{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:30:53Z","timestamp":1764588653624,"version":"3.46.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017590","name":"Universit\u00e4tsklinikum Essen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017590","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cell-free DNA (cfDNA) has emerged as a relevant biomarker reflecting disease severity in hospitalised COVID-19 patients, correlating with respiratory failure and mortality. However, its utility has not yet been evaluated in general practitioner setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A prospective single-centre, two-arm, parallel, longitudinal cohort study conducted in a German general practice with four doctors between 8\/2021 and 4\/2022.\n                      <jats:italic>Participants<\/jats:italic>\n                      : Sixty-one outpatients with flu-like symptoms participated: 31 (10 men, 21 women) tested SARS-CoV-2 positive (COVID group); 30 (12 men, 18 women) were controls (control group). The groups were demographically similar.\n                      <jats:italic>Primary outcome measures<\/jats:italic>\n                      : Comparison of cfDNA levels between groups at day 0, 7 and 14.\n                      <jats:italic>Secondary outcome measures<\/jats:italic>\n                      : Correlations between cfDNA levels and laboratory and clinical parameters like blood counts, respiratory rate and oxygen saturation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      cfDNA levels did not differ significantly between groups (F [1, 59]\u2009=\u20091.538,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.22): day 0: mean (\u00b1\u2009standard deviation)\u2009=\u200914.45 (\u00b1\u20096.24) ng\/ml (COVID group) vs. 11.32 (\u00b1\u20094.79) ng\/ml (control group); day 7: 14.46 (\u00b1\u20096.57) ng\/ml vs. 12.53 (\u00b1\u20096.67) ng\/ml; day 14: 12.94 (\u00b1\u20096.66) ng\/ml vs. 12.93 (\u00b1\u20097.02) ng\/ml. However, at t0, the integrity index was significantly lower in the COVID group (t0: 0.30 [\u00b1- 0.15] vs. 0.41 [\u00b1\u20090.1];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0127) increasing at t1 (0.38 [\u00b1\u20090.17];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.008) and at t2 (0.42 [\u00b1\u20090.22];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Unlike hospitalised patients, cfDNA levels did not differ significantly between outpatient groups. Therefore, a decision on the need for hospitalisation based on clinical and serological factors is still required. The significantly lower integrity index of the SARS-CoV-2 infected individuals indicates that their DNA kinetics differ from those of individuals infected with other respiratory pathogens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>: German Clinical Trials Register: DRKS00024722, Registration date: 10 March 2021.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12985-025-03016-x","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:27:51Z","timestamp":1764588471000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CfDNA as a surrogate marker for COVID-19 severity in patients with influenza-like symptoms with and without SARS-CoV-2 infection in general practice: a prospective cohort study"],"prefix":"10.1186","volume":"22","author":[{"given":"Dorothea","family":"Dehnen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzan","family":"Botzenhardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterini","family":"Giagkou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kira","family":"Enders","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Hoeter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perikles","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elmo W.I.","family":"Neuberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"3016_CR1","unstructured":"World Health Organization. Statement on the fifteenth meeting of the IHR. (2005) Emergency Committee on the COVID-19 pandemic 2023. Available at: https:\/\/www.who.int\/news\/item\/05-05-2023-statement-on-the-fifteenth-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-coronavirus-disease-(COVID-19)-pandemic Accessed August 24, 2023."},{"key":"3016_CR2","unstructured":"World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Available at: https:\/\/data.who.int\/dashboards\/COVID19\/cases Accessed December 08, 2022."},{"key":"3016_CR3","unstructured":"Robert Koch-Institut. Wochenberichte der AGI. Available at: https:\/\/influenza.rki.de\/Wochenberichte.aspx"},{"issue":"15","key":"3016_CR4","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1001\/jama.2020.3204","volume":"323","author":"BE Young","year":"2020","unstructured":"Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. 2020;323(15):1488\u201394.","journal-title":"JAMA"},{"issue":"10229","key":"3016_CR5","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","volume":"395","author":"F Zhou","year":"2020","unstructured":"Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054\u201362. https:\/\/doi.org\/10.1016\/S0140-6736(20)30566-3.","journal-title":"Lancet"},{"issue":"10335","key":"3016_CR6","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1016\/S0140-6736(22)00327-0","volume":"399","author":"C Menni","year":"2022","unstructured":"Menni C, Valdes AM, Polidori L, et al. Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of Omicron and delta variant dominance: a prospective observational study from the ZOE COVID study. Lancet. 2022;399(10335):1618\u201324. https:\/\/doi.org\/10.1016\/S0140-6736(22)00327-0.","journal-title":"Lancet"},{"key":"3016_CR7","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.ijid.2022.04.029","volume":"120","author":"Y Liu","year":"2022","unstructured":"Liu Y, Yu Y, Zhao Y, et al. Reduction in the infection fatality rate of Omicron variant compared with previous variants in South Africa. Int J Infect Dis. 2022;120:146\u20139. https:\/\/doi.org\/10.1016\/j.ijid.2022.04.029.","journal-title":"Int J Infect Dis"},{"issue":"10360","key":"3016_CR8","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/S0140-6736(22)01656-7","volume":"400","author":"U Agrawal","year":"2022","unstructured":"Agrawal U, Bedston S, McCowan C, et al. Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales. Lancet. 2022;400(10360):1305\u201320.","journal-title":"Lancet"},{"key":"3016_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00806-5","author":"P Bager","year":"2025","unstructured":"Bager P, Svalgaard IB, Lomholt FK, et al. The hospital and mortality burden of COVID-19 compared with influenza in Denmark: a national observational cohort study, 2022-24. Lancet Infect Dis. 2025. https:\/\/doi.org\/10.1016\/S1473-3099(24)00806-5.","journal-title":"Lancet Infect Dis"},{"issue":"16","key":"3016_CR10","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1056\/NEJMoa2119451","volume":"386","author":"N Andrews","year":"2022","unstructured":"Andrews N, Stowe J, Kirsebom F. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N Engl J Med. 2022;386(16):1532\u201346. https:\/\/doi.org\/10.1056\/NEJMoa2119451.","journal-title":"N Engl J Med"},{"issue":"12","key":"3016_CR11","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/S1473-3099(22)00692-2","volume":"22","author":"SY Tartof","year":"2022","unstructured":"Tartof SY, Slezak JM, Puzniak L, et al. BNT162b2 vaccine effectiveness against SARS-CoV-2 Omicron BA.4 and BA.5. Lancet Infect Dis. 2022;22(12):1663\u20135. https:\/\/doi.org\/10.1016\/S1473-3099(22)00692-2.","journal-title":"Lancet Infect Dis"},{"issue":"9","key":"3016_CR12","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/s1473-3099(24)00220-2","volume":"24","author":"IR Moustsen-Helms","year":"2024","unstructured":"Moustsen-Helms IR, Bager P, Larsen TG, et al. Relative vaccine protection, disease severity, and symptoms associated with the SARS-CoV-2 Omicron subvariant BA.2.86 and descendant JN.1 in Denmark: a nationwide observational study. Lancet Infect Dis. 2024;24(9):964\u201373. https:\/\/doi.org\/10.1016\/s1473-3099(24)00220-2.","journal-title":"Lancet Infect Dis"},{"key":"3016_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.940562","volume":"13","author":"W K\u00fclper-Schiek","year":"2022","unstructured":"K\u00fclper-Schiek W, Piechotta V, Pilic A, et al. Facing the Omicron variant-how well do vaccines protect against mild and severe COVID-19? Third interim analysis of a living systematic review. Front Immunol. 2022;13:940562. https:\/\/doi.org\/10.3389\/fimmu.2022.940562.","journal-title":"Front Immunol"},{"issue":"13","key":"3016_CR14","first-page":"213","volume":"120","author":"M Weigert","year":"2023","unstructured":"Weigert M, Beyerlein A, Katz K, et al. Vaccine-Induced or hybrid immunity and COVID-19-Associated mortality during the Omicron wave. Dtsch Arztebl Int. 2023;120(13):213\u201320.","journal-title":"Dtsch Arztebl Int"},{"key":"3016_CR15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2022-072141","volume":"379","author":"JM Ferdinands","year":"2022","unstructured":"Ferdinands JM, Rao S, Dixon BE, et al. Waning of vaccine effectiveness against moderate and severe COVID-19 among adults in the US from the VISION network: test negative, case-control study. BMJ. 2022;379:e072141. https:\/\/doi.org\/10.1136\/bmj-2022-072141.","journal-title":"BMJ"},{"key":"3016_CR16","unstructured":"Robert Koch-Institut. Impfquoten in Deutschland \u2013 aktuelle Ergebnisse aus dem RKI-Impfquotenmonitoring 2025."},{"issue":"1","key":"3016_CR17","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1080\/07853890.2022.2034936","volume":"54","author":"W Wen","year":"2022","unstructured":"Wen W, Chen C, Tang J, et al. Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19: a meta-analysis. Ann Med. 2022;54(1):516\u201323.","journal-title":"Ann Med"},{"key":"3016_CR18","doi-asserted-by":"publisher","unstructured":"Wang L, Berger NA, Davis PB et al. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022. medRxiv 2022. https:\/\/doi.org\/10.1101\/2022.06.21.22276724 [published Online First: 22 June 2022].","DOI":"10.1101\/2022.06.21.22276724"},{"issue":"2","key":"3016_CR19","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1152\/japplphysiol.00002.2014","volume":"117","author":"S Breitbach","year":"2014","unstructured":"Breitbach S, Sterzing B, Magallanes C, et al. Direct measurement of cell-free DNA from serially collected capillary plasma during incremental exercise. J Appl Physiol. 2014;117(2):119\u201330. https:\/\/doi.org\/10.1152\/japplphysiol.00002.2014.","journal-title":"J Appl Physiol"},{"issue":"7","key":"3016_CR20","doi-asserted-by":"publisher","first-page":"565","DOI":"10.2165\/11631380-000000000-00000","volume":"42","author":"S Breitbach","year":"2012","unstructured":"Breitbach S, Tug S, Simon P. Circulating cell-free DNA: an up-coming molecular marker in exercise physiology. Sports Med. 2012;42(7):565\u201386.","journal-title":"Sports Med"},{"issue":"40","key":"3016_CR21","doi-asserted-by":"publisher","first-page":"E5503","DOI":"10.1073\/pnas.1508736112","volume":"112","author":"K Sun","year":"2015","unstructured":"Sun K, Jiang P, Chan KCA, et al. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments. Proc Natl Acad Sci U S A. 2015;112(40):E5503-12. https:\/\/doi.org\/10.1073\/pnas.1508736112.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1\u20132","key":"3016_CR22","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.cellimm.2014.08.002","volume":"292","author":"S Tug","year":"2014","unstructured":"Tug S, Helmig S, Menke J, et al. Correlation between cell free DNA levels and medical evaluation of disease progression in systemic lupus erythematosus patients. Cell Immunol. 2014;292(1\u20132):32\u20139.","journal-title":"Cell Immunol"},{"key":"3016_CR23","doi-asserted-by":"publisher","unstructured":"Li X, Hu R, Luo T, et al. Serum cell-free DNA and progression of diabetic kidney disease: a prospective study. BMJ Open Diabetes Res Care. 2020;8(1). https:\/\/doi.org\/10.1136\/bmjdrc-2019-001078.","DOI":"10.1136\/bmjdrc-2019-001078"},{"issue":"7","key":"3016_CR24","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1093\/infdis\/jiaa241","volume":"222","author":"N Zhang","year":"2020","unstructured":"Zhang N, Zhu L, Zhang Y, et al. Circulating rather than alveolar extracellular deoxyribonucleic acid levels predict outcomes in influenza. J Infect Dis. 2020;222(7):1145\u201354.","journal-title":"J Infect Dis"},{"key":"3016_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.663098","volume":"12","author":"X Chen","year":"2021","unstructured":"Chen X, Wu T, Li L, et al. Transcriptional start site coverage analysis in plasma cell-free DNA reveals disease severity and tissue specificity of COVID-19 patients. Front Genet. 2021;12:663098. https:\/\/doi.org\/10.3389\/fgene.2021.663098.","journal-title":"Front Genet"},{"key":"3016_CR26","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147610","author":"TE Andargie","year":"2021","unstructured":"Andargie TE, Tsuji N, Seifuddin F, et al. Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury. JCI Insight. 2021. https:\/\/doi.org\/10.1172\/jci.insight.147610.","journal-title":"JCI Insight"},{"key":"3016_CR27","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.16072","volume":"11","author":"K Hoeter","year":"2023","unstructured":"Hoeter K, Neuberger E, Fischer S, et al. Evidence for the utility of CfDNA plasma concentrations to predict disease severity in COVID-19: a retrospective pilot study. PeerJ. 2023;11:e16072. https:\/\/doi.org\/10.7717\/peerj.16072.","journal-title":"PeerJ"},{"issue":"6","key":"3016_CR28","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1373\/clinchem.2006.068577","volume":"52","author":"N Umetani","year":"2006","unstructured":"Umetani N, Kim J, Hiramatsu S, et al. Increased integrity of free circulating DNA in sera of patients with colorectal or periampullary cancer: direct quantitative PCR for ALU repeats. Clin Chem. 2006;52(6):1062\u20139.","journal-title":"Clin Chem"},{"issue":"2","key":"3016_CR29","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s12291-022-01082-4","volume":"38","author":"S Mishra","year":"2023","unstructured":"Mishra S, Dubey DB, Agarwal K, et al. Circulating cell-free DNA level in prediction of COVID-19 severity and mortality: correlation of with haematology and serum biochemical parameters. Indian J Clin Biochem. 2023;38(2):172\u201381. https:\/\/doi.org\/10.1007\/s12291-022-01082-4.","journal-title":"Indian J Clin Biochem"},{"key":"3016_CR30","unstructured":"Robert Koch-Institut. Wochenberichte zu COVID-19 (bis 8.6.2023): W\u00f6chentlicher Lagebericht des RKI zur Coronavirus-Krankheit-2019 (COVID-19). Available at: https:\/\/www.rki.de\/DE\/Themen\/Infektionskrankheiten\/Infektionskrankheiten-A-Z\/C\/COVID-19-Pandemie\/Situationsberichte\/Wochenbericht\/Wochenberichte.html?nn=16911042"},{"issue":"2","key":"3016_CR31","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3947\/ic.2020.52.2.212","volume":"52","author":"H Jeong","year":"2020","unstructured":"Jeong H, Lee J, Kim J, et al. Self-assessment questionnaire for efficient and safe evaluation of patients with mild COVID-19. Infect Chemother. 2020;52(2):212\u20135.","journal-title":"Infect Chemother"},{"issue":"1","key":"3016_CR32","doi-asserted-by":"publisher","first-page":"13581","DOI":"10.1038\/s41598-021-92826-4","volume":"11","author":"EWI Neuberger","year":"2021","unstructured":"Neuberger EWI, Brahmer A, Ehlert T, et al. Validating quantitative PCR assays for CfDNA detection without DNA extraction in exercising SLE patients. Sci Rep. 2021;11(1):13581. https:\/\/doi.org\/10.1038\/s41598-021-92826-4. [published Online First: 30 June 2021].","journal-title":"Sci Rep"},{"key":"3016_CR33","unstructured":"National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline: managing the long-term effects of COVID-19. London 2020."},{"issue":"6","key":"3016_CR34","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-058647","volume":"12","author":"D Dehnen","year":"2022","unstructured":"Dehnen D, Neuberger E, der in Schmitten J, et al. Cfdna as a surrogate marker for COVID-19 severity in patients with influenza-like symptoms with and without SARS-CoV-2 infections in general practice: a study protocol for a prospective cohort study. BMJ Open. 2022;12(6):e058647. https:\/\/doi.org\/10.1136\/bmjopen-2021-058647.","journal-title":"BMJ Open"},{"key":"3016_CR35","unstructured":"R Foundation for Statistical Computing. R: A Language and Environment for Statistical Computing. 2023. Available at: https:\/\/www.R-project.org\/"},{"issue":"8","key":"3016_CR36","doi-asserted-by":"publisher","first-page":"e192","DOI":"10.1016\/s1473-3099(20)30483-7","volume":"20","author":"WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection","year":"2020","unstructured":"WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020;20(8):e192\u20137. https:\/\/doi.org\/10.1016\/s1473-3099(20)30483-7. [published Online First: 12 June 2020].","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"3016_CR37","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.medj.2021.01.001","volume":"2","author":"AP Cheng","year":"2021","unstructured":"Cheng AP, Cheng MP, Gu W, et al. Cell-free DNA tissues of origin by methylation profiling reveals significant cell, tissue, and organ-specific injury related to COVID-19 severity. Med. 2021;2(4):411\u2013e4225. https:\/\/doi.org\/10.1016\/j.medj.2021.01.001. [published Online First: 16 January 2021].","journal-title":"Med"},{"issue":"1","key":"3016_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2024.116367","volume":"110","author":"H Erdem","year":"2024","unstructured":"Erdem H, Balkan \u0130\u0130, Karaali R, et al. Cell free DNA as a new prognostic biomarker for COVID-19, a prospective cohort study. Diagn Microbiol Infect Dis. 2024;110(1):116367. https:\/\/doi.org\/10.1016\/j.diagmicrobio.2024.116367.","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"1","key":"3016_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01718-3","volume":"22","author":"S Shouman","year":"2024","unstructured":"Shouman S, El-Kholy N, Hussien AE, et al. SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147. Cell Commun Signal. 2024;22(1):349. https:\/\/doi.org\/10.1186\/s12964-024-01718-3.","journal-title":"Cell Commun Signal"},{"issue":"11","key":"3016_CR40","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1111\/imj.13239","volume":"46","author":"P Higgins","year":"2016","unstructured":"Higgins P, Runnegar N, Bird RJ, et al. Rates of neutropenia in adults with influenza A or B: a retrospective analysis of hospitalised patients in South East Queensland during 2015. Intern Med J. 2016;46(11):1328\u201332.","journal-title":"Intern Med J"},{"issue":"1","key":"3016_CR41","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0002-9343(84)90754-X","volume":"76","author":"RT Schooley","year":"1984","unstructured":"Schooley RT, Densen P, Harmon D, et al. Antineutrophil antibodies in infectious mononucleosis. Am J Med. 1984;76(1):85\u201390.","journal-title":"Am J Med"},{"key":"3016_CR42","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g5340","volume":"349","author":"D Hay","year":"2014","unstructured":"Hay D, Hill M, Littlewood T. Neutropenia in primary care. BMJ. 2014;349:g5340. https:\/\/doi.org\/10.1136\/bmj.g5340.","journal-title":"BMJ"},{"key":"3016_CR43","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.ijid.2020.04.061","volume":"95","author":"TP Velavan","year":"2020","unstructured":"Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infect Dis. 2020;95:304\u20137. https:\/\/doi.org\/10.1016\/j.ijid.2020.04.061.","journal-title":"Int J Infect Dis"},{"key":"3016_CR44","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13040746","author":"MB Khadzhieva","year":"2023","unstructured":"Khadzhieva MB, Gracheva AS, Belopolskaya OB, et al. Serial changes in blood-cell-count-derived and CRP-derived inflammatory indices of COVID-19 patients. Diagnostics. 2023. https:\/\/doi.org\/10.3390\/diagnostics13040746.","journal-title":"Diagnostics"},{"issue":"7","key":"3016_CR45","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1080\/07853890.2020.1802061","volume":"52","author":"X Wu","year":"2020","unstructured":"Wu X, Liu L, Jiao J, et al. Characterisation of clinical, laboratory and imaging factors related to mild vs. severe COVID-19 infection: a systematic review and meta-analysis. Ann Med. 2020;52(7):334\u201344.","journal-title":"Ann Med"},{"issue":"1","key":"3016_CR46","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s11606-020-05983-z","volume":"36","author":"T Mikami","year":"2021","unstructured":"Mikami T, Miyashita H, Yamada T, et al. Risk factors for mortality in patients with COVID-19 in New York City. J Gen Intern Med. 2021;36(1):17\u201326. https:\/\/doi.org\/10.1007\/s11606-020-05983-z.","journal-title":"J Gen Intern Med"},{"issue":"3","key":"3016_CR47","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41440-023-01490-w","volume":"47","author":"K Sakurai","year":"2024","unstructured":"Sakurai K, Chubachi S, Asakura T, et al. Prognostic significance of hypertension history and blood pressure on admission in Japanese patients with coronavirus disease 2019: integrative analysis from the Japan COVID-19 task force. Hypertens Res. 2024;47(3):639\u201348. https:\/\/doi.org\/10.1038\/s41440-023-01490-w.","journal-title":"Hypertens Res"},{"issue":"8","key":"3016_CR48","doi-asserted-by":"publisher","first-page":"4635","DOI":"10.1007\/s10072-022-06136-2","volume":"43","author":"I Scala","year":"2022","unstructured":"Scala I, Bellavia S, Luigetti M, et al. Autonomic dysfunction in non-critically ill COVID-19 patients during the acute phase of disease: an observational, cross-sectional study. Neurol Sci. 2022;43(8):4635\u201343. https:\/\/doi.org\/10.1007\/s10072-022-06136-2.","journal-title":"Neurol Sci"},{"issue":"18","key":"3016_CR49","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14578","volume":"8","author":"B Hajikhani","year":"2020","unstructured":"Hajikhani B, Calcagno T, Nasiri MJ, et al. Olfactory and gustatory dysfunction in COVID-19 patients: a meta-analysis study. Physiol Rep. 2020;8(18):e14578.","journal-title":"Physiol Rep"},{"issue":"3","key":"3016_CR50","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00405-020-06266-3","volume":"278","author":"MJ Rojas-Lechuga","year":"2021","unstructured":"Rojas-Lechuga MJ, Izquierdo-Dom\u00ednguez A, Chiesa-Estomba C, et al. Chemosensory dysfunction in COVID-19 out-patients. Eur Arch Otorhinolaryngol. 2021;278(3):695\u2013702. https:\/\/doi.org\/10.1007\/s00405-020-06266-3.","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"5","key":"3016_CR51","doi-asserted-by":"publisher","DOI":"10.21037\/atm-24-36","volume":"12","author":"Y Takegoshi","year":"2024","unstructured":"Takegoshi Y, Nagaoka K, Kido T, et al. Association between sore throat and early immune responses against COVID-19 before and after the emergence of the Omicron variant. Ann Transl Med. 2024;12(5):87. https:\/\/doi.org\/10.21037\/atm-24-36.","journal-title":"Ann Transl Med"},{"issue":"5","key":"3016_CR52","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1007\/s11739-020-02377-1","volume":"15","author":"L Bertolino","year":"2020","unstructured":"Bertolino L, Vitrone M, Durante-Mangoni E. Does this patient have COVID-19? A practical guide for the internist. Intern Emerg Med. 2020;15(5):791\u2013800. https:\/\/doi.org\/10.1007\/s11739-020-02377-1.","journal-title":"Intern Emerg Med"},{"issue":"10","key":"3016_CR53","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1158\/2159-8290.CD-21-1252","volume":"13","author":"AK Mattox","year":"2023","unstructured":"Mattox AK, Douville C, Wang Y, et al. The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer. Cancer Discov. 2023;13(10):2166\u201379.","journal-title":"Cancer Discov"}],"container-title":["Virology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-03016-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12985-025-03016-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12985-025-03016-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:27:56Z","timestamp":1764588476000},"score":1,"resource":{"primary":{"URL":"https:\/\/virologyj.biomedcentral.com\/articles\/10.1186\/s12985-025-03016-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3016"],"URL":"https:\/\/doi.org\/10.1186\/s12985-025-03016-x","relation":{},"ISSN":["1743-422X"],"issn-type":[{"value":"1743-422X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"assertion":[{"value":"21 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was issued on 2021-03-01 by the Ethics Committee Essen under the number 21-9916-BO. All participants received written information leaflets and provided signed informed consent forms.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"390"}}