Circulating Cell-Free DNA Level in Prediction of COVID-19 Severity and Mortality: Correlation of with Haematology and Serum Biochemical Parameters

Sridhar Mishra; Devanshi B Dubey; Krachi Agarwal; Deval B Dubey; Shweta Verma; Nida Shabbir; Rashmi Kushwaha; D Himanshu Reddy; Uma Shankar Singh; Wahid Ali

doi:10.1007/s12291-022-01082-4

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 Apr;38(2):172-181. doi: 10.1007/s12291-022-01082-4. Epub 2022 Aug 21.

Authors

Affiliations

¹ Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Sciences, Gomti Nagar, Lucknow, Uttar Pradesh 22610 India.
² Department of Pathology, King George Medical University, Lucknow, Chowk, Uttar Pradesh 226003 India.
³ Department of Internal Medicine, King George Medical University, Lucknow, Chowk, Uttar Pradesh 226003 India.

^# Contributed equally.

Abstract

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the β-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6-1258) as compared to MCOV-19 at 219.8 ng/ml (167.7-299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.

Keywords: COVID-19; Cell-free DNA; Diagnosis; Immune dysregulation; Prognosis.

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