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All Studies   All Outcomes    Recent:   

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

Geng et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2024.2007, NCT05576662
Jun 2024  
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0 0.5 1 1.5 2+ Relief at week 10 -24% Improvement Relative Risk Alleviation at week 10 -3% Mild/no symp., all symp.. -3% Mild/no symp., fatigue -82% Mild/no symp., brain fog -100% Mild/no symp., body aches 24% Mild/no symp., cardiova.. 27% Mild/no symp., dyspnea 24% Mild/no symp., gastrointes.. 29% Paxlovid  Geng et al.  LATE TREATMENT  DB RCT  LONG COVID Is paxlovid beneficial for long COVID (PASC)? Double-blind RCT 155 patients in the USA (November 2022 - September 2023) No significant difference in recovery c19early.org Geng et al., JAMA Internal Medicine, Jun 2024 Favors paxlovid Favors control
RCT 155 adults with long COVID (PASC) showing no significant benefit with nirmatrelvir+ritonavir (paxlovid) compared to ritonavir.
no relief at week 10, 24.3% higher, RR 1.24, p = 0.04, treatment 69 of 102 (67.6%), control 30 of 53 (56.6%), adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk.
no alleviation at week 10, 3.3% higher, RR 1.03, p = 0.62, treatment 95 of 102 (93.1%), control 47 of 53 (88.7%), adjusted per study, inverted to make RR<1 favor treatment, odds ratio converted to relative risk.
mild/no symp., 3.4% higher, RR 1.03, p = 0.88, treatment 102, control 53, adjusted per study, all symptoms combined.
mild/no symp., 81.8% higher, OR 1.82, p = 0.02, treatment 102, control 53, adjusted per study, inverted to make OR<1 favor treatment, fatigue, RR approximated with OR.
mild/no symp., 100% higher, OR 2.00, p = 0.005, treatment 102, control 53, adjusted per study, inverted to make OR<1 favor treatment, brain fog, RR approximated with OR.
mild/no symp., 24.2% lower, OR 0.76, p = 0.35, treatment 102, control 53, adjusted per study, inverted to make OR<1 favor treatment, body aches, RR approximated with OR.
mild/no symp., 27.0% lower, OR 0.73, p = 0.30, treatment 102, control 53, adjusted per study, inverted to make OR<1 favor treatment, cardiovascular, RR approximated with OR.
mild/no symp., 24.2% lower, OR 0.76, p = 0.36, treatment 102, control 53, adjusted per study, inverted to make OR<1 favor treatment, dyspnea, RR approximated with OR.
mild/no symp., 28.6% lower, OR 0.71, p = 0.25, treatment 102, control 53, adjusted per study, inverted to make OR<1 favor treatment, gastrointestinal, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Geng et al., 7 Jun 2024, Double Blind Randomized Controlled Trial, USA, peer-reviewed, 33 authors, study period 8 November, 2022 - 12 September, 2023, trial NCT05576662 (history). Contact: geng@stanford.edu, usingh@stanford.edu.
This PaperPaxlovidAll
Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection
MD, PhD Linda N Geng, MD Hector Bonilla, PhD Haley Hedlin, MD Karen B Jacobson, DSc Lu Tian, MD Prasanna Jagannathan, MD Phillip C Yang, MD Aruna K Subramanian, PhD Jane W Liang, PhD Sa Shen, MA Yaowei Deng, MS Blake J Shaw, MS Bren Botzheim, PhD Manisha Desai, MS Divya Pathak, MPH Yasmin Jazayeri, BS Daniel Thai, Andrew O’donnell, BS Sukanya Mohaptra, BS Zenita Leang, BS Gabriella Z M Reynolds, MS Erin F Brooks, MD Ami S Bhatt, PhD Robert W Shafer, MD Mitchell G Miglis, MD Tom Quach, Anushri Tiwari, PhD Anindita Banerjee, MPH Rene N Lopez, PhD Magdia De Jesus, MD Lawrence R Charnas, PhD Paul J Utz, MD Upinder Singh
JAMA Internal Medicine, doi:10.1001/jamainternmed.2024.2007
IMPORTANCE There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS Participants were randomized 2:1 to treatment with oral nirmatrelvirritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days. MAIN OUTCOMES AND MEASURES 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. RESULTS 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 = 153) 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. CONCLUSIONS AND RELEVANCE 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.
Author Contributions: Drs Geng and Singh had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Bonilla, Hedlin, and Jacobson contributed equally. Concept and design: Geng, Bonilla, Hedlin, Jacobson, Jagannathan, Yang, Subramanian, Liang, Desai, Pathak, Banerjee, Lopez, De Jesus, Utz, Singh. Acquisition, analysis, or interpretation of data: Geng, Bonilla, Hedlin, Jacobson, Tian, Jagannathan, Yang, Subramanian, Liang, Shen, Deng, Shaw, Botzheim, Desai, Jazayeri, Thai, O'Donnell, Mohapatra, Leang, Reynolds, Brooks, Bhatt, Shafer, Miglis, Quach, Tiwari, Lopez, Charnas, Singh. Drafting of the manuscript: Geng, Bonilla, Hedlin, Jacobson, Tian, Liang, Shaw, Jazayeri, Thai, Reynolds, Brooks, Bhatt, De Jesus, Charnas, Singh. Critical review of the manuscript for important intellectual content: Geng, Bonilla, Hedlin, Jacobson, Jagannathan, Yang, Subramanian, Liang, Shen, Deng, Shaw, Botzheim, Desai, Pathak, Jazayeri, O'Donnell, Mohapatra, Leang, Shafer, Miglis, Quach, Tiwari, Banerjee, Lopez, De Jesus, Charnas, Utz, Singh. Conflict of
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{ '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. M.', 'family': 'Reynolds', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Erin F.', 'family': 'Brooks', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Ami S.', 'family': 'Bhatt', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Robert W.', 'family': 'Shafer', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}]}, { 'given': 'Mitchell G.', 'family': 'Miglis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Neurology and Neurological Sciences, Stanford ' 'University School of Medicine, Stanford, California'}]}, { 'given': 'Tom', 'family': 'Quach', 'sequence': 'additional', 'affiliation': [{'name': 'Stanford University, Stanford, California'}]}, { 'given': 'Anushri', 'family': 'Tiwari', 'sequence': 'additional', 'affiliation': [{'name': 'Stanford University, Stanford, California'}]}, { 'given': 'Anindita', 'family': 'Banerjee', 'sequence': 'additional', 'affiliation': [ { 'name': 'Pfizer Research and Development, Pfizer Inc, Cambridge, ' 'Massachusetts'}]}, { 'given': 'Rene N.', 'family': 'Lopez', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical Research Collaborations COE, Worldwide Medical and ' 'Safety, Pfizer Inc, Groton, Connecticut'}]}, { 'given': 'Magdia', 'family': 'De Jesus', 'sequence': 'additional', 'affiliation': [ { 'name': 'Strategic Planning, Worldwide Medical and Safety, Pfizer Inc, ' 'New York, New York'}]}, { 'given': 'Lawrence R.', 'family': 'Charnas', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical Research Collaborations COE, Worldwide Medical and ' 'Safety, Pfizer Inc, Groton, Connecticut'}]}, { 'given': 'Paul J.', 'family': 'Utz', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}, { 'name': 'Institute for Immunity, Transplantation and Infection, Stanford ' 'University, Stanford, California'}]}, { 'given': 'Upinder', 'family': 'Singh', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine, Stanford University School of Medicine, ' 'Stanford, California'}, { 'name': 'Department of Microbiology and Immunology, Stanford University ' 'School of Medicine, Stanford, California'}]}], 'member': '10', 'published-online': {'date-parts': [[2024, 6, 7]]}, 'reference': [ { 'issue': '16', 'key': 'ioi240036r1', 'doi-asserted-by': 'publisher', 'first-page': '1604', 'DOI': '10.1001/jama.2022.18931', 'article-title': 'Estimated global proportions of individuals with persistent fatigue, ' 'cognitive, and respiratory symptom clusters following symptomatic ' 'COVID-19 in 2020 and 2021.', 'volume': '328', 'author': 'Wulf Hanson', 'year': '2022', 'journal-title': 'JAMA'}, { 'key': 'ioi240036r2', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.eclinm.2022.101762', 'article-title': 'The prevalence and long-term health effects of long COVID among ' 'hospitalised and non-hospitalised populations: a systematic review and ' 'meta-analysis.', 'volume': '55', 'author': 'O’Mahoney', 'year': '2022', 'journal-title': 'EClinicalMedicine'}, { 'issue': '1', 'key': 'ioi240036r4', 'doi-asserted-by': 'publisher', 'first-page': '7717', 'DOI': '10.1038/s41598-023-34678-8', 'article-title': 'Impaired health-related quality of life in long-COVID syndrome after ' 'mild to moderate COVID-19.', 'volume': '13', 'author': 'Malesevic', 'year': '2023', 'journal-title': 'Sci Rep'}, { 'key': 'ioi240036r5', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.eclinm.2021.101019', 'article-title': 'Characterizing long COVID in an international cohort: 7 months of ' 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'doi-asserted-by': 'publisher', 'first-page': '226', 'DOI': '10.1136/gutjnl-2021-324280', 'article-title': 'Residual SARS-CoV-2 viral antigens detected in GI and hepatic tissues ' 'from five recovered patients with COVID-19.', 'volume': '71', 'author': 'Cheung', 'year': '2022', 'journal-title': 'Gut'}, { 'issue': '7941', 'key': 'ioi240036r28', 'doi-asserted-by': 'publisher', 'first-page': '758', 'DOI': '10.1038/s41586-022-05542-y', 'article-title': 'SARS-CoV-2 infection and persistence in the human body and brain at ' 'autopsy.', 'volume': '612', 'author': 'Stein', 'year': '2022', 'journal-title': 'Nature'}, { 'key': 'ioi240036r29', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ebiom.2021.103230', 'article-title': 'SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell ' 'responses.', 'volume': '64', 'author': 'Vibholm', 'year': '2021', 'journal-title': 'EBioMedicine'}, { 'issue': '10', 'key': 'ioi240036r30', 'doi-asserted-by': 'publisher', 'DOI': 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symptoms: 4 cases and ' 'rationale for systematic studies.', 'volume': '7', 'author': 'Peluso', 'year': '2022', 'journal-title': 'Pathog Immun'}, { 'issue': '1', 'key': 'ioi240036r44', 'doi-asserted-by': 'publisher', 'first-page': '16144', 'DOI': '10.1038/s41598-021-95565-8', 'article-title': 'More than 50 long-term effects of COVID-19: a systematic review and ' 'meta-analysis.', 'volume': '11', 'author': 'Lopez-Leon', 'year': '2021', 'journal-title': 'Sci Rep'}, { 'issue': '8', 'key': 'ioi240036r45', 'doi-asserted-by': 'publisher', 'first-page': '1706', 'DOI': '10.1038/s41591-022-01909-w', 'article-title': 'Symptoms and risk factors for long COVID in non-hospitalized adults.', 'volume': '28', 'author': 'Subramanian', 'year': '2022', 'journal-title': 'Nat Med'}, { 'key': 'ioi240036r46', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fneur.2023.1090747', 'article-title': 'Myalgic encephalomyelitis/chronic fatigue syndrome is common in ' 'post-acute sequelae of SARS-CoV-2 infection (PASC): results from a ' 'post-COVID-19 multidisciplinary clinic.', 'volume': '14', 'author': 'Bonilla', 'year': '2023', 'journal-title': 'Front Neurol'}, { 'key': 'ioi240036r47', 'doi-asserted-by': 'crossref', 'DOI': '10.3389/fneur.2022.1012668', 'article-title': 'Characterization of autonomic symptom burden in long COVID: a global ' 'survey of 2,314 adults.', 'volume': '13', 'author': 'Larsen', 'year': '2022', 'journal-title': 'Front Neurol'}, { 'issue': '1', 'key': 'ioi240036r49', 'doi-asserted-by': 'publisher', 'first-page': '2', 'DOI': '10.1097/HCR.0000000000000336', 'article-title': '1-Minute Sit-to-Stand Test: systematic review of procedures, ' 'performance, and clinimetric properties.', 'volume': '39', 'author': 'Bohannon', 'year': '2019', 'journal-title': 'J Cardiopulm Rehabil Prev'}, { 'issue': '2', 'key': 'ioi240036r51', 'doi-asserted-by': 'publisher', 'first-page': '359', 'DOI': '10.1093/biomet/72.2.359', 'article-title': 'Combining dependent tests with incomplete repeated measurements.', 'volume': '72', 'author': 'Wei', 'year': '1985', 'journal-title': 'Biometrika'}, { 'issue': '2', 'key': 'ioi240036r52', 'doi-asserted-by': 'publisher', 'first-page': '223', 'DOI': '10.1093/biostatistics/4.2.223', 'article-title': 'Combining dependent tests for linkage or association across multiple ' 'phenotypic traits.', 'volume': '4', 'author': 'Xu', 'year': '2003', 'journal-title': 'Biostatistics'}, { 'issue': '5', 'key': 'ioi240036r54', 'doi-asserted-by': 'publisher', 'first-page': '881', 'DOI': '10.1016/j.cell.2022.01.014', 'article-title': 'Multiple early factors anticipate post-acute COVID-19 sequelae.', 'volume': '185', 'author': 'Su', 'year': '2022', 'journal-title': 'Cell'}, { 'issue': '1', 'key': 'ioi240036r55', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmjmed-2022-000385', 'article-title': 'Effect of covid-19 vaccination on long COVID: systematic review.', 'volume': '2', 'author': 'Byambasuren', 'year': '2023', 'journal-title': 'BMJ Med'}, { 'issue': '6', 'key': 'ioi240036r56', 'doi-asserted-by': 'publisher', 'first-page': '566', 'DOI': '10.1001/jamainternmed.2023.0750', 'article-title': 'Risk factors associated with post-COVID-19 condition: a systematic ' 'review and meta-analysis.', 'volume': '183', 'author': 'Tsampasian', 'year': '2023', 'journal-title': 'JAMA Intern Med'}, { 'issue': '1', 'key': 'ioi240036r57', 'doi-asserted-by': 'publisher', 'first-page': '1812', 'DOI': '10.1038/s41467-022-29513-z', 'article-title': 'Course of post COVID-19 disease symptoms over time in the COMPARE long ' 'COVID prospective e-cohort.', 'volume': '13', 'author': 'Tran', 'year': '2022', 'journal-title': 'Nat Commun'}, { 'issue': '3', 'key': 'ioi240036r58', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmjgh-2022-011276', 'article-title': 'Conceptualising the episodic nature of disability among adults living ' 'with long COVID: a qualitative study.', 'volume': '8', 'author': 'O’Brien', 'year': '2023', 'journal-title': 'BMJ Glob Health'}, { 'key': 'ioi240036r59', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj-2022-074425', 'article-title': 'Recovery and symptom trajectories up to two years after SARS-CoV-2 ' 'infection: population based, longitudinal cohort study.', 'volume': '381', 'author': 'Ballouz', 'year': '2023', 'journal-title': 'BMJ'}, { 'key': 'ioi240036r60', 'doi-asserted-by': 'publisher', 'first-page': '67', 'DOI': '10.1016/j.ijid.2023.05.007', 'article-title': 'Trajectories of the evolution of post-COVID-19 condition, up to two ' 'years after symptoms onset.', 'volume': '133', 'author': 'Servier', 'year': '2023', 'journal-title': 'Int J Infect Dis'}, { 'issue': '22', 'key': 'ioi240036r61', 'doi-asserted-by': 'publisher', 'first-page': '1934', 'DOI': '10.1001/jama.2023.8823', 'article-title': 'Development of a definition of postacute sequelae of SARS-CoV-2 ' 'infection.', 'volume': '329', 'author': 'Thaweethai', 'year': '2023', 'journal-title': 'JAMA'}, { 'key': 'ioi240036r62', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/bmj-2022-070230', 'article-title': 'Development and validation of the symptom burden questionnaire for long ' 'COVID (SBQ-LC): rasch analysis.', 'volume': '377', 'author': 'Hughes', 'year': '2022', 'journal-title': 'BMJ'}, { 'issue': '10', 'key': 'ioi240036r68', 'doi-asserted-by': 'publisher', 'first-page': '797', 'DOI': '10.1038/s41573-019-0034-3', 'article-title': 'Adaptive platform trials: definition, design, conduct and reporting ' 'considerations.', 'volume': '18', 'author': 'Adaptive Platform Trials Coalition', 'year': '2019', 'journal-title': 'Nat Rev Drug Discov'}, { 'key': 'ioi240036r3', 'unstructured': 'US Centers for Disease Control and Prevention. Long COVID-19—Household ' 'Pulse Survey—COVID-19. Published October 11, 2023. Accessed October 18, ' '2023. https://www.cdc.gov/nchs/covid19/pulse/long-covid.htm'}, { 'key': 'ioi240036r43', 'unstructured': 'US Centers for Disease Control and Prevention. COVID-19 Vaccination: ' 'Clinical & Professional Resources. Published October 4, 2023. Accessed ' 'February 1, 2024. https://www.cdc.gov/vaccines/covid-19/index.html'}, { 'key': 'ioi240036r48', 'unstructured': 'HealthMeasures. Patient-Reported Outcomes Measurement Information ' 'System. Accessed February 1, 2024. ' 'https://www.healthmeasures.net/explore-measurement-systems/promis'}, { 'key': 'ioi240036r50', 'unstructured': 'eProvide Mapi Research Trust. Patient Global Impressions scale: Change, ' 'Improvement, Severity. Published October 5, 2023. Accessed February 1, ' '2024. ' 'https://eprovide.mapi-trust.org/instruments/patient-global-impressions-scale-change-improvement-severity'}, { 'key': 'ioi240036r53', 'unstructured': 'The R Project for Statistical Computing. R software. Accessed October ' '31, 2023. https://www.r-project.org/'}, { 'key': 'ioi240036r63', 'unstructured': 'Zimmerman? KO. RECOVER-VITAL: a platform protocol for evaluation of ' 'interventions for viral persistence, viral reactivation, and immune ' 'dysregulation in post-acute sequelae of SARS-CoV-2 infection (PASC). ' '2024. Accessed December 31, 2023. ' 'https://clinicaltrials.gov/study/NCT05595369'}, { 'key': 'ioi240036r64', 'unstructured': 'Krumholz? HM. An Interventional decentralized phase 2, randomized, ' 'double-blind, 2-arm study to investigate the efficacy and safety of ' 'orally administered nirmatrelvir/ritonavir compared with ' 'placebo/ritonavir in participants with long COVID. 2023. Accessed ' 'December 31, 2023. https://clinicaltrials.gov/study/NCT05668091'}, { 'key': 'ioi240036r65', 'unstructured': 'Brodin? P. An interventional, double-blinded, 2-arm study to investigate ' 'the efficacy of orally administered nirmatrelvir/ritonavir compared with ' 'placebo/ritonavir in non-hospitalized adult participants suffering from ' 'post-COVID. 2023. Accessed December 31, 2023. ' 'https://clinicaltrials.gov/study/NCT05823896'}, { 'key': 'ioi240036r66', 'unstructured': 'Henrich? T. placebo-controlled, randomized trial of ensitrelvir ' '(s-217622) for viral persistence and inflammation in people experiencing ' 'long COVID (PREVAIL-LC). 2023. Accessed December 31, 2023. ' 'https://clinicaltrials.gov/study/NCT06161688'}, { 'key': 'ioi240036r67', 'unstructured': 'Peluso? M. An exploratory, randomized, double-blind placebo-controlled ' 'study to assess the safety of an anti-SARS-CoV-2 monoclonal antibody and ' 'response to treatment in individuals with long COVID (OutSMART-LC). ' '2024. Accessed December 31, 2023. ' 'https://clinicaltrials.gov/study/NCT05877508'}], 'container-title': 'JAMA Internal Medicine', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/2819901/jamainternal_geng_2024_oi_240036_1717508980.16662.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 6, 7]], 'date-time': '2024-06-07T19:30:48Z', 'timestamp': 1717788648000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2819901'}}, 'subtitle': ['The STOP-PASC Randomized Clinical Trial'], 'short-title': [], 'issued': {'date-parts': [[2024, 6, 7]]}, 'references-count': 68, 'URL': 'http://dx.doi.org/10.1001/jamainternmed.2024.2007', 'relation': {}, 'ISSN': ['2168-6106'], 'subject': [], 'container-title-short': 'JAMA Intern Med', 'published': {'date-parts': [[2024, 6, 7]]}}
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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