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Virol J . CfDNA as a surrogate marker for COVID-19 severity in patients with influenza-like symptoms with and without SARS-CoV-2 infection in genera

tetano

Editor, Senior Moderator
Virol J


. 2025 Dec 1;22(1):390.
doi: 10.1186/s12985-025-03016-x. 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

Dorothea Dehnen[SUP] 1 [/SUP], Suzan Botzenhardt[SUP] 2 [/SUP], Ekaterini Giagkou[SUP] 3 [/SUP], Kira Enders[SUP] 4 [/SUP], Katharina Hoeter[SUP] 5 [/SUP], Perikles Simon[SUP] 4 [/SUP], Elmo W I Neuberger[SUP] 4 [/SUP]



Affiliations
Abstract

Background: 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.
Methods: 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.
Participants: 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.
Primary outcome measures: Comparison of cfDNA levels between groups at day 0, 7 and 14.
Secondary outcome measures: Correlations between cfDNA levels and laboratory and clinical parameters like blood counts, respiratory rate and oxygen saturation.
Results: cfDNA levels did not differ significantly between groups (F [1, 59] = 1.538, p = 0.22): day 0: mean (± standard deviation) = 14.45 (± 6.24) ng/ml (COVID group) vs. 11.32 (± 4.79) ng/ml (control group); day 7: 14.46 (± 6.57) ng/ml vs. 12.53 (± 6.67) ng/ml; day 14: 12.94 (± 6.66) ng/ml vs. 12.93 (± 7.02) ng/ml. However, at t0, the integrity index was significantly lower in the COVID group (t0: 0.30 [±- 0.15] vs. 0.41 [± 0.1]; p = 0.0127) increasing at t1 (0.38 [± 0.17]; p = 0.008) and at t2 (0.42 [± 0.22]; p < 0.001).
Conclusion: 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.
Trial registration: German Clinical Trials Register: DRKS00024722, Registration date: 10 March 2021.

Keywords: Cell-free DNA (cfDNA); Flu/influenza; General practice; Predictive marker; SARS-CoV-2 infection.

 
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