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Clin Infect Dis ; 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2077719


BACKGROUND: 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 March 14th and December 30th, 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 1,569 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 eight 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. CONCLUSION: 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.

Cell ; 185(3): 485-492.e10, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1588148


An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021-the first large outbreak mostly in vaccinated individuals in the US-prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response.

COVID-19/epidemiology , COVID-19/immunology , COVID-19/transmission , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Contact Tracing/methods , Disease Outbreaks , Female , Genome, Viral , Humans , Infant , Infant, Newborn , Male , Massachusetts/epidemiology , Middle Aged , Molecular Epidemiology , Phylogeny , SARS-CoV-2/classification , Vaccination , Whole Genome Sequencing , Young Adult