{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:27:16Z","timestamp":1788794836080,"version":"build-2803163510"},"reference-count":31,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004033","name":"University of Mainz","doi-asserted-by":"crossref","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}],"id":[{"id":"10.13039\/501100004033","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Essen","award":["No grant number"],"award-info":[{"award-number":["No grant number"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,5,20]]},"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The clinical course of patients with a SARS-CoV-2 (COVID-19) infection varies widely, from symptom-free to severe courses that can lead to death. Laboratory values of SARS-CoV-2 patients such as lymphocyte counts or C-reactive protein (CRP) do not allow a prediction of the actual course of the disease. To identify a possible predictive marker for the differentiation and prognosis of illness with influenza-like symptoms with and without SARS-CoV-2 infections in general practice, we will analyse the concentrations of cell-free DNA (cfDNA) levels, laboratory and clinical parameters, temperature, oxygen saturation, breathing rate and concomitant symptoms in patients with flu-like symptoms with and without a SARS-CoV-2 infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is a single-centre, two-arm, parallel longitudinal cohort study with a total of 44 patients. 22 patients with flu-like symptoms without a SARS-CoV-2 infection and 22 patients with flu-like symptoms with a SARS-CoV-2 infection will be recruited. The primary objective is to compare cfDNA levels in ambulatory patients in general practice with flu-like symptoms with SARS-CoV-2 infection with those with influenza like symptoms without a SARS-CoV-2 infection during the disease (day 7 and day 14). The secondary objective is to determine whether there is a correlation between cfDNA concentrations on the one hand, and laboratory and clinical parameters on the other hand. cfDNA, differential blood count, high-sensitive CRP and erythrocyte sedimentation rate will be measured in blood samples, concomitant symptoms will be surveyed via a self-assessment questionnaire, and oxygen saturation, breathing rate and examination of the lungs will be reported by treating physicians.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Ethical approval was issued on 1 March 2021 by the Ethics Committee Essen under the number 21-9916-BO. Findings will be published in peer-reviewed open-access journals and presented at national and international conferences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>DRKS00024722.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-058647","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T11:11:51Z","timestamp":1655377911000},"page":"e058647","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["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"],"prefix":"10.1136","volume":"12","author":[{"given":"Dorothea","family":"Dehnen","sequence":"first","affiliation":[{"name":"Institute of General Practice, Medical Faculty, University of Duisburg-Essen Faculty of Medicine, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmo","family":"Neuberger","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes Gutenberg Universitat Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"in der Schmitten","sequence":"additional","affiliation":[{"name":"Institute of General Practice, Medical Faculty, University of Duisburg-Essen Faculty of Medicine, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterini","family":"Giagkou","sequence":"additional","affiliation":[{"name":"Institute of General Practice, Medical Faculty, University of Duisburg-Essen Faculty of Medicine, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perikles","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes Gutenberg Universitat Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7648-086X","authenticated-orcid":false,"given":"Suzan","family":"Botzenhardt","sequence":"additional","affiliation":[{"name":"Institute of General Practice, Medical Faculty, University of Duisburg-Essen Faculty of Medicine, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"2025101811015609000_12.6.e058647.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"2025101811015609000_12.6.e058647.2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York city area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"key":"2025101811015609000_12.6.e058647.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb6105"},{"key":"2025101811015609000_12.6.e058647.4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4372"},{"key":"2025101811015609000_12.6.e058647.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30566-3"},{"key":"2025101811015609000_12.6.e058647.6","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1001\/jama.2020.5394","article-title":"Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy","volume":"323","author":"Grasselli","year":"2020","journal-title":"JAMA"},{"key":"2025101811015609000_12.6.e058647.7","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/S2213-2600(20)30165-X","article-title":"Understanding pathways to death in patients with COVID-19","volume":"8","author":"Vincent","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2025101811015609000_12.6.e058647.8","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/S2213-2600(20)30161-2","article-title":"Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations","volume":"8","author":"Phua","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2025101811015609000_12.6.e058647.9","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00002.2014"},{"key":"2025101811015609000_12.6.e058647.10","doi-asserted-by":"publisher","DOI":"10.2165\/11631380-000000000-00000"},{"key":"2025101811015609000_12.6.e058647.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.050"},{"key":"2025101811015609000_12.6.e058647.12","doi-asserted-by":"publisher","DOI":"10.1101\/gr.242719.118"},{"key":"2025101811015609000_12.6.e058647.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1508736112"},{"key":"2025101811015609000_12.6.e058647.14","doi-asserted-by":"crossref","DOI":"10.1186\/1745-6215-14-314","article-title":"Psychodynamic motivation and training program (PMT) for the secondary prevention in patients with stable coronary heart disease: study protocol for a randomized controlled trial of feasibility and effects","volume":"14","author":"Michal","year":"2013","journal-title":"Trials"},{"key":"2025101811015609000_12.6.e058647.15","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-015-3207-8"},{"key":"2025101811015609000_12.6.e058647.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2014.08.002"},{"key":"2025101811015609000_12.6.e058647.17","doi-asserted-by":"crossref","unstructured":"Zuo Y , Yalavarthi S , Shi H , et al . Neutrophil extracellular traps in COVID-19. JCI Insight 2020.doi:10.1172\/jci.insight.138999","DOI":"10.1172\/jci.insight.138999"},{"key":"2025101811015609000_12.6.e058647.18","doi-asserted-by":"crossref","unstructured":"Chen X . Time-series plasma cell-free DNA analysis reveals disease severity of COVID19 patients. Medrxiv 2020.doi:10.1101\/2020.06.08.20124305","DOI":"10.1101\/2020.06.08.20124305"},{"key":"2025101811015609000_12.6.e058647.19","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.147610","article-title":"Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury","volume":"6","author":"Andargie","year":"2021","journal-title":"JCI Insight"},{"key":"2025101811015609000_12.6.e058647.20","doi-asserted-by":"crossref","unstructured":"Zhang N . Circulating rather than alveolar extracellular DNA levels predict outcomes in influenza: a cohort study. J Infect Dis 2020.doi:10.21203\/rs.2.19578\/v1","DOI":"10.21203\/rs.2.19578\/v1"},{"key":"2025101811015609000_12.6.e058647.21","unstructured":"ARE-Wochenbericht. Available: https:\/\/influenza.rki.de\/Wochenberichte\/2021_2022\/2022-10.pdf"},{"key":"2025101811015609000_12.6.e058647.22","unstructured":"Wochenberichte Der AgI. Available: https:\/\/influenza.rki.de\/wochenberichte.aspx"},{"key":"2025101811015609000_12.6.e058647.23","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3947\/ic.2020.52.2.212","article-title":"Self-Assessment questionnaire for efficient and safe evaluation of patients with mild COVID-19","volume":"52","author":"Jeong","year":"2020","journal-title":"Infect Chemother"},{"key":"2025101811015609000_12.6.e058647.24","unstructured":"NICE Guidel . LNI for H and Ce. COVID-19 rapid guideline: managing the long-term effects of COVID-19. 188, 2020."},{"key":"2025101811015609000_12.6.e058647.25","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/ijlh.13354","article-title":"A meta-analysis of SARS-CoV-2 patients identifies the combinatorial significance of D-dimer, C-reactive protein, lymphocyte, and neutrophil values as a predictor of disease severity","volume":"43","author":"Singh","year":"2021","journal-title":"Int J Lab Hematol"},{"key":"2025101811015609000_12.6.e058647.26","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.ijid.2020.09.012","article-title":"Risk factors for non-invasive\/invasive ventilatory support in patients with COVID-19 pneumonia: a retrospective study within a multidisciplinary approach","volume":"100","author":"Suardi","year":"2020","journal-title":"Int J Infect Dis"},{"key":"2025101811015609000_12.6.e058647.27","doi-asserted-by":"crossref","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern Med"},{"key":"2025101811015609000_12.6.e058647.28","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1966"},{"key":"2025101811015609000_12.6.e058647.29","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-020-01735-2"},{"key":"2025101811015609000_12.6.e058647.30","doi-asserted-by":"crossref","unstructured":"Strau\u00df R , Ewig S , Richter K , et al . The prognostic significance of respiratory rate in patients with pneumonia. Dtsch Aerzteblatt Online 2014.doi:10.3238\/arztebl.2014.0503","DOI":"10.3238\/arztebl.2014.0503"},{"key":"2025101811015609000_12.6.e058647.31","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30483-7"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-058647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T18:02:06Z","timestamp":1760810526000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-058647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,16]]},"published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1136\/bmjopen-2021-058647"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-058647","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6]]}}}