Finding Long-COVID: Temporal Topic Modeling of Electronic Health Records from the N3C and RECOVER Programs.

Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long-COVID, encompasses a variety of complex and varied outcomes following COVID-19 infection that are still poorly understood. We clustered over 600 million condition diagnoses from 14 million patients available through the National COVID Cohort Collaborative (N3C), generating hundreds of highly detailed clinical phenotypes. Assessing patient clinical trajectories using these clusters allowed us to identify individual conditions and phenotypes strongly increased after acute infection. We found many conditions increased in COVID-19 patients compared to controls, and using a novel method to associate patients with clusters over time, we additionally found phenotypes specific to patient sex, age, wave of infection, and PASC diagnosis status. While many of these results reflect known PASC symptoms, the resolution provided by this unprecedented data scale suggests avenues for improved diagnostics and mechanistic understanding of this multifaceted disease.

The prevalence of postacute sequelae of coronavirus disease 2019 in solid organ transplant recipients: Evaluation of risk in the National COVID Cohort Collaborative.

Postacute sequelae after the coronavirus disease (COVID) of 2019 (PASC) is increasingly recognized, although data on solid organ transplant (SOT) recipients (SOTRs) are limited. Using the National COVID Cohort Collaborative, we performed 1:1 propensity score matching (PSM) of all adult SOTR and nonimmunosuppressed/immunocompromised (ISC) patients with acute COVID infection (August 1, 2021 to January 13, 2023) for a subsequent PASC diagnosis using International Classification of Diseases, 10th Revision, Clinical Modification codes. Multivariable logistic regression was used to examine not only the association of SOT status with PASC, but also other patient factors after stratifying by SOT status. Prior to PSM, there were 8769 SOT and 1 576 769 non-ISC patients with acute COVID infection. After PSM, 8756 SOTR and 8756 non-ISC patients were included; 2.2% of SOTR (n = 192) and 1.4% (n = 122) of non-ISC patients developed PASC (P value < .001). In the overall matched cohort, SOT was independently associated with PASC (adjusted odds ratio [aOR], 1.48; 95% confidence interval [CI], 1.09-2.01). Among SOTR, COVID infection severity (aOR, 11.6; 95% CI, 3.93-30.0 for severe vs mild disease), older age (aOR, 1.02; 95% CI, 1.01-1.03 per year), and mycophenolate mofetil use (aOR, 2.04; 95% CI, 1.38-3.05) were each independently associated with PASC. In non-ISC patients, only depression (aOR, 1.96; 95% CI, 1.24-3.07) and COVID infection severity were. In conclusion, PASC occurs more commonly in SOTR than in non-ISC patients, with differences in risk profiles based on SOT status.

Hormone replacement therapy and COVID-19 outcomes in solid organ transplant recipients compared with the general population.

Exogenous estrogen is associated with reduced coronavirus disease (COVID) mortality in nonimmunosuppressed/immunocompromised (non-ISC) postmenopausal females. Here, we examined the association of estrogen or testosterone hormone replacement therapy (HRT) with COVID outcomes in solid organ transplant recipients (SOTRs) compared to non-ISC individuals, given known differences in sex-based risk in these populations. SOTRs ≥45 years old with COVID-19 between April 1, 2020 and July 31, 2022 were identified using the National COVID Cohort Collaborative. The association of HRT use in the last 24 months (exogenous systemic estrogens for females; testosterone for males) with major adverse renal or cardiac events in the 90 days post-COVID diagnosis and other secondary outcomes were examined using multivariable Cox proportional hazards models and logistic regression. We repeated these analyses in a non-ISC control group for comparison. Our study included 1135 SOTRs and 43 383 immunocompetent patients on HRT with COVID-19. In non-ISC, HRT use was associated with lower risk of major adverse renal or cardiac events (adjusted hazard ratio [aHR], 0.61; 95% confidence interval [CI], 0.57-0.65 for females; aHR, 0.70; 95% CI, 0.65-0.77 for males) and all secondary outcomes. In SOTR, HRT reduced the risk of acute kidney injury (aHR, 0.79; 95% CI, 0.63-0.98) and mortality (aHR, 0.49; 95% CI, 0.28-0.85) in males with COVID but not in females. The potentially modifying effects of immunosuppression on the benefits of HRT requires further investigation.