August 19, 2022
By Natalie Slivinski
There's little doubt long COVID is real. The federal government recognizes long COVID as a condition and said in two reports issued in August that one in five adult COVID-19 survivors have a health condition related to their illness.
COVID-19 can damage multiple organs in the body. Sometimes this damage leads to long COVID; sometimes other are reasons at play. Doctors are beginning to sort it out.
There's a difference between long COVID and an acute infection with lasting effects, doctors say.
"COVID itself can actually cause prolonged illness, and we don't really call that long COVID," says Nisha Viswanathan, MD, a doctor at UCLA Health in Los Angeles. But if symptoms extend beyond 12 weeks, that puts patients in the realm of long COVID, she says.
Symptoms can range from mild to severe and can keep people from resuming their normal lives and jobs. Sometimes they last for months, according to the U.S. Department of Health and Human Services.
Lung scarring and other lung problems are common after COVID, says Leora Horwitz, MD, an internal medicine specialist at the New York University Grossman School of Medicine. Even after a mild case, people can have breathing issues for months, a team at Johns Hopkins Medicine says in an online briefing. One study published in the journal Radiology found damage in people a full year after a COVID-19 diagnosis.
Some people have persistent heart, kidney, liver, and nervous system problems after COVID-19. A study published in 2020 in the journal JAMA Cardiology found 60% of people who had COVID-19 had ongoing signs of heart inflammation. Nearly a third of people hospitalized for COVID-19 get kidney damage that can become chronic, and some end up needing dialysis or a transplant, says C. John Sperati, MD, a kidney specialist at Johns Hopkins Medicine in Baltimore
This might be, in part, because SARS-CoV-2, the virus that causes COVID-19, directly infects the cells in many organs.
Nicole Bhave, MD, a cardiologist at University of Michigan Health, is concerned that COVID-19 appears to increase the risk of heart problems in some people.
"Some of the uptick may just be recognition bias, in that people with symptoms are seeking care," she says. "But there's definitely a biological basis by which COVID could tip people over into a new diagnosis of heart failure."
Inflammation is probably a key part of the long-term effects of COVID-19.
Some people have a serious immune reaction to COVID-19 called a cytokine storm, says Nitra Aggarwal Gilotra, MD, a cardiologist at Johns Hopkins Medicine. This release of inflammation-causing molecules called cytokines is meant to attack the invading virus. But it can be so severe that it wreaks havoc on healthy tissues and organs and causes lasting damage – if patients even survive it.
In some people, inflammation can affect the heart, causing myocarditis. Myocarditis symptoms include chest pain, breathlessness, and heart palpitations. Though rare, it can be serious and can raise the risk of other heart problems, including heart failure, down the line.
Long COVID may also trigger an autoimmune condition, says Eline Luning Prak, MD, PhD, a pathologist at the Hospital of the University of Pennsylvania. Long COVID can share many hallmark symptoms with autoimmune diseases, including fatigue, widespread pain, memory problems, and mood disorders, Prak says.
Studies have shown the overcharged inflammatory response to COVID-19 can cause blood clots. This sometimes overwhelming clotting was an early hallmark of COVID-19 infection, and when clots restrict blood flow in the brain, lungs, kidneys, or limbs, they can cause long-term damage. Some can be deadly. Researchers in Sweden found patients were at risk of deep vein thrombosis – a blood clot usually in the leg – up to 3 months after infection and at higher risk of a blood clot in the lung, called pulmonary embolism, for as long as 3 months.
The virus itself may also linger in a patient's body, causing continued symptoms and, potentially, new flare-ups. Harvard Medical School's Zoe Swank, PhD, and colleagues reported in a pre-print study that they found pieces of the SARS-CoV-2 virus in the blood of most patients with long COVID symptoms they tested – some as long as a year after infection. The study has not yet been peer-reviewed.
Another team found evidence of the virus in stool up to 7 months later, which suggests the virus hides out in the gut. Other early studies have found bits of viral RNA in the appendix, breast tissue, heart, eyes, and brain.
Diabetes is a risk factor for getting severe COVID-19, and multiple studies have shown people can get diabetes both while battling infection and afterward. One study of veterans found COVID-19 survivors were about 40% more likely to get diabetes over the next year.
Some studies have suggested a few ways this might happen. Insulin-producing cells in the pancreas have SARS-CoV-2 receptors – a type of molecular doorway the coronavirus can attach to. Damage to these cells could make the body less able to produce insulin, which in turn can lead to diabetes. The virus could also disrupt the balance in the body or cause inflammation that leads to insulin resistance, which can develop into diabetes, Ziad Al-Aly, MD, of the Veterans Affairs St. Louis Health Care System, and colleagues wrote in The Lancet Diabetes and Endocrinology.
Nervous System Issues
People who get COVID-19 are also more vulnerable to postural orthostatic tachycardia syndrome (POTS). This affects what's known as the autonomic nervous system, which regulates blood circulation, and includes those things that happen in your body without your having to think about them, like breathing, heartbeat, and digestion. POTS can cause common long COVID neurologic symptoms, including headaches, fatigue, brain fog, insomnia, and problems thinking and concentrating. "This was a known condition prior to COVID, but it was incredibly rare," says Viswanathan, the UCLA Health doctor. "After COVID, I've seen it with increasing frequency."
Lasting issues after COVID-19 are much more likely after a moderate or severe infection. Still, plenty of people are battling them even after a mild illness. "As for why, that's the billion-dollar question," says Horwitz, the internal medicine specialist. "It's well-known that viral infections can cause long-term dysregulation. Why that is, we really just don't know."
Whether it's virus hiding out in the body, long-term organ damage, or an autoimmune reaction likely differs from person to person. "I'm believing, increasingly, that it's a combination of all of these, just based on how different patients are responding to different medications," says Viswanathan. "One patient will respond to something beautifully, and another patient won't at all."
But it's clear a significant number of people are facing long-term health struggles because of COVID-19, which has infected at least 580 million people globally and 92 million – likely many more – in the U.S., according to Johns Hopkins University.
Even a small increased risk of conditions like heart disease or diabetes translates to a huge number of people, Horwitz says. "If even 1% of people getting COVID have long-term symptoms, that's a major public health crisis, because that's 1% of pretty much everybody in the country," she says.
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Leora Horwitz, health systems specialist, co-leader, Clinical Science Core, NIH RECOVER Initiative, NYU Langone Health.
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Nicole Bhave, cardiologist, University of Michigan Health.
Nisha Viswanathan, MD, co-director, Long COVID program, UCLA Health.
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