Post-Acute COVID-19 Disease Severity

COVID-19, like many viral diseases, continues to impact patients’ health even after they have resolved their initial infections. Symptoms manifest across different organ systems with varying levels of severity. A literature review published March 22, 2021 in Nature Medicine by Nalbandian et al. surveyed the current research on post-acute COVID-19 disease. Across different studies of post-acute sequelae of SARS-CoV-2 infection (PASC), researchers observed pulmonary, cardiovascular, neuropsychiatric, hematologic, renal, endocrine, gastrointestinal, and dermatologic conditions, underscoring the complex, heterogeneous nature of the syndrome.1

In a prospective cohort study of 1,733 Chinese patients observed at six months from the onset of COVID-19 symptoms, Huang et al. found that a majority of the patients (76 percent) reported at least one PASC symptom. Fatigue or muscular weakness were the most commonly reported symptom (63 percent), in line with other studies.2 Chronic fatigue has been observed after numerous other acute infections, like SARS coronavirus.3 In one analysis, nearly all (97 percent) of a cohort of 29 patients admitted to a rehabilitation center after overcoming severe COVID-19 still experienced gait speed deficits at discharge from the rehabilitation center.4

Pulmonary complications are notably prevalent as well, with over one-fifth (23 percent) of participants in the study by Huang et al. experiencing dyspnea.2 In smaller studies conducted over shorter follow-up periods, this number was as high as 40 percent. Other observed symptoms include cough and persistent oxygen requirements. Those who had more severe acute COVID-19, including patients who required a high-flow nasal cannula or mechanical ventilation, may be at risk for serious long-term complications like pulmonary fibrosis and pneumonia.1

Neuropsychiatric complications continue to impact the quality of life and daily activities of a significant number of COVID-19 survivors. In the study by Huang et al., 23 percent of individuals experienced anxiety or depression and 26 percent had sleep difficulties.2 In a small United Kingdom study, 30 percent of hospitalized COVID-19 patients had symptoms of PTSD. In all of the studies summarized by Nalbandian et al., loss of taste and smell was experienced by over 10 percent of study participants. Cognitive impairment has widely been noted as well, with many suffering from “brain fog” (difficulties with concentration, memory, executive function and more).1

Beyond impacting individuals’ wellbeing, cognitive and physical fatigue associated with post-acute COVID-19 will alter productivity and the economy. Chronic fatigue symptoms bear resemblance to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which currently poses an estimated financial burden of between $17 and $24 billion in the U.S. each year. Experts propose that even if only 25 million Americans contract COVID-19 by the end of 2021 and only 10 percent subsequently suffer from an illness meeting the ME/CFS definition, the number of Americans suffering from ME/CFS would at least double over one year. Globally, they estimate that the number of people suffering from ME/CFS would increase to 110 million during 2021.3

Pulmonary complications will also pose economic consequences. While only one year of data is available thus far on the healthcare costs associated with COVID-19, the Kaiser Family Foundation studied these figures to estimate that the annual cost of treating COVID-19 cases only for uninsured Americans might range from $13.9 billion to $41.8 billion.5 It is also necessary to consider healthcare costs for managing conditions that can be exacerbated by lasting damage from a previous COVID-19 infection, such as pneumonia. Before the pandemic, roughly 1.5 million people were hospitalized for pneumonia each year in the U.S., at an average cost of $20,000 per stay.

The novelty of COVID-19 and the limited opportunities to observe its ongoing impacts mean that much is unknown about the prevalence and characteristics of post-acute conditions. Hypotheses about their causes abound: the effects of hospitalization, acute respiratory distress syndrome, and the impact of the hyperinflammatory response associated with COVID-19 may all play roles. Other important factors are confounding health disparities, social determinants of health, and the psychosocial impact of the pandemic.6

In December, Congress promised $1.15 billion over four years for the National Institutes of Health to fund research on the prolonged health consequences of COVID-19.7 Moreover, over 30 U.S. hospitals and health systems have already established clinics solely devoted to post-COVID-19 research and care.8 The long-term effects of COVID-19 remain unclear, and health systems, researchers, and clinicians are still in the initial stages of learning about how to best care for patients.


  1. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601-615. 
  1. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2021;397(10270):220-232. 
  1. Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Front Med (Lausanne). 2020;7:606824. 
  1. Olezene CS, Hansen E, Steere HK, et al. Functional outcomes in the inpatient rehabilitation setting following severe COVID-19 infection. PLoS One. 2021;16(3):e0248824. 
  1. Dovere E-I. Vaccine refusal will come at a cost—for all of us. Atl Mon. Published online April 10, 2021. 
  1. Bhadelia, N. “Post Acute Sequelae of SARS-CoV-2 (PAS-C)” Lecture presented at MassCPR Scientific Symposium: COVID-19 Diagnostic Testing and Clinical Management; March 30, 2021;  
  1. NIH launches new initiative to study “Long COVID.” NIH. Published February 23, 2021. 
  1. Carbajal E. 30 hospitals, health systems that have launched post-COVID-19 clinics. Beckers Hospital Review.