High Dimensional Characterization of Post-acute Sequalae of COVID-19: analysis of health outcomes and clinical manifestations at 6 months

Abstract

\n The coronavirus disease 2019 (COVID-19) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2. The acute clinical manifestations of COVID-19 are well characterized. The post-acute sequalae of COVID-19 have not been comprehensively described. Here, we use the national healthcare databases of the US Department of Veterans Affairs to undertake a high dimensional approach to comprehensively identify 6-months outcomes of incident clinical manifestations including diagnoses, medication use, and laboratory abnormalities in people who survived the first 30 days of COVID-19. We first describe the clinical manifestations in people with COVID-19 compared to users of the Veterans Affairs healthcare system. We then provide a comparative evaluation of the post-acute sequalae in 30-day survivors who were hospitalized for COVID-19 vs. seasonal influenza. We show that beyond the first 30 days of illness, people with COVID-19 are at higher risk of death and health resource utilization. Our approach identifies incident clinical manifestations in the respiratory system and several other manifestations including the nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, and signs and symptoms related to poor generalized wellbeing including malaise, fatigue, musculoskeletal pain, and anemia. There was increased incident use of pain medications (opioids and non-opioids), antidepressants, anxiolytics, antihypertensives, antihyperlipidemic, insulin, and several other medication classes. The findings show that beyond the first 30 days of illness, substantial burden of health loss — spanning pulmonary and several extrapulmonary organ systems — is experienced by COVID-19 survivors. The results provide a roadmap to inform health system planning and development of multidisciplinary care strategies aimed at reducing chronic health loss and optimizing wellness among COVID-19 survivors.