SARS-CoV-2 infection and risk of clinical sequelae during the post-acute phase: a retrospective cohort study
Authors: Daugherty Sarah E. , Guo Yinglong , Heath Kevin , Dasmariñas Micah C. , Jubilo Karol Giuseppe , Samranvedhya Jirapat , Lipsitch Marc , Cohen Ken 
Published: March 2021

AbstractObjectiveClinical sequelae have not been well characterized during the post-acute phase of SARS-CoV-2 among adults 18 to 65 years old, and this study sought to fill that gap by evaluating excess risk and relative hazards for developing incident clinical sequelae during the post-acute phase.DesignRetrospective cohort study including three propensity-matched groups.SettingThis study merged three data sources from a large United States health plan: a large national administrative claims database, an outpatient lab testing database, and an inpatient hospital admissions database.ParticipantsIndividuals 18 to 65 years old with continuous health plan enrollment from January 2019 to date of SARS-CoV-2 diagnosis. Three comparator groups were identified and propensity-score matched to individuals infected with SARS-CoV-2: a 2020 comparator group, a historical 2019 comparator group and a historical comparator group with viral lower respiratory tract illness (vLRTI).Main outcome measuresOver 50 clinical sequelae during the post-acute phase (index date + 21 days) were ascertained using ICD-10 codes. Excess risk due to SARS-CoV-2 during the 4 months following the acute phase of illness and hazard ratios with 95% Bonferroni-corrected confidence intervals were calculated.ResultsThis study found 14% of adults ≤65 years of age who were infected with SARS-CoV-2 (n=193113) had at least one new clinical sequelae that required medical attention during the post-acute phase of illness. When considering risk for specific sequelae attributable to SARS-Cov-2 infection during the post-acute phase, clinical outcomes including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia (memory difficulty), diabetes, liver test abnormalities, myocarditis, anxiety and fatigue were significantly elevated compared to the three propensity-matched comparator groups (2020, 2019, vLRTI). Significant risk differences due to SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people and hazard ratios ranged from 1.24 to 25.65 when compared to the 2020 comparator group.ConclusionsOur results confirm excess risk for developing clinical sequelae due to SARS-CoV-2 during the post-acute phase, including specific types of sequelae less commonly seen among other viral illnesses. Although individuals who were older, had pre-existing conditions, and were hospitalized due to COVID-19 were at greatest excess risk, younger adults (≤50 years), adults who did not have pre-existing conditions or adults who were not hospitalized due to COVID-19 were still at elevated risk for developing new clinical sequelae. The elevated risk for incident sequelae during the post-acute phase is relevant for healthcare planning.Summary BoxWhat is already known on this topicSmall observational studies and case reports of hospitalized patients have shown some COVID-19 survivors suffer from short- and long-term sequelae. Few studies have characterized the excess risk of clinical sequelae attributable to SARS-CoV-2 during the post-acute phase among adults ≤65 years of age in a large generalizable sample.What this study addsThis study found 14% of individuals ≤65 years of age who were infected with SARS-CoV-2 (n=193113) had a diagnosis of at least one new sequelae that required medical attention during the post-acute phase of illness. Elevated risk for specific clinical sequelae during the post-acute phase of illness was noted across a range of organ systems including cardiovascular, neurologic, kidney, respiratory, and mental health complications. The risk for incident sequelae increases with age, pre-existing conditions, and hospitalization for COVID-19; however, even among adults ≤ 50 years of age and individuals without pre-existing conditions or hospitalization due to COVID-19, risk for some clinical sequelae is still elevated. These results indicate where additional diagnostic follow-up, rehabilitation, and symptom management may be warranted among younger adults with milder infection.