent long COVID" and understood like the chronic conditions myalgic encephalomyelitis/chronic fatigue syndrome, or fibromyalgia, which can be features of long COVID or risk factors for it.

Waning attention
One British study suggested almost a third of those reporting symptoms at 12 weeks recovered after 12 months. Others, particularly among patients who had been hospitalized, show far lower rates of recovery.

In a study run by the UK's Office for National Statistics, 2 million people self-reported long COVID symptoms this past March. Roughly 700,000, or 30.6%, said they first experienced symptoms at least three years previously.

Globally, accepted estimates have suggested between 65 million and 200 million people have long COVID. That could mean between 19.5 million and 60 million people face years of impairment based on the initial estimates, Sivan said.

The United States and some countries like Germany continue to fund long COVID research.

But more than two dozen experts, patient advocates and pharmaceutical executives told Reuters that money and attention for the condition is dwindling in other wealthy countries that traditionally fund large-scale studies. In low- and middle-income countries, it was never there.

"The attention has shifted," said Amitava Banerjee, a professor at University College London who co-leads a large trial of repurposed drugs and rehabilitation programs.

He says long COVID should be viewed as a chronic condition that can be treated to improve patients' lives rather than cured, like heart disease or arthritis.

'Profoundly disabling'
Leticia Soares, 39, from northeast Brazil, was infected in 2020 and has battled intense fatigue and chronic pain ever since. On a good day, she spends five hours out of bed.

When she can work, Soares is a co-lead and researcher at Patient-Led Research Collaborative, an advocacy group involved in a review of long COVID evidence published recently in Nature.

Soares said she believes recovery seldom happens beyond 12 months. Some patients may find their symptoms abate, only to recur, a kind of remission that can be mistaken for recovery, she said.

"It's so profoundly disabling and isolating. You spend every time wondering, 'Am I going to get worse after this?'" she said of her own experience.

Soares takes antihistamines and other commonly available treatments to cope with daily life. Four long COVID specialist doctors in different countries said they prescribe such medicines, which are known to be safe. Some evidence suggests they help.

Others have less success with mainstream medicine.

Gichohi's illness was dismissed by her doctor, and she turned to a functional medicine practitioner, who focused on more holistic treatments.

She moved out of her hectic home city of Nairobi to a small town near Mount Kenya, policing her activity levels to prevent fatigue and receiving acupuncture and trauma therapy.

She has tried the addiction treatment naltrexone, which has some evidence of benefit for long COVID symptoms, and the controversial anti-parasitic infection drug ivermectin, which does not but she says helped her.

She said shifting from "chasing recovery" to living in her new reality was important.

A piecemeal treatment approach is to be expected while research progresses, and perhaps longer-term, said Anita Jain, a long COVID specialist at the World Health Organization.

Meanwhile, long-haulers face a new challenge with each spike in COVID cases. A handful of studies have suggested re-infection can exacerbate existing long COVID.

Shannon Turner, a 39-year-old cabaret singer from Philadelphia, got COVID in late March or early April of 2020.

She was already living with psoriatic arthritis and antiphospholipid antibody syndrome, autoimmune diseases for which she regularly took steroids and an immunotherapy. Such conditions may increase the risk of developing long COVID, researchers say.

This past summer, Turner got COVID again. Once again, she is extraordinarily tired and uses a walker for mobility.

Turner is determined to pursue her music career despite ongoing pain, dizziness and a racing heart rate, which regularly land her in hospital.

"I don't want to live my life in bed," she said.

Erica Hayes, 40, hasn't felt healthy since November 2020 when she first fell ill with COVID.

Hayes is too sick to work, so she's spent much of the last four years sitting on her beige couch, often curled up under an electric blanket.

"My blood flow now sucks, so my hands and my feet are freezing. Even if I'm sweating my toes are cold," says Hayes, who lives in Western Pennsylvania. She misses feeling well enough to play with her 9-year-old son, or attend her 17-year-old son's baseball games.

Dr. Benjamin Jin, a biologist, works on immunotherapy for HPV+ cancers, in a lab at the National Cancer Institute at the National Institutes of Health (NIH) in Bethesda, Md. in 2018. The NIH funds research into cancer treatments among many other diseases. Experimental trials are ongoing at the National Institutes of Health Clinical Center, a US government-funded research hospital where doctors are trying to partially replace patients' immune systems with T-cells that would specifically attack cancers caused by the human papillomavirus (HPV), a common sexually transmitted infection. A person's T-cells will naturally try to kill off any invader, including cancer, but usually fall short because tumors can mutate, hide, or simply overpower the immune system. Immunotherapies that have seen widespread success, such as chimeric antigen receptor (CAR-T) cell therapies, mainly target blood cancers like lymphoma, myeloma and leukemia, which have a tumor antigen -- like a flag or a signal -- on the surface of the cells so it is easy for immune cells to find and target the harmful cells. But many common cancers lack this clear, surface signal. Hinrichs' approach focuses on HPV tumors because they contain viral antigens that the immune system can easily recognize.

Along with claiming the lives of 1.2 million Americans, the COVID pandemic has been described as a mass disabling event. Hayes is one of millions of Americans who suffer from long COVID. Depending on the patient, the condition can rob someone of energy, scramble the autonomic nervous system, or fog their memory, among many other symptoms.

Estimates of prevalence range considerably, depending on how researchers define long COVID in a given study, but the Centers for Disease Control and Prevention puts it at 17 million adults.

Despite long COVID's vast reach, the federal government's investment in researching the disease — to the tune of $1.15 billion to date — has so far failed to bring any new treatments to market. This disappoints and angers the patient community.

"It's unconscionable that more than four years since this began, we still don't have one FDA- approved drug," says Meighan Stone, executive director of Long COVID Campaign, a patient-led advocacy organization. Stone was among several people with long COVID who spoke at a workshop hosted by the National Institutions of Health in September where patients, clinicians and researchers discussed their priorities and frustrations around the agency's approach to long COVID research.

Some researchers are also critical of the agency's research initiative, called RECOVER, or Researching COVID to Enhance Recovery. Without clinical trials, physicians specializing in treating long COVID must rely on hunches to guide their clinical decisions, says Dr. Ziyad Al-Aly, the chief of research and development at the VA St Louis Healthcare System.

"What [RECOVER] lacks, really, is clarity of vision and clarity of purpose," says Al-Aly, saying he agrees that the NIH has had enough time and money to produce more meaningful progress.

Now the NIH is starting to determine how to allocate another $515 million of funding for long COVID research, which it says will have a significant focus on clinical trials. At the end of October, RECOVER issued a request for clinical trial ideas that look at potential therapies, including medications, saying its goal is, "to work rapidly, collaboratively, and transparently to advance treatments for Long COVID."

This turn suggests the NIH has begun to respond to patients and has stirred cautious optimism among those who say that the agency's approach to long COVID has lacked urgency in the search for effective treatments.

"The patient community has been really clear for years that we want to see trials that test real interventions that patients can't access without a doctor's prescription," says Stone. "So we don't want to see clinical trials for over-the-counter supplements … exercise therapy or cognitive behavioral therapy."

Good science 'takes time'
n December 2020, Congress appropriated $1.15 billion for the NIH to launch RECOVER, raising hopes in the long COVID patient community.

Then-NIH director Dr. Francis Collins explained that RECOVER's goal was to better understand long COVID as a disease and that clinical trials of potential treatments would come later.

According to RECOVER's website, it has funded eight clinical trials to test the safety and effectiveness of an experimental treatment or intervention. Just one of those trials has published results.

On the other hand, RECOVER has supported more than 200 observational studies, such as research on how long COVID affects pulmonary function, or which symptoms are most common. And the initiative has funded more than 40 pathobiology studies, which focus on the basic cellular and molecular mechanisms of long COVID.

RECOVER's website says this research has led to crucial insights on the risk factors for developing long COVID, and understanding how the disease interacts with pre-existing conditions.

It notes that observational studies are important in helping scientists to design and launch evidence-based clinical trials.

Good science takes time, says Dr. Leora Horwitz, the co-principal investigator for the RECOVER-Adult Observational Cohort at New York University. And, long COVID is an "exceedingly complicated" illness that appears to affect nearly every organ system, said Horwitz through email.

This makes it more difficult to study than many other diseases. Because long COVID harms the body in so many different ways, with widely variable symptoms, it's harder to identify precise targets for treatment.

"Simply trying treatments because they are available without any evidence about whether or why they may be effective reduces the likelihood of successful trials and may put patients at risk of harm," Horwitz says.

Dashed hopes or incremental progress?
The consensus from patient advocacy groups is that RECOVER should have done more to prioritize clinical trials from the outset. Patients also say RECOVER leadership ignored their priorities and experiences when determining which studies to fund.

RECOVER has scored some gains, says JD Davids, co-director of Long COVID Justice. This includes findings on differences in long COVID between adults and kids. But Davids says the NIH shouldn't have named the initiative "RECOVER," since it wasn't designed as a streamlined effort to develop treatments.

"The name's a little cruel and misleading," he says.

RECOVER's initial allocation of $1.15 billion probably wasn't enough to develop a new medication to treat long COVID, says Dr. Ezekiel J. Emanuel, the co-director of the University of Pennsylvania's Healthcare Transformation Institute.

But the results of preliminary clinical trials could have spurred pharmaceutical companies to fund more studies on drug development, as well as testing how existing drugs influence a patient's immune response.

Emanuel is one of the authors of a March 2022 COVID roadmap report. He notes that RECOVER's lack of focus on new treatments was a problem. "Only 15% of the budget is for clinical studies. That is a failure in itself — a failure of having the right priorities," he told NPR via email.

And though the NYU biobank has been impactful, there needs to be more focus on how existing drugs influence immune response.

Emanuel says some clinical trials that RECOVER has funded are "ridiculous," because they've focused on symptom amelioration, for example, to study the benefits of over-the-counter medication to improve sleep. Other studies looked at non-pharmacological interventions, such as exercise and "brain training" to help with cognitive fog.

People with long COVID say this type of clinical research contributes to the gaslighting they experience from doctors, who sometimes blame a patient's symptoms on anxiety or depression, rather than acknowledging long COVID as a real illness with a physiological basis.

"I'm just disgusted," says long COVID patient Hayes. "You wouldn't tell somebody with diabetes to breathe through it."

Chimére L. Sweeney, the director and founder of the Black Long COVID Experience, says she's even taken breaks from seeking treatment after getting fed up with being told that her symptoms were due to her diet or mental health.

"You're at the whim of somebody who may not even understand the spectrum of long COVID," Sweeney says.

Insurance battles over experimental treatments
Since there are still no FDA-approved long COVID treatments, anything a physician prescribes is classified as either experimental — for unproven treatments — or an off-label use of a drug approved for other conditions. This means patients can struggle to get insurance to cover prescriptions.

Dr. Michael Brode — the medical director of UT Health Austin's Post-COVID-19 Program — says he writes many appeal letters. And some people pay for their own treatment.

For example, intravenous immunoglobulin therapy, low-dose naltrexone and hyperbaric oxygen are all promising treatments, he says.

For hyperbaric oxygen, two small randomized controlled studies show improvements for the chronic fatigue and brain fog that often plagues long COVID patients. The theory is that higher oxygen concentration and increased air pressure can help heal tissues that were damaged during a COVID infection.

However, the out-of-pocket cost for a series of sessions in a hyperbaric chamber can run as much as $8,000, Brode says.

"Am I going to look a patient in the eye and say, 'You need to spend that money for an unproven treatment?'" he says. "I don't want to hype up a treatment that is still experimental. But I also don't want to hide it."

There's a host of pharmaceuticals that have promising off-label uses for long COVID, says microbiologist Amy Proal, president and chief scientific officer of the Massachusetts-based PolyBio Research Foundation. For instance, she's collaborating on a clinical study that repurposes two HIV drugs to treat long COVID.

Proal says research on treatments can move forward based on what's already understood about the disease. For instance, she says that scientists have evidence — partly due to RECOVER research — that some patients continue to harbor small amounts of viral material after a COVID infection. She has not received RECOVER funds but is researching antivirals.

But to vet a range of possible treatments for the millions suffering now — and to develop new drugs specifically targeting long COVID — clinical trials are needed. And that requires money.

The House Select Subcommittee on the Coronavirus Pandemic released its final report Monday, laying out numerous conclusions from its review of the federal pandemic response, including what the Republican-controlled panel believes to be the likely origins of the virus.

The 520-page document encompassed a wide range of issues relating to the pandemic including vaccinations, public health guidance, state-level actions and use of relief funds.

The subcommittee’s hearings were often marked by contentious back-and-forth between members and witnesses. Several interviews were held behind closed doors, including two days of interviews with Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, earlier this year.

Wenstrup listed seven specific findings in his letter, including that the National Institutes of Health funded controversial gain-of-function research at the Wuhan Institute of Virology, Operation Warp Speed was “tremendous success” and the public school closures will have an “enduring impact” on American children.

Here are three takeaways from the report:
Lab leak theory
The report starts with the finding that the SARS-CoV-2 virus “likely emerged because of a laboratory or research related accident.”

This finding was supported by remarks from people like Robert Redfield, the former director of the Centers for Disease Control and Prevention (CDC), former Director of National Intelligence John Ratcliffe and former U.K. Prime Minister Boris Johnson, all of whom publicly stated their support for the lab leak theory.

“Based on my initial analysis of the data, I came to believe — and still believe today — that it indicates COVID-19 infections more likely were the result of an accidental lab leak than the result of a natural spillover event,” Redfield is quoted as saying.

The report also found Fauci “prompted” the 2020 study titled “The proximal origin of SARS-CoV-2,” which supported the natural origins theory, to “disprove” the lab leak theory.

When he testified before the committee in June, Fauci reiterated that he did not edit the study or help to “suppress” the lab leak theory.

Different federal agencies have drawn different conclusions about the most likely origin of the virus, but it remains a mystery.

Mitigation efforts
The report is critical of many of the mitigation measures that were employed early on in the pandemic.

It found that masks and mask mandates were “ineffective at controlling the spread of COVID-19.” Several studies, including one published this August, have found masking in public has an effect on lowering respiratory viral transmission, though this should not be the sole measure used to mitigate spread.

Further, the report concluded lockdowns caused “more harm than good” to the economy, overall health of Americans and development of children.

The 6-foot social distancing guidance was also blasted as not being “supported by science.”

“Even though it was CDC guidance and not a mandate, it was forcefully implemented by state and local governments and caused lots of strife amongst Americans,” the report states.

However, there were some measures that the subcommittee found to have had some benefit or merit.

The public-private partnerships that were made to enable widespread COVID-19 testing early on in the pandemic allowed for “readily available and accurate tests,” though COVID-19 testing was called “flawed” in the report.

Travel restrictions were also cited as having saved lives.

“With four years of hindsight, it is clear the international travel restrictions early in the pandemic delayed spread of the virus but did not prevent COVID-19 from entering the U.S.,” states the report.

EcoHealth probes
The subcommittee’s report paid particular attention to the actions of EcoHealth Alliance, the nongovernmental organization that sub-awarded NIH grants to global labs including the Wuhan Institute of Virology.

Echoing criticism from members of the subcommittee, the report found EcoHealth failed to carry out proper oversight of the experiments it provided funding for, facilitated gain-of-function research and misled the NIH on the details of its research projects.

The NIH in turn also was found to have failed in its oversight of EcoHealth.

The report found that the Justice Department had empaneled a criminal grand jury to investigate the origins of COVID-19.

“EcoHealth was subject to numerous federal investigations regarding both its potential role in the COVID-19 pandemic, but also multiple accusations surrounding violated federal grant policies. The outcomes of most of these investigations are public,” it states.

“However, the Select Subcommittee discovered that DOJ was also investigating the origins of COVID-19,” it continued. “The specific details of the investigation are unknown but, based on documents, it appears the DOJ’s investigation involves EcoHealth’s role in the COVID-19 pandemic.”

The report says the results of the DOJ’s investigation are not public as of “December 4, 2024,” when the subcommittee plans to mark up the report.

Winter is almost here, so does that mean COVID is going around again?

A map of COVID activity in the U.S. shows some states have higher rates than others, but overall COVID rates are low in the U.S., with emergency department visits, deaths and hospitalizations stable or decreasing around the country, a Centers for Disease Control and Prevention (CDC) spokesperson tells TODAY.com.

That said, rates are expected to increase in the coming weeks as more people gather indoors for the holidays. Typically we see a large winter wave around this time, but there’s no national wave just yet — though there’s a lot of uncertainty in the data, Michael Hoerger, Ph.D., associate professor at Tulane University and public health expert on tracking COVID-19 infections, tells TODAY.com.

“This is the most uncertain time in pandemic forecasting in the past two years,” he adds.

Here's what to know about COVID in the U.S. as winter 2024 to 2025 approaches.

Is there a COVID-19 surge in the U.S. right now?
Multiple experts say there is no COVID-19 surge currently.

“In fact, we are entering the holiday season at the one of the lowest COVID rates in the past few years,” Dr. Scott Roberts, associate medical director of infection prevention at Yale School of Medicine in New Haven, Connecticut, tells TODAY.com.

He suspects many Americans still have immunity from getting infected during the most recent summer COVID-19 wave, which peaked in August.

“However, based on CDC modeled estimates of epidemic growth, we predict COVID-19 illness will increase as it usually does in the winter,” adds the CDC spokesperson.

Dr. Aaron Glatt, chief of infectious diseases at Mount Sinai South Nassau Hospital, expects cases to increase as more people stay indoors during the holidays but is hopeful that serious complications will remain relatively low because of vaccination and prior COVID exposures.

Which states currently have the highest COVID-19 rates?
Overall, the COVID prevalence is low, with the highest activity in the Midwest,” Dr. Kartik Cherabuddi, chief hospital epidemiology officer at Tampa General Hospital, tells TODAY.com.

According to viral activity in wastewater — one of the most accurate ways to measure cases since the CDC stopped tracking overall cases, — the states with the highest COVID rates, as of Nov. 30, are:

New Mexico
Arizona
Minnesota
Missouri
Montana
Nebraska
New Hampshire
Rhode Island
South Dakota

That said, many regions of the country are reporting low rates of COVID-19 positive tests — often defined by experts at less than 5%.

The CDC spokesperson says that the five states with the highest COVID-19 test positivity rates are:
Nevada (7.1%)
Hawaii (7.1%)
California (7.1%)
Arizona (7.1%)
Wyoming (6.3%)
But Cherabuddi reminds test positivity data depends on the tests reported.

“Our testing data is incomplete. We do not perform as much testing as we did during the pandemic,” he notes.

What will COVID look like for the rest of winter?
“It is difficult to predict the rest of the winter because it depends on a number of factors including virus evolution, weather (and) levels of protection, to name a few,” Cherabuddi says.

The United States may experience an increase in the spring as immunity from the fall wanes, adds Glatt.

After getting COVID-19, people develop antibodies to fight the virus, so the virus evolves to “escape” this immunity to cause re-infection.

But the current subvariants have not evolved to “escape” immunity as quickly as usual, Hoerger says.

“CDC expects the 2024-2025 fall and winter respiratory disease season will likely have a similar or lower number of combined peak hospitalizations due to COVID-19, influenza, and RSV compared to last season,” the CDC spokesperson says.

COVID-19 symptoms 2024
People may experience a wide range of symptoms, but mild respiratory symptoms are the most common, like congestion and sneezing.

These symptoms can be often confused with other respiratory illnesses, like influenza (flu), past research shows.

There is no way to tell you have COVID-19 by symptoms alone, though loss of taste and smell are more common with COVID-19 compared to other viral respiratory diseases, according to a previous study.

The most frequent COVID complication is pneumonia, which often presents with fever, cough, shortness of breath and/or chills, experts say.

COVID symptoms generally start within two to 14 days after an exposure, according to the CDC.

The agency notes some possible COVID symptoms include:

Sore throat
Runny nose
Fevers
Cough
Shortness of breath
Feeling tired
Loss of taste and smell
Headache
Nausea, vomiting or diarrhea
Muscle aches
Experts say the current dominant subvariant called XEC so far presents with similar symptoms and does not cause more severe disease compared to recent variants.

How to prevent COVID spread
“There are many effective tools like handwashing, masking and increased ventilation to prevent spreading COVID-19 or becoming seriously ill,” the CDC spokesperson notes.

Cherabuddi reminds to avoid crowed areas and taking extra precautions when traveling — especially during key steps of travel such as boarding and leaving the aircraft.

If you get sick or think you have COVID, the CDC provides these recommendations:

Get tested right away
Ask your doctor if you need any prescription medications, like Paxlovid
Stay home when you feel sick
Try to avoid being around your family members
Practice good hygiene: Cover your mouth if you cough or sneeze, wash your hands with soap and water often, and clean surfaces that are touched frequently.
The CDC also advises to make sure you have the cleanest air possible at home.

This means opening doors and windows in your home as much as possible and considering portable high-efficiency particulate air (HEPA) cleaners.

If your home has a central heating, ventilation and air conditioning system (HVAC), remember to change the filter according to the manufacturer’s instructions, which is usually every three months.

Americans should also stay up to date with COVID-19 vaccination.

“CDC expects the 2024-2025 COVID-19 vaccine to work well for currently circulating variants,” the CDC spokesperson says.

“There is still time to benefit from getting your recommended immunizations to reduce your risk of illness this season, especially severe illness and hospitalization.”

How to treat COVID
The CDC lists the following as the best options for treating COVID:

Antiviral medications, such as Paxlovid, which can prevent the virus from multiplying if administered early enough
Over-the-counter medications, such as acetaminophen, ibuprofen, cough medicine and fever reducers
Rest
Eating healthy
Staying hydrated

After a relatively slow start to the respiratory virus season, Covid-19 levels in the United States began ramping up just ahead of the winter holidays.

In previous years, Covid-19 levels have typically started to rise in early November and reach their seasonal peak by the end of December. But this year, levels were nearly the lowest they’ve ever been through October and all of November, according to wastewater surveillance data from the US Centers for Disease Control and Prevention.

Trends started to shift in early December, though, with levels rising from low to high by the middle of the month. In the week ending December 21, there was nearly three times as much Covid-19 circulating in the US than there was during the week ending December 7, CDC data shows.

This surge happened in all regions of the country, but there has been a particularly sharp uptick in the Midwest, where Covid-19 levels are nearly twice as high as they are in other parts of the country.

Some experts worry that the rapid rise after an unusually long lull could have left many people vulnerable to disease spread at the height of the holiday season.

In a social media post in mid-December, Dr. Michael Hoerger, a researcher at the Tulane University School of Medicine, called the latest wave of Covid-19 transmission a “’silent surge,’ coming on late out of nowhere.”

Hoerger runs a Covid-19 forecasting model that pulls heavily from the CDC wastewater surveillance data, and his estimates suggest that without any testing or isolation policies in place, there was a 1 in 8 chance of Covid-19 exposure at a gathering of 10 people on Christmas Day. On a plane of more than 100 people, there was a 3 in 4 chance of exposure.

The rapid rise in cases corresponds with a newly dominant coronavirus variant called XEC.

XEC is a hybrid of two JN.1 variants, which was the Omicron subvariant that accounted for most cases during last winter’s surge, according to the CDC. Agency data shows that the XEC variant has been circulating in the US for months but overtook one of the so-called FLiRT variants – KP.3.1.1 – between the end of November and the first week of December. From December 8 to 21, XEC accounted for 45% of new cases, up from 15% of cases two months earlier.

The currently circulating variants are similar enough to each other that the latest Covid-19 vaccines are still expected to be effective against severe illness or death, but vaccination rates are lagging. Only about 21% of adults and 10% of children have gotten their Covid-19 vaccine this season, according to CDC estimates.

And despite Covid-19’s slow start, the latest forecasts from the CDC’s official models predict that there could be as many hospitalizations for respiratory viruses as there were last year.

Overall, respiratory virus activity in the US is high. Flu levels had been high and rising for a few weeks before Covid-19 levels started to rise, and RSV levels are increasing, too. There were about 6 respiratory virus hospitalizations for every 100,000 people in the US during the third week of December, according to CDC data, twice as many as a month earlier.

And outbreaks of some other contagious diseases – including whooping cough and norovirus – are worse than they’ve been in more than a decade.

Norovirus is a common and very contagious virus that causes gastrointestinal symptoms. There have been nearly 500 outbreaks reported since August, according to CDC surveillance systems, a third more than this time last year.

Whooping cough, also known as pertussis, is a very contagious respiratory illness. For many, the bacterial infection starts with symptoms similar to the common cold — a runny nose, sneezing, a low-grade fever and a tickly cough — but a painful, full-body cough can develop after a week or two. These coughing fits can be so severe that they cause patients to vomit or break ribs, and they’re often accompanied by a whooping sound as the person tries to catch their breath.

Children now have the highest rate of emergency department visits for flu and RSV, according to the latest CDC data. Visits for Covid-19 are most common among seniors, followed closely by children younger than 5.