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. 2023 Oct;29(10):1328-1333.
doi: 10.1016/j.cmi.2023.06.016. Epub 2023 Jun 17.

Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalizations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5, and XBB transmission

Liang En Wee  1 , An Ting Tay  2 , Calvin Chiew  3 , Barnaby Edward Young  4 , Betty Wong  2 , Ruth Lim  2 , Ching Li Lee  2 , Joyce Tan  2 , Shawn Vasoo  5 , David Chien Lye  5 , Kelvin Bryan Tan  6
Affiliations

Real-world effectiveness of nirmatrelvir/ritonavir against COVID-19 hospitalizations and severe COVID-19 in community-dwelling elderly Singaporeans during Omicron BA.2, BA.4/5, and XBB transmission

Liang En Wee et al. Clin Microbiol Infect. 2023 Oct.

Abstract

Objectives: Real-world data on continued effectiveness of nirmatrelvir/ritonavir against hospitalization and severe COVID-19 in the context of widespread booster mRNA vaccine uptake and more immune-evasive Omicron sub-variants are lacking. We conducted a retrospective cohort study in adult Singaporeans aged ≥60 years presenting to primary care with SARS-CoV-2 infection, during waves of Omicron BA.2/4/5/XBB transmission.

Methods: Binary logistic regression was used to estimate the effect of treatment (receiving nirmatrelvir/ritonavir) on outcomes (hospitalization, severe COVID-19). Additional sensitivity analyses, including inverse-probability-of-treatment-weighting-adjusted analysis and adjustment using overlap weights, were performed to account for observed differences in baseline characteristics among treated/untreated cohorts.

Results: We included 3959 nirmatrelvir/ritonavir recipients and 139 379 untreated controls. Almost 95% received ≥3 doses of mRNA vaccines; 5.4% had preceding infection. Overall 26.5% of infections occurred during the Omicron XBB period and 1.7% were hospitalized. On multivariable logistic regression, receipt of nirmatrelvir/ritonavir was independently associated with lower odds of hospitalization (adjusted odds ratio [aOR] = 0.65, 95% CI = 0.50-0.85). Consistent estimates were obtained after inverse-probability-of-treatment-weighting adjustment (aOR for hospitalization = 0.60, 95% CI = 0.48-0.75) and adjustment using overlap weights (aOR for hospitalization = 0.64, 95% CI = 0.51-0.79). Although receipt of nirmatrelvir/ritonavir was associated with lower odds of severe COVID-19, it was not statistically significant.

Discussion: Outpatient usage of nirmatrelvir/ritonavir was independently associated with reduced odds of hospitalization amongst boosted older community-dwelling Singaporeans during successive waves of Omicron transmission, including Omicron XBB; however, it did not significantly reduce the already low risk of severe COVID-19 in a highly vaccinated population.

Keywords: COVID-19; Hospitalization; Nirmatrelvir-ritonavir; Omicron; SARS-CoV-2.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart showing final study population (N=143,338)
See this image and copyright information in PMC

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References

    1. Hammond J., Leister-Tebbe H., Gardner A., Abreu P., Bao W., Wisemandle W., Baniecki M., Hendrick V.M., Damle B., Simón-Campos A., Pypstra R., Rusnak J.M., Investigators E.P.I.C.-H.R. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397–1408. doi: 10.1056/NEJMoa2118542. - DOI - PMC - PubMed
    1. Nyberg T., Ferguson N.M., Nash S.G., Webster H.H., Flaxman S., Andrews N., Hinsley W., Bernal J.L., Kall M., Bhatt S., Blomquist P., Zaidi A., Volz E., Aziz N.A., Harman K., Funk S., Abbott S., COVID-19 Genomics UK (COG-UK) consortium. Hope R., Charlett A., Chand M., Ghani A.C., Seaman S.R., Dabrera G., De Angelis D., Presanis A.M., Thelwall S. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet. 2022 Apr 2;399(10332):1303–1312. doi: 10.1016/S0140-6736(22)00462-7. - DOI - PMC - PubMed
    1. Arbel R., Wolff Sagy Y., Hoshen M., Battat E., Lavie G., Sergienko R., Friger M., Waxman J.G., Dagan N., Balicer R., Ben-Shlomo Y., Peretz A., Yaron S., Serby D., Hammerman A., Netzer D. Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge. N Engl J Med. 2022 Sep 1;387(9):790–798. doi: 10.1056/NEJMoa2204919. - DOI - PMC - PubMed
    1. Dryden-Peterson S., Kim A., Kim A.Y., Caniglia E.C., Lennes I.T., Patel R., Gainer L., Dutton L., Donahue E., Gandhi R.T., Baden L.R., Woolley A.E. Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study. Ann Intern Med. 2023 Jan;176(1):77–84. doi: 10.7326/M22-2141. - DOI - PMC - PubMed
    1. Aggarwal N.R., Molina K.C., Beaty L.E., Bennett T.D., Carlson N.E., Mayer D.A., Peers J.L., Russell S., Wynia M.K., Ginde A.A. Real-world use of nirmatrelvir–ritonavir in outpatients with COVID-19 during the era of omicron variants including BA.4 and BA.5 in Colorado, USA: a retrospective cohort study. Lancet Infect Dis. 2023 doi: 10.1016/S1473-3099(23)00056-7. [Epub ahead of print] - DOI - PMC - PubMed