https://www.vox.com/2020/5/8/21251899/coronavirus-long-term-effects-symptoms

“It is a true roller coaster of symptoms and severities, with each new day offering many unknowns.”

At first, Lauren Nichols tried to explain away her symptoms. In early March, the healthy 32-year-old felt an intense burning sensation, like acid reflux, when she breathed. Embarrassed, she didn’t initially seek medical care. When her shortness of breath kept getting worse, her doctor tested her for Covid-19.

Her results came back positive. But for Nichols, that was just the beginning. Over the next eight weeks, she developed wide and varied symptoms, including extreme and chronic fatigue, diarrhea, nausea, tremors, headaches, difficulty concentrating, and short-term memory loss.

“The guidelines that were provided by the CDC [Centers for Disease Control and Prevention] were not appropriately capturing the symptoms that I was experiencing, which in turn meant that the medical community was unable to ‘validate’ my symptoms,” she says. “This became a vicious cycle of doubt, confusion, and loneliness.”

An estimated 40 to 45 percent of people with Covid-19 may be asymptomatic, and others will have a mild illness with no lasting symptoms. But Nichols is one of many Covid-19 patients who are finding their recovery takes far longer than the two weeks the World Health Organization says people with mild cases can expect. (The WHO says those with severe or critical cases can expect three to six weeks of recovery.)

Because Covid-19 is a new disease, there are no studies about its long-term trajectory for those with more severe symptoms; even the earliest patients to recover in China were only infected a few months ago. But doctors say the novel coronavirus can attach to human cells in many parts of the body and penetrate many major organs, including the heart, kidneys, brain, and even blood vessels.

“The difficulty is sorting out long-term consequences,” says Joseph Brennan, a cardiologist at the Yale School of Medicine. While some patients may fully recover, he and other experts worry others will suffer long-term damage, including lung scarring, heart damage, and neurological and mental health effects.

The UK National Health Service assumes that of Covid-19 patients who have required hospitalization, 45 percent will need ongoing medical care, 4 percent will require inpatient rehabilitation, and 1 percent will permanently require acute care. Other preliminary evidence, as well as historical research on other coronaviruses like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), suggests that for some people, a full recovery might still be years off. For others, there may be no returning to normal.

There’s a lot we still don’t know, but here are a few of the most notable potential long-term impacts that are already showing up in some Covid-19 patients.

Lung scarring

Melanie Montano, 32, who tested positive for Covid-19 in March, says that more than seven weeks after she first got sick, she still experiences symptoms on and off, including burning in her lungs and a dry cough.

Brennan says symptoms like that occur because “this virus creates an incredibly aggressive immune response, so spaces [in the lungs] are filled with debris and pus, making your lungs less pliable.”

On CT scans, while normal lungs appear black, Covid-19 patients’ lungs frequently have lighter gray patches, called “ground-glass opacities” — which may not heal.

One study from China found that this ground-glass appearance showed up in scans of 77 percent of Covid-19 patients. In another study out of China, published in Radiology, 66 of 70 hospitalized patients had some amount of lung damage in CT scans, and more than half had the kind of lesions that are likely to develop into scars. (A third study from China suggests this is not just for critically ill patients; its authors found that of 58 asymptomatic patients, 95 percent also had evidence of these ground-glass opacities in their lungs. More than a quarter of these individuals went on to develop symptoms within a few days.)

“These kinds of tissue changes can cause permanent damage,” says Ali Gholamrezanezhad, a radiologist at the Keck School of Medicine at the University of Southern California.

Although it’s still too early to know if patients with ongoing lung symptoms like Montano will have permanent lung damage, doctors can learn more about what to expect from looking back to people who have recovered from SARS and MERS, other coronaviruses that resulted in similar lung tissue changes.

One small longitudinal study published in Nature followed 71 SARS patients from 2003 until 2018 and found that more than a third had reduced lung capacity. MERS is a little harder to extrapolate from, since fewer than 2,500 people were infected, and somewhere between 30 and 40 percent died. But one study found that about a third of 36 MERS survivors also had long-term lung damage.

Gholamrezanezhad has recently done a literature review of SARS and MERS and says that for this subset of people, “The pulmonary function never comes back; their ability to do normal activities never goes back to baseline.”

Additionally, Covid-19 scarring rates may end up being higher than SARS and MERS patients because those illnesses often attacked only one lung. But Covid-19 appears to often affect both lungs, which Gholamrezanezhad says escalates the risks of lung scarring.

He has already seen residual scarring in Covid-19 patients and is now designing a study to identify what factors might make some people at higher risk of permanent damage. He suspects having any type of underlying lung disease, like asthma, or other health conditions, like hypertension, might increase the risk of having longer-term lung issues. Additionally, “the older you are, probably the higher your chance of scarring,” he says.

For people with this kind of lung scarring, normal activities may become more challenging. “Routine things, like running up a flight of stairs, would leave these individuals gasping for air,” Brennan says.

Stroke, embolisms, and blood clotting

Many patients hospitalized for Covid-19 are experiencing unexpectedly high rates of blood clots, likely due to inflammatory responses to the infection. These can cause lung blockages, strokes, heart attacks, and other complications with serious, lasting effects.

Blood clots that form in or reach the brain can cause a stroke. Although strokes are more typically seen in older people, strokes are now being reported even in young Covid-19 patients. In Wuhan, China, about 5 percent of hospitalized Covid-19 patients had strokes, and a similar pattern was reported with SARS.

In younger people who have strokes, mortality rates are relatively low compared to those who are older, and many people recover. But studies show only between 42 and 53 percent are able to return to work.

Blood clots can also cut off circulation to part of the lungs, a condition known as a pulmonary embolism, which can be deadly. In France, two studies suggest that between 23 and 30 percent of people with severe Covid-19 are also having pulmonary embolisms.

One analysis found that after a pulmonary embolism, “symptoms and functional limitations are frequently reported by survivors.” These include fatigue, heart palpitations, shortness of breath, marked limitation of physical activity, and inability to do physical activity without discomfort.

Blood clots in other major organs can also cause serious problems. Renal failure has been a common challenge in many severe Covid-19 patients, and patients’ clotted blood has been clogging dialysis machines. Some of these acute kidney injuries may be permanent, requiring ongoing dialysis.

Clots outside organs can be serious, too. Deep vein thrombosis, for example, occurs when a blood clot forms in a vein, often the legs. Nick Cordero, a Tony-nominated Broadway and television actor, recently had to have his right leg amputated after Covid-related blood clots.

Abnormal blood clotting even seems to be happening in people after they’ve appeared to recover. One 32-year-old woman in Chicago, for example, had been discharged from the hospital for a week when she died suddenly with a severely swollen leg, a sign of deep vein thrombosis, according to local broadcaster WGN9. Or take Troy Randle, a 49-year-old cardiologist in New Jersey, who was declared safe to go back to work after recovering from Covid-19 when he developed a vicious headache. A CT scan confirmed he’d had a stroke.

Although there’s still a shortage of data, one study found that as many as 31 percent of ICU patients with Covid-19 infections had these kinds of clotting problems. In the meantime, the International Society on Thrombosis and Haemostasis has issued guidelines that recovered Covid-19 patients should continue taking anticoagulants even after being discharged from the hospital.

Heart damage

Being critically ill, especially with low oxygen levels, puts additional stress on the heart. But doctors now think that in Covid-19 patients, viral particles might also be specifically inflaming the heart muscle. (The heart has many ACE2 receptors, which scientists have identified as an entry point for the SARS-CoV-2 virus.)

“In China, doctors noted some people coming [in] with chest pain,” says Mitchell Elkind, president-elect of the American Heart Association and professor of neurology and epidemiology at Columbia University. “They had a heart attack, and then developed Covid symptoms or tested positive after.”

One study from Wuhan in January found 12 percent of Covid-19 patients had signs of cardiovascular damage. These patients had higher levels of troponin, a protein released in the blood by an injured heart muscle. Since then, other reports suggest the virus may directly cause acute myocarditis and heart failure. (Heart failure was also seen with MERS and is known to be correlated with even the seasonal flu.)

In March, another study looked at 416 hospitalized Covid-19 patients and found 19 percent showed signs of heart damage. University of Texas Health Science Center researchers warn that in survivors, Covid-19 may cause lingering cardiac damage, as well as making existing cardiovascular problems worse, further increasing the risk for heart attack and stroke.

A pulmonary critical care doctor at Mount Sinai Hospital in New York City, for example, recovered from Covid-19, only to learn she had developed cardiomyopathy, a condition in which your heart has trouble delivering blood around your body. Although previously healthy, when she returned to work, she told NBC, “I couldn’t run around like I always do.”

The specific consequences may vary depending on how the heart is affected. For example, Covid-19 has been linked to myocarditis, a condition where inflammation weakens the heart, creates scar tissue, and makes it work harder to circulate the body’s oxygen. The Myocarditis Foundation recommends these patients avoid cigarettes and alcohol, and stay away from rigorous exercise until approved by their doctor.

Neurocognitive and mental health impacts

Covid-19 also seems to affect the central nervous system, with potentially long-lasting consequences. In one study from China, more than a third of 214 people hospitalized with confirmed Covid-19 had neurological symptoms, including dizziness, headaches, impaired consciousness, vision, taste/smell impairment, and nerve pain while they were ill. These symptoms were more common in patients with severe cases, where the incidence increased to 46.5 percent. Another study in France found neurologic features in 58 of 64 critically ill Covid-19 patients.

As the pandemic goes on, Elkind says, “We need to be on the lookout for long-term neurocognitive problems.”

Looking back to SARS and MERS suggests that Covid-19 patients may have slightly delayed onset of neurological impacts. Andrew Josephson, a doctor at the University of California San Francisco, wrote in JAMA, “Although the SARS epidemic was limited to about 8,000 patients worldwide, there were some limited reports of neurologic complications of SARS that appeared in patients 2 to 3 weeks into the course of the illness.” These included muscular weakness, burning or prickling, and numbness, and the breakdown of muscle tissue into the blood. Neurological injuries, including impaired balance and coordination, confusion, and coma, were also found with MERS.

Long-term complications of Covid-19 — whether caused by the virus itself or the inflammation it triggers — could include decreased attention, concentration, and memory, as well as dysfunction in peripheral nerves, “the ones that go to your arms, legs, fingers, and toes,” Elkind says.

There are other cognitive implications for people who receive intensive treatment in hospitals. For example, delirium — an acutely disturbed state of mind that can result in confusion and seeing or hearing things that aren’t there — affects a third or more of ICU patients, and research suggests the presence of delirium during severe illness predicts future long-term cognitive decline.

Previous research on acute respiratory distress syndrome (ARDS) more generally may also provide clues to what neurological issues critically ill Covid-19 patients might see after leaving the hospital.

Research shows one in five ARDS survivors experiences long-term cognitive impairment, even five years after being discharged. Continuing impairments can include short-term memory problems and difficulty with learning and executive function. These can lead to challenges like difficulty working, impaired money management, or struggling to perform daily tasks.

ARDS survivors frequently have increased rates of depression and anxiety, and many experience post-traumatic stress. Although it’s still too early to have much data on Covid-19, during the SARS outbreak, former patients struggled with psychological distress and stress for at least a year after the outbreak.

“I felt imprisoned within my body, imprisoned within my home, and tremendously ignored and misunderstood by the general public, and even those closest to me,” Nichols says about her battle with Covid-19. “I feel incredibly alone.”

Jane, who prefers to use a pseudonym because she fears retribution at the hospital where she works, tested positive for Covid-19 more than a month ago. She’s still struggling with fevers, heart issues, and neurological issues, but the most difficult part, she says, is how tired she is of “being treated like I am a bomb that no one knows how to disarm.” Jane, a nurse who cared for AIDS patients during the ’90s, says, “This is exactly what those people went through. There is a terrible stigma.” In addition to the stigma, uncertainty has added to her mental health burden.

“People need to know this disease can linger and wreck your life and health,” she says. “And no one knows what to do for us.”

Childhood inflammation, male infertility, and other possible lasting effects

The novel coronavirus continues to frustrate scientists and patients alike with its mysteries. One of these is a small but growing number of children who recently began showing up at doctors’ offices in Britain, Italy, and Spain with strange symptoms, including a rash, a high fever, and heart inflammation.

On May 4, the New York City Health Department noted that at least 15 children with these symptoms had been hospitalized there, too. These cases present like a severe immune response called Kawasaki disease, where blood vessels can begin to leak, and fluid builds up in the lungs and other major organs. Although only some of these children have tested positive for Covid-19, Russell Viner, president of the Royal College of Pediatrics and Child Health, told the New York Times, “the working hypothesis is that it’s Covid-related.”

Children who survive Kawasaki-like conditions can suffer myocardial and vascular complications in adulthood. But it’s too early to know how Covid-related cases will develop. Many of the small number of reported cases appear to be responding well to treatment.

Other researchers are suggesting that Covid-19 may pose particular problems for men beyond their disproportionate mortality from the illness. The testicles contain a high number of ACE2 receptors, explained researcher Ali Raba, in a recent letter to the World Journal of Urology. “There is a theoretical possibility of testicular damage and subsequent infertility following COVID-19 infection,” he wrote.

Another study, looking at 38 patients in China who had been severely ill with Covid-19, found that during their illness, 15 had virus RNA in their semen samples, as did two of 23 recovering patients. (The presence of viral RNA doesn’t necessarily indicate infectious capacity.)

Another recent study also showed that in 81 men with Covid-19, male hormone ratios were off, which could signal trouble for fertility down the line. The authors called for more attention to be paid, particularly on “reproductive-aged men.” An April 20 paper published in Nature went so far as to suggest, “After recovery from COVID-19, young men who are interested in having children should receive a consultation regarding their fertility.”

And we are just at the beginning of figuring out what this complex infection means for other organ systems and their recovery. For example, a recent preprint from Chinese doctors looked at 34 Covid-19 survivors’ blood. While they saw a difference between severe and mild cases, the researchers found that regardless of the severity of the disease, after recovered patients were discharged from the hospital, many biological measures “failed to return to normal.” The most concerning measures suggested ongoing impaired liver function.

What all of this means for survivors and researchers

As all this preliminary research shows, we are still in the early days of understanding what this virus might mean for the growing number of Covid-19 survivors — what symptoms they might expect to have, how long it might take them to get back to feeling normal (if they ever will), and what other precautions they might need to be taking.

Many people aren’t even receiving adequate information about when it might be safe for them to stop self-isolating. Nichols and other survivors report feeling better one day and terrible the next.

But in the chaos Covid-19 has caused in the medical systems, survivors say it’s hard to get attention for their ongoing struggles. “The support and awareness is simply lacking,” Nichols says. “It is a true roller coaster of symptoms and severities, with each new day offering many unknowns: I may feel healthier one day but may feel utterly debilitated and in pain the next.”