ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

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Background Genetic variants at the CLU, CR1 and PICALM loci associate with risk for late-onset Alzheimer’s disease (LOAD) in genome-wide association studies (GWAS). In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in African-American and Caucasian subjects. Methods We pursued an association study between single nucleotide polymorphism (SNP) genotypes at the CLU, CR1 and PICALM loci and memory endophenotypes. We assessed African-American subjects (AA: 44 with LOAD, 224 controls) recruited at Mayo Clinic Florida and Caucasians recruited at Mayo Clinic Minnesota (RS: 372 with LOAD, 1,690 controls) and Florida (JS: 60 with LOAD, 529 controls). SNPs at the LOAD risk loci CLU (rs11136000), CR1 (rs6656401, rs3818361) and PICALM (rs3851179) were genotyped and tested for association with Logical Memory immediate recall (LMIR), delayed recall (LMDR) and percent retention (LMPR) and Visual Reproduction (VRIR, VRDR, VRPR) scores from Wechsler Memory Scale-Revised, using multivariable linear regression analysis, adjusting for age-at-exam, sex, education and APOE ε4 dosage. Results We identified nominally significant or suggestive associations between the LOAD risky CR1 variants and worse LMIR scores in the African-Americans (p=0.068 - 0.046, β= −2.7 to −1.2). The LOAD protective CLU variant is associated with better logical memory endophenotypes in the Caucasian subjects (p=0.099-0.027, β= 0.31 to 0.93). The CR1 associations persisted when the control subjects from the African-American series were assessed separately. The CLU associations appeared to be driven by one of the Caucasian series (RS) and were also observed when the control subset from RS was analyzed. Conclusion These results suggest for the first time that LOAD risk variants at CR1 may influence memory endophenotypes in African-Americans. Additionally, CLU LOAD protective variant may confer enhanced memory in Caucasians. Although these results would not remain significant after stringent corrections for multiple testing, they need to be considered in the context of the LOAD associations, with which they have biological consistency. They also provide estimates for effect sizes on memory endophenotypes that could guide future studies. The detection of memory effects for these variants in clinically normal subjects, implies that these LOAD risk loci might modify memory prior to clinical diagnosis of AD.

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