San Francisco Chronicle - (Sunday)
Coronavirus damage could last long after disease passes
The roulette wheel of infection that determines which COVID-19 patients live and die has gripped the world in fear, but researchers are looking into another insidious danger — that the disease could be inflicting lasting, even permanent, damage on its victims.
Infectious disease specialists have learned that the health problems caused by the coronavirus sometimes linger for months, raising fears that the virus may have longterm consequences for people’s health.
“There’s no doubt there has been anecdotal evidence of symptoms lingering for a while, but we don’t know if it’s 1%, 5%, 20% or 50%” of the cases, said Jeffrey Martin, a clinical epidemiologist and professor of epidemiology and biostatistics at UCSF. “We need to find out how common that is. It’s important that we separate the rare anecdotes from the true frequency.”
Cases of chronic fatigue, heart problems, lung
damage, blood clotting and neurological symptoms like dizziness and confusion have been documented in numerous patients long after the initial symptoms of COVID-19 have gone away.
The discovery of chronic symptoms could have a significant impact on human behavior as divisions erupt around the country over the speed with which businesses, parks, movie theaters and other gathering spots reopen. Boozy beach parties and concerts may not have the same lure for the young and healthy if the bacchanalia includes the prospect of prolonged disease and longterm disability.
It is what happened to Cliff Morrison, 68, of Oakland, who is still suffering from mood swings, headaches, blurry vision, aching joints and other strange symptoms nobody warned him about nearly two months after he first fell ill with COVID-19.
“I still have shortness of breath and some of the cough and no energy or strength,” said Morrison, a nurse and health care administrator, who contracted the disease through his work. “My vision has improved but it’s still a little blurry. No one told me that it would go on as long as it has.” Morrison, who worked as an AIDS coordinator in the 1980s, is one of 50 patients infected by COVID-19 who are enrolled in a study that Dr. Martin and a team of researchers at UCSF and San Francisco General Hospital are conducting. The investigation, called the Longterm Impact of Infection with Novel Coronavirus, or Liinc, is to determine what symptoms linger and how long the health problems last.
The study subjects, all of whom have been feverfree and tested negative for at least three weeks, were chosen because they had a wide spectrum of symptoms, from mild to severe.
Morrison, who lives alone, said he was very sick, unable to get out of bed except to go to the bathroom for three weeks. Besides being short of breath and feverish, his symptoms included vision problems, confusion and memory problems — he said there is a 10day stretch when he can barely remember anything.
He suffered from unusually intense mood swings, ranging from deep depression to extreme anger. At one point he developed a rash over the lower half of his body that turned into sores, like the chicken pox, lasting two weeks.
Martin said the plan is to interview, take blood and saliva samples, and chart lingering health problems in study subjects for up to two years. It is important, he said, because the disease has not been around long enough to determine whether the lingering symptoms represent an abnormally long recovery process or a longterm problem.
It appears from the early evidence that Morrison’s case is not unusual. Many recovering coronavirus patients have reported residual problems months after the initial infection, far longer than the experts thought was possible. The World Health Organization says patients with mild cases of COVID-19 should expect a twoweek recovery process while severe infections could last up to six weeks before they clear up.
The evidence of more chronic problems is preliminary, but it is mounting.
Studies in China have found that most COVID-19 patients — well over 70% — showed lesions or patches of irritation in the lungs known as “ground glass opacities” that could develop into permanent scars, or pulmonary fibrosis.
The SARS-CoV-2 virus that causes the illness is known to target ACE2 receptors, a protein on the surface of human cells that the spiky virus attaches to. Many of the receptors are in the heart muscle. Various studies indicate cardiovascular damage is common, with one study finding it in 12% of patients studied and another showing heart damage in 19% of the patients.
High rates of blood clots have been reported in China and France. Studies in the two countries found that between 5% and 30% of the hospitalized patients suffered strokes, blockages of arteries or pulmonary embolisms, which are obstructions in the lungs.
Tonynominated Canadian actor Nick Cordero had his right leg amputated after numerous COVID-related blood clots. The Broadway actor has now been in the hospital for about two months, much of that time on a ventilator.
Others have suffered strokes and heart attacks after being declared disease free and discharged from hospitals. The clots, which are likely caused by immune system responses to the infection, can also cause longterm problems, including heart palpitations and severe shortness of breath.
The virus also appears to attack the central nervous system, causing delirium and hallucinations in about a third of the patients in intensive care units. Morrison never had to go to the hospital, but he nevertheless suffered cognitive issues, which have mostly cleared up.
But many of the longterm problems may be a direct result of the severity of the infection. For instance, most critical patients end up suffering from acute respiratory distress syndrome, or ARDS, which is characterized by fluid in the lungs. Previous studies have shown that as many as 20% of ARDS survivors experience longterm cognitive impairment, including concentration and memory lapses, epidemiologists say.
Timothy Henrich, an associate professor of medicine and Martin’s colleague at UCSF, said lingering problems can be expected in severe cases involving organ dysfunction, clotting and ARDS, but some people with mild cases of COVID-19 have also reported postinfection problems.
“It’s not clear whether this is only in the severe cases,” said Henrich, an infectious disease clinician, virologist and immunologist. “This may be happening in a more subacute fashion as well, but it needs to be studied.”
Recovering COVID-19 victims, including some of Martin and Henrich’s colleagues, have reported feeling foggy and having trouble focusing on work. Others say their coughs, fevers and breathing issues have cycled on and off for a month after the initial symptoms.
People have reported coughing up blood, losing their sense of smell, migrainelike headaches and shortterm memory loss long after being cleared by doctors to go back to their normal routines.
Matt Willis, Marin County’s public health officer, said he is still tired, weak, short of breath and has lingering circulation problems two months after his initial diagnosis.
“I feel like my lungs have been traumatized by this,” said Willis, who is not part of the UCSF study. “I’m still close enough to the illness that I’m attributing some of these symptoms to postviral inflammation.”
But Henrich said some of these problems continue even after PCR, or polymerase chain reaction, tests no longer detect the virus, indicating an overzealous reaction by the human immune system.
“We are seeing immune activation even after the PCR tests are negative, suggesting that the body has cleared the initial virus, but the immune response is ongoing for quite some time,” he said. “What we are interested in learning is: How long does this inflammation last, is there an ongoing immune activation?”
Infectious disease specialists believe that many of the more severe symptoms, including ARDS, are being caused by overly robust immune responses to the infection.
The human immune response may also be responsible for an inflammatory reaction similar to Kawasaki disease that has recently been affecting children exposed to the coronavirus, according to a Centers for Disease Control and Prevention warning. Experts say the ailment, known as pediatric multisystem inflammatory syndrome, can cause rashes, fevers and heart inflammation more than a month after exposure to the virus.
Doctors at UCSF’s Benioff Children’s Hospital have recently seen dozens of children with reddishpurple lesions on the feet and hands known as acral perniosis. The rashes all appeared weeks or months after exposure to adult relatives with flulike symptoms, leading researchers to believe it is an afterthefact inflammatory reaction to COVID19.
Martin said the study at San Francisco General Hospital will test patients for antibodies and try to figure out what is going on with their immune responses. Researchers will also try to determine whether the 30 patients in the study have developed immunity and how long that immunity prevents them from being reinfected.
Morrison said the lingering fatigue, shortness of breath and blurred vision are concerns, but he is happy the phenomenon is being studied.
“We’re only four months into this pandemic,” he said, “and there is still so much that we don’t know.”