{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T09:59:53Z","timestamp":1770371993144,"version":"3.49.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011082","name":"School of Medicine, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011082","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007890","name":"University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","award":["COVID-19 Response Fund\/Health Foundation"],"award-info":[{"award-number":["COVID-19 Response Fund\/Health Foundation"]}],"id":[{"id":"10.13039\/100007890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007327","name":"Gillings School of Public Health","doi-asserted-by":"publisher","award":["Innovation Lab Award"],"award-info":[{"award-number":["Innovation Lab Award"]}],"id":[{"id":"10.13039\/100007327","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002489"],"award-info":[{"award-number":["UL1TR002489"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32A1007151"],"award-info":[{"award-number":["T32A1007151"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006292","name":"Infectious Diseases Society of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006292","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biomedomics Inc."}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early in the SARS-CoV-2 pandemic, description of COVID-19 illness among non-hospitalized patients was limited. Data from household cohorts can help reveal the full spectrum of disease and the potential for long-term sequelae, even in non-severe disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Daily symptom diaries were collected in a US household cohort of SARS-CoV-2 infection from April to November 2020, during the pre-COVID vaccine period. SARS-CoV-2 nasal viral loads were measured at study entry and weekly until day 21; serologic testing was performed at study entry and day 28. A subset of volunteers underwent an additional assessment 8\u201310 months later. Participants who met the criteria for early infection\u2014testing antibody-negative at study entry but PCR-positive either at baseline or during follow-up\u2014were included in this analysis (n\u2009=\u2009143).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Daily symptoms were ascertained in 143 outpatients with acute COVID-19, including 60 index cases who sought testing and 83 of their household contacts. Asymptomatic cases comprised 16% (13\/83) of SARS-CoV-2 infections detected among household contacts. Among 119 persons with mild or moderate illness, the number of symptoms peaked 3 or 4 days after symptom onset. Fever and anosmia occurred in nearly half of participants. Symptom severity was associated with increased age, viral load, and cardiovascular disease. Increased BMI was associated with a higher antibody level at day 28, independent of symptom severity. Those with a higher day 28 antibody level were more likely to develop symptoms consistent with post-acute sequelae of SARS-CoV-2 (PASC), also known as long COVID-19, 8\u201310 months later.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fever, anosmia, as well as asymptomatic infection were common features of COVID-19 non-severe illness when the D614G variant circulated in the US, before the availability of vaccines or outpatient therapies. Antibody levels following acute infection were linked to the development of symptoms of PASC 8\u201310 months later.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0313467","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:42:07Z","timestamp":1770316927000},"page":"e0313467","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Symptom burden, viral load, and antibody response to ancestral SARS-CoV-2 strain [D614G] in an outpatient household cohort"],"prefix":"10.1371","volume":"21","author":[{"given":"Mehal","family":"Churiwal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Tompkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle","family":"Streeter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christy","family":"Litel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sydney","family":"Mason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1497-476X","authenticated-orcid":true,"given":"Kelly","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith","family":"Muller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srijana","family":"Chhetri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia","family":"Belvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng-Chang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Basham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Whittelsey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7166-1015","authenticated-orcid":true,"given":"Tyler","family":"Rapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lakshmanane","family":"Premkumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Cerami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-723X","authenticated-orcid":true,"given":"Jessica T.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"issue":"5","key":"pone.0313467.ref001","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1473-3099(20)30196-1","article-title":"Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: An observational cohort study","volume":"20","author":"KK-W To","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"32","key":"pone.0313467.ref002","article-title":"Clinical characteristics of COVID-19: Clinical dynamics of mild severe acute respiratory syndrome coronavirus 2 infection detected by early active surveillance","volume":"35","author":"HJ Suh","year":"2020","journal-title":"J Korean Med Sci"},{"issue":"1","key":"pone.0313467.ref003","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1080\/22221751.2020.1762515","article-title":"Kinetics of SARS-CoV-2 specific IgM and IgG responses in COVID-19 patients","volume":"9","author":"B Sun","year":"2020","journal-title":"Emerg Microbes Infect"},{"issue":"13","key":"pone.0313467.ref004","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a Report of 72\u00a0314 cases from the chinese center for disease control and prevention","volume":"323","author":"Z Wu","year":"2020","journal-title":"JAMA"},{"issue":"10","key":"pone.0313467.ref005","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1093\/cid\/ciab701","article-title":"Household transmission of severe acute respiratory syndrome coronavirus 2 in the United States: Living density, viral load, and disproportionate impact on communities of color","volume":"74","author":"C Cerami","year":"2022","journal-title":"Clin Infect Dis"},{"key":"pone.0313467.ref006","unstructured":"Centers for Disease Control and Prevention. CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. In: CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. https:\/\/www.fda.gov\/media\/134922\/download"},{"issue":"2","key":"pone.0313467.ref007","doi-asserted-by":"crossref","first-page":"115469","DOI":"10.1016\/j.diagmicrobio.2021.115469","article-title":"Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings","volume":"101","author":"MS Muller","year":"2021","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"48","key":"pone.0313467.ref008","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abc8413","article-title":"The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients","volume":"5","author":"L Premkumar","year":"2020","journal-title":"Sci Immunol"},{"key":"pone.0313467.ref009","unstructured":"Coronavirus Disease 2019 (COVID-19) 2020 interim case definition, approved august 5, 2020. 2022 [cited 28 Aug 2024]. https:\/\/ndc.services.cdc.gov\/case-definitions\/coronavirus-disease-2019-2020-08-05\/"},{"issue":"7","key":"pone.0313467.ref010","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/ciaa1072","article-title":"A prospective cohort study in nonhospitalized household contacts with severe acute respiratory syndrome coronavirus 2 infection: Symptom profiles and symptom change over time","volume":"73","author":"AR Yousaf","year":"2021","journal-title":"Clin Infect Dis"},{"issue":"13","key":"pone.0313467.ref011","doi-asserted-by":"crossref","first-page":"377","DOI":"10.15585\/mmwr.mm6913e1","article-title":"Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - King County, Washington, March 2020","volume":"69","author":"A Kimball","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"22","key":"pone.0313467.ref012","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1056\/NEJMoa2008457","article-title":"Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility","volume":"382","author":"MM Arons","year":"2020","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0313467.ref013","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jinf.2020.04.014","article-title":"Viral dynamics of SARS-CoV-2 across a spectrum of disease severity in COVID-19","volume":"81","author":"G Lui","year":"2020","journal-title":"J Infect"},{"key":"pone.0313467.ref014","article-title":"Symptom burden in patients of different ages with acute COVID-19 infection quarantining at home","author":"AS Gershon","year":"2022","journal-title":"B57 Cutting Edge COVID Research"},{"issue":"4","key":"pone.0313467.ref015","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ajic.2021.10.039","article-title":"Clinical characteristics and symptom duration among outpatients with COVID-19","volume":"50","author":"A Lane","year":"2022","journal-title":"Am J Infect Control"},{"issue":"2","key":"pone.0313467.ref016","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab007","article-title":"The clinical course of COVID-19 in the outpatient setting: A prospective cohort study","volume":"8","author":"PW Blair","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"pone.0313467.ref017","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofaa420","article-title":"Characterization of prolonged COVID-19 symptoms in an outpatient telemedicine clinic","volume":"7","author":"M Cellai","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"pone.0313467.ref018","doi-asserted-by":"crossref","first-page":"841","DOI":"10.15585\/mmwr.mm6926e3","article-title":"Characteristics of adult outpatients and inpatients with COVID-19 - 11 academic medical centers, United States, March-May 2020","volume":"69","author":"MW Tenforde","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"2","key":"pone.0313467.ref019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0263813","article-title":"Outcomes of COVID-19 adults managed in an outpatient versus hospital setting","volume":"17","author":"NT Nguyen","year":"2022","journal-title":"PLoS One"},{"key":"pone.0313467.ref020","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.3201\/eid2704.204709","article-title":"Characteristics and risk factors of hospitalized and nonhospitalized COVID-19 patients, Atlanta, Georgia, USA, March-April 2020","volume":"27","author":"K Pettrone","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"pone.0313467.ref021","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.2147\/IJGM.S305295","article-title":"Epidemiology, Clinical characteristics, and outcomes of a large cohort of COVID-19 outpatients in Michigan","volume":"14","author":"A Halalau","year":"2021","journal-title":"Int J Gen Med"},{"key":"pone.0313467.ref022","doi-asserted-by":"crossref","first-page":"1036556","DOI":"10.3389\/fmed.2022.1036556","article-title":"Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients","volume":"9","author":"M P\u0142ywaczewska-Jakubowska","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"pone.0313467.ref023","doi-asserted-by":"crossref","first-page":"836826","DOI":"10.3389\/fmed.2021.836826","article-title":"Viral Load in COVID-19 patients: Implications for prognosis and vaccine efficacy in the context of emerging SARS-CoV-2 variants","volume":"8","author":"SJR da Silva","year":"2022","journal-title":"Front Med (Lausanne)"},{"issue":"6","key":"pone.0313467.ref024","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1007\/s12250-020-00329-9","article-title":"Viral and antibody kinetics of COVID-19 patients with different disease severities in acute and convalescent phases: A 6-month follow-up study","volume":"35","author":"X Zhang","year":"2020","journal-title":"Virol Sin"},{"issue":"2","key":"pone.0313467.ref025","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofab005","article-title":"SARS-CoV-2 seroconversion and viral clearance in patients hospitalized with COVID-19: Viral load predicts antibody response","volume":"8","author":"M Masi\u00e1","year":"2021","journal-title":"Open Forum Infect Dis"},{"issue":"10","key":"pone.0313467.ref026","doi-asserted-by":"crossref","first-page":"5235","DOI":"10.1172\/JCI138759","article-title":"Kinetics of viral load and antibody response in relation to COVID-19 severity","volume":"130","author":"Y Wang","year":"2020","journal-title":"J Clin Invest"},{"key":"pone.0313467.ref027","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.virol.2020.09.008","article-title":"Molecular and serological characterization of SARS-CoV-2 infection among COVID-19 patients","volume":"551","author":"L Li","year":"2020","journal-title":"Virology"},{"issue":"1","key":"pone.0313467.ref028","doi-asserted-by":"crossref","first-page":"12269","DOI":"10.1038\/s41598-022-15791-6","article-title":"COVID-19 symptom severity predicts neutralizing antibody activity in a community-based serological study","volume":"12","author":"A Sancilio","year":"2022","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0313467.ref029","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1093\/infdis\/jiab411","article-title":"Determinants and dynamics of SARS-CoV-2 infection in a diverse population: 6-month evaluation of a prospective cohort study","volume":"224","author":"DB Horton","year":"2021","journal-title":"J Infect Dis"},{"issue":"5","key":"pone.0313467.ref030","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1002\/jmv.26899","article-title":"Antibody response patterns in COVID-19 patients with different levels of disease severity in Japan","volume":"93","author":"K Imai","year":"2021","journal-title":"J Med Virol"},{"issue":"9","key":"pone.0313467.ref031","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S1473-3099(20)30364-9","article-title":"SARS-CoV-2 shedding and seroconversion among passengers quarantined after disembarking a cruise ship: A case series","volume":"20","author":"IF-N Hung","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"pone.0313467.ref032","doi-asserted-by":"crossref","first-page":"1287388","DOI":"10.3389\/fimmu.2023.1287388","article-title":"SARS-CoV-2 specific immune responses in overweight and obese COVID-19 patients","volume":"14","author":"TB Onyango","year":"2023","journal-title":"Front Immunol"},{"issue":"7","key":"pone.0313467.ref033","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.4049\/jimmunol.2101156","article-title":"SARS-CoV-2 antibody response is associated with age and body mass index in convalescent outpatients","volume":"208","author":"B Zhai","year":"2022","journal-title":"J Immunol"},{"issue":"9","key":"pone.0313467.ref034","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/oby.23208","article-title":"The association between obesity and peak antibody titer response in COVID-19 infection","volume":"29","author":"S Soffer","year":"2021","journal-title":"Obesity (Silver Spring)"},{"issue":"12","key":"pone.0313467.ref035","article-title":"Elevated BMI reduces the humoral response to SARS-CoV-2 infection","volume":"12","author":"MZ Tong","year":"2023","journal-title":"Clin Transl Immunology"},{"issue":"11","key":"pone.0313467.ref036","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.3390\/v13112235","article-title":"Epidemiological and immunological features of obesity and SARS-CoV-2","volume":"13","author":"EJ Nilles","year":"2021","journal-title":"Viruses"},{"issue":"11","key":"pone.0313467.ref037","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2022.40985","article-title":"Long-lasting symptoms after an acute COVID-19 infection and factors associated with their resolution","volume":"5","author":"O Robineau","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"5","key":"pone.0313467.ref038","article-title":"Multiple early factors anticipate post-acute COVID-19 sequelae","volume":"185","author":"Y Su","year":"2022","journal-title":"Cell"},{"issue":"1","key":"pone.0313467.ref039","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41467-023-44090-5","article-title":"Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes: Results from the IMPACC study","volume":"15","author":"A Ozonoff","year":"2024","journal-title":"Nat Commun"},{"key":"pone.0313467.ref040","doi-asserted-by":"crossref","first-page":"1348041","DOI":"10.3389\/fimmu.2024.1348041","article-title":"Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals","volume":"15","author":"JM Leung","year":"2024","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0313467.ref041","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.09.032","article-title":"Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant","volume":"183","author":"L Yurkovetskiy","year":"2020","journal-title":"Cell"},{"issue":"18","key":"pone.0313467.ref042","first-page":"1746","article-title":"National Academies of Sciences, Engineering, and Medicine Committee on Examining the Working Definition for Long Covid. Long Covid Defined","volume":"391","author":"EW Ely","year":"2024","journal-title":"N Engl J Med"},{"issue":"6","key":"pone.0313467.ref043","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofac171","article-title":"Mission, organization, and future direction of the serological sciences network for COVID-19 (SeroNet) epidemiologic cohort studies","volume":"9","author":"JC Figueiredo","year":"2022","journal-title":"Open Forum Infect Dis"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313467","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:42:14Z","timestamp":1770316934000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313467"}},"subtitle":[],"editor":[{"given":"Sanjai","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0313467","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]}}}