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This study evaluated whether SARS-CoV-2 infection led to persistent changes in common clinical laboratory tests in people with prior infection compared with those without prior infection and whether people with postacute sequelae of SARS-CoV-2 infection (PASC) have persistent laboratory changes compared with those who are unlikely to have PASC. Visual Abstract. Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort: This study evaluated whether SARS-CoV-2 infection led to persistent changes in common clinical laboratory tests in people with prior infection compared with those without prior infection and whether people with postacute sequelae of SARS-CoV-2 infection (PASC) have persistent laboratory changes compared with those who are unlikely to have PASC. Background: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). Objective: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. Design: Propensity score–weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024) Setting: 83 enrolling sites. Participants: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. Measurements: Participants completed questionnaires and standard clinical laboratory tests. Results: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 10 9 cells/L [95% CI, 264.5 to 267.4 × 10 9 cells/L]) than participants without known prior infection (275.2 × 10 9 cells/L [CI, 268.5 to 282.0 × 10 9 cells/L]), as well as higher mean hemoglobin A 1c (HbA 1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin–creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA 1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. Limitation: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. Conclusion: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]