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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.)

Background: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs., Methods: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence., Results: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL., Conclusions: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Immunomodulating therapies for COVID-19 may carry risks of reactivating latent infections in foreign-born people. We conducted a rapid review of infection-related complications of immunomodulatory therapies for COVID-19. We convened a committee of specialists to formulate a screening and management strategy for latent infections in our setting. Dexamethasone, used in severe COVID-19, is associated with reactivation of latent tuberculosis, hepatitis B, and dissemination/hyperinfection of Strongyloides species and should prompt screening and/ or empiric treatment in appropriate epidemiologic contexts. Other immunomodulators used in COVID-19 may also increase risk, including interleukin-6 receptor antagonist (e.g., tocilizumab) and kinase inhibitors. People with specific risk factors should also be screened for HIV, Chagas disease, and endemic mycoses. Racial and ethnic minorities in North America, including foreign-born persons, who receive immunomodulating agents for COVID-19 may be at risk for reactivation of latent infections. We develop a screening and management pathway for such patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We describe an approach to the evaluation and isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) at a large US academic medical center. Only a small proportion (2.9%) of PUIs with 1 or more repeated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) after a negative NAAT were diagnosed with COVID-19.

Among hospitalized persons under investigation for coronavirus disease 2019 (COVID-19), more repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs) after a negative NAAT were positive from lower than from upper respiratory tract specimens (1.9% vs 1.0%, P =.033). Lower respiratory testing should be prioritized among patients displaying respiratory symptoms with moderate-to-high suspicion for COVID-19 after 1 negative upper respiratory NAAT. [ABSTRACT FROM AUTHOR]

Background Concerns about false-negative (FN) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification tests (NAATs) have prompted recommendations for repeat testing if suspicion for coronavirus disease 2019 (COVID-19) infection is moderate to high. However, the frequency of FNs and patient characteristics associated with FNs are poorly understood. Methods We retrospectively reviewed test results from 15 011 adults who underwent ≥1 SARS-CoV-2 NAATs; 2699 had an initial negative NAAT and repeat testing. We defined FNs as ≥1 negative NAATs followed by a positive NAAT within 14 days during the same episode of illness. We stratified subjects with FNs by duration of symptoms before the initial FN test (≤5 days versus >5 days) and examined their clinical, radiologic, and laboratory characteristics. Results Sixty of 2699 subjects (2.2%) had a FN result during the study period. The weekly frequency of FNs among subjects with repeat testing peaked at 4.4%, coinciding with peak NAAT positivity (38%). Most subjects with FNs had symptoms (52 of 60; 87%) and chest radiography (19 of 32; 59%) consistent with COVID-19. Of the FN NAATs, 18 of 60 (30%) were performed early (ie, ≤1 day of symptom onset), and 18 of 60 (30%) were performed late (ie, >7 days after symptom onset) in disease. Among 17 subjects with 2 consecutive FNs on NP NAATs, 9 (53%) provided lower respiratory tract (LRT) specimens for testing, all of which were positive. Conclusions Our findings support repeated NAATs among symptomatic patients, particularly during periods of higher COVID-19 incidence. The LRT testing should be prioritized to increase yield among patients with high clinical suspicion for COVID-19. [ABSTRACT FROM AUTHOR]