• Michael Klompas, Caroline S McKenna, Sanjat Kanjilal, Theodore Pak, Chanu Rhee, and Tom Chen.
• Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts (M.K., S.K., T.P., C.R.).
• Ann. Intern. Med. 2024 Aug 1; 177 (8): 107810881078-1088.

BackgroundMany hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era.ObjectiveTo estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients' outcomes during the pre-Omicron and Omicron periods.DesignRetrospective matched cohort study.Setting5 acute care hospitals in Massachusetts, December 2020 to April 2023.PatientsAdults testing positive for SARS-CoV-2 on or after hospital day 5, after negative SARS-CoV-2 test results on admission and on hospital day 3, were matched to control participants by hospital, service, time period, days since admission, and propensity scores that incorporated demographics, comorbid conditions, vaccination status, primary diagnosis category, vital signs, and laboratory test values.MeasurementsPrimary outcomes were hospital mortality and time to discharge. Secondary outcomes were intensive care unit (ICU) admission, need for advanced oxygen support, discharge destination, hospital-free days, and 30-day readmissions.ResultsThere were 274 cases of hospital-onset SARS-CoV-2 infection during the pre-Omicron period and 1037 cases during the Omicron period (0.17 vs. 0.49 cases per 100 admissions). Patients with hospital-onset SARS-CoV-2 infection were older and had more comorbid conditions than those without. During the pre-Omicron period, hospital-onset SARS-CoV-2 infection was associated with increased risk for ICU admission, increased need for high-flow oxygen, longer time to discharge (median difference, 4.7 days [95% CI, 2.9 to 6.6 days]), and higher mortality (risk ratio, 2.0 [CI, 1.1 to 3.8]) versus matched control participants. During the Omicron period, hospital-onset SARS-CoV-2 infection remained associated with increased risk for ICU admission and increased time to discharge (median difference, 4.2 days [CI, 3.6 to 5.0 days]). The association with increased hospital mortality was attenuated but still significant (risk ratio, 1.6 [CI, 1.2 to 2.3]).LimitationResidual confounding may be present.ConclusionHospital-onset SARS-CoV-2 infection during the Omicron period remains associated with increased morbidity and mortality.Primary Funding SourceHarvard Medical School Department of Population Medicine.

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