Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants : A Propensity-Matched Analysis.

BACKGROUND: Many 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. OBJECTIVE: To estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients' outcomes during the pre-Omicron and Omicron periods. DESIGN: Retrospective matched cohort study. SETTING: 5 acute care hospitals in Massachusetts, December 2020 to April 2023. PATIENTS: Adults 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. MEASUREMENTS: Primary 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. RESULTS: There 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]). LIMITATION: Residual confounding may be present. CONCLUSION: Hospital-onset SARS-CoV-2 infection during the Omicron period remains associated with increased morbidity and mortality. PRIMARY FUNDING SOURCE: Harvard Medical School Department of Population Medicine.

Assessment of Racial, Ethnic, and Sex-Based Disparities in Time-to-Antibiotics and Sepsis Outcomes in a Large Multihospital Cohort.

OBJECTIVES: To characterize associations between race/ethnicity/sex, time-to-antibiotics, and mortality in patients with suspected sepsis or septic shock. DESIGN: Retrospective cohort study, with race/ethnicity/sex as the exposure, and time-to-antibiotics (relative to emergency department arrival) and in-hospital mortality as the outcome. SETTING: Five Massachusetts hospitals. PATIENTS: Forty-nine thousand six hundred nine adults admitted 2015-2022 with suspected sepsis or septic shock (blood cultures drawn and IV antibiotics administered within 24 hr of arrival, plus evidence of organ dysfunction for sepsis, and hypotension or lactate ≥ 4.0 mmol/L for septic shock). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among included patients, 22,598 (46%) were women, 36,626 (75%) were White, and 4,483 (9.2%) were Black. Women had longer median time-to-antibiotics than men when presenting with either suspected sepsis (203 vs. 190 min) or septic shock (160 vs. 142 min). Differences in time-to-antibiotics for women vs. men persisted after adjusting for age, race, comorbidities, source of infection, and severity of illness (adjusted odds ratio [aOR] for 3-6 vs. < 3 hr; 1.16 [95% CI, 1.07-1.25] for sepsis and aOR, 1.09 [95% CI, 1.01-1.18] for septic shock). Median time-to-antibiotics was also longer for Black vs. White patients for both sepsis (215 vs. 194 min; aOR for 3-6 vs. < 3 hr; 1.24 [95% CI, 1.06-1.45]) and septic shock (median 159 vs. 148 min; aOR, 1.32 [95% CI, 1.12-1.55]). There was no association between race/ethnicity/sex and in-hospital mortality for sepsis without shock; however, women with septic shock had higher mortality (aOR, 1.16; 95% CI, 1.04-1.29) vs. men. Higher mortality for women with septic shock persisted when also adjusting for time-to-antibiotics (aOR, 1.16; 95% CI, 1.03-1.32). CONCLUSIONS: In a large cohort of patients with sepsis, time-to-antibiotics was longer for both women and Black patients even after detailed risk-adjustment. Women with septic shock had higher adjusted in-hospital mortality than men, but this association was not moderated by time-to-antibiotics.

Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.

BACKGROUND: Influential studies conclude that each hour until antibiotics increases mortality in sepsis. However, these analyses often (1) adjusted for limited covariates, (2) included patients with long delays until antibiotics, (3) combined sepsis and septic shock, and (4) used linear models presuming each hour delay has equal impact. We evaluated the effect of these analytic choices on associations between time-to-antibiotics and mortality. METHODS: We retrospectively identified 104 248 adults admitted to 5 hospitals from 2015-2022 with suspected infection (blood culture collection and intravenous antibiotics ≤24 h of arrival), including 25 990 with suspected septic shock and 23 619 with sepsis without shock. We used multivariable regression to calculate associations between time-to-antibiotics and in-hospital mortality under successively broader confounding-adjustment, shorter maximum time-to-antibiotic intervals, stratification by illness severity, and removing assumptions of linear hourly associations. RESULTS: Changing covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed associations between time-to-antibiotics and mortality. In a fully adjusted model of patients treated ≤6 hours, each hour was associated with higher mortality for septic shock (adjusted odds ratio [aOR]: 1.07; 95% CI: 1.04-1.11) but not sepsis without shock (aOR: 1.03; .98-1.09) or suspected infection alone (aOR: .99; .94-1.05). Modeling each hour separately confirmed that every hour of delay was associated with increased mortality for septic shock, but only delays >6 hours were associated with higher mortality for sepsis without shock. CONCLUSIONS: Associations between time-to-antibiotics and mortality in sepsis are highly sensitive to analytic choices. Failure to adequately address these issues can generate misleading conclusions.