How to Prevent Long Covid
I don’t fear dying of Covid anymore. I dread developing long Covid. This is why I wear an N95 mask while seeing patients in tiny rooms, why I stay up to date with recommended jabs, and why I’m still being more careful than most other people. Brain fog, memory problems, depression, anxiety, profound fatigue, breathlessness, muscle pains, headaches… it all sounds worth avoiding. And even though we’ve been churning through the winter with a staggering 3,000 deaths per week in the United States, the sad truth is that we’ve adjusted to this horror, visited as it is primarily on the elderly or unhealthy. And so, in the spirit of my last post about being prepared, here’s how I’m planning to game against long Covid myself, and for any patients who want to be proactive.
When diagnosed with Covid, and within 5 and 7 days of the onset of symptoms respectively, Paxlovid and now metformin have been shown to reduce the risk of developing long Covid.
The evidence on Paxlovid has been out there for a while, and I’ve been prescribing it for severe disease risk reduction as well as prevention of long Covid. Here’s what I wrote in November 2022, as gleaned and synthesized from the experts and the evidence. A nice 25% reduction was observed in a population of mostly male, average 60-year-old subjects. Since long Covid is more common in middle aged people, some speculate that the 40-somethings might derive even greater risk reduction. Let’s guess up to 40%?
A new preprint study just published in The Lancet and digested by two other doctors I read (
and Eric Topol’s) is of much higher quality. It is a randomized, placebo controlled trial that looked at 3 potential medications in the race to find ways to prevent long Covid. Ivermectin did not work. Fluvoxamine did not work. But metformin, a generic medication we use safely all the time for treatment of type 2 diabetes DID WORK. It reduced the risk of long Covid by 42%.The median age of the patients studied was 45 years old. They were all overweight (a risk factor for severe disease and long Covid). Over half were female. By taking metformin (in the dosage noted in the above graphic) patients were diagnosed with long Covid 42% less often than those taking placebo.
The absolute numbers are always less eye-catching, so for full disclosure:
10.6% of all people with Covid went on to be diagnosed with long haul symptoms, consistent with other studies.
Only 6.3% of metformin-treated patients developed long Covid (~42% risk reduction). That means that 1 case of long-haul misery can be prevented for every 22 people treated… which is actually pretty good in medicine.
Unvaccinated people developed long haul syndromes at twice the rate of vaccinated individuals (14% vs. 7%), consistent with previous studies.
33% of hospitalized patients were subsequently diagnosed with long Covid, the highest rate of any subgroup studied.
Limitations of this metformin trial include the fact that only patients over age 30 were studied. Only overweight subjects were included. And the diagnosis of “long Covid” was only gleaned from physician diagnoses on the medical records instead of a strict definition of persistent symptoms for over 12 weeks.
Nonetheless, primary care docs and endocrinologists treating diabetes have absolute familiarity and comfort with prescribing metformin. It is first line for new onset diabetes, has a very low risk of hypoglycemia, and is often used for early and borderline cases. Until recently, some guidelines even recommended using it for diabetes prevention. The most common side effects I see are gastrointestinal ones… but if you already have Covid, and you’re just taking this for 2 weeks, it should be manageable. Paxlovid + metformin will probably = quite a few loose bowel and GI upset calls. That’s OK.
Metformin is an incredibly cheap medicine, which will be hard for conspiracy theorists to challenge. Big Pharma has nothing to potentially gain from this study. It probably works against long Covid because of some combination of action with protein translation, direct antiviral activity, anti-inflammatory mechanisms, and antithrombotic properties. There are other precautions to be aware of with metformin, including for those people with kidney issues… but does this change my prescribing behaviors and recommendations to patients overnight?
Yes. That’s why I stayed up late reviewing and writing!
I’ll be offering this to people today. Unfortunately, I expect to have the opportunity, so keep staying safe out there! But this is good news.
Metformin is not recommended for the treatment of Covid, as clinical evidence has not supported its efficacy against severe disease, death, and hospitalization. But if you’re doing what you can to keep from getting sick, including staying mostly careful out there, keeping up to date with vaccinations and boosters, and considering Paxlovid when sick - then your game is probably preventing long Covid, too.
And we have a new tool that helps.
~ Addendum: here is a paper summarizing theoretical mechanisms by which metformin could mitigate Covid, and not just lower blood sugar.
would the recommendation be to take paxlovid and metformin together? Or would you have to finish the course of paxlovid before starting on metformin?
I’m glad we have options. Long Covid is a big fear of mine. I feel lucky I didn’t get it first time I got Covid, Paxlovid for the win!