UNTREATED RISK OF HOSPITALIZATION AND DEATH AMONG HIGH-RISK PATIENTS WITH MILD-TO-MODERATE COVID-19 IN THE UNITED STATES: A SYSTEMATIC LITERATURE REVIEW UPDATE
Author(s)
Nikolina Boskovic, MPH1, Tendai Mugwagwa, MSc2, David Campbell, MS, PharmD1, Sarah Katsandres, MPH1, Athira Ajith, PharmD1, Cynthia L. Gong, PharmD, PhD1, Tobias Bergroth, PhD3, Maria Carolina Pein, MS4, Kristen Migliaccio-Walle, BS1.
1Curta Inc, Seattle, WA, USA, 2Pfizer inc, Tadworth, United Kingdom, 3Pfizer, Stockholm, Sweden, 4Pfizer, Buenos Aires, Argentina.
1Curta Inc, Seattle, WA, USA, 2Pfizer inc, Tadworth, United Kingdom, 3Pfizer, Stockholm, Sweden, 4Pfizer, Buenos Aires, Argentina.
OBJECTIVES: To update a systematic literature review (Migliaccio-Walle et al., 2026) characterizing the real-world 28-30-day untreated risk of hospitalization and death among patients with mild-to-moderate COVID-19 at high risk for progression in the United States (US) during the Omicron-dominant era.
METHODS: The original SLR identified US real-world evidence studies published December 21, 2021 - January 30, 2024; this update extended the search through August 21, 2025, across PubMed, Embase, MedRxiv, and conference proceedings (ECCMID, IDWeek, and ERS). Eligible studies included adults and adolescents (≥12 years) with mild-to-moderate COVID-19 at high risk for disease progression, untreated, or treated with nirmatrelvir/ritonavir. To address heterogeneity, outcomes included observed unadjusted, within-study adjusted, and standardized adjusted risk, the latter calculated using the relative risk reduction from Lewnard et al. (2023). The review followed PRISMA/Cochrane guidelines (CRD420251140217).
RESULTS: Of 469 records screened, 9 observational retrospective studies were included, with predominantly vaccinated populations. For 28-30-day all-cause hospitalization (n=7), the observed risk ranged from 0.0% to 7.1%, comparable to the original review (0.9-7.7%). Within-study adjusted risk estimates (n=5) ranged from 1.5% to 6.5%, while standardized adjusted risks (n=7) spanned 0.0% to 20.6%, exceeding the original review (2.3-6.9%). For the composite endpoint of all-cause hospitalization or death (n=3), observed risk ranged 2.6% to 11.7%, and within-study adjusted risk ranged 2.5% to 11.9%, both higher than prior estimates. Standardized adjusted risks were notably elevated, ranging from 7.4% to 31.9%. For all-cause mortality, observed risk (n=5) was 0.0% to 0.4%, while within-study adjusted risk (n=3) was 0.3% to 0.4%, both consistent with prior findings, slightly higher when adjusted. Notably, no studies reported outcomes specifically for COVID-19-related combined hospitalization or death.
CONCLUSIONS: The findings highlight continued clinical burden among high-risk COVID-19 patients during the Omicron era in the US, with risks consistent with the original review, informing payer coverage decisions.
METHODS: The original SLR identified US real-world evidence studies published December 21, 2021 - January 30, 2024; this update extended the search through August 21, 2025, across PubMed, Embase, MedRxiv, and conference proceedings (ECCMID, IDWeek, and ERS). Eligible studies included adults and adolescents (≥12 years) with mild-to-moderate COVID-19 at high risk for disease progression, untreated, or treated with nirmatrelvir/ritonavir. To address heterogeneity, outcomes included observed unadjusted, within-study adjusted, and standardized adjusted risk, the latter calculated using the relative risk reduction from Lewnard et al. (2023). The review followed PRISMA/Cochrane guidelines (CRD420251140217).
RESULTS: Of 469 records screened, 9 observational retrospective studies were included, with predominantly vaccinated populations. For 28-30-day all-cause hospitalization (n=7), the observed risk ranged from 0.0% to 7.1%, comparable to the original review (0.9-7.7%). Within-study adjusted risk estimates (n=5) ranged from 1.5% to 6.5%, while standardized adjusted risks (n=7) spanned 0.0% to 20.6%, exceeding the original review (2.3-6.9%). For the composite endpoint of all-cause hospitalization or death (n=3), observed risk ranged 2.6% to 11.7%, and within-study adjusted risk ranged 2.5% to 11.9%, both higher than prior estimates. Standardized adjusted risks were notably elevated, ranging from 7.4% to 31.9%. For all-cause mortality, observed risk (n=5) was 0.0% to 0.4%, while within-study adjusted risk (n=3) was 0.3% to 0.4%, both consistent with prior findings, slightly higher when adjusted. Notably, no studies reported outcomes specifically for COVID-19-related combined hospitalization or death.
CONCLUSIONS: The findings highlight continued clinical burden among high-risk COVID-19 patients during the Omicron era in the US, with risks consistent with the original review, informing payer coverage decisions.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EPH173
Topic
Epidemiology & Public Health
Topic Subcategory
Public Health
Disease
Infectious Disease (non-vaccine)