{"subscriber":false,"subscribedOffers":{}} Why Do Some Recover From COVID-19 Quickly, While Others Seem Likely To Face Long-Term Disability? | Health Affairs

Health Affairs Forefront

Why Do Some Recover From COVID-19 Quickly, While Others Seem Likely To Face Long-Term Disability?

Never in the modern scientific era have so many people been infected with the same virus in such a short period of time. And if the history of medicine is a guide, a proportion of COVID-19 survivors will not fully recover and will develop disabling and chronic neurological dysfunctions and other disorders.

In recent decades, outbreaks of other infectious diseases—such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), both also arising from coronaviruses, as well as West Nile virus, H1N1 influenza, and Ebola—have been followed by a range of long-term complaints. These have included, among others, severe muscle pain; headaches; loss of balance; paralyzing fatigue; and declines in memory, concentration, and other cognitive functions. Yet, we know very little about why most patients get better from episodes of infectious disease while a smaller number continue to suffer from troubling and sometimes devastating symptoms.

As society grapples with the immediate demands of the coronavirus pandemic, we need to anticipate and prepare for a likely wave of post-COVID-19 illness. It is critical that the US and other key players in global health implement a coordinated international tracking system of COVID-19 patients, with harmonized data collection and biological sampling at regular intervals.

Although much remains unknown about the novel coronavirus, reports of non-respiratory symptoms and clinical events have been widespread. These include loss of sense of smell or taste, confusion and cognitive impairments, fainting, sudden muscle weakness or paralysis, seizures, ischemic strokes, kidney damage, and—most recently—a sometimes fatal pediatric inflammatory syndrome. Other research has shown slowed brain wave patterns, brain inflammation, and evidence of virus in cerebrospinal fluid.

To date, it is clear that some symptoms can persist in susceptible patients for at least a couple of months after infection. Identifying such medical concerns in real time could help unlock the secrets of these post-viral illnesses, prevent them in the future, and find better treatments for those who suffer from them—including post-COVID-19 patients themselves.

Benefits Beyond COVID-19

It is also important to recognize that such research has benefits that extend beyond just the population of individuals with COVID-19. For example, it could benefit up to 3.4 million Americans estimated to be suffering from myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS)—a disease or cluster of related diseases characterized by profound exhaustion after minimal exertion, sleep disorders, cognitive lapses, and other symptoms. Some get better, but few regain full function. A quarter of patients are largely home-bound or bed-bound. In the US, the annual costs of ME/CFS, including medical expenses and lost productivity, could be as much as $24 billion, according to the Centers for Disease Control and Prevention.

Many if not most ME/CFS patients date the start of their illness either to a case of mononucleosis, a cold, or some other acute infectious episode. Although efforts to link the condition to a specific pathogen have failed, viruses, bacteria, and parasites all appear capable of triggering these extended states of poor health.

In an Australian study, investigators followed 253 patients with mononucleosis, Ross River virus, or Q fever, a bacterial infection. At six months, 11 percent met diagnostic criteria for what the authors called chronic fatigue syndrome. The research, published in the BMJ in 2006, also found that more severe acute illness increased the risk for these later complications. “Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome,” noted the authors.

It is possible an initial infection is like a hit-and-run accident—even though the acute illness passes, it leaves behind serious damage in vulnerable individuals. It is also possible, for example, that a new infection could help trigger the reactivation of latent viral infections or skew the bacterial communities that make up the gut microbiome, with consequences for the immune system and metabolic processes. While research has documented a range of neurologic, immunologic, metabolic, and other dysfunctions in ME/CFS patients, no causes have been confirmed. As a result, patients have often been unfairly accused of exaggerating their symptoms or diagnosed as suffering from psychiatric or psychosomatic disorders.

In the case of COVID-19, the coronavirus could be directly implicated in some of the non-respiratory symptoms through infection of the nervous system or other organs. Yet, it is already known that some of the severity of the disease relates to additional processes, such as aberrant production of inflammatory molecules, known as “cytokine storms,” and disruption of blood clotting pathways. How the virus contributes to these events remains unclear.

Start The Research Now

Research on the long-term impacts of SARS and other epidemic diseases has often been retrospective—that is, it looks backward to determine why some patients continue to experience symptoms. Such investigations, while useful, provide much less authoritative and reliable information than prospective research that follows people from diagnosis and over an extended period of time. For example, biological samples acquired early on may reveal evidence of key aspects of the disease process. And patients might forget details that could be important clues to pathophysiologic changes if they are only asked about them after the fact.

With the coronavirus, now is the time to implement such prospective research and start documenting the biological pathways from initial illness to chronic neurological dysfunctions and other disorders. Some specialty medical associations and research groups have already initiated or announced valuable efforts to gather such data, yet post-COVID-19 monitoring and biobanking plans remain extremely limited and fragmented. Unless nationwide and global surveillance and registry mechanisms are established soon, our best opportunity to discover the factors that impede or hasten long-term recovery—and to translate these findings into effective interventions—will rapidly slip away.

Such an initiative would require bold leadership from the National Institutes of Health, to rally the cooperation of other key institutional governmental and non-governmental bodies, both domestic and international. And it would obviously require large funding commitments. But the unprecedented scale of events, and the potential economic, societal, and human toll of a secondary wave of post-COVID-19 disability, call for an unprecedented global research investment to meet this public health challenge head on.

Authors’ Note

Dr. Hornig has joined with Solve ME/CFS Initiative and other groups worldwide to establish a global initiative for serial collections of clinical data and biological samples from COVID-19 patients to facilitate research into long-term health consequences. Dr. Tuller’s position at Berkeley is supported through crowdfunding efforts on Berkeley’s crowdfunding platform, and many ME/CFS patients donate.

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