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COVID-19’s Long-Term Effects Raise the Stakes of the Game.

This isn’t “just a flu.”

Despite the surge of new cases of COVID-19, increases in the percentage of positive tests, and scores of ICUs at or near capacity, some commentators are still saying things like, “The so-called surge in cases is more fake news pushed by media cheerleaders eager to destroy the U.S. economy and culture if it makes Trump a one-term president,” and “in fact, our pandemic nightmare might well be coming to an end.” They and others emphasize that the daily number of Covid-19 deaths has been trending down since April (due to better medical management and the decreasing age of those infected, who have better outcomes than older persons). That is, of course, good news, but it is far from the whole story. The quotes above are from July 6 and 7, respectively. Only ten days later, the daily number of U.S. cases of Covid-19 reached an all-time high of almost 76,000, and hospitals were becoming overwhelmed in parts of several sunbelt states.

[W]e now know that many who recover from the initial symptoms of COVID-19 experience serious and long-lasting sequelae, or abnormalities resulting from the illness.

Earlier this month, I wrote about the importance to public health of “flattening the curve” of COVID-19 infections, to “spread out the demands on hospitals, which must have sufficient space, supplies, and healthy staff to care for all those who need hospital-level care—whether for COVID-19, a stroke, trauma, emergency surgery, or childbirth.”  But there are other, more important benefits to avoiding infection: we now know that many who recover from the initial symptoms of COVID-19 experience serious and long-lasting sequelae, or abnormalities resulting from the illness.

This is a lesson that is apparently lost on some pundits, as well as politicians like Missouri’s Governor Mike Parson, who, when asked about children returning to school, said, “They’re at the lowest risk possible. And if they do get COVID-19, which they will—and they will when they go to school—they’re not going to the hospitals. They’re not going to have to sit in doctor’s offices. They’re going to go home and they’re going to get over it.” Maybe, but maybe not.  

Coronavirus.

Coronavirus.

THE ALARMING REALIZATION ABOUT POST-ACUTE COVID-19 SYMPTOMS

COVID-19 is more than a transient respiratory infection. Although it often presents with pulmonary symptoms, and can cause severe pneumonia (which can lead to “post-Covid pulmonary fibrosis),” there have been numerous reports of non-respiratory manifestations, including loss of sense of smell or taste, confusion and cognitive impairments, fainting, sudden muscle weakness or paralysis, abnormal blood-coagulation tests, seizures, ischemic strokes, kidney damage, and, rarely, a severe pediatric inflammatory syndrome.

Moreover, recovery is often incomplete, with various symptoms persisting after the acute infection itself has subsided.  A recent article published in the journal JAMA found that, in a small study of patients who had recovered from COVID-19, 87.4% reported persistence of at least one symptom, particularly fatigue and dyspnea (i.e., shortness of breath).

The frequency of post-acute COVID-19 symptoms they found is shown here: 

Citation required.

Credit: JAMA.

Extrapolating those findings (which are from the JAMA article cited above) to the U.S., and making certain conservative assumptions, physician, epidemiologist, and statistician Bob Morris estimates the frequency of symptoms in the U.S. thusly:

Credit: Bob Morris.

Credit: Bob Morris.

Possibly overlapping with Dr. Morris’s “3 or more category” are reports of patients experiencing long-term adverse effects that resemble a condition variously known as myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). As the name suggests, ME/CFS is a syndrome, or a group of symptoms that seem to characterize or define an illness, even if we don’t know how they’re related or what causes them. (Syndromes differ from better-understood, more clearly defined illnesses such as solid tumors, rheumatoid arthritis, or stroke, for example).

The signs and symptoms of ME/CFS may include fatigue, loss of memory or concentration, sore throat, swelling of the neck or armpit lymph nodes, unexplained muscle or joint pain, headaches, non-restorative sleep, and extreme exhaustion that lasts more than 24 hours after physical exercise or mental stimulation (“post-exertional malaise”). People with ME/CFS are often incapable of performing ordinary activities, and sometimes become completely debilitated, unable even to get out of bed. (A good account of ME/CFS was provided in an interview of three COVID-19 patients on NPR’s July 11 broadcast of “Weekend Edition,” who described, in poignant terms, their ongoing symptoms and their frustration).

The manifestations of ME/CFS can persist for years, although we can’t yet know what the typical, long-term post-COVID-19 symptomatology will be. What we do know, however, is that in recent decades, outbreaks of other infectious diseases, including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) (both of which are also caused by coronaviruses), as well as West Nile virus, H1N1 influenza, and Ebola—have all been followed by a range of long-term complaints that resemble those of ME/CFS. Therefore, it’s no surprise to see this phenomenon repeated in COVID-19 patients.

The appearance of serious COVID-19 sequelae, such as ME/CFS, has important implications.

First, fatalities aside, the increase in cases and the high numbers of hospitalizations in epicenters of infection cannot be dismissed as simply a self-limited, “flu-like illness.” For one thing, the effects of the common flu are usually done and gone in a week or so, but we are realizing that, as shown in the figure above, various effects of COVID-19 often persist.

These findings are a potent argument for aggressively suppressing and mitigating COVID-19.  The fewer new cases, the fewer lingering illnesses there will be—with all their attendant misery and expense.  (Corollaries: “COVID parties” are dangerous and colossally stupid, as is letting infections spread to attain “herd immunity,” which, in any case, will fail.)

Second, the persistence of debilitating symptoms argues strongly against vaccine “challenge trials,” in which infectious SARS-CoV-2 virus is intentionally administered to test subjects, some of whom have received a trial vaccine while others have gotten a placebo.  In the absence of very effective drugs to treat COVID-19, such studies would, in my opinion, be unethical. Dr. Michael Rosenblatt, entrepreneur and former dean of the Tufts University School of Medicine, has offered additional persuasive arguments against challenge trials—including delays in performing them, the question of their broad applicability (given that they would likely be performed in lower-risk, young people), and the possibility that deaths or significant morbidity in the test subjects could retard research.

Finally, we need to prioritize research on the long-term effects of COVID-19. We need to better understand the pathophysiology of both the acute viral infection and its relationship to ME/CFS and other sequelae. This could be done by allocating government research funding to this area, and by encouraging collaborations with scientists in countries that have experienced large numbers of cases of COVID-19.

The sad truth is that, in terms of both the number of infections, and an understanding of COVID-19, we are still in the early days of this pandemic. There is much to learn, and much to be done.

 

Henry I. Miller, a physician, molecular biologist, and Senior Fellow at the Pacific Research Institute. Henry was a research fellow at the National Institute of Child Health and Human Development, and the founding director of the FDA's Office of Biotechnology. He was the co-discoverer of a critical enzyme in the influenza virus. You can find him online or on Twitter at @henryimiller.

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