{"doi":"10.1101/2022.06.14.22276393","title":"Nirmatrelvir plus ritonavir for early COVID-19 and hospitalization in a large US health system","abstract":"Background: In 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. Objective: To 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. Design: Population-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. Setting: A 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. Patients: 30,322 non-hospitalized adults (87.2% vaccinated) aged 50 and older with COVID-19 and without contraindications to nirmatrelvir plus ritonavir. Measurement: Primary outcome was hospitalization within 14 days of COVID-19 diagnosis. Results: During 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. Limitations: Potential for residual confounding due to differential access and uptake of COVID-19 vaccines, diagnostics, and treatment. Conclusions: The 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. Funding: National Institutes of Health (P30 AI060354 and R01 CA236546).","journal":"medRxiv","year":2022,"id":296439,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":92146,"name":"Andy Kim","orcid":"0000-0001-6551-2881","position":1,"is_corresponding":false},{"id":237353,"name":"Arthur Y. Kim","orcid":"0000-0003-4712-2657","position":2,"is_corresponding":false},{"id":459866,"name":"Ellen C. Caniglia","orcid":"0000-0001-8667-6471","position":3,"is_corresponding":false},{"id":736030,"name":"Inga T. Lennes","orcid":"0000-0003-0783-3411","position":4,"is_corresponding":false},{"id":983236,"name":"Rajesh Patel","orcid":"0000-0002-7043-4192","position":5,"is_corresponding":false},{"id":983803,"name":"Lindsay Gainer","orcid":null,"position":6,"is_corresponding":false},{"id":983237,"name":"Lisa Dutton","orcid":"0000-0003-1174-0760","position":7,"is_corresponding":false},{"id":755785,"name":"Elizabeth Donahue","orcid":"0009-0003-0461-7286","position":8,"is_corresponding":false},{"id":88092,"name":"Rajesh T. Gandhi","orcid":"0000-0002-9701-6062","position":9,"is_corresponding":false},{"id":3841,"name":"Lindsey R. Baden","orcid":null,"position":10,"is_corresponding":false},{"id":16976,"name":"Ann E. Woolley","orcid":"0000-0002-2810-1618","position":11,"is_corresponding":false},{"id":498926,"name":"Scott Dryden‐Peterson","orcid":"0000-0002-8487-9731","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:31:16.555318Z","pmid":"35734084","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}