PRIMA cohort reports low 30-day hospitalization or death among high-risk Italian outpatients treated early with nirmatrelvir/ritonavir

In an Italian multicenter retrospective cohort study, 30-day hospitalization or death occurred in 0.9% of 3,916 symptomatic, high-risk outpatients who started nirmatrelvir/ritonavir within five days of symptom onset. Hospitalization was reported in 0.7% of participants and mortality in 0.4%. The study was conducted at 15 centers and characterized outcomes, adverse events and factors associated with disease progression among people treated early for COVID-19.

The reported population had a median age of 66 years and a median of three vaccine doses. Participants were non-hospitalized adults who met the study’s high-risk criteria. The primary outcome was a composite of all-cause hospitalization or death within 30 days. Based on the published abstract, the analysis assessed real-world clinical outcomes, tolerability and predictors of progression in a largely triple-vaccinated and frail cohort. As a retrospective observational study without an untreated or alternative-treatment comparison reported in the abstract, it establishes associations among treated patients rather than demonstrating that nirmatrelvir/ritonavir caused the low observed event rates.

In adjusted multivariable analysis using backward selection, solid neoplasms, lymphoma and leukemia were the strongest independent predictors of the 30-day composite outcome. Solid neoplasms were associated with an odds ratio of 6.32 (95% confidence interval 1.91–20.87), lymphoma with an odds ratio of 14.33 (5.15–39.88), and leukemia with an odds ratio of 5.81 (1.24–27.37). These estimates identify groups with a higher observed likelihood of hospitalization or death within the treated cohort; they do not quantify the causal effect of treatment or provide comparative risks for untreated patients.

Adverse events were reported in 10.7% of participants, with dysgeusia and gastrointestinal symptoms identified as the main events. Treatment was discontinued because of toxicity in 0.7% of the cohort. Overall, the abstract reports few adverse events and very low rates of severe outcomes among the high-risk outpatients who received early nirmatrelvir/ritonavir, while active solid or hematologic malignancies remained associated with greater risk. The findings should be interpreted in light of the retrospective design, the selected high-risk population and the absence of a comparison group described in the abstract. In addition, only the abstract was supplied for this report, so the full study methods, detailed results and limitations could not be independently assessed.

Subject of Research: Clinical outcomes and progression predictors among high-risk Italian COVID-19 outpatients treated with nirmatrelvir/ritonavir

Article Title: Clinical outcomes, safety and predictors of disease progression in high-risk COVID-19 outpatients treated with nirmatrelvir/ritonavir: an Italian multicenter retrospective cohort study (PRIMA study)

Article References: Gentile, I., Buonomo, A. R., Lichtner, M., Cattelan, A., Campoli, C., Coppola, L., Tumbarello, M., Pellegrino, M. C., Mastroianni, C., Torti, C., Coppola, N., Marino, A., Cascio, A., Leone, S., Masullo, A., Codella, A. V., Nicastri, E., Borgo, C. D., Scaglione, V., … Giulia, Z. (2026). Clinical outcomes, safety and predictors of disease progression in high-risk COVID-19 outpatients treated with nirmatrelvir/ritonavir: an Italian multicenter retrospective cohort study (PRIMA study). BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14363-7

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DOI: 10.1186/s12879-026-14363-7

Keywords: COVID-19, nirmatrelvir/ritonavir, outpatients, retrospective cohort, disease progression, hospitalization, mortality, malignancy, adverse events, Italy, Clinical, outcomes