ABSTRACT
BackgroundIn the EPIC-HR trial, nirmatrelvir plus ritonavir led to an 88% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. Clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. ObjectiveTo assess whether nirmatrelvir plus ritonavir reduces risk of hospitalization among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune evasive SARS-CoV-2 lineages. DesignPopulation-based cohort study analyzed to emulate a clinical trial utilizing two-stage, inverse-probability weighted models to account for anticipated bias in testing and treatment. SettingA large healthcare system providing care for 1.5 million patients in Massachusetts and New Hampshire during Omicron wave (January 1 to May 15, 2022) with staged access and capacity to prescribe nirmatrelvir plus ritonavir. Patients30,322 non-hospitalized adults (87.2% vaccinated) aged 50 and older with COVID-19 and without contraindications to nirmatrelvir plus ritonavir. MeasurementPrimary outcome was hospitalization within 14 days of COVID-19 diagnosis. ResultsDuring the study period, 6036 (19.9%) patients were prescribed nirmatrelvir plus ritonavir and 24,286 (80.1%) patients were not. Patients prescribed nirmatrelvir were more likely to be older, have more comorbidities, and be unvaccinated. Hospitalization occurred in 40 (0.66%) and 232 (0.96%) patients prescribed and not prescribed nirmatrelvir plus ritonavir, respectively. The adjusted risk ratio was 0.55 (95% confidence interval 0.38 to 0.80, p = 0.002). Observed risk reduction was greater among unvaccinated patients and obese patients. LimitationsPotential for residual confounding due to differential access and uptake of COVID-19 vaccines, diagnostics, and treatment. ConclusionsThe overall risk of hospitalization was already low (<1%) following an outpatient diagnosis of COVID-19, but this risk was 45% lower among patients prescribed nirmatrelvir plus ritonavir. FundingNational Institutes of Health (P30 AI060354 and R01 CA236546).
ABSTRACT
BackgroundEffective vaccine-based containment strategies for SARS-CoV-2 require equitable coverage of communities at greatest risk of infection. We sought to examine the alignment of vaccination and SARS-CoV-2 risk in Massachusetts to inform public health response. MethodsWe aggregated cumulative SARS-CoV-2 testing and vaccination data from the Massachusetts Department of Public Health and the Boston Public Health Commission from January 29, 2020 to April 9, 2021. We used two approaches to assess vaccination equity: vaccination-to-infection risk (VIR) ratio and Lorenz curves. The VIR ratio was calculated for each community as the quotient of the number of fully vaccinated individuals divided by the cumulative number of confirmed SARS-CoV-2 infections. Lorenz curves were used to describe vaccination relative to COVID-19 burden. A multivariable Poisson model was used to assess predictors of VIR ratio. ResultsA total of 607,120 (8.9%) SARS-CoV-2 infections were confirmed in Massachusetts residents and 1,485,266 (21.8%) residents were fully vaccinated. Communities with increased socioeconomic vulnerability had lower VIR ratios indicating less equitable vaccination relative to infection risk. In multivariable analysis, decreased vaccination relative to infection risk was independently associated with increasing socioeconomic vulnerability (aRR 0.82 per quartile increase, 95% CI 0.77 to 0.87) and with greater than 20% of the community identified as Black and/or Latinx (aRR 0.67, 95% CI 0.56 to 0.81). Improved community vaccine delivery was associated with higher community proportion of residents aged 65 or older (aRR 1.23 per 5% increase in proportion, 95% CI 1.15 to 1.31). Lorenz curves indicated considerable inequity (Gini 0.46 between communities). An estimated 330,000 full vaccination courses would need to be diverted to under-vaccinated communities to achieve equity. ConclusionIn conclusion, disparities in vaccine delivery highlight ongoing inequities in our approach to COVID-19 and imperil efforts to control the pandemic.
