Long-haul COVID: heed the lessons from other infection-triggered illnesses

According to the Johns Hopkins Coronavirus Resource Center, more than 115 million people worldwide have been infected with SARS-CoV-2 during the COVID-19 pandemic, with extensive implications for morbidity and mortality. Description of long-term effects of COVID-19 are apparing in the medical literature; the first large cohort study¹ with 6-months' follow-up has been published, and more data are sure to follow. A small number of studies point not only to persistent imaging and testing abnormalities across several organ systems in the postacute period, but to a high frequency of patient-reported symptoms such as fatigue, insomnia, anxiety and depression, autonomic disturbances, cognitive difficulties, pain, and others. The presence of patient support groups, and the rapid expansion of clinics to manage or treat these symptoms, validate further their existence and impact.

Although the frequency, severity, and potentially the etiology of persistent symptoms can vary, sequelae after COVID-19 appears poised to join the range of other postinfectious syndromes described in the field of infectious diseases.² These often share a common symptom phenotype, which might also meet case definitions for myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, or post-treatment Lyme disease. We hope that researchers and clinicians will draw on these other conditions as they continue to advance scientific understanding of so-called long-haul or persistent COVID-19. We would also argue that there are important lessons to learn and pitfalls to avoid; our specific area of clinical care and research (post-treatment Lyme disease) has remained a fiercely contentious condition for more than 30 years.³

To quantify severity and measure improvements are inherently easier in objective abnormalities than in patient-reported symptoms. Furthermore, a scientific knowledge gap surrounds the cause of persistent symptoms after acute infections, such as fatigue. Both factors contribute to the risk of dismissing patient-reported complaints, particularly those that might appear vague, difficult to explain, multifactorial, or unexpected. Although peer-reviewed research is needed, patients with persistent symptoms after COVID-19 are already facing illness invalidation and disbelief from health-care providers, family, and friends.⁴ In listening to patients, the resolution of objective abnormalities is often not the whole story of their illness, and symptoms such as fatigue could instead be the most devastating to patients' quality of life. Postinfectious syndromes, including persistent symptoms after COVID-19, present a considerable challenge to clinicians and researchers. However, they also present the opportunity for novel, scientifically rigorous, inclusive, open-minded research with the aim of helping patients with these poorly understood conditions recover their health.