SARS-CoV-2 infection and risk of clinical sequelae during the post-acute phase: a retrospective cohort study

Abstract

Objective: Clinical 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. Design: Retrospective cohort study including three propensity-matched groups. Setting: This 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. Participants: Individuals 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 measures: Over 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. Results: This 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. Conclusions: Our 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.

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: cohort study in OpenSAFELY using linked primary care, secondary care and death registration data

“…15 Interestingly, recent data from Denmark suggest limited post-acute complications following non-hospitalised COVID-19; 19 this is in contrast to a recent study using US health insurance data which found raised risks of a range of outcomes among a relatively young cohort with mostly (92%) non-hospitalised COVID-19 disease, compared with both the general population and people with a record of other viral lower respiratory tract infections. 14 Our data showed that COVID-19 hospitalised patients were more likely to have baseline comorbidities than general population controls, reflecting known associations between comorbidities and risks of severe COVID-19 outcomes. 6 Differences in outcomes between hospitalised patients and general population controls might therefore reflect baseline differences not fully captured in our adjustment models, and might also reflect a generic adverse effect of hospitalisation.…”

“…Another US study limited to people aged <65 years also found excess risks of a range of clinical outcomes ascertained from health insurance data among people with a record of SARS-CoV-2 infection. 14 A UK study of routinelycollected primary care and hospitalisation data described raised rates of all-cause hospital admission and death among patients discharged following a COVID-19 hospitalisation; the authors also noted raised risks of adverse respiratory and cardiovascular sequalae among the selected outcomes investigated. 15 Only a general population comparator was used, making it difficult to disentangle risks specific to COVID-19 from those associated with hospitalisation more generally; furthermore, a hospitalised cohort is likely to have been more prone to health problems at the outset than the general population comparator group.…”

Post-COVID und die Lunge

“…Es deutet sich jedoch an, dass ca. 5 % der Patienten mit COVID-19 einen bildgebend darstellbaren Residualbefund aufweisen [6]. Ob sich hieraus therapeutische Konsequenzen ergeben, wird Gegenstand dieser Untersuchungen sein.…”

New‐onset diabetes in “long COVID”

“…14 In another retrospective cohort study of three data sources from a large United States health plan, among 193 113 COVID-19 patients aged ≤65 years, NOD was the sixth most common post-acute clinical sequelae over a median follow-up of 2.9 months. 15 Possible mechanisms explaining the occurrence of NOD with SARS-CoV-2 infection during the acute phase are cytolytic effects of the virus on pancreatic β-cells, 16 activation of the hypothalamic-pituitary-adrenal and sympathoadrenal axes causing an increase in counterregulatory hormones, activation of the renin-angiotensin system resulting in unopposed deleterious actions of angiotensin II, and enhanced autoimmunity. 17,18 However, it is yet to be determined whether these mechanisms persist in the post-acute phase for the development of NOD in long COVID.…”

“…22 The COVID-19 pandemic has now persisted for over a year, and researchers across the globe are studying its long-term effects. 2,[12][13][14][15]23,24 It is now high time to consider NOD as a metabolic clinical sequela of SARS-CoV-2 infection to understand the role of COVID-19 in driving the diabetes pandemic.…”