A Longitudinal Study of COVID-19 Sequelae and Immunity

National Institute Of Allergy And Infectious Diseases

Investigators

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Abstract

COVID-19 was identified in early 2020, and this newly recognized viral disease went on to become a worldwide pandemic. The clinical characteristics and spectrum of disease severity of acute COVID-19 were being defined, with a significant portion of those infected developing severe disease manifestations including pneumonia, acute respiratory distress syndrome with respiratory failure, and, in some cases, death. Very little was known about possible clinical sequelae that could persist after resolution of the acute infection. In addition, the characteristics of the initial cellular immune and antibody response to SARS-CoV-2 (the virus that causes COVID-19) were being defined and it was not known if the immune responses generated by infection provides long-term protective immunity. We mobilized quickly to study this new infection and designed a study to establish a longitudinal cohort of patients who recovered from COVID-19 to characterize the medical sequalae and persistent symptoms following recovery from COVID-19; estimate the incidence and risk factors for post-COVID-19 medical sequalae; and characterize antibody and cell-mediated immune responses to SARS-CoV-2 in disease survivors and these responses over time. Participants in the study are self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of symptoms or severity of the acute illness. The control group includes persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, who are recruited regardless of their current health status. All participants have the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. Samples of peripheral blood mononuclear cells, serum, and plasma has been collected from all participants. The baseline findings of the study were published in July 2022 at the Annals of Internal Medicine. These include the results from 309 participants who enrolled during the first year of the study. These are 189 patients with COVID-19 (12% of whom were hospitalized during acute illness) and 120 controls. At enrollment, symptoms consistent with postacute sequelae of SARS-CoV-2 infection (PASC) were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. Limitations include the possibilities that persons with PASC may have been more motivated to enroll (leading to overestimation of PASC prevalence) and that PASC that resolved before enrollment was not captured in the study (leading to underestimation of PASC prevalence). The study showed that there is a high burden of persistent symptoms in persons after COVID-19, but extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases.