Long COVID-19 has had an air of mystery around it for months. Doctors have struggled to explain or understand why some people who contract COVID-19 end up having lingering symptoms like fatigue, difficulty thinking clearly, or shortness of breath weeks or even months later.
A new study published in the journal Cell helps shed some light on the condition, for the first time identifying four factors that can help predict whether someone will develop long COVID-19.
“Being able to identify the factors that can cause the disease, cause the chronic condition, is the first step towards defining that it actually is a condition that can be treatable,” Jim Heath, president of the Institute for Systems Biology in Seattle, and an author of the study, said in an interview. “And then some of these factors also are in fact the kind of things one can imagine developing treatments for.”
The most important factor the study identified in predicting long COVID-19 is the presence of certain kinds of antibodies called autoantibodies, which mistakenly attack healthy parts of the body. Autoantibodies are associated with autoimmune diseases, like lupus, where your immune system attacks your own body.
But someone does not have to have an autoimmune disease to have autoantibodies present and be at higher risk for long COVID-19, Heath said.
“Most people that have autoantibodies don’t really know it,” he said. “They’re what you call subclinical … maybe you have a risk of some autoimmune disease but it hasn’t developed.”
Still, he said one practical application of the study is that lupus treatments could be “worth exploring” as treatments for long COVID-19.
The second factor that can lead to long COVID-19 is the reactivation of a different virus called Epstein-Barr Virus (EBV), which is extremely common, infecting up to 90 percent of people at some point, and often causes only mild symptoms.
The virus usually becomes inactive in the body following the initial infection, but it can be reactivated when someone gets COVID-19, helping lead to long COVID-19 symptoms.
Heath said EBV could become reactivated when the immune system is distracted by fighting COVID-19.
“It could be that the large distraction that’s COVID-19 infection is taking that attention away,” he said.
The third factor identified is how much of the virus that causes COVID-19, officially called SARS-Cov-2, is present in the blood, known as the “viral load.”
This factor along with the role of EBV suggests that new antiviral drugs that fight the immediate effects of COVID-19 infection, like the Pfizer pill Paxlovid, might also be useful in treating long COVID-19.
“Two of these predictive factors are virus levels that are in the blood,” Heath said. “So that suggests that these antivirals that are being used to treat acute disease probably have a role for long COVID as well.”
The final of the four factors that can predict long COVID-19 is more easily identifiable: if a patient has Type 2 diabetes.
While these four factors are a step forward in understanding what causes long COVID-19 and helping develop treatments, the mechanism for why they are associated with long COVID-19 is still not fully clear.
“They have a flavor of mechanistic factors,” Heath said. “The actual mechanism is not clear.”
The study followed 309 COVID-19 patients, taking blood and swab samples at different points in time.
In addition, one way to likely cut the risk of long COVID-19 is vaccination. A separate study from the United Kingdom found that vaccinated people were 41 percent less likely to develop long COVID-19.
Merck antiviral drug molnupiravir received emergency authorization, joining Pfizer’s Paxlovid as the only authorized oral antiviral drugs for treating Covid-19. Though the Merck and Pfizer antivirals appear to work against the omicron variant, FDA officials stressed that these drugs are authorized only for certain patients and they are not a substitute for vaccination.
Merck’s oral antiviral drug molnupiravir now has FDA emergency use authorization for treating mild-to-moderate Covid-19, a Thursday decision that comes one day after the regulator authorized use of a pill from Pfizer. The FDA actions come as the highly infectious omicron variant becomes the dominant strain of the novel coronavirus, fueling a rise in Covid-19 cases that is pushing hospitals to capacity across the country.
The Merck and Pfizer antivirals both work by interfering with the virus’s ability to replicate, though in different ways. Molnupiravir introduces errors into the genetic code of SARS-CoV-2, while Paxlovid targets a key viral enzyme called main protease. Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, said both drugs should work against omicron.
“The available data that we have indicate that both Paxlovid and molnupiravir are effective against omicron,” Cavazzoni said, speaking during a Thursday morning media briefing. “Both drugs interfere with aspects of the virus’s replication apparatus, and that apparatus is preserved across variants.”
Molnupiravir’s authorization, which comes three weeks after an FDA advisory committee meeting for the drug, covers its use in adults diagnosed with Covid-19 who are at a high risk of their disease progressing to hospitalization or death. The Merck drug is to be used when other treatment options are not accessible or appropriate. It can only be prescribed to those 18 and older because the drug can affect bone and cartilage growth.
Authorized use of Pfizer’s antiviral, Paxlovid, extends to pediatric patients. The FDA’s guidelines state the drug may be used for treating Covid-19 patients 12 and older weighing at least 40 kg (about 88 pounds). The FDA did not convene an advisory meeting for the Pfizer drug. John Farley, director of FDA’s Office of Infectious Diseases, said there were no pressing scientific questions about Paxlovid that would benefit from an advisory committee discussion.
Both molunupiravir and Paxlovid are available only by prescription. The FDA said treatment with these drugs should begin as soon as possible after a positive Covid-19 diagnosis, and within five days of the start of symptoms. These drugs aren’t for patients who are already hospitalized. Earlier this year, Merck stopped testing molnupiravir in those who are hospitalized after an early look at Phase 2 trial data indicated that the drug was unlikely to help these patients.
Authorization of Merck’s antiviral is based on a placebo-controlled clinical trial enrolling non-hospitalized adults with Covid-19 who were at high risk of progressing to severe disease or hospitalization. These higher risk patients include those who have a chronic medical condition or those who had not or could not receive a Covid-19 vaccine. The main goal was to measure the percentage of people hospitalized or dead from any cause during the 29 days after the course of treatment. The FDA said that of the 709 people in the study who received molnupiravir, 6.8% were hospitalized or died. By comparison, 9.7% of the 699 people given a placebo were hospitalized or died. During the follow-up period, one patient treated with molnupiravir died compared to nine of those given a placebo. Side effects reported include diarrhea, nausea, and dizziness.
In the clinical trial for Pfizer’s antiviral, Paxlovid led to an 88% reduction in Covid-19-related hospitalization or death from any cause compared to placebo. Of the 1,039 patients treated with Paxlovid, 0.8% of patients were hospitalized or died during the 28-day follow-up period, compared to 6% of those given a placebo.
Farley said that patients should consult with their physician to determine the best treatment. While molnupiravir is indicated for those who don’t have other treatment options, there are some groups of patients in which Paxlovid would not be appropriate. Examples include patients taking other medications that could interact with the Pfizer drug, Farley said. Paxlovid is also not recommended for patients who have severe kidney problems or cirrhosis of the liver. The key feature of both drugs is that they are oral, which enables patients to take these medication at home. Authorized antibody therapies from Regeneron, Eli Lilly, partners Vir Biotechnology and GlaxoSmithKline, and Roche, are infusions that must be administered in a clinical setting.
Patients take Merck’s molnupiravir as four pills, twice a day. Patients prescribed Pfizer’s Paxlovid must take more pills. The drug is taken with ritonavir, a drug that slows the breakdown of Paxlovid and helps it remain in the body for a longer period of time. Dosing of the Pfizer drug requires two tablets of Paxlovid and one of ritonavir, twice daily. The duration of treatment for both the Merck and Pfizer antivirals is five days.
1. While “vaccination” briefly appeared onscreen in a list of options, it didn’t merit a mention in the video.
2. The surgeon general listed guidance on “emerging” treatments that was … remarkably on point.
The absence of focus on vaccines in the video is unfortunate, if entirely in keeping with the GOP’s willingness to play to its anti-vax base. That’s bad, but not surprising.
What was surprising was No. 2. The information Ladapo shared about treatments was fairly accurate. In the video, he told Floridians to ask their doctor about monoclonal antibodies, fluvoxamine, and inhaled budesonide should they come down with Covid-19.
I’ve been reporting on the Covid-19 treatment beat for much of this year, and I’ve uncovered a massively confusing pile of contradictory information. But those are the top three treatments I’d recommend sick loved ones talk to doctors about, and while there’s much we still don’t know, solid science suggests they have real promise.
That said, the fact that such important (and accurate) information stood out in a government PSA indicates just how dismal the state of public communications on treatments is — and just how much misinformation and distrust are hampering the fight against Covid-19.
What should you take if you get Covid-19?
There’s been little public health communication about which treatments to pursue if you get Covid-19, perhaps because for much of the pandemic, it’s been unclear what options are better for mild Covid than just resting at home. While in 2021 the best treatment recommendations have gotten clearer, public health messaging over the last year has rightly been focused on vaccination.
The official CDC page on what to do if you get sick with Covid-19 advises you to wear a mask, wash your hands, and clean high-touch surfaces to avoid infecting those around you. If your breathing deteriorates or you show signs of severe illness like confusion or an inability to stay awake, the CDC advises you to go to the hospital.
All sound guidance — but what it doesn’t offer is advice on a question that patients who aren’t sick enough for hospitalization might desperately need to know: What medication should I take if I come down with Covid-19?
Meanwhile, large, high-quality, peer-reviewed, and published randomized controlled trials (RCTs) have found promise for cheap therapies that are already FDA approved for other purposes and have an established safety profile.
Research underway will help provide a better understanding of both of these therapies, but there’s enough evidence that some doctors are already prescribing them to patients. If you have the opportunity to enroll in an ongoing clinical trial of these medications, you can get access to a potentially promising treatment and help contribute to our scientific understanding of whether these treatments really work.
Another exciting treatment in the pipeline is Paxlovid, an antiviral developed by Pfizer that showed impressive 90 percent efficacy in preventing hospitalization — so effective that in November, the clinical trial stopped enrolling new participants because investigators concluded it’d be unethical to put them in the control group. It has not yet been approved by the FDA, but it might be a game changer if, as is expected, it’s approved in January.
Why is it so hard to find good guidance about treatments?
The US government has communicated little about Covid-19 treatment options. NIH guidelines about treatments like fluvoxamine haven’t been updated since this past spring, meaning results from recent high-quality studies haven’t been incorporated into that guidance. Without it, physicians considering whether to prescribe these medications can’t turn to official public health resources for help.
From a certain perspective, that reticence is understandable. Learning which Covid-19 treatments work is very hard. While large-scale RCTs found promising evidence for fluvoxamine and inhaled budesonide, “promising” is still the most we can say — it could absolutely turn out that the real-world effects are much smaller than hoped for, or even fail to materialize altogether.
But it’s precisely because this area is so difficult to navigate for doctors and patients that the CDC, FDA, and NIHcould play an important role in pointing out good treatments — yet it’s a role they have been puzzlingly reluctant to play.
Perhaps because of the dearth of formal federal government guidance on treatments — and because of politically driven crazes over drugs like hydroxychloroquine and ivermectin, which evidence thus far suggests do little to fight Covid-19 — Florida media hasbeencritical of Ladapo’s PSA and its recommendations.
But that justified irritation shouldn’t get in the way of a needed conversation about the possible benefits and drawbacks of monoclonal antibodies, fluvoxamine, and budesonide. As the US braces for an omicron surge that is likely to hit even vaccinated people, effective treatment is going to be essential for saving lives. Yes, promoting vaccines is a must, but tens of thousands of Americans are getting sick each day, which makes clear, accurate communication about which treatments to ask your doctor about extremely important.
The more society and public health get aligned on what works, the better off we’ll be in confronting omicron and other future variants.
Regulators in Britain granted approval to the experimental drug molnupiravir from U.S. pharmaceutical giant Merck on Thursday, marking the first authorization from a public health body for an oral antiviral treatment for covid-19 in adults.
Experts have said that if widely authorized, the medicine could have huge potential to help fight the coronavirus pandemic: Pills are easier to take, manufacture and store, making them particularly useful in lower- to middle-income countries with weaker infrastructure and limited vaccine supplies.
“We will continue to move with both rigor and urgency to bring molnupiravir to patients around the world as quickly as possible,”Merck President Robert M. Davis said in a statement.
The company, which added that it would submit applications to other regulatory agencies, has applied to the U.S. Food and Drug Administration for emergency use authorization, while the European Medicines Agency has launched a rolling review of the drug.
“Today is a historic day for our country,” British Health Secretary Sajid Javid said in Thursday’s announcement. “This will be a game changer for the most vulnerable … who will soon be able to receive the ground-breaking treatment.”
In a global clinical trial, the pill reduced hospitalizations and deaths by nearly half among higher-risk adult coronavirus patients diagnosed with mild to moderate illness, according to Merck, which developed the drug with Ridgeback Biotherapeutics after it was discovered at Emory University. The first dose given to a volunteer in the trial was in the United Kingdom.
The U.K. medicines regulator approved the use of the treatment in people who are above 60 years old or have at least one other factor that puts them at risk of covid-19 developing into severe illness, such as obesity and heart disease. The agency found it “safe and effective” at curbing the risk after “a rigorous review.”
Britain became known during the pandemic for its speed in authorizing vaccines. It was the first country in the world to approve a coronavirus vaccine tested in a large clinical trial when it granted emergency-use authorization to the Pfizer-BioNTech shot last December.
The United States has made an advance purchase of 1.7 million courses of molnupiravir at a cost of about $1.2 billion, or roughly $700 per treatment course. Other countries have also reached agreements with Merck to buy the pills, including Australia, Singapore and South Korea.
The U.S. drugmakersaid it expects to produce 10 million courses of the treatment by the end of this year, along with at least 20 million in 2022, and that it plans to adopt a “tiered pricing approach” taking into account each country’s ability to pay.
The firm has also agreed to share its license for the pill with several Indian manufacturers and with a U.N.-backed nonprofit organization to allow production around the world and help boost access to more than 100 low- and middle-income countries.
The move stood out in a pandemic that has seen pharmaceutical companies lobbying to keep rights to vaccines. Some advocacy organizations, however, have criticized Merck for leaving out upper-middle-income countries hit hard by the pandemic.
Suerie Moon, co-director of the Global Health Center in Geneva, described the first approval of molnupiravir as “a big step forward.”
“I would say it’s very significant in terms of giving patients and the public a large confidence that this treatment can be widely used,” she said.
The drug — which received a type of conditional market authorization for products that fulfill an unmet medical need — will go by the name Lagevrio in Britain. It works by introducing errors that garble the genetic code of the virus and prevent it from making copies of itself. The window in which it can be administered and still work may be narrow, though, and the British regulator recommended taking it “as soon as possible” after a positive coronavirus test and within five days of symptoms onset.
The U.K. health secretary, Javid, called it “an excellent addition to our armory,” while urging people to keep getting their covid-19 shots. Doctors maintain the vaccines remain the principal tool against the coronavirus, as they seek to help prevent people from catching it rather than treating the disease after infection.
The pill is notably easy to use compared to monoclonal antibodies, a costly treatment that is infused or injected. Virologists have said they are hopeful that as well as limiting the risk of developing severe illness, the treatment could help reduce transmission of the virus too.
A new drug by Merck significantly reduces the risk of hospitalization and death in people who take it early in the course of their COVID-19 illness, according to the interim results of a major study released today. It is the first oral antiviral found to be effective against this coronavirus.
People who took this drug, called molnupiravir—four pills twice a day for five days—within five days of showing symptoms were about half as likely to be hospitalized as those taking the placebo. They were also less likely to die, with eight deaths in the placebo group reported within a month of treatment and none in those who received the medicine.
“Having a pill that would be easy for people to take at home would be terrific. If this was available through a drug store, more people could get it,” says Albert Shaw, an infectious diseases specialist at Yale Medicine in New Haven, Connecticut, who was not involved with the research. All of the antiviral medicines available today, including remdesivir and the monoclonal antibodies, must be administered through an IV in a medical setting. Monoclonal antibodies are much more effective against COVID-19 and cut the risk of hospitalization and death by up to 85 percent, but this treatment costs almost three times as much as molnupiravir.
How the antiviral works
Antiviral drugs are used against many viruses, including for herpes and the flu. These drugs take advantage of the fact that viruses need to replicate inside a person’s cells in order to sicken them. Antivirals stop the replication process so the illness doesn’t progress.
The Merck drug works by introducing RNA-like building blocks into the virus’s genome as it multiplies, which creates numerous mutations, disrupts replication, and kills the virus.
Keeping the virus from multiplying is important because the more it replicates, destroying cell after cell, the sicker a person usually becomes, says Waleed Javaid, an epidemiologist and director of infection prevention and control at Mount Sinai Downtown in New York, who was not involved in the study. Additionally, when enough virus is inside the body the immune system may go into overdrive. “At a certain point the body detects a virus it has never seen and will throw everything against it, like a tank coming at a small target.” he says. This helps the body eliminate the virus but can cause sometimes deadly collateral damage throughout the body in its wake.
The research, which was conducted in numerous sites around the world, was stopped early because the results were so promising, Merck says. The drug was even effective against variants like Delta and Mu. Based on this interim analysis in 775 people, the company plans to submit an application for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration as well as regulatory bodies in other countries in hopes the drug can be made available. When that will happen is not clear, but the U.S. government has already agreed to purchase 1.7 million courses of treatment at $700 each, Merck notes.
Who can get the drug?
It’s also not known who would ultimately be authorized to take the medicine. The study included only people who were sick and unvaccinated and had at least one risk factor for developing a severe case of COVID-19, says Aaron Weinberg, national director of clinical research at Carbon Health, a for-profit provider of primary and urgent care, and a principal investigator of the study. This includes people who are older than 60, obese, immunocompromised from another condition, or have underlying heart or pulmonary disease, among others.
If the FDA does authorize the drug, it could limit who gets it to people like those in the research, Javaid says.
Although this drug looks promising, it’s a treatment but not a prophylactic like the vaccine. The medicine does not negate the need for unvaccinated people to get their shot, Shaw says. Some people taking the pills still got sick enough to be hospitalized. And while side effects in this study were mild—generally gastrointestinal issues, Weinberg says, and at comparable rates in the treatment and placebo groups—safety issues might emerge when the drug is given more broadly, Shaw says. Meanwhile, hundreds of millions of people have already gotten the vaccines with no major consequences.
Still, the results of this study should be celebrated, Javaid says. “Saving eight lives is huge, as is halving hospitalization,” he says. Perhaps another drug being studied will later prove to be more effective, reducing hospitalization by 80 or even 100 percent, he says. “But this is better than any oral antivirals we have right now, which is none,” he says.
Interest in the antiparasitic drug Ivermectin has increased drastically as of late thanks to the belief that it can help to prevent and/or treat Covid-19. In today’s episode we examine recent data on the efficacy of Ivermectin as an antiviral and discuss the history behind how it gained this reputation.
Just as other industries are rolling back some consumer-friendly changes made early in the pandemic — think empty middle seats on airplanes — so, too, are health insurers.
Many voluntarily waived all deductibles, copayments and other costs for insured patients who fell ill with covid-19 and needed hospital care, doctor visits, medications or other treatment.
Setting aside those fees was a good move from a public relations standpoint. The industry got credit for helping customers during tough times. And it had political and financial benefits for insurers, too.
But nothing lasts forever.
Starting at the end of last year — and continuing into the spring — a growing number of insurers are quietly ending those fee waivers for covid treatment on some or all policies.
“When it comes to treatment, more and more consumers will find that the normal course of deductibles, copayments and coinsurance will apply,” said Sabrina Corlette, research professor and co-director of the Center on Health Insurance Reforms at Georgetown University.
Even so, “the good news is that vaccinations and most covid tests should still be free,” added Corlette.
That’s because federal law requires insurers to waive costs for covid testing and vaccination.
Guidance issued early in President Joe Biden’s term reinforced that Trump administration rule about waiving cost sharing for testing and said it applies even in situations in which an asymptomatic person wants a test before, say, visiting a relative.
But treatment is different.
Insurers voluntarily waived those costs, so they can decide when to reinstate them.
Indeed, the initial step not to charge treatment fees may have preempted any effort by the federal government to mandate it, said Cynthia Cox, a vice president at KFF and director for its program on the Affordable Care Act.
In a study released in November, researchers found about 88% of people covered by insurance plans — those bought by individuals and some group plans offered by employers — had policies that waived such payments at some point during the pandemic, said Cox, a co-author. But many of those waivers were expected to expire by the end of the year or early this year.
Some did.
Anthem, for example, stopped them at the end of January. UnitedHealth, another of the nation’s largest insurers, began rolling back waivers in the fall, finishing up by the end of March. Deductible-free inpatient treatment for covid through Aetna expired Feb. 28.
A few insurers continue to forgo patient cost sharing in some types of policies. Humana, for example, has left the cost-sharing waiver in place for Medicare Advantage members, but dropped it Jan. 1 for those in job-based group plans.
Not all are making the changes.
For example, Premera Blue Cross in Washington and Sharp Health Plan in California have extended treatment cost waivers through June. Kaiser Permanente said it is keeping its program in place for members diagnosed with covid and has not set an end date. Meanwhile, UPMC in Pittsburgh planned to continue to waive all copayments and deductibles for in-network treatment through April 20.
What It All Means
Waivers may result in little savings for people with mild cases of covid that are treated at home. But the savings for patients who fall seriously ill and wind up in the hospital could be substantial.
Emergency room visits and hospitalization are expensive, and many insured patients must pay a portion of those costs through annual deductibles before full coverage kicks in.
Deductibles have been on the rise for years. Single-coverage deductibles for people who work for large employers average $1,418, while those for employees of small firms average $2,295, according to a survey of employers by KFF. (KHN is an editorially independent program of KFF.)
Annual deductibles for Affordable Care Act plans are generally higher, depending on the plan type.
Both kinds of coverage also include copayments, which are flat-dollar amounts, and often coinsurance, which is a percentage of the cost of office visits, hospital stays and prescription drugs.
Ending the waivers for treatment “is a big deal if you get sick,” said Robert Laszewski, an insurance industry consultant in Maryland. “And then you find out you have to pay $5,000 out-of-pocket that your cousin didn’t two months ago.”
Costs and Benefits
Still, those patient fees represent only a slice of the overall cost of caring for a hospitalized patient with covid.
While it helped patients’ cash flow, insurers saw other kinds of benefits.
For one thing, insurers recognized early on that patients — facing stay-at-home orders and other restrictions — were avoiding medical care in droves, driving down what insurers had to fork out for care.
“I think they were realizing they would be reporting extraordinarily good profits because they could see utilization dropping like a rock,” said Laszewski. “Doctors, hospitals, restaurants and everyone else were in big trouble. So, it was good politics to waive copays and deductibles.”
Besides generating goodwill, insurers may benefit in another way.
Under the ACA, insurers are required to spend at least 80% of their premium revenue on direct health care, rather than on marketing and administration. (Large group plans must spend 85%.)
By waiving those fees, insurers’ own spending went up a bit, potentially helping offset some share of what are expected to be hefty rebates this summer. That’s because insurers whose spending on direct medical care falls short of the ACA’s threshold must issue rebates by Aug. 1 to the individuals or employers who purchased the plans.
A record $2.5 billion was rebated for policies in effect in 2019, with the average rebate per person coming in at about $219.
Knowing their spending was falling during the pandemic helped fuel decisions to waive patient copayments for treatment, since insurers knew “they would have to give this money back in one form or another because of the rebates,” Cox said.
It’s a mixed bag for consumers.
“If they completely offset the rebates through waiving cost sharing, then it strictly benefits only those with covid who needed significant treatment,” noted Cox. “But, if they issue rebates, there’s more broad distribution.”
Even with that, insurers can expect to send a lot back in rebates this fall.
In a report out this week, KFF estimated that insurers may owe $2.1 billion in rebates for last year’s policies, the second-highest amount issued under the ACA. Under the law, rebate amounts are based on three years of financial data and profits. Final numbers aren’t expected until later in the year.
The rebates “are likely driven in part by suppressed health care utilization during the COVID-19 pandemic,” the report says.
Still, economist Joe Antos at the American Enterprise Institute says waiving the copays and deductibles may boost goodwill in the public eye more than rebates. “It’s a community benefit they could get some credit for,” said Antos, whereas many policyholders who get a small rebate check may just cash it and “it doesn’t have an impact on how they think about anything.”
Anti-inflammatory oral drug colchicine improved COVID-19 outcomes for patients with relatively mild cases, according to certain topline results from the COLCORONA trial announced in a brief press release.
Overall, the drug used for gout and rheumatic diseases reduced risk of death or hospitalizations by 21% versus placebo, which “approached statistical significance.”
However, there was a significant effect among the 4,159 of 4,488 patients who had their diagnosis of COVID-19 confirmed by a positive PCR test:
25% fewer hospitalizations
50% less need for mechanical ventilation
44% fewer deaths
If full data confirm the topline claims — the press release offered no other details, and did not mention plans for publication or conference presentation — colchicine would become the first oral drug proven to benefit non-hospitalized patients with COVID-19.
“Our research shows the efficacy of colchicine treatment in preventing the ‘cytokine storm’ phenomenon and reducing the complications associated with COVID-19,” principal investigator Jean-Claude Tardif, MD, of the Montreal Heart Institute, said in the press release. He predicted its use “could have a significant impact on public health and potentially prevent COVID-19 complications for millions of patients.”
Currently, the “tiny list of outpatient therapies that work” for COVID-19 includes convalescent plasma and monoclonal antibodies, which “are logistically challenging (require infusions, must be started very early after symptom onset),” tweeted Ilan Schwartz, MD, PhD, an infectious diseases researcher at the University of Alberta in Edmonton.
The COLCORONA findings were “very encouraging,” tweeted Martin Landray, MB ChB, PhD, of the Big Data Institute at the University of Oxford in England. His group’s RECOVERY trial has already randomized more than 6,500 hospitalized patients to colchicine versus usual care as one of the arms of the platform trial, though he did not offer any findings from that study.
“Different stage of disease so remains an important question,” he tweeted. “Maybe old drugs can learn new tricks!” Landray added, pointing to dexamethasone.
A small open-label, randomized trial from Greece had also shown less clinical status deterioration in hospitalized patients on colchicine.
“I think this is an exciting time. Many groups have been pursuing lots of different questions related to COVID and its complications,” commented Richard Kovacs, MD, immediate past-president of the American College of Cardiology. “We’re now beginning to see the fruit of those studies.”
The COLCORONA announcement came late Friday, following closely on the heels of the topline results from the ACTIVE-4a, REMAP-CAP, and ATTACC trials showing a significant morbidity and mortality advantage to therapeutic-dose anticoagulation in non-ICU patients in the hospital for COVID-19.
COLCORONA was conducted remotely, without in-person contact, with participants across Canada, the U.S., Europe, South America, and South Africa. It randomized participants double-blind to colchicine 0.5 mg or a matching placebo twice daily for the first 3 days and then once daily for the last 27 days.
Participants were ages 40 and older, not hospitalized at the time of enrollment, and had at least one risk factor for COVID-19 complications: age 70-plus, obesity, diabetes, uncontrolled hypertension, known asthma or chronic obstructive pulmonary disease, known heart failure, known coronary disease, fever of ≥38.4°C (101.12°F) within the last 48 hours, dyspnea at presentation, or certain blood cell abnormalities.
It had been planned as a 6,000-patient trial, but whether it was stopped for efficacy at a preplanned interim analysis or for some other reason was not spelled out in the press release. Whether the PCR-positive subgroup was preplanned also wasn’t clear. Key details such as confidence intervals, adverse effects, and subgroup results were omitted as well.
While a full manuscript is reportedly underway, “we don’t know enough to bring this into practice yet,” argued Kovacs.
Some physicians also warned about the potential for misuse of the findings and attendant risks.
Dhruv Nayyar, MD, of the University of Toronto, tweeted that he has already had “patients inquiring why we are not starting colchicine for them. Science by press release puts us in a difficult position while providing care. I just want to see the data.”
Angela Rasmussen, MD, a virologist with the Georgetown Center for Global Health Science and Security’s Viral Emergence Research Initiative in Washington, agreed, tweeting:“When HCQ [hydroxychloroquine] was promoted without solid data, there was at least one death from an overdose. We don’t need people self-medicating with colchicine.”
As was the case with hydroxychloroquine before the papers proved little efficacy in COVID-19, Kovacs told MedPage Today: “We always get concerned when these drugs are repurposed that we might see an unintended run on the drug and lessen the supply.”
Citing the well-known diarrheal side effect of colchicine, infectious diseases specialist Edsel Salvana, MD, of the University of Pittsburgh and University of the Philippines in Manila, tweeted a plea for use only in the trial-proven patient population with confirmed COVID-19 — not prophylaxis.
The dose used was on par with that used in cardiovascular prevention and other indications, so the diarrhea incidence would probably follow the roughly 10% rate seen in the COLCOT trial, Kovacs suggested.
In the clinic, too, there are some cautions. As Elin Roddy, MD, a respiratory physician at Shrewsbury and Telford Hospital NHS Trust in England, tweeted: “Lots of drug interactions with colchicine potentially — statins, macrolides, diltiazem — we have literally been running up to the ward to cross off clarithromycin if RECOVERY randomises to colchicine.”
Vic Gara, 57, at his home in West Granby Dec. 10, 2020. Gara survived COVID-19 in a hospital ICU bed on a ventilator. Months later, he discovered he was experiencing long-term complications from the virus.
In early March, Vic Gara came down with severe muscle aches, headaches and a rising blood pressure, indicators of COVID-19 that weren’t well understood early on in the pandemic.
“Taking a shower, just the water hurt my body,” he said. “I couldn’t sleep. I slowly became hypoxic. I just couldn’t breathe.”
Eventually, he was admitted to Hartford Hospital, where he was quarantined immediately and separated from his wife, Laura.
“My wife was walking in from after parking the car, and I saw her from maybe 15, 20 feet away and I just barely raised my hand and said goodbye to her,” Gara recalled. “And I was there for a month.”
The 57-year-old was intubated and spent 11 days on a ventilator, which helped him breathe, before he regained consciousness. Like so many others who required intensive care, Gara was first transferred to a rehabilitation hospital for a short time before he could return to his home in West Granby.
He thought the worst was behind him. But by midsummer, Gara struggled with exhaustion, his headaches returned, he had poor balance and trouble speaking and “brain fog” had set in. Then he joined an online support group for COVID-19 survivors.
“Not until I was contacted did I find out, ‘Oh my god, there’s other people like me that are suffering almost identical situations,’” he said.
There is an untold number of COVID-19 survivors worldwide who struggle with long-term symptoms and complications from the virus. Scientists don’t yet know how common this occurs, but what they do know is symptoms can be both physical and mental in nature, and they can delay people from making a full recovery.
As the phenomenon becomes more well-known and researched, health organizations across Connecticut and the country are creating and expanding dedicated COVID-19 recovery programs to help survivors.
“We’re now seeing patients that have had some of those symptoms for eight, nine months,” said Dr. Jerry Kaplan, outpatient medical director at Gaylord Hospital in Wallingford. He runs the organization’s new COVID-19 recovery and rehabilitation program.
The hospital created an online support group over the summer for former COVID-19 rehab patients like Gara. Kaplan said that’s when patients came forward with a wide range of lingering health issues.
Gaylord opened its specialized outpatient program in early fall, and it provides COVID-19 survivors with occupational and physical therapies, nutrition education, psychological treatment and other services.
“Even if you can’t do everything you were doing before, we can get you to the highest possible functional level,” Kaplan said, “and that’s really what the program is designed to do.”
The program has picked up in the last several months as long-term complications from COVID-19 illness become more well-known.
“As we see more patients hospitalized with COVID now, we will continue to see the need for COVID recovery programs in the future,” Kaplan said.
The Post-COVID-19 Recovery Program at Yale Medicine opened several months ago as a Friday clinic with a small patient roster. Dr. Denyse Lutchmansingh said it has now expanded to three days a week as more patients and medical clinicians discover the program.
“I think early on, people would say, give it a couple of weeks and you should feel better,” she said. “And now we’re well past that give-it-a-couple-of-weeks period and people are still having symptoms.”
Lutchmansingh, a pulmonary and critical care physician who leads the Yale recovery program, said she and her colleagues initially expected that patients who had had moderate to severe COVID-19 illness, like Gara, would be the ones needing long-term recovery services the most.
That’s only been partly true.
“Patients who were classified as mild disease have also had persistent symptoms almost as severe as a patient who was hospitalized in an intensive care unit, and that has been quite eye-opening,” she said.
Lutchmansingh said the clinic is also seeing a surprisingly young population. She has patients in their 30s and 40s who were runners, athletically inclined, or generally in good health prior to getting a mild case of COVID-19 “who now struggle to walk up a flight of stairs.”
It’s some of these patients that Lutchmansingh has seen struggle the most mentally with their persistent symptoms.
“Because they expected to recover very quickly and move on,” she said.
Dr. Serena Spudich is the division chief of neurological infections and global neurology at Yale School of Medicine and leads a designated neuro-COVID clinic, which opened in October.
Her team collaborates with Lutchmansingh and other clinicians in the greater community to get referrals for COVID-19 survivors suffering with tingling and numbness, loss or impaired senses of smell, taste and hearing, headaches, cognitive impairment and other complications.
Many of these patients were never hospitalized or never required intensive care for COVID-19.
This is where more research can help make sense of the trends that health providers are seeing in their COVID-19 “long hauler” patients, Spudich said.
“I think it’s really important to try to understand why some people get these neurologic issues, and many people don’t seem to,” she said. “I know lots of people who’ve recovered from COVID who seem completely fine.”
Scientists are still trying to estimate exactly how many people in the world ever had COVID-19, including those who never got tested or people who got false negative results — cases that have not been recorded.
Only then might health experts know how common or rare long-term complications are among survivors, Spudich said.
“I think it’s important to be aware of them, to understand them and of course provide treatment for them,” she said. “But I worry that it’s sort of a fire that can take off where all the social media, all the press attention will suddenly make a lot of people think, ‘Oh, I’m having post-COVID problems.’”
“What is really, really important is getting patients who are having symptoms to a provider who can really critically take care of them and try to understand clinically what’s happening with them.”
What patients often want to know is, when will their health get back to what it was prior to COVID-19? And health experts don’t yet have a good answer to that as scientists continue to follow survivors in their recovery.
“We always make it clear to the patients that we don’t have all the answers. We are looking for answers,” Lutchmansingh said. “We remain hopeful, we have seen patients improve and build back to baseline, but it is a long pathway and it is not necessarily an easy pathway.”
For Gara, he continues recovery treatment at Gaylord on an outpatient basis. He tries to get outside more and build up his endurance with walks. For the most part, he takes it one day at a time.
“I went into it with an open mind and trying to stay positive,” he said. “I learned how to be more positive and look for the good rather than the bad. It helps.”
When Ashley Antonio contracted covid-19 in late March, the Canadian criminal lawyer fought against the common symptoms that come with most cases: fever, body aches, fatigue, headaches.
She would manage her symptoms at home and eventually overcome them, she assured herself. After all, she was a healthy 35-year-old with no underlying conditions who boxed and did strength training four times a week.
Except the symptoms never really went away — they intensified.
Now, 259 days later, Antonio is still suffering the repercussions of a virus that has upended almost every aspect of her life.
She has been in and out of the hospital four times in almost nine months. Her doctors have diagnosed Antonio with arthritis and a condition that causes her heartbeat to dramatically increase when she stands up. Both are long-term effects of the virus, they told her. They also don’t know if, and when, those symptoms will go away.
“Everyone is just told you either recover or you die,” Antonio told The Washington Post on Tuesday. “There’s never talk of all the people that are trapped somewhere in the middle with all of these long-term effects. We’re not recovered. We’re just not covid-positive anymore.”
Antonio is not alone. Doctors still aren’t sure why “long-haulers” continue to suffer the consequences of the disease months later or whether the symptoms will stay with them for the rest of their lives. But public health experts say it’s increasingly clear that many thousands of patients face long-term effects from the virus.
Long-haulers “are in every country, in every language,” Igor J. Koralnik, who started a program for covid-19 neurocognitive problems at Northwestern Memorial Hospital in Chicago, told The Post in October. “It’s going to be a big problem. It’s not going to go away.”
So far, clinicians have learned the long-term effects can impact both the old and the young, regardless of whether the case was mild or required hospitalization. Many long-haulers have turned to social media groups to share their experiences and advice.
Antonio, who lives in Edmonton and whose story was first reported by the CBC, said she had been taking precautions and working from home for a month before she got sick. Her best guess is that she caught the virus on a run to the grocery store. She began feeling symptoms around March 25.
But because she did not have a cough, which doctors and health experts then said was one of covid-19′s main symptoms, Antonio thought she only had a stomach flu.
She stayed home and started to feel like herself again days later. But every time she thought she was recovering, symptoms would return. In the next three months, old symptoms and new, graver ones left Antonio tied to her couch. The fatigue was so bad she could shower only a couple of times a week. Her blood oxygen levels would drop dangerously low whenever she took short steps. One day, her brain was so foggy that she could not remember how to hold a glass.
It wasn’t until mid-May when she was taken to the emergency room for the first time. Alone in her bedroom and fighting a high fever, Antonio began hallucinating. Then, she could not feel half of her body or her face. The hospital tested her for the coronavirus, but her results came back negative so she was sent home. About a week later, she was back. She would return two more times in the following months.
“I had every test you could imagine,” she said. But her doctors could still not figure out what exactly was wrong with her. An emergency room doctor suggested she might have long-term covid-19 effects and referred her to a special clinic.
In June, she tested positive for coronavirus antibodies. In July, doctors at a clinic for coronavirus survivors diagnosed her with arthritis and a condition that causes her heartbeat to raise significantly when standing. “But doctors couldn’t explain why my oxygen was still dropping every time I walked or any other symptoms,” she said.
Antonio turned to other long-haulers for more information, joining a Facebook group where she learned, for example, that she wasn’t alone in smelling cigarettes when no one was smoking near her. Other people experienced random smells too, they told her.
“I had a lot of questions and the doctors didn’t have a lot of answers. It was all so new to everyone,” Antonio said. “I just wanted to see if what I was experiencing was ‘normal.’ It was very comforting to know that I wasn’t alone.”
Although her symptoms persisted, in August, Antonio voluntarily returned to the law firm where she works as a criminal lawyer. Some days, she feels okay. But the increased heart rate, shortness of breath, joint pain and headaches are usually daily ailments. She also still suffers from blurry vision and gets skin rashes. Her doctors have now told her it’s possible that her long-term symptoms will come and go for the rest of her life. For now, Antonio said she is taking it one day at a time.
“I’m definitely worried it will be permanent,” she said. “It’s very overwhelming if I think that this is how the rest of my life is going to be.”
Antonio added: “When I have a good day, I no longer think that it will be over. I know I’ll have bad days again. It makes you feel hopeless.”
HENRY KOTULA 