Long COVID Comes Into the Light
Jeff Wise

Even before 2020’s first horrific wave of COVID-19 deaths subsided, reports surfaced warning of a brutal second punch: Instead of recovering quickly after a mild infection, some people were suffering from symptoms that lingered or even intensified in the weeks and months that followed.

The condition came to be called long COVID. In those early days, everything about it was uncertain, from what symptoms it caused to how long they’d last and how hard they would hit. Some speculated that the effects might be effectively incurable, and that a large percentage of those infected with SARS-CoV-2 would wind up succumbing to this life-altering condition. “Months of illness could turn into years of disability,” warned the Atlantic’s Ed Yong. Given the bodies piling up in makeshift morgues, it seemed reasonable to assume the worst.

The first reports of how COVID seemed to fundamentally change people were scrabbled together from anecdotal accounts and preliminary studies. The picture they painted was frightening: As many as a third of all people who’d tested positive went on to report long COVID, according to a report published a year after the pandemic began. Few of these people had recovered much, and many were debilitated, unable to work or attend school. Newspapers and magazines ran articles that vividly described the complex litany of suffering endured by patients who weren’t getting any answers from their doctors. One early and influential story was by the British epidemiologist Paul Garner, who wrote in the medical journal BMJ about being flattened by a “roller coaster of ill health, extreme emotions, and utter exhaustion.” He described experiencing relentless, extreme fatigue, a “muggy head,” breathlessness, muscle pain, and a “weird sensation in the skin”—a parade of “constantly shifting, bizarre symptoms” that left him bedridden.

Long COVID is an unusual condition not only in its kaleidoscope of symptoms but also in the fact that it hadn’t been identified initially by doctors who encountered similar sets of symptoms in their patients. It was, rather, described by COVID patients themselves who, in the early months of the pandemic, found themselves mysteriously unable to get better. The complaints of early “long-haulers” were then picked up and amplified by activists, whose lobbying persuaded the government to allocate more than $1 billion in research funds. “Long COVID has a strong claim to be the first illness created through patients finding one another on Twitter,” researchers Felicity Callard and Elisa Perego wrote in the journal Social Science & Medicine. (They both suffered from long COVID themselves.) Patients desperately searching for answers were understandably dismayed to find little clarity from the medical community about their strange illness.

Now, three years later, the research is catching up to the anecdotal reports and the early evidence, and a clearer picture of long COVID has emerged. It turns out that, like COVID-19 itself, a lot of our early guesses about it turned out to be considerably wide of the mark. This time, fortunately, the surprises are mostly on the positive side. Long COVID is neither as common nor as severe as initially feared. As the U.S. government moves to end the country’s state of emergency, it’s another reassuring sign that, as President Biden put it during his State of the Union address, “COVID no longer controls our lives.”

As vaccines rolled out across the country in 2021, researchers at the Mayo Clinic analyzed the symptoms of 108 patients who’d come for post-COVID care. Their results suggested that these patients fell into two main camps. Some, mostly men, suffered severe illness and were still being plagued by symptoms like chest pain and shortness of breath. Then there were others, mostly women, who had experienced relatively mild illness, or no symptoms at all, but were subsequently dogged by “widespread pain, fatigue,” and “cognitive impairment, including the commonly reported “brain fog.” The authors noted that this cluster of symptoms resembled a class of broadly similar conditions like chronic fatigue syndrome, fibromyalgia, and POTS (postural orthostatic tachycardia syndrome), all of which can leave sufferers incapacitated for years at a time.

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How long could long COVID symptoms be expected to last? Researchers in Australia tried to answer that question by conducting phone interviews with every single person who was diagnosed with COVID-19 in the state of New South Wales between January and May 2020. They found that recovery followed a curve, with 80 percent of patients fully recovered after 30 days and 91 percent recovered after 60 days. Thereafter, the population of symptomatic patients continued to slowly dwindle, with 4 percent of the original patient population still suffering symptoms after four months. Their most common complaints were coughing and fatigue.

Other work suggested that long COVID could affect a much larger slice of the population. In one influential study from early 2021, researchers at the University of Washington sent a questionnaire to 234 COVID patients between three and nine months after they fell ill. Of the 177 who responded, about a third reported ongoing symptoms like fatigue, brain fog, and loss of smell. A subsequent Brookings Institution report used this statistic to estimate that 31 million working-age Americans “may have experienced, or be experiencing, lingering COVID-19 symptoms.”

There are several problems with survey-based research, however. One is that there’s a risk of selection bias, in that people who feel that they have long COVID are more likely to want to complete a questionnaire on the topic. Another is that people may report having symptoms post-COVID that they also had pre-COVID, and so their maladies may not actually have been caused by the disease.

To get around these problems, scientists began carrying out what are called retrospective cohort studies. These involve sifting through anonymized electronic medical records to find patients who tested positive for COVID and then returned complaining of subsequent symptoms. Patients who experienced the same symptoms both before and after they got COVID are filtered out. Those remaining are then compared with a second population, of COVID-negative patients, with whom they have been matched by age, gender, and other medically relevant criteria. The difference in the groups’ rate of post-COVID symptoms reveals just what medical mayhem the SARS-CoV-2 virus is leaving in its wake.

This kind of research isn’t quick, because, by definition, it concerns the patients whose maladies take the longest to resolve. But as 2022 progressed, results started to come in.

Researchers expected to find many chronic aftereffects of COVID. Instead, they concluded there were very few.

One study of patients in an Israeli health network looked at the incidence of 70 commonly reported long COVID symptoms in 150,000 patients. The researchers found that patients who’d been infected were more likely than people in a control group to suffer for extended periods from certain symptoms, in particular loss of taste and smell, concentration and memory problems, difficulty breathing, weakness, hair loss, palpitations, and chest pain. But the difference between the infected and controls largely disappeared by the end of the first year, and to the extent that they remained, they affected a relatively small number of patients. For instance, 407 of the COVID patients reported having persistent concentration and memory problems at the end of the first year, while 276 of the controls also did. That meant that for every 10,000 people, only about 13 had cognitive difficulties that were attributable specifically to COVID.

The researchers had gone into the project expecting to find a large number of chronic COVID aftereffects. Instead, they concluded that there were actually very few. “As we analyzed the data,” the lead authors told Stat in January, “we were surprised to find only a small number of symptoms that were related to COVID and remained for a year post infection and the low number of people affected by them.”

Other studies produced similar results. Researchers at the University of Oxford in the U.K. combed through the health records of more than a million patients in a retrospective cohort study that compared those who’d tested positive for COVID with those who’d had other respiratory infections but had not been diagnosed with COVID-19 or tested positive for SARS-CoV-2. After following patients’ symptoms for two years, they reported in the Lancet Psychiatry last August that they “found no evidence of a greater overall risk of any first neurological or psychiatric diagnosis after COVID-19 than after any other respiratory infection.” There was an elevated risk for certain symptoms, however. They found that 6.4 percent of COVID patients experienced “cognitive deficit (known as brain fog),” compared with 5.5 percent of patients who’d had other respiratory infections. Although the Oxford researchers were looking at a different set of cognitive symptoms than the Israeli researchers were, the upshot was similar: In both cases, nearly as many controls suffered the symptom as COVID patients did.

Meanwhile, researchers at Montefiore Medical Center in the Bronx looked at 18,811 patients who’d tested positive for COVID-19 and 5,772 who’d had influenza. The number of patients reporting new-onset neuropsychiatric symptoms after COVID-19 was 388, or 2 percent. This figure was actually less than that for patients with influenza, which was 2.5 percent.