Ortega, Victor E.

ImportancePersistent symptoms and disability following SARS-CoV-2 infection, known as post–COVID-19 condition or “long COVID,” are frequently reported and pose a substantial personal and societal burden.ObjectiveTo determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.Design, Setting, and ParticipantsFor this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health–funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection.ExposurePreinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires.Main Outcomes and MeasuresProbability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days.ResultsOf 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections.Conclusions and RelevanceIn this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Abstract Rationale Ground-glass opacities (GGOs) in the absence of interstitial lung disease are understudied. Objectives To assess the association of GGOs with white blood cells (WBCs) and progression of quantified chest computed tomography emphysema. Methods We analyzed data of participants in the SPIROMICS study (Subpopulations and Intermediate Outcome Measures in COPD Study). Chest radiologists and pulmonologists labeled regions of the lung as GGOs, and the adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGOs (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBCs, changes in percentage emphysema, and clinical outcomes. Measurements and Main Results Among 2,714 participants, 1,680 had chronic obstructive pulmonary disease (COPD) and 1,034 had normal spirometry. Among participants with COPD, on the basis of multivariable analysis, current smoking and chronic productive cough were associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBC and neutrophil concentrations. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at 1-year follow-up visit by 11.7% (relative increase; 95% confidence interval, 7.5–16.1%; P < 0.001). We found no association between %GGOAMFM and 1-year FEV1 decline, but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up of 1,544 days (interquartile interval, 1,118–2,059). Among normal spirometry participants, we found similar results, except that %GGOAMFM was associated with progression to COPD at 1-year follow-up. Conclusions Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.