High-dimensional characterization of post-acute sequelae of COVID-19

Ziyad Al-Aly, Yan Xie, Benjamin Bowe

The acute clinical manifestations of COVID-19 are well characterized1,2; however, its post-acute sequalae have not been comprehensively described. Here, we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequalae including diagnoses, medication use, and laboratory abnormalities in 30-day survivors of COVID-19. We show that beyond the first 30 days of illness, people with COVID-19 exhibit higher risk of death and health resource utilization. Our high dimensional approach identifies incident sequalae in the respiratory system and several others including nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain, and anemia. We show increased incident use of several therapeutics including pain medications (opioids and non-opioids), antidepressants, anxiolytics, antihypertensives, and oral hypoglycemics and evidence of laboratory abnormalities in multiple organ systems. Analysis of an array of pre-specified outcomes reveals a risk gradient that increased across severity of the acute COVID-19 infection (non-hospitalized, hospitalized, admitted to intensive care). The findings show that beyond the acute 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 to reduce chronic health loss among COVID-19 survivors.