ABSTRACT
Background: Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. Interpretation: Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.
Subject(s)
COVID-19 , DeathABSTRACT
BackgroundCOVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises. ObjectiveWe aim to describe the impact of the COVID-19 pandemic on AMR across healthcare settings. Data SourceA search was conducted in December 2021 in World Health Organizations COVID-19 Research Database with forward citation searching up to June 2022. Study EligibilityStudies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted. MethodsPooling was done separately for Gram-negative and Gram-positive organisms. Random effects meta-analysis was performed. ResultsOf 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n=25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (IRR 0.99, 95% CI: 0.67 to 1.47) or proportion (RR 0.91, 95% CI: 0.55 to 1.49) of MRSA or VRE cases. A non-statistically significant increase was noted for resistant Gram-negatives (i.e., ESBL, CRE, MDR or carbapenem-resistant Pseudomonas or Acinetobacter species, IRR 1.64, 95% CI: 0.92 to 2.92; RR 1.08, 95% CI: 0.91 to 1.29). The absence of enhanced IPAC and/or ASP initiatives was associated with an increase in Gram-negative AMR (RR 1.11, 95%CI: 1.03 to 1.20), while studies that did report implementation of these initiatives noted no change in Gram-negative AMR (RR 0.80, 95%CI: 0.38 to 1.70). However, a test for subgroup differences showed no statistically significant difference between these groups (P=0.40) ConclusionThe COVID-19 pandemic could play an important role in the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. There is considerable heterogeneity in both the AMR metrics utilized and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic. PROSPERO registration: CRD42022325831This research was carried out as part of routine work, no funding was received Data collection template, data, and analytic code are available upon request.