{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:38:34Z","timestamp":1780997914630,"version":"3.54.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ZZ1802V"],"award-info":[{"award-number":["01ZZ1802V"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>With increasing numbers of patients recovering from COVID-19, there is increasing evidence for persistent symptoms and the need for follow-up studies. This retrospective study included patients without comorbidities, who recovered from COVID-19 and attended an outpatient clinic at a university hospital for follow-up care and potential convalescent plasma donation. Network analysis was applied to visualize symptom combinations and persistent symptoms. Comprehensive lab-testing was ascertained at each follow-up to analyze differences regarding patients with vs without persistent symptoms. 116 patients were included, age range was 18\u201369\u00a0years (median: 41) with follow-ups ranging from 22 to 102\u00a0days. The three most frequent persistent symptoms were Fatigue (54%), Dyspnea (29%) and Anosmia (25%). Lymphopenia was present in 13 of 112 (12%) cases. Five of 35 cases (14%) had Lymphopenia in the later follow-up range of 80\u2013102\u00a0days. Serum IgA concentration was the only lab parameter with significant difference between patients with vs without persistent symptoms with reduced serum IgA concentrations in the patient cohort of persistent symptoms (<jats:italic>p<\/jats:italic>\u2009=\u20090.0219). Moreover, subgroup analyses showed that patients with lymphopenia experienced more frequently persistent symptoms.\u00a0In conclusion, lymphopenia persisted in a noticeable percentage of recovered patients. Patients with persistent symptoms had significantly lower serum IgA levels. Furthermore,\u00a0our data provides evidence that lymphopenia is associated with persistence of COVID-19 symptoms.<\/jats:p>","DOI":"10.1038\/s41598-021-91270-8","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T10:03:09Z","timestamp":1623924189000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Persistent symptoms and lab abnormalities in patients who recovered from COVID-19"],"prefix":"10.1038","volume":"11","author":[{"given":"Julian","family":"Varghese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sandmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Ochs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga-Marie","family":"Schrempf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Fr\u00f6mmel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dugas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut H.","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Vollenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil-Robin","family":"Tepasse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,17]]},"reference":[{"issue":"5","key":"91270_CR1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","volume":"20","author":"E Dong","year":"2020","unstructured":"Dong, E., Du, H. & Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. Lancet. Infect. Dis 20(5), 533\u2013534 (2020).","journal-title":"Lancet. Infect. Dis"},{"issue":"395","key":"91270_CR2","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","volume":"28","author":"F Zhou","year":"2020","unstructured":"Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 28(395), 1054\u20131062 (2020).","journal-title":"Lancet"},{"key":"91270_CR3","first-page":"3566166","volume":"21","author":"A Kumar","year":"2020","unstructured":"Kumar, A. et al. Clinical features of COVID-19 and factors associated with severe clinical course: a systematic review and meta-analysis. SSRN 21, 3566166 (2020).","journal-title":"SSRN"},{"issue":"2","key":"91270_CR4","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1111\/his.14134","volume":"77","author":"T Menter","year":"2020","unstructured":"Menter, T. et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 77(2), 198\u2013209 (2020).","journal-title":"Histopathology"},{"issue":"7","key":"91270_CR5","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/s41591-020-0968-3","volume":"26","author":"A Gupta","year":"2020","unstructured":"Gupta, A. et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 26(7), 1017\u20131032 (2020).","journal-title":"Nat. Med."},{"issue":"13","key":"91270_CR6","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1001\/jama.2020.2648","volume":"323","author":"Z Wu","year":"2020","unstructured":"Wu, Z. & McGoogan, J. M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA 323(13), 1239\u20131242 (2020).","journal-title":"JAMA"},{"key":"91270_CR7","doi-asserted-by":"publisher","unstructured":"Li J, Huang DQ, Zou B, Yang H, Hui WZ, Rui F, et al. Epidemiology of COVID-19: A systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes. Journal of Medical Virology [Internet]. [cited 2020 Sep 15];n\/a(n\/a). Available from: https:\/\/onlinelibrary.wiley.com\/doi\/abs\/https:\/\/doi.org\/10.1002\/jmv.26424","DOI":"10.1002\/jmv.26424"},{"issue":"6","key":"91270_CR8","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/jmv.25757","volume":"92","author":"L Li","year":"2020","unstructured":"Li, L. et al. COVID-19 patients\u2019 clinical characteristics, discharge rate, and fatality rate of meta-analysis. J. Med. Virol. 92(6), 577\u2013583 (2020).","journal-title":"J. Med. Virol."},{"issue":"6","key":"91270_CR9","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1001\/jama.2020.12603","volume":"324","author":"A Carf\u00ec","year":"2020","unstructured":"Carf\u00ec, A., Bernabei, R. & Landi, F. Persistent symptoms in patients after acute COVID-19. JAMA 324(6), 603\u2013605 (2020).","journal-title":"JAMA"},{"issue":"7","key":"91270_CR10","first-page":"CD013665","volume":"7","author":"T Struyf","year":"2020","unstructured":"Struyf, T. et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease. Cochrane Database Syst. Rev. 7(7), CD013665 (2020).","journal-title":"Cochrane Database Syst. Rev."},{"key":"91270_CR11","doi-asserted-by":"crossref","unstructured":"Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020;369.","DOI":"10.1136\/bmj.m1985"},{"issue":"7","key":"91270_CR12","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1002\/ajh.25829","volume":"95","author":"E Terpos","year":"2020","unstructured":"Terpos, E. et al. Hematological findings and complications of COVID-19. Am. J. Hematol. 95(7), 834\u2013847 (2020).","journal-title":"Am. J. Hematol."},{"issue":"1","key":"91270_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-019-0089-y","volume":"5","author":"L Tan","year":"2020","unstructured":"Tan, L. et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct. Target. Ther. 5(1), 1\u20133 (2020).","journal-title":"Signal Transduct. Target. Ther."},{"issue":"96","key":"91270_CR14","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.ijid.2020.04.086","volume":"1","author":"Q Zhao","year":"2020","unstructured":"Zhao, Q. et al. Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis. Int. J. Infect. Dis. 1(96), 131\u2013135 (2020).","journal-title":"Int. J. Infect. Dis."},{"key":"91270_CR15","doi-asserted-by":"publisher","unstructured":"Dugas M, Grote-Westrick T, Vollenberg R, Lorentzen E, Brix T, Schmidt H, et al. Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1). (2020).https:\/\/doi.org\/10.1101\/2020.10.12.20211599.","DOI":"10.1101\/2020.10.12.20211599"},{"key":"91270_CR16","unstructured":"iGraph package. https:\/\/igraph.org\/ [Internet]. [cited 2020 Nov 18]. Available from: https:\/\/igraph.org\/"},{"key":"91270_CR17","unstructured":"Sandmann S. Network analysis of onset and persistent symptoms in COVID 19 patients. [Internet]. 2020 [cited 2020 Nov 18]. Available from: https:\/\/sand-imi-uni-muenster.shinyapps.io\/CovidSymptomNetwork\/"},{"key":"91270_CR18","unstructured":"Common symptoms of ongoing symptomatic COVID-19 and post-COVID-19 syndrome | COVID-19 rapid guideline: managing the long-term effects of COVID-19 | Guidance | NICE [Internet]. NICE; [cited 2021 Apr 18]. Available from: https:\/\/www.nice.org.uk\/guidance\/ng188\/chapter\/Common-symptoms-of-ongoing-symptomatic-COVID-19-and-post-COVID-19-syndrome"},{"key":"91270_CR19","unstructured":"CDC. Healthcare Workers [Internet]. Centers for Disease Control and Prevention. 2020 [cited 2021 Apr 18]. Available from: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/hcp\/clinical-care\/post-covid-conditions.html"},{"issue":"5","key":"91270_CR20","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.medmal.2020.04.006","volume":"50","author":"T Klopfenstein","year":"2020","unstructured":"Klopfenstein, T. et al. Features of anosmia in COVID-19. Med. Mal. Infect. 50(5), 436\u2013439 (2020).","journal-title":"Med. Mal. Infect."},{"key":"91270_CR21","doi-asserted-by":"crossref","unstructured":"Bilinska K, Butowt R. Anosmia in COVID-19: A Bumpy Road to Establishing a Cellular Mechanism. ACS Chem Neurosci. 11(15), 2152-2155 (2020).","DOI":"10.1021\/acschemneuro.0c00406"},{"key":"91270_CR22","doi-asserted-by":"crossref","unstructured":"Carvalho-Schneider C, Laurent E, Lemaignen A, Beaufils E, Bourbao-Tournois C, Laribi S, et al. Follow-up of adults with non-critical COVID-19 two months after symptoms\u2019 onset. Clin Microbiol Infect. (2020).","DOI":"10.1016\/j.cmi.2020.09.052"},{"key":"91270_CR23","doi-asserted-by":"crossref","unstructured":"Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect 81(6). (2020)https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7445491\/","DOI":"10.1016\/j.jinf.2020.08.029"},{"issue":"1","key":"91270_CR24","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","volume":"9","author":"Y Xiong","year":"2020","unstructured":"Xiong, Y. et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect. 9(1), 761\u2013770 (2020).","journal-title":"Emerg Microbes Infect."},{"issue":"15","key":"91270_CR25","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1093\/cid\/ciaa248","volume":"71","author":"C Qin","year":"2020","unstructured":"Qin, C. et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan China. Clin Infect Dis. 71(15), 762\u2013768 (2020).","journal-title":"Clin Infect Dis."},{"key":"91270_CR26","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3389\/fimmu.2020.00827","volume":"11","author":"B Diao","year":"2020","unstructured":"Diao, B. et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol. 11, 827 (2020).","journal-title":"Front Immunol."},{"issue":"7","key":"91270_CR27","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.1038\/s41375-020-0887-9","volume":"34","author":"MZ Ratajczak","year":"2020","unstructured":"Ratajczak, M. Z. & Kucia, M. SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine \u201cstorm\u201d and risk factor for damage of hematopoietic stem cells. Leukemia 34(7), 1726\u20131729 (2020).","journal-title":"Leukemia"},{"issue":"6","key":"91270_CR28","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.ijid.2004.07.014","volume":"9","author":"Z He","year":"2005","unstructured":"He, Z. et al. Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets. Int. J. Infect Dis. 9(6), 323\u2013330 (2005).","journal-title":"Int. J. Infect Dis."},{"key":"91270_CR29","doi-asserted-by":"crossref","unstructured":"Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequalae of COVID-19. Nature. 2021.","DOI":"10.1038\/s41586-021-03553-9"},{"issue":"6","key":"91270_CR30","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.4049\/jimmunol.146.6.1972","volume":"146","author":"KB Renegar","year":"1991","unstructured":"Renegar, K. B. & Small, P. A. Passive transfer of local immunity to influenza virus infection by IgA antibody. J. Immunol. 146(6), 1972\u20131978 (1991).","journal-title":"J. Immunol."},{"issue":"1","key":"91270_CR31","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/mi.2007.6","volume":"1","author":"AJ Macpherson","year":"2008","unstructured":"Macpherson, A. J., McCoy, K. D., Johansen, F.-E. & Brandtzaeg, P. The immune geography of IgA induction and function. Mucosal. Immunol. 1(1), 11\u201322 (2008).","journal-title":"Mucosal. Immunol."},{"key":"91270_CR32","doi-asserted-by":"publisher","unstructured":"Hasan Ali O, Bomze D, Risch L, Brugger SD, Paprotny M, Weber M, et al. Severe COVID-19 is associated with elevated serum IgA and antiphospholipid IgA-antibodies. Clin Infect Dis [Internet]. [cited 2020 Oct 22]; Available from: https:\/\/academic.oup.com\/cid\/advance-article\/doi\/https:\/\/doi.org\/10.1093\/cid\/ciaa1496\/5913451","DOI":"10.1093\/cid\/ciaa1496\/5913451"},{"key":"91270_CR33","doi-asserted-by":"crossref","unstructured":"Dahlke C, Heidepriem J, Kobbe R, Santer R, Koch T, Fathi A, et al. Distinct early IgA profile may determine severity of COVID-19 symptoms: an immunological case series. medRxiv. 2020 Apr 17;2020.04.14.20059733.","DOI":"10.1101\/2020.04.14.20059733"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91270-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91270-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91270-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T13:21:12Z","timestamp":1672492872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-91270-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,17]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["91270"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-91270-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,17]]},"assertion":[{"value":"4 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12775"}}