{"doi":"10.1101/2022.09.12.22279866","title":"Real-world Use of Nirmatrelvir-Ritonavir in COVID-19 Outpatients During the Emergence of Omicron Variants BA.2/BA2.12.1","abstract":"ABSTRACT Background Ritonavir-boosted Nirmatrelvir (NMV-r), a protease inhibitor with in vitro activity against SARS-CoV-2, has been shown to reduce risk of progression to severe COVID-19 among high-risk individuals during the Delta-variant phase. We sought to determine the effectiveness of NMV-r against Omicron lineage variants BA.2/BA2.12.1, and assess for evidence of a clinical rebound effect. Methods We conducted a retrospective observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from March 26 th , 2022 to June 23 rd , 2022, using records from a statewide health system linked to vaccine and mortality data. Propensity score matching was performed on NMV-r treated outpatients with outpatients not treated with antiviral therapy. The primary outcome was 28-day all-cause hospitalization; secondary outcomes were COVID-19-related hospitalization, 28-day all-cause mortality, and 28-day ED visits. Logistic regression was used to determine NMV-r treatment effectiveness; subgroup analyses were performed to assess for heterogeneity in treatment effect. Results Of 14,953 SARS-CoV-2 infected outpatients, 3,614 NMV-r treated patients were matched to 4,835 untreated outpatients. NMV-r was associated with significantly lower odds of 28-day all-cause hospitalization as compared to no antiviral treatment [31 (0.9%) vs. 64 (1.3%), adjusted odds ratio (aOR): 0.48 (95% CI 0.31-0.75)]. NMV-r was also associated with lower odds of COVID-19 related hospitalization [aOR (95% CI): 0.42 (0.25-0.68)] and 28-day all-cause mortality [aOR (95% CI): 0.05 (0.00-0.38)]. Using ED visits within 28 days as a surrogate for rebound symptoms, we observed no clinically evident rebound effect with NMV-r treatment [140 (3.9%) vs 205 (4.2%), aOR: 0.81 (95% CI 0.65-1.02), p = 0.075]. Conclusion Real-world evidence during an Omicron BA.2/BA2.12.1 predominant period demonstrated an association of NMV-r treatment with reduced 28-day hospitalization and all-cause mortality, and without an increase in rebound symptoms as assessed by ED visits within 28 days after treatment.","journal":"medRxiv","year":2022,"id":297564,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"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":705144,"name":"Kyle C. Molina","orcid":"0000-0002-6764-5984","position":1,"is_corresponding":false},{"id":862342,"name":"Laurel Beaty","orcid":"0000-0001-8021-7872","position":2,"is_corresponding":false},{"id":49886,"name":"Tellen D. Bennett","orcid":"0000-0003-1483-4236","position":3,"is_corresponding":false},{"id":519059,"name":"Nichole E. Carlson","orcid":"0000-0003-0679-6663","position":4,"is_corresponding":false},{"id":105999,"name":"Adit A. Ginde","orcid":"0000-0003-2325-206X","position":5,"is_corresponding":false},{"id":985647,"name":"Neil Krishan Aggarwal","orcid":"0000-0001-9430-0861","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"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":[]}