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Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort

Erlandson KM 1 , Geng LN 2 , Selvaggi CA 3 , Thaweethai T 3 , Chen P 4 , Erdmann NB 5 Show all authors , Goldman JD 6 , Henrich TJ 7 , Hornig M 8 , Karlson EW 9 , Katz SD 10 , Kim C 11 , Cribbs SK 12 , Laiyemo AO 13 , Letts R 11 , Lin JY 14 , Marathe J 15 , Parthasarathy S 16 , Patterson TF 17 , Taylor BD 18 , Duffy ER 19 , Haack M 20 , Julg B 21 , Maranga G 22 , Hernandez C 23 , Singer NG 24 , Han J 25 , Pemu P 26 , Brim H 27 , Ashktorab H 28 , Charney AW 29 , Wisnivesky J 29 , Lin JJ 29 , Chu HY 30 , Go M 2 , Singh U 2 , Levitan EB 31 , Goepfert PA 5 , Nikolich JŽ 32 , Hsu H 33 , Peluso MJ 34 , Kelly JD 34 , Okumura MJ 35 , Flaherman VJ 36 , Quigley JG 37 , Krishnan JA 38 , Scholand MB 39 , Hess R 39 , Metz TD 40 , Costantine MM 41 , Rouse DJ 42 , Taylor BS 17 , Goldberg MP 43 , Marshall GD 44 , Wood J 45 , Warren D 46 , Horwitz L 47 , Foulkes AS 3 , McComsey GA 48 , RECOVER-Adult Cohort

Affiliations 

  • 1 Department of Medicine, Division of Infectious Diseases, University of Colorado, Anschutz Medical Campus, Aurora, Colorado (K.M.E.)
  • 2 Department of Medicine, Stanford University, Stanford, California (L.N.G., M.G., U.S.)
  • 3 Massachusetts General Hospital Biostatistics, Boston, Massachusetts (C.A.S., T.T., A.S.F.)
  • 4 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, and Women's Guild Lung Institute at Cedars-Sinai Medical Center, New York, New York (P.C.)
  • 5 Department of Medicine, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama (N.B.E., P.A.G.)
  • 6 Swedish Center for Research and Innovation, Providence Swedish Medical Center, and Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington (J.D.G.)
  • 7 Division of Experimental Medicine, University of California San Francisco, San Francisco, California (T.J.H.)
  • 8 CORe Community Inc., and Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York (M.H.)
  • 9 Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (E.W.K.)
  • 10 Department of Medicine, NYU Grossman School of Medicine, New York, New York (S.D.K.)
  • 11 RECOVER Initiative, New York, New York (C.K., R.L.)
  • 12 Department of Medicine, Emory University School of Medicine, and Atlanta Veterans Affairs Medical Center, Atlanta, Georgia (S.K.C.)
  • 13 Department of Medicine, Division of Gastroenterology, Howard University College of Medicine, Washington, DC (A.O.L.)
  • 14 Department of Emergency Medicine, University of Illinois Chicago, Chicago, Illinois (J.Y.L.)
  • 15 Department of Medicine, Division of Infectious Diseases, Boston University Medical Campus, Boston, Massachusetts (J.M.)
  • 16 Department of Medicine, University of Arizona, Tucson, Arizona (S.P.)
  • 17 Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas (T.F.P., B.S.T.)
  • 18 RECOVER Initiative, New York, New York, and American Heart Association, Health Strategies, Atlanta, Georgia (B.D.T.)
  • 19 Boston Medical Center, Boston, Massachusetts (E.R.D.)
  • 20 Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (M.H.)
  • 21 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston, Massachusetts (B.J.)
  • 22 Department of Population Health, NYU Grossman School of Medicine, New York, New York (G.M.)
  • 23 Departments of Pediatrics and Medicine, Case Western Reserve University, Cleveland, Ohio (C.H.)
  • 24 Departments of Pediatrics and Medicine and Division of Rheumatology, Case Western Reserve University, Cleveland, Ohio (N.G.S.)
  • 25 Department of Medicine, Emory University School of Medicine, and Grady Hospital, Atlanta, Georgia (J.H.)
  • 26 Department of Medicine, Morehouse School of Medicine, Atlanta, Georgia (P.P.)
  • 27 Department of Pathology, Howard University, Washington, DC (H.B.)
  • 28 Department of Medicine, Howard University, Washington, DC (H.A.)
  • 29 Icahn School of Medicine at Mount Sinai Hospital, New York, New York (A.W.C., J.W., J.L.)
  • 30 Division of Global Health, University of Washington, Seattle, Washington (H.Y.C.)
  • 31 Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama (E.B.L.)
  • 32 Department of Immunobiology, University of Arizona College of Medicine-Tucson, and Arizona Center on Aging, Tucson, Arizona (J.ŽN.)
  • 33 Banner University Medical Center, Tucson, Arizona (H.H.)
  • 34 Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California (M.J.P., J.D.K.)
  • 35 Departments of Medicine and Pediatrics, University of California San Francisco, San Francisco, California (M.O.)
  • 36 Department of Pediatrics, University of California San Francisco, San Francisco, California (V.J.F.)
  • 37 Department of Medicine, Division of Hematology/Oncology, University of Illinois Chicago, Chicago, Illinois (J.G.Q.)
  • 38 Department of Medicine, University of Illinois Chicago, Chicago, Illinois (J.A.K.)
  • 39 Department of Medicine, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, Utah (M.B.S., R.H.)
  • 40 Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah (T.D.M.)
  • 41 Division of Maternal Fetal Medicine, The Ohio State University, Columbus, Ohio (M.M.C.)
  • 42 Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island (D.J.R.)
  • 43 Department of Neurology, University of Texas Health San Antonio, San Antonio, Texas (M.P.G.)
  • 44 Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi (G.D.M.)
  • 45 The Gill Heart and Vascular Institute and Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky (J.W.)
  • 46 Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska (D.W.)
  • 47 Department of Population Health, NYU Grossman School of Medicine, and Center for Healthcare Innovation and Delivery Science, NYU Langone Health, New York, New York (L.H.)
  • 48 Departments of Pediatrics and Medicine, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio (G.A.M.)
Ann Intern Med, 2024 Sep;177(9):1209-1221.
PMID: 39133923 DOI: 10.7326/M24-0737

Abstract

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 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) 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 HbA1c 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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