{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:10:02Z","timestamp":1768561802475,"version":"3.49.0"},"posted":{"date-parts":[[2023,3,5]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":34,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Oral nirmatrelvir\/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir\/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353\/988 (35.7%) treated and 1258\/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir\/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir\/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Within this cohort, treatment with nirmatrelvir\/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.03.02.23286730","type":"posted-content","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T13:10:19Z","timestamp":1678194619000},"source":"Crossref","is-referenced-by-count":4,"title":["Association of Nirmatrelvir\/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7612-3352","authenticated-orcid":false,"given":"Matthew S.","family":"Durstenfeld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-6230","authenticated-orcid":false,"given":"Michael J.","family":"Peluso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah D.","family":"Peyser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Isasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas W.","family":"Carton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Henrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey E.","family":"Olgin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Pletcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8405-7386","authenticated-orcid":false,"given":"Alexis L.","family":"Beatty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5197-7696","authenticated-orcid":false,"given":"Gregory M.","family":"Marcus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla Y.","family":"Hsue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023030809051441000_2023.03.02.23286730v1.1","doi-asserted-by":"crossref","unstructured":"Soriano JM, J ; Diaz, JV ; Murthy, S; ; Relan, P. A clinical case definition of post COVID- 19 condition by a Delphi consensus. In: Organization WH. 2021.1 ed:, 2021.","DOI":"10.1016\/S1473-3099(21)00703-9"},{"key":"2023030809051441000_2023.03.02.23286730v1.2","doi-asserted-by":"crossref","unstructured":"Watanabe A , Iwagami M , Yasuhara J , Takagi H , Kuno T. Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis. Vaccine 2023.","DOI":"10.1016\/j.vaccine.2023.02.008"},{"key":"2023030809051441000_2023.03.02.23286730v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.01.014"},{"key":"2023030809051441000_2023.03.02.23286730v1.4","doi-asserted-by":"crossref","unstructured":"Antar AAR , Yu T , Demko ZO , et al. Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection. medRxiv 2023: 2023.01.18.23284742.","DOI":"10.1101\/2023.01.18.23284742"},{"issue":"7941","key":"2023030809051441000_2023.03.02.23286730v1.5","doi-asserted-by":"crossref","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","year":"2022","journal-title":"Nature"},{"key":"2023030809051441000_2023.03.02.23286730v1.6","doi-asserted-by":"crossref","unstructured":"Swank Z , Senussi Y , Manickas-Hill Z , et al. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae. Clin Infect Dis 2022.","DOI":"10.1101\/2022.06.14.22276401"},{"issue":"6","key":"2023030809051441000_2023.03.02.23286730v1.7","first-page":"371","article-title":"Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection","volume":"3","year":"2022","journal-title":"Med (N Y)"},{"key":"2023030809051441000_2023.03.02.23286730v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26350"},{"key":"2023030809051441000_2023.03.02.23286730v1.9","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2118542"},{"issue":"1","key":"2023030809051441000_2023.03.02.23286730v1.10","first-page":"95","article-title":"Effect of Oral Nirmatrelvir on Long COVID Symptoms: 4 Cases and Rationale for Systematic Studies","volume":"7","year":"2022","journal-title":"Pathog Immun"},{"key":"2023030809051441000_2023.03.02.23286730v1.11","first-page":"1003103","article-title":"Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS- CoV-2 antigen persistence","volume":"9","year":"2022","journal-title":"Front Med (Lausanne)"},{"issue":"000","key":"2023030809051441000_2023.03.02.23286730v1.12","doi-asserted-by":"crossref","first-page":"000","DOI":"10.14218\/ERHM.2022.00045","article-title":"The Use of Nirmatrelvir-ritonavir in a Case of Breakthrough Long COVID","volume":"000","year":"2023","journal-title":"Exploratory Research and Hypothesis in Medicine"},{"key":"2023030809051441000_2023.03.02.23286730v1.13","doi-asserted-by":"crossref","unstructured":"Bajema KL , Berry K , Streja E , et al. Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes. medRxiv 2022: 2022.12.05.22283134.","DOI":"10.1101\/2022.12.05.22283134"},{"issue":"8","key":"2023030809051441000_2023.03.02.23286730v1.14","doi-asserted-by":"crossref","first-page":"e28169","DOI":"10.2196\/28169","article-title":"The COVID-19 Citizen Science Study: Protocol for a Longitudinal Digital Health Cohort Study","volume":"10","year":"2021","journal-title":"JMIR Res Protoc"},{"key":"2023030809051441000_2023.03.02.23286730v1.15","doi-asserted-by":"crossref","unstructured":"Durstenfeld MS , Peluso MJ , Peyser ND , et al. Factors Associated with Long Covid Symptoms in an Online Cohort Study. Open Forum Infectious Diseases 2023.","DOI":"10.1101\/2022.12.01.22282987"},{"key":"2023030809051441000_2023.03.02.23286730v1.16","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"2023030809051441000_2023.03.02.23286730v1.17","unstructured":"Administration FaD. Fact Sheet for Healthcare Providers. 2022."},{"key":"2023030809051441000_2023.03.02.23286730v1.18","unstructured":"Pfizer. Pfizer Reports Additional Data on PAXLOVID\u2122 Supporting Upcoming New Drug Application Submission to U.S. FDA. 2022."},{"issue":"3","key":"2023030809051441000_2023.03.02.23286730v1.19","first-page":"e342","article-title":"Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients","volume":"76","year":"2022","journal-title":"Clin Infect Dis"},{"issue":"1","key":"2023030809051441000_2023.03.02.23286730v1.20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7326\/M22-2141","article-title":"Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study","volume":"176","year":"2023","journal-title":"Ann Intern Med"},{"key":"2023030809051441000_2023.03.02.23286730v1.21","doi-asserted-by":"crossref","first-page":"100602","DOI":"10.1016\/j.lanwpc.2022.100602","article-title":"Association of Molnupiravir and Nirmatrelvir- Ritonavir with preventable mortality, hospital admissions and related avoidable healthcare system cost among high-risk patients with mild to moderate COVID-19","volume":"30","year":"2023","journal-title":"Lancet Reg Health West Pac"},{"issue":"1","key":"2023030809051441000_2023.03.02.23286730v1.22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ajt.2022.12.004","article-title":"Paxlovid associated with decreased hospitalization rate among adults with COVID-19 - United States, April-September 2022","volume":"23","year":"2023","journal-title":"Am J Transplant"},{"issue":"12","key":"2023030809051441000_2023.03.02.23286730v1.23","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/S1473-3099(22)00507-2","article-title":"Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong\u2019s omicron BA.2 wave: a retrospective cohort study","volume":"22","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"2023030809051441000_2023.03.02.23286730v1.24","doi-asserted-by":"crossref","unstructured":"Qi T , Jin Y , Wang H , et al. Nirmatrelvir-ritonavir Therapy and COVID-19 Vaccination Improve Clinical Outcomes of SARS-CoV-2 Omicron Variant Infection. J Med Virol 2023.","DOI":"10.1002\/jmv.28497"},{"issue":"1","key":"2023030809051441000_2023.03.02.23286730v1.25","doi-asserted-by":"crossref","first-page":"e28443","DOI":"10.1002\/jmv.28443","article-title":"Early administration of Paxlovid reduces the viral elimination time in patients infected with SARS-CoV-2 Omicron variants","volume":"95","year":"2023","journal-title":"J Med Virol"},{"key":"2023030809051441000_2023.03.02.23286730v1.26","doi-asserted-by":"crossref","unstructured":"Xie Y CT , Al-Aly Z. Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19 medRxiv 2022.","DOI":"10.1101\/2022.11.03.22281783"},{"issue":"12","key":"2023030809051441000_2023.03.02.23286730v1.27","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1093\/qjmed\/hcab297","article-title":"Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?","volume":"114","year":"2022","journal-title":"Qjm"},{"issue":"1","key":"2023030809051441000_2023.03.02.23286730v1.28","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1038\/s41467-022-33825-5","article-title":"Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial","volume":"13","year":"2022","journal-title":"Nature Communications"},{"key":"2023030809051441000_2023.03.02.23286730v1.29","doi-asserted-by":"crossref","unstructured":"Bramante CT , Buse JB , Liebovitz D , et al. Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10- month follow-up. medRxiv 2022.","DOI":"10.1101\/2022.12.21.22283753"},{"key":"2023030809051441000_2023.03.02.23286730v1.30","doi-asserted-by":"crossref","unstructured":"Reis G , Wilson L , Ayers D , et al. Effectiveness of early-treatment interventions on self- reported long COVID: A multi-arm, multi-stage adaptive platform control trial. Preprint at researchsquareorg 2022.","DOI":"10.21203\/rs.3.rs-2027075\/v1"},{"issue":"3","key":"2023030809051441000_2023.03.02.23286730v1.31","first-page":"e537","article-title":"Rebound Phenomenon After Nirmatrelvir\/Ritonavir Treatment of Coronavirus Disease 2019 (COVID-19) in High-Risk Persons","volume":"76","year":"2022","journal-title":"Clinical Infectious Diseases"},{"key":"2023030809051441000_2023.03.02.23286730v1.32","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ijid.2020.07.070","article-title":"Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19","volume":"99","year":"2020","journal-title":"Int J Infect Dis"},{"key":"2023030809051441000_2023.03.02.23286730v1.33","doi-asserted-by":"crossref","unstructured":"Durstenfeld MS , Peluso MJ , Kaveti P , et al. Inflammation during early post-acute COVID-19 is associated with reduced exercise capacity and Long COVID symptoms after 1 year. Preprint at medrxivorg (Posted May 19, 2022) 2022.","DOI":"10.1101\/2022.05.17.22275235"},{"issue":"2","key":"2023030809051441000_2023.03.02.23286730v1.34","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/acn3.51498","article-title":"Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19","volume":"9","year":"2022","journal-title":"Ann Clin Transl Neurol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.03.02.23286730","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:29:04Z","timestamp":1768505344000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.03.02.23286730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,5]]},"references-count":34,"URL":"https:\/\/doi.org\/10.1101\/2023.03.02.23286730","relation":{},"subject":[],"published":{"date-parts":[[2023,3,5]]},"subtype":"preprint"}}