Distinguishing Severe Acute Respiratory Syndrome Coronavirus 2 Persistence and Reinfection: A Retrospective Cohort Study.

Autor: Turbett SE; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Department of Pathology, Massachusetts General Hospital (MGH), Boston, Massachusetts, USA., Tomkins-Tinch CH; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA.; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA., Anahtar MN; Department of Pathology, Massachusetts General Hospital (MGH), Boston, Massachusetts, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA., Dugdale CM; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Hyle EP; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Shenoy ES; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts, USA., Shaw B; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA.; David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA., Egbuonu K; Massachusetts Institute of Technology, Boston, Massachusetts, USA., Bowman KA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA., Zachary KC; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts, USA., Adams GC; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA., Hooper DC; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Infection Control Unit, Massachusetts General Hospital, Boston, Massachusetts, USA., Ryan ET; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA., LaRocque RC; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA., Bassett IV; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Medical Practice Evaluation Center, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Triant VA; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA., Siddle KJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA., Rosenberg E; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Department of Pathology, Massachusetts General Hospital (MGH), Boston, Massachusetts, USA., Sabeti PC; FAS Center for Systems Biology, Harvard University, Boston, Massachusetts, USA., Schaffner SF; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA.; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA., MacInnis BL; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA., Lemieux JE; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, Massachusetts, USA., Charles RC; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2023 Mar 04; Vol. 76 (5), pp. 850-860.
DOI: 10.1093/cid/ciac830
Abstrakt: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments.
Methods: All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value <35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value <35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians.
Results: Among 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections.
Conclusions: Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.
Competing Interests: Potential conflicts of interest. M. N. A. is an equity holder and consultant to Day Zero Diagnostics (company does not work on SARS-CoV-2). P. C. S. is a co-founder of, shareholder in, and scientific advisor to Sherlock Biosciences, Inc (2019–present); she is also a Board member of and shareholder in Danaher Corporation (2019–present), and co-founder and consultant to Delve Bio (2022–present). P. C. S. has filed IP related to genome sequencing and analysis. P. C. S. also reports that Sherlock Biosciences has licensed technology from the author and her lab on CRISPR-based diagnostics and has received consulting fees from the same; stock or stock options with Polaris Genomics (investor and future scientific advisory board [SAB] member) and NextGen Jane (former SAB member and investor). I. V. B. reports an unrelated NIH grant number R01AI042006-24S1. E. S. S. reports unrelated grants or contracts from CDC, Assistant Secretary for Preparedness and Response, MIT/Quanta; payment or honoraria as a writer for Up To Date (2022 to current) and for a single lecture on COVID Infection Prevention to Vertex Pharmaceuticals, 2020; roles as President of Massachusetts Infectious Diseases Society, Vice-Chair of Public Policy and Government Affairs Committee, Society for Healthcare Epidemiology of America, and Member of Boston Biosafety Committee, Boston Public Health Commission. K. A. B, reports NIH training grant 5T32 AI007387-32, unrelated to this work. C. M. D. reports grants paid to institution (NIH/National Institute of Child Health and Human Development [NICHD] grant number K08 HD101342; Harvard University Center for AIDS Research [CFAR]; and MGH Executive Committee on Research), payments to institution from CDC; and contracts to institution from International AIDS Vaccine Initiative and NIH/IMPAACT Network. R. C. L. reports grant from CDC: U01-CK000633; UpToDate: Royalties for Authorship; payment or honoraria from CDC Foundation: Editorial Services; a leadership or fiduciary role on the board of Greater Boston Physicians for Social Responsibility. J. E. L. reports consulting fees 2019–2020 from Sherlock Biosciences; and honorarium from Virology Education. E. R. reports participation as PPD member of the Moderna Clinical Endpoint Adjudication Committee. S. E. T. reports royalties from UpToDate; travel support for attending Duke Clinical Research Institute meeting on preparing for the next pandemic; and reports that her husband is a partner and has equity in an economic consulting firm (Analysis Group Inc.) that provides consulting services for life science companies among many others. E. P. H. reports grants or contracts unrelated to this work and paid to institution from NIH and MGH; royalties paid to author from UpToDate. All other authors report no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze: MEDLINE