Objective To evaluate the excess risk and relative hazards for developing incident clinical sequelae after the acute phase of SARS-CoV-2 infection in adults aged 18-65. Design Retrospective cohort study. Setting Three merged data sources from a large United States health plan: a large national administrative claims database, an outpatient laboratory testing database, and an inpatient hospital admissions database. Participants Individuals aged 18-65 with continuous enrollment in the health plan from January 2019 to the date of a diagnosis of SARS-CoV-2 infection. Three comparator groups, matched by propensity score, to individuals infected with SARS-CoV-2: a 2020 comparator group, an historical 2019 comparator group, and an historical comparator group with viral lower respiratory tract illness. Main outcome measures More than 50 clinical sequelae after the acute phase of SARS-CoV-2 infection (defined as the date of first SARS-CoV-2 diagnosis (index date) plus 21 days) were identified using ICD-10 (international classification of diseases, 10th revision) codes. Excess risk in the four months after acute infection and hazard ratios with Bonferroni corrected 95% confidence intervals were calculated. Results 14% of adults aged ≤65 who were infected with SARS-CoV-2 (27 074 of 193 113) had at least one new type of clinical sequelae that required medical care after the acute phase of the illness, which was 4.95% higher than in the 2020 comparator group. The risk for specific new sequelae attributable to SARS-Cov-2 infection after the acute phase, including chronic respiratory failure, cardiac arrythmia, hypercoagulability, encephalopathy, peripheral neuropathy, amnesia (memory difficulty), diabetes, liver test abnormalities, myocarditis, anxiety, and fatigue, was significantly greater than in the three comparator groups (2020, 2019, and viral lower respiratory tract illness groups) (all P<0.001). Significant risk differences because of SARS-CoV-2 infection ranged from 0.02 to 2.26 per 100 people (all P<0.001), and hazard ratios ranged from 1.24 to 25.65 compared with the 2020 comparator group. Conclusions The results indicate the excess risk of developing new clinical sequelae after the acute phase of SARS-CoV-2 infection, including specific types of sequelae less commonly seen in other viral illnesses. Although individuals who were older, had pre-existing conditions, and were admitted to hospital because of covid-19 were at greatest excess risk, younger adults (aged ≤50), those with no pre-existing conditions, or those not admitted to hospital for covid-19 also had an increased risk of developing new clinical sequelae. The greater risk for incident sequelae after the acute phase of SARS-CoV-2 infection is relevant for healthcare planning.

Objective To characterize the risk of persistent and new clinical sequelae in adults aged ≥65 years after the acute phase of SARS-CoV-2 infection. Design Retrospective cohort study. Setting UnitedHealth Group Clinical Research Database: deidentified administrative claims and outpatient laboratory test results. Participants Individuals aged ≥65 years who were continuously enrolled in a Medicare Advantage plan with coverage of prescription drugs from January 2019 to the date of diagnosis of SARS-CoV-2 infection, matched by propensity score to three comparison groups that did not have covid-19: 2020 comparison group (n=87 337), historical 2019 comparison group (n=88 070), and historical comparison group with viral lower respiratory tract illness (n=73 490). Main outcome measures The presence of persistent and new sequelae at 21 or more days after a diagnosis of covid-19 was determined with ICD-10 (international classification of diseases, 10 th revision) codes. Excess risk for sequelae caused by infection with SARS-CoV-2 was estimated for the 120 days after the acute phase of the illness with risk difference and hazard ratios, calculated with 95% Bonferroni corrected confidence intervals. The incidence of sequelae after the acute infection was analyzed by age, race, sex, and whether patients were admitted to hospital for covid-19. Results Among individuals who were diagnosed with SARS-CoV-2, 32% (27 698 of 87 337) sought medical attention in the post-acute period for one or more new or persistent clinical sequelae, which was 11% higher than the 2020 comparison group. Respiratory failure (risk difference 7.55, 95% confidence interval 7.18 to 8.01), fatigue (5.66, 5.03 to 6.27), hypertension (4.43, 2.27 to 6.37), memory difficulties (2.63, 2.23 to 3.13), kidney injury (2.59, 2.03 to 3.12), mental health diagnoses (2.50, 2.04 to 3.04), hypercoagulability 1.47 (1.2 to 1.73), and cardiac rhythm disorders (2.19, 1.76 to 2.57) had the greatest risk differences compared with the 2020 comparison group, with similar findings to the 2019 comparison group. Compared with the group with viral lower respiratory tract illness, however, only respiratory failure, dementia, and post-viral fatigue had increased risk differences of 2.39 (95% confidence interval 1.79 to 2.94), 0.71 (0.3 to 1.08), and 0.18 (0.11 to 0.26) per 100 patients, respectively. Individuals with severe covid-19 disease requiring admission to hospital had a markedly increased risk for most but not all clinical sequelae. Conclusions The results confirm an excess risk for persistent and new sequelae in adults aged ≥65 years after acute infection with SARS-CoV-2. Other than respiratory failure, dementia, and post-viral fatigue, the sequelae resembled those of viral lower respiratory tract illness in older adults. These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus.

No 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.