Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection

{ 'indexed': {'date-parts': [[2024, 6, 8]], 'date-time': '2024-06-08T00:36:05Z', 'timestamp': 1717806965898}, 'reference-count': 68, 'publisher': 'American Medical Association (AMA)', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:sec><jats:title>Importance</jats:title><jats:p>There is an urgent need to identify ' 'treatments for postacute sequelae of SARS-CoV-2 infection ' '(PASC).</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess the ' 'efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC ' 'symptoms.</jats:p></jats:sec><jats:sec><jats:title>Design, Setting, and ' 'Participants</jats:title><jats:p>This was a 15-week blinded, placebo-controlled, randomized ' 'clinical trial conducted from November 2022 to September 2023 at Stanford University ' '(California). The participants were adults with moderate to severe PASC symptoms of 3 months ' 'or longer ' 'duration.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>Participants ' 'were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) ' 'or with placebo-ritonavir (PBO/r) twice daily for 15 ' 'days.</jats:p></jats:sec><jats:sec><jats:title>Main Outcomes and ' 'Measures</jats:title><jats:p>Primary outcome was a pooled severity of 6 PASC symptoms ' '(fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and ' 'cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes ' 'included symptom severity at different time points, symptom burden and relief, patient global ' 'measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, ' 'orthostatic vital signs, and sit-to-stand test change from ' 'baseline.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of the 155 ' 'participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to ' 'the NMV/r group and 53 to the PBO/r group. Nearly all participants (n\u2009=\u2009153) had ' 'received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 ' 'infection and randomization was 17.5 (9.1) months. There was no statistically significant ' 'difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 ' 'weeks between the NMV/r and PBO/r groups. No statistically significant between-group ' 'differences were found at 10 weeks in the Patient Global Impression of Severity or Patient ' 'Global Impression of Change scores, summative symptom scores, and change from baseline to 10 ' 'weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse ' 'event rates were similar in NMV/r and PBO/r groups and mostly of low ' 'grade.</jats:p></jats:sec><jats:sec><jats:title>Conclusions and ' 'Relevance</jats:title><jats:p>The results of this randomized clinical trial showed that a ' '15-day course of NMV/r in a population of patients with PASC was generally safe but did not ' 'demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated ' 'cohort with protracted symptom duration. Further studies are needed to determine the role of ' 'antivirals in the treatment of PASC.</jats:p></jats:sec><jats:sec><jats:title>Trial ' 'Registration</jats:title><jats:p>ClinicalTrials.gov Identifier: <jats:ext-link ' 'xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" ' 'xlink:href="https://classic.clinicaltrials.gov/ct2/show/NCT05576662">NCT05576662</jats:ext-link></jats:p></jats:sec>', 'DOI': '10.1001/jamainternmed.2024.2007', 'type': 'journal-article', 'created': {'date-parts': [[2024, 6, 7]], 'date-time': '2024-06-07T19:30:40Z', 'timestamp': 1717788640000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection', 'prefix': '10.1001', 'author': [ { 'given': 'Linda N.', 'family': 'Geng', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Hector', 'family': 'Bonilla', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Haley', 'family': 'Hedlin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Karen B.', 'family': 'Jacobson', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}, { 'name': 'Kaiser Permanente Northern California Division of Research, ' 'Oakland'}]}, { 'given': 'Lu', 'family': 'Tian', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Biomedical Data Science, Stanford School of ' 'Medicine, Stanford, California'}]}, { 'given': 'Prasanna', 'family': 'Jagannathan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Phillip C.', 'family': 'Yang', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Aruna K.', 'family': 'Subramanian', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Jane W.', 'family': 'Liang', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Sa', 'family': 'Shen', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Yaowei', 'family': 'Deng', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Blake J.', 'family': 'Shaw', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Bren', 'family': 'Botzheim', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Manisha', 'family': 'Desai', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Divya', 'family': 'Pathak', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Yasmin', 'family': 'Jazayeri', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Daniel', 'family': 'Thai', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Andrew', 'family': 'O’Donnell', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Sukanya', 'family': 'Mohaptra', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Zenita', 'family': 'Leang', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Gabriella Z. 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