The year 2025 marks five years since the COVID-19 pandemic went global. Among the many who contracted COVID-19 and recovered from the acute infection, some feel as though the disease has changed their day-to-day health for the worse. Many report a “brain fog” in which it has become harder for them to focus or think clearly, while others have various symptoms, including fatigue, pain, or even digestion issues.
This collection of symptoms has many names, but it became most commonly known as “long COVID.” When it was first observed a few years ago, physicians and researchers were divided on how to define, diagnose, or even treat it. Even less was known about why long COVID occurs and who is at risk of developing it.
Today, the medical and research communities have come a long way in understanding and tackling long COVID, says David Putrino, PhD, Director of Rehabilitation Innovation at the Mount Sinai Health System. There are, unfortunately, still misconceptions about long COVID among patients and even some health providers, and dispelling such myths is key to proper treatment, he adds.
In this Q&A, Dr. Putrino discusses to say what is known about long COVID today.
Is there a clear definition for long COVID today?
Physicians now have clear clinical guidelines and criteria for diagnosing long COVID. According to the National Academies of Science, Engineering, and Medicine, long COVID is an infection-associated chronic condition whereby somebody who has survived an acute infection with SARS-CoV-2—the virus that causes COVID-19—fails to return to their pre-infection health status within a period of three months.
Long COVID symptoms can present in different ways:
- Continuous, where symptoms remain constant and do not go away
- Progressive, where symptoms worsen over time
- Relapsing and remitting, where a patient can feel good for a while, and then have a period of feeling very poorly, and back and forth
“We need to start thinking about long COVID in the same way that cancer researchers have been thinking about cancer for the past three or four decades.” —David Putrino, PhD, Director of Rehabilitation Innovation at the Mount Sinai Health System
What different kinds of long COVID symptoms can patients have?
Long COVID has been described as a highly diverse disease state, with studies collectively noting more than 200 symptoms.
The most commonly reported symptom, which affects more than 90 percent of patients, tends to be fatigue and a phenomenon known as post-exertional malaise. The latter is a distinct kind of energy limiting illness where if you ask someone to perform an action—such as walking on a treadmill or riding a bike—they are able to do so. But after they exert themselves, they experience a significant worsening of symptoms or a cluster of new symptoms that persist weeks to months afterwards.
Cognitive symptoms are also common, such as a worsened ability to make decisions, plan things in advance, or even regulate emotions. People speak of “brain fog,” which includes changes in attention and in short- and long-term memory, and it is evident that SARS-CoV-2 infection can significantly affect cognition. In fact, a study published in The New England Journal of Medicine in 2024 showed that any person who survives a COVID-19 infection experiences, on average, a loss of six IQ points. This is a sobering fact that makes a strong case for all healthy individuals to avoid SARS-CoV-2 infections by taking the appropriate precautions.
Some people also report gastrointestinal disturbances. These can be wide-ranging, including having diarrhea, having to go to the bathroom more than usual, increased difficulty in food moving through the body, and/or extreme constipation. In addition, some might gain new intolerances to certain kinds of food, have difficulty finishing a meal, or reduced appetite.
Recently, researchers are discovering that around 50 percent of long COVID patients might have new-onset pain. This is a disease state that really affects every organ system.
In 2024, about 17 million adults report having long COVID
For adults with long COVID, 79% say long COVID has limited their activities
Of those who said long COVID limited their activities, 25% say it has done so by a lot
The group most likely to experience long COVID is adults ages 35-49
Women are more likely to experience long COVID than men, with 8.5% of women reporting past long COVID, compared to 5.2% for men
Do we know why long COVID happens?
We are starting to understand that in some cases, it could be just one path causing the symptom. In other cases, it could be a combination of pathologies. Here’s what we have found so far:
- Viral persistence: Different studies have identified the presence of SARS-CoV-2 remaining in the bodies of patients with long COVID, even after the acute COVID-19 phase. There is evidence of circulating viral antigens, spike proteins in plasma, viral fragments in the gut, and so forth. We are seeing that the persistence is not latent and it’s not harmless for people with long COVID—it’s causing problems.
- Latent pathogen reactivation: For some people, even if persistent SARS-CoV-2 does not cause any damage to organs, it could have caused immune dysregulation, leading to reactivation of other latent viruses. There are studies that have shown herpes virus reactivations, such as Epstein-Barr virus, in patients with long COVID, and others showing reactivation of Bartonella infection as well. It may be that the SARS-CoV-2 viral infection kicks up other pathogens that were smoldering below the surface, causing inflammation and other problems.
- Autonomic nervous system dysfunction: This is the part of your nervous system that controls blood pressure, digestion, sweating, and temperature control. And we’re seeing that the virus can knock this system out of balance. When it is disrupted, people can experience something called postural orthostatic tachycardia syndrome: when they go from lying down flat to standing, they experience unpredictable blood pressure and heart rate changes that can lead them to feel as though they’re about to pass out. This is frequently misdiagnosed as anxiety or panic attacks.
- Autoimmunity: Relating to immune dysregulation, we are starting to see evidence that for a subset of people with long COVID, they have functional autoantibodies circulating in their body that are designed to attack and cause damage to the body’s own tissues. We have animal studies where mice that were injected with IgG antibodies from patients with long COVID started to develop symptoms similar to that of the patient, especially in new-onset pain, whereas that phenomenon was not seen in mice receiving IgG from healthy controls.
- Hormonal dysregulation: There are multiple papers on long COVID impacts on hormones like cortisol, which affect wakefulness and inflammation, as well as androgenic hormones, such as testosterone and estradiol. So women with long COVID are much more likely to have extremely low levels of testosterone, and men with long COVID might have low levels of estradiol. This may also explain why long COVID is more frequently diagnosed in women compared with men.
Are there any misconceptions about long COVID?
For the clinical community, we’ve been focusing on getting out a main message, which is that long COVID requires a precision response. If a physician is asking, “Is there a cure—singular—for long COVID,” that is the wrong question. The correct question should be, “What are the tests and techniques I should be using to identify the symptoms of the patient with long COVID in front of me, and how do I proceed from there?”
We need to start thinking about long COVID in the same way that cancer researchers have been thinking about cancer for the past three or four decades. We have seen attitudes about cancer change, starting in the ‘80s when patients were told they got cancer because they had a “Type A” personality, to one today where a patient gets individualized treatment based on age, sex, gene profile, and so much more.
That’s the sort of precision we need in long COVID. What is your medical history? Your immune history? Any genetic expression that might predispose you to chronic illnesses?
Long COVID is classified as an infection-associated chronic condition, which includes chronic Lyme disease and myalgic encephalomyelitis/chronic fatigue syndrome. Historically, these chronic conditions have been viewed as largely psychogenic, and people have been told they can be cured with cognitive behavioral therapy and exercise.
I cannot stress how damaging this is to patients, and perhaps in 30 years, we will be looking back at our approaches and be ashamed of how we were framing long COVID for patients.
Long COVID affects many people, and it disproportionately affects young people too. These are people who are in their active, prime years and we need to help them lead their best lives.
