Credit for the image: San Diego Tribune
NEJM — Perspectives
Steven Phillips, M.D., M.P.H., and Michelle A. Williams, Sc.D.
June 30, 2021
Now that more than half of U.S. adults have been vaccinated against SARS-CoV-2, masking and distancing mandates have been relaxed, and Covid-19 cases and deaths are on the decline, there is a palpable sense that life can return to normal.
Though most Americans may be able to do so, restoration of normality does not apply to the 10% to 30% of those who are still experiencing debilitating symptoms months after being infected with Covid-19.1
Unfortunately, current numbers and trends indicate that “long-haul Covid” (or “long Covid”) is our next public health disaster in the making.
What form will this disaster take, and what can we do about it?
To understand the landscape, we can start by charting the scale and scope of the problem and then apply the lessons of past failures in approaching postinfection chronic disease syndromes.
The Centers for Disease Control and Prevention (CDC) estimates that more than 114 million Americans had been infected with Covid-19 through March 2021.
Factoring in new infections in unvaccinated people, we can conservatively expect more than 15 million cases of long Covid resulting from this pandemic.
And though data are still emerging, the average age of patients with long Covid is about 40, which means that the majority are in their prime working years. Given these demographics, long Covid is likely to cast a long shadow on our health care system and economic recovery.
The cohort of patients with long Covid will face a difficult and tortuous experience with our multispecialty, organ-focused health care system, in light of the complex and ambiguous clinical presentation and “natural history” of long Covid. There is currently no clearly delineated consensus definition for the condition; indeed, it is easier to describe what it is not than what it is.
Long Covid is not a condition for which there are currently accepted objective diagnostic tests or biomarkers.
It is not blood clots, myocarditis, multisystem inflammatory disease, pneumonia, or any number of well-characterized conditions caused by Covid-19. Rather, according to the CDC, long Covid is “a range of symptoms that can last weeks or months…[that] can happen to anyone who has had Covid-19.” The symptoms may affect a number of organ systems, occur in diverse patterns, and frequently get worse after physical or mental activity.
No one knows what the time course of long Covid will be or what proportion of patients will recover or have long-term symptoms. It is a frustratingly perplexing condition.
The pathophysiology is also unknown, though there are hypotheses involving persistent live virus, autoimmune or inflammatory sequelae, or dysautonomia, all of which have some “biological plausibility.”2 Intriguing links between long Covid and postural orthostatic tachycardia syndrome (POTS) have also been made. But conventional evidence connecting possible causes to outcomes is currently lacking.
To understand why long Covid represents a looming catastrophe, we need look no further than the historical antecedents: similar postinfection syndromes.
Experience with conditions such as
- myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS),
- post-treatment Lyme disease syndrome,
- chronic Epstein–Barr virus,
- and even the 19th-century diagnosis of neurasthenia could foreshadow the suffering of patients with long Covid in the months and years after infection.
The health care community, the media, and most people with long Covid have treated this syndrome as an unexpected new phenomenon.
But given the long arc and enigmatic history of “new” postinfection syndromes, the emergence of long Covid should not be surprising.
Equally unsurprising has been the medical community’s ambivalence about recognizing long Covid as a legitimate disease or syndrome. Extrapolating from the experience with other postinfection syndromes, the varied elements of the biomedical and media ecosystems are coalescing into two familiar polarized camps.
One camp believes that long Covid is a new pathophysiological syndrome that merits its own thorough investigation.
The other believes it is likely to have a nonphysiological origin.
Some commentators have characterized it as a mental illness, and those embracing this psychogenic paradigm are reluctant to endorse a substantial societal focus on research or to follow traditional organ-specific clinical pathways to addressing patients’ concerns.
All of which augurs poorly for many people with long Covid.
If the past is any guide, they will be disbelieved, marginalized, and shunned by many members of the medical community. Such a response will leave patients feeling misunderstood, aggrieved, and dissatisfied. Because of a lack of support from the medical community, patients with long Covid and activists have already formed online support groups. One such organization, the Body Politic Covid-19 Support Group, has attracted more than 25,000 members.
Some of the disregard can be attributed to the fact that long Covid has disproportionately affected women.
Our medical system has a long history of minimizing women’s symptoms and dismissing or misdiagnosing their conditions as psychological. Women of color with long Covid, in particular, have been disbelieved and denied tests that their White counterparts have received.3,4
What needs to be done to help these patients and competently address this surge?
Unless we proactively develop a health care framework and strategy based on unified, patient-centric, supportive principles, we will leave millions of patients in the turbulent breach.
The majority will be women; many will have chronic, incapacitating conditions and will bounce around the health care system for years.
The media will continue to report extensively on the travails and heroics of the long-haul phenomenon that lacks apparent remedy or end.
There is, therefore, an urgent need for coordinated national health policy action and response, which we believe should be built on five essential pillars.
- The first is primary prevention. As many as 35% of eligible Americans may ultimately choose not to be vaccinated against Covid-19. Vaccine education campaigns should emphasize the avoidable scourge of long Covid and target high-risk, hesitant populations with culturally attuned messaging.
- Second, we need to continue to build out a formidable, well-funded domestic and international research agenda to identify causes, mechanisms, and ultimately means for prevention and treatment of long Covid. This effort is already under way. In February, the National Institutes of Health (NIH) launched a $1.15 billion, multiyear research initiative, including a prospective cohort of patients with long Covid who will be followed to study the trajectory of their symptoms and long-term effects. The World Health Organization (WHO) is working to harmonize global research efforts, including the development of standard terminology and case definitions.5 Many countries and research institutions have identified long Covid as a priority and launched ambitious clinical and epidemiologic studies.
- Third, there are valuable lessons to apply from extensive prior experience with postinfection syndromes. The relationship of long Covid to ME/CFS has been brought into focus by the CDC, the NIH, the WHO, and Anthony Fauci, the chief medical advisor to President Joe Biden and director of the National Institute of Allergy and Infectious Diseases. Going forward, research may yield complementary insights into the causation and clinical management of both conditions. The CDC has developed guidelines and resources on the clinical management of ME/CFS that may also be applicable to patients with long Covid.
- Fourth, to respond holistically to the complex clinical needs of these patients, more than 30 U.S. hospitals and health systems — including some of the most prestigious centers in the country — have already opened multispecialty long Covid clinics.
This integrative patient care model should continue to be expanded.
- Fifth, the ultimate success of the research-and-development and clinical management agendas in ameliorating the impending catastrophe is critically dependent on health care providers’ believing and providing supportive care to their patients. These beleaguered patients deserve to be afforded legitimacy, clinical scrutiny, and empathy.
Addressing this postinfection condition effectively is bound to be an extended and complex endeavor for the health care system and society as well as for affected patients themselves.
But taken together, these five interrelated efforts may go a long way toward mitigating the mounting human toll of long Covid.
Disclosure forms provided by the authors are available at NEJM.org.
This article was published on June 30, 2021, at NEJM.org.
Steven Phillips, M.D., M.P.H., and Michelle A. Williams, Sc.D.
From the COVID Collaborative, Washington, DC (S.P.); and the
Harvard T.H. Chan School of Public Health, Boston (M.A.W.).
Originally published at https://www.nejm.org.