Coronavirus Updates February 2025

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Paxlovid: Worth a Long Look for Easing Long COVID​

Sara Novak

February 1, 2025


Paxlovid, one of the most well-known treatments for COVID-19, has also been shown to ease symptoms of some patients with long COVID — and new research suggests the antiviral medication could prove to be an important treatment for some with the condition.

A study published in Communication Medicine found that some patients experienced improvement in their long COVID symptoms after taking the medication for a longer period, up to 30 days in some cases. The most common symptom improvements included a decrease in fatigue and neurocognitive symptoms like brain fog and memory loss.

“This is all observational data, so we weren’t able to make causal claims, but what we can say is that extended use of the medication may have meaningful benefits for some people with long COVID but not others,” said lead study author Alison Cohen, PhD, an epidemiologist at the University of California, San Francisco.


Commonly prescribed to treat acute COVID and for the prevention of long COVID, the data are less clear on whether Paxlovid is effective at treating patients who already have the condition, but it has been shown to help some patients, but not others with the condition.

Prevention but Not Necessarily a Cure​

Paxlovid has a clear role in preventing long COVID in patients with acute COVID, which has been shown in the data, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of Research and Development at the Veterans Affairs St. Louis Health Care System. A study led by Al-Aly in JAMA Internal Medicine found that Paxlovid was tied to a 26% reduced risk of developing long COVID over a 6-month period.





“It’s good for prevention, but in those who already have it, the evidence is very preliminary,” said Al-Aly. “Some people did improve, but we can’t draw broad conclusions from the study about whether they would have improved anyway without taking the medication.”


Nisha Viswanathan, MD, director of the University of California, Los Angeles long COVID program, agrees. While she has prescribed it for use in treating acute COVID, she’s never prescribed it for long COVID and notes that while a shorter 15-day course of the antiviral was found safe, it was ineffective at treating patients with long COVID, as documented in a study published last June in JAMA Internal Medicine.

“The reason that we haven’t been seeing success with using any one intervention is likely because different patients have different root causes of long COVID, which is why some might be responding well to Paxlovid and others not,” said Viswanathan.

By shutting down the viral reservoir that, in some patients with long COVID, causes the condition, some may experience symptom improvement. “But it’s still a matter of targeting the right patients,” adds Viswanathan.

Paxlovid’s Severe Side Effects​

Ritonavir was previously used as an HIV medication that lessened the viral load in the blood of patients, reducing their likelihood of developing AIDS. It may have a similar effect in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. But according to Viswanathan, this powerful antiviral also comes with a heavy set of side effects, most of which are gastrointestinal and include diarrhea, abdominal pain, and pancreatitis.

Still, for many patients, the severity of their long COVID symptoms makes some side effects more tolerable and even worth it, adds David Putrino, the Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness and a national leader in the treatment of long COVID. Not only does it have numerous side effects, but it can also have serious and sometimes life-threatening interactions with other medications that patients may be taking. This means patients absolutely must consult with their doctor before trying the medication.

There’s also a concern that some pathogens, potentially including SARS-CoV-2, hide in tissue and in the gut rather than the bloodstream, and many antivirals are not good at penetrating tissue, another reason why Paxlovid seems to work inconsistently.

Additionally, added Putrino, “It doesn’t eradicate the virus and instead only stops it from replicating, which means it might not be the best approach to solving the problem of persistent virus in the body.”

Alternative Treatments for Persistent Virus​

Instead, Putrino thinks that we should be using monoclonal antibodies that are capable of reversing severe long COVID in more patients. A study published last year in The American Journal of Emergency Medicine found “the striking rapid and complete remissions” of a small number of patients with severe long COVID symptoms.

A larger trial led by Michael Peluso also at the University of California, San Francisco, is currently underway looking at the potential for the use of monoclonal antibodies for the treatment of persistent virus in the body. The study will be completed in July of 2025.


Still, we’re 5 years into the COVID-19 pandemic with no US Food and Drug Administration–approved treatments for long COVID. And as a result, patients with the condition are desperate for treatments. This most recent research was an observational study of people who were already taking the medication. They were looking for anything that might work on their symptoms, and some found that it did, said Cohen. She added that the next step needs to be trials that show how and why it worked for some and why it didn’t for others, as well as the course length that’s most effective for patients.

“Patients are eager for rigorous and accessible clinical trials that can test medications to meaningfully improve symptoms and address the underlying root causes of the condition,” said Cohen.



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Ophthalmology
COMMENTARY

Is COVID Just the Common Cold?​

Matthew F Watto, MD; Paul N Williams, MD


Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams — the perfect person to be talking about common colds or upper respiratory infections (URIs).


The common cold is benign; it’s self-limited by definition, and now COVID-19 for most people is like a common cold, and it’s going to be treated that way. We’ll talk about isolation a little later in the video.

Many patients can be treated over the phone or even with some back-and-forth patient portal messages. Hey, my sinuses are a little stuffy. What can I try?Our guest, Dr Amber Bird, said that if she gets two or three portal messages back and forth from a patient, that’s when she says, “Just come in.”





But if it’s just one question, Hey, what can I take for this symptom? You can answer that with the portal message, especially if it’s a patient who is otherwise healthy and not immunocompromised.


If patients make it into the office, their vital signs are very high yield because if they have a normal temperature, heart rate, blood pressure, respiratory rate, and oxygen saturation, your worry for that person goes way down.

But Paul, what exam are you doing?

Paul N. Williams, MD: I’m trying to primarily rule out pneumonia or possibly sinusitis, the two things that the exam might be most helpful for. But I mainly do the exam for validation of the patient’s symptoms, so they don’t feel foolish for going to the doctor. This goes a long way when you’re doing the counseling later on because it feels bad to be sick.


Basically, I’m doing an exam of the organ systems that are affected. I’ll look in the eyes. I’ll look up the nose. I’ll look in the ears. I’ll look in the throat. I will also listen to the lungs, make sure there’s no wheezing or any evidence of consolidation or anything that would be embarrassing to miss.

You want to make sure that you’re not anchoring to the common cold and missing something a little bit more sinister. Especially during cold season, it’s very easy to be dismissive if you’re not careful.

Watto: What about testing? A lot of patients come in asking me for a rapid strep test or a flu swab. Do you think those are helpful?

Williams: To some extent, yes. Our guest, Dr Bird, acknowledged that they don’t change management all that often. If you catch it in the time course — if you actually pick up influenza early enough, certainly that is a reason to test, and the same goes for COVID in a patient who is high risk. That can be a benefit, but it doesn’t change much of what you do.

It may change counseling. It’s important to think about your patient’s exposures and who they’re going to be around once you send them home. If they are going home to someone who is immunocompromised or sick or works in healthcare, then knowing that they have the flu or COVID becomes more important in terms of counseling on isolation, hygiene, and return to work. It may not change your management in terms of treatments, but it may change how you counsel them in terms of when they go back to work and related issues.

Watto: Some patients really want to know what they have. And the isolation guidelines have changed. I get a lot of questions about this. Basically, now they have lumped all URIs together, with the same guidance. It’s what we did before the pandemic to some extent.

As long as they haven’t had a fever in 24 hours and their symptoms are generally getting better, they can return to being around other people. The guidance for everyone regardless of what respiratory infection they have — whether it’s COVID or not — is to be cautious for 5 days. Don’t breathe in anyone’s face for 5 days, essentially. It might be reasonable to mask or make sure that there is good air circulation for 5 days afterwards. I feel like that’s just common courtesy with any respiratory infection.

Williams: It’s what we should have been doing for years anyway, the COVID pandemic notwithstanding.

Watto: What about the counseling? Counseling is key when you’re seeing a patient with a cold because these people feel bad, and they just want you to tell them that it will eventually go away and that they will feel better again.

Williams: By definition, these infections tend to be self-limited. So, if you’ve made the diagnosis correctly, then this is about a 5- to 7-day course of just feeling kind of crummy. The cough, however, can linger, and it’s important to counsel patients about that. It’s an average of 18 days or so after the illness that the cough can hang on for. Patients expect to be completely done but they can be coughing for a couple of weeks afterward, so it’s important to let patients know that. They shouldn’t be alarmed if their symptoms do persist a little bit, because that’s not abnormal.

What about treatment for URIs?


Watto: For treatment, I ask them about their most bothersome symptom and then try to target that.

We don’t have great evidence for any of the treatments. You might find a positive trial, but you also find a negative trial for any of these treatments. In general, if it’s sinus congestion, Dr Bird said that fluticasone — an intranasal steroid — and nasal saline irrigation seem to help, and perhaps topical decongestants such as oxymetazoline or phenylephrine nasal spray.

Oral decongestants such as pseudoephedrine are behind the pharmacy counter, at least in the United States. Oral phenylephrine doesn’t work and might be taken off shelves eventually.


What if the patient has more of a cough — what are you reaching for in that case?

Williams: Even for cough, none of the treatments have superheavy evidence to support them. I think there’s some evidence for dextromethorphan, so it’s one of those things where you can try and see if it helps.

I really appreciate the conversation in this episode about benzonatate, which I think we have all prescribed because it’s a prescription cough medication, so we feel like we are doing something, but the evidence is not super great. Benzonatate has toxicities, especially with kids, so make sure that medication is properly secured, if you do prescribe it, and you counsel patients around that.


Watto: Yes, kids can overdose on it. That is terrifying. I had no idea.

Williams: Dextromethorphan and benzonatate are probably the main options. There is anecdotal evidence for guaifenesin, but it’s not very compelling. If a patient feels one of these treatments helps them, I say, go with God, but I don’t advocate strongly for one treatment vs another.

Watto: It’s often the sinuses that are causing the cough and congestion, so I mostly go after the sinuses. My threshold for antibiotics is when the patient has “double sickening,” where they felt bad for a couple of days, then got better, but then started to feel worse again. Or if they have persistent symptoms after 7-10 days — that’s when I’m thinking about a 5-day antibiotic course, usually with amoxicillin. Doxycycline would be my second choice if the patient is allergic to penicillin.

We also talked on the podcast about some of the traditional remedies listed here.


I would recommend that people listen to the full podcast episode here.

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Rheumatologists Concerned by Broad Long COVID Definition

Seven rheumatology researchers have authored a paper questioning the utility of the 2024 National Academies’ broad definition of long COVID.

www.medscape.com

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Rheumatologists Concerned by Broad Long COVID Definition​

Miriam E. Tucker

February 12, 2025


A group of researchers in rheumatology has raised concerns about the 2024 definition of long COVID from the National Academies of Science, Engineering, and Medicine (NASEM), citing both lack of specificity and the inclusion of autoimmune rheumatic diseases despite inconsistent evidence that they’re linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

The twofold concerns were outlined in a “Notes from the Field” commentary, published on January 16, 2025, in Arthritis & Rheumatology, by Leonard H. Calabrese, DO, head of the Section of Clinical Immunology, Cleveland Clinic, Cleveland, and six other researchers in rheumatology and infectious diseases, including two affiliated with Harvard Medical School, Boston.

In June 2024, the NASEM defined long COVID as “an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems."


According to NASEM, people with long COVID may present with one or more of a long list of symptoms, such as shortness of breath, rapid heartbeat, extreme fatigue, post-exertional malaise, or sleep disturbance, or with single or multiple diagnosable conditions, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, diabetes, or autoimmune diseases including rheumatoid arthritis, lupus, or Sjögren disease.

The definition does not require laboratory confirmation or other proof of initial infection. Long COVID can follow SARS-CoV-2 infection of any severity, including asymptomatic infections, regardless of whether they were initially recognized.





“They wanted to make the definition very broadly inclusive…This case definition tends to be highly sensitive, not leaving anyone behind. But, by definition, that results in the risk of low specificity and false positives,” Calabrese told Medscape Medical News.


Moreover, the definition doesn’t specify a timeframe between the diagnosis of COVID-19 and the subsequent diagnosis. “You don't really have to prove that you have COVID, and then a disease arises at some timepoint. It doesn't say 30 days or 30 months or 30 years…It arises at some point in time. This disease could be considered long COVID.”

In addition, Calabrese said, the inclusion of specific autoimmune rheumatologic diseases isn’t fully supported by data, given that autoantibodies are also seen following other infectious diseases and are often transient, and epidemiologic studies have been inconsistent in finding a link between COVID-19 and specific autoimmune rheumatologic conditions.

“Ninety-five percent of people have had COVID. If that person walks in the door with a new diagnosis, how do we apply these criteria to those patients? It’s not just rheumatology. Does every person with new-onset diabetes have long COVID because they had COVID? It will require a critical appraisal of data, and that will change over time,” Calabrese said.

NASEM Authors Respond​

Asked for a response, NASEM definition co-author Betty Diamond, MD, director of the Institute of Molecular Medicine & Maureen and Ralph Nappi Professor of Autoimmune Diseases, Feinstein Institutes for Medical Research, Manhasset, New York, said that “the concern expressed in the article is valid, and not just for rheumatic disease. But I think one has to point out the concerns with too narrow a definition.”

Diamond, the only rheumatologist among the NASEM authors, added: “This broader definition may also permit clinicians and researchers to obtain information on an increasing or decreasing incidence of a disease following COVID.”

Harvey Fineberg, MD, president of the Gordon and Betty Moore Foundation and chair of the NASEM committee that wrote the report, told Medscape Medical News, “In crafting its definition, the [NASEM] committee recognized that new knowledge and clinical circumstances can and should affect the application of the definition to individual patients, and the committee called for clinicians to use clinical judgment in reaching a diagnosis. Many conditions, including rheumatologic conditions, preexisted COVID and are not uniquely attributable to prior SARS-CoV-2 infection. Making a diagnosis in a patient who has experienced COVID involves a balance between false-positive and false-negative classifications, and only through scientific advances in understanding of disease etiology can both types of error be reduced.”

‘We Do Not Have the Answers’​

Calabrese and colleagues end their paper with a call for greater research and education for rheumatologists and other medical specialists. “Although we have raised important concerns, we admit that we do not have the answers to these important questions. From a clinical perspective of the rheumatology practitioner and the individual patient, the current case definition clearly provides much leeway in diagnosing long COVID based on history and clinical judgment when needed for patient care.”

The intent of their paper, Calabrese said, was “to bring attention to these criteria, since our specialty and many other specialties are not in the thick of diagnosing and managing long COVID. But with this definition, we now become a much more relevant kind of group, as others do, and if you're not aware of what's going on in this area, you should be.”

A NASEM spokesperson told Medscape Medical News, “The committee report recommended that the definition be reexamined and updated in light of new scientific knowledge. However, the committee, as with all National Academies committees, concluded its work with the release of its report. Work on an updated definition will depend on government and other sponsors and decisions by the National Academies or other responsible professional organizations.”


Calabrese has received consulting fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, GSK, Janssen Pharmaceuticals, UCB, Sanofi-Genzyme, Regeneron, Galvani, Mymee, PPD, Fate Therapeutics, Open Evidence, and payment or honoraria from Amgen, Janssen Pharmaceuticals, Sanofi, Regeneron, AstraZeneca, and UCB. Diamond and Fineberg had no disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker.


Cite this: Rheumatologists Concerned by Broad Long COVID Definition - Medscape - February 12, 2025.


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