Evaluating the Relationship Between Plasma Cell-Free Mitochondrial DNA (cf-mtDNA) Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis.

The objective of the study was to evaluate the convergence between cell-free mitochondrial DNA (cf-mtDNA) and COVID-19. This was a systematic review and meta-analysis of cohort and cross-sectional studies, considering the best level of evidence available and the protocol was registered in PROSPERO (CRD 42024508173). After the criteria were established, the search encompassed three databases (MEDLINE, EMBASE, and Web of Science) to identify studies that evaluated the possible convergence between cf-mtDNA and the development of COVID-19, verifying its relationship with survival and severity. A Microsoft Excel spreadsheet was used for data extraction, and R software for analysis. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. After the identification and screening processes, eleven studies were selected for the final analysis, that revealed a convergence between elevated levels of cf-mtDNA and the development of COVID-19 (MD=0.70, IC95% 0.39-1.01, p<0.001) and its relationship with the disease severity (MD=1.08, IC95% 0.35-1.82, p=0.004), but not with survival (MD=0.58, IC95% -0.24-1.41, p=0.16).

Conclusions

These findings contribute to a better understanding of cf-mtDNA's role in COVID-19 pathogenesis, its potential as a promising biomarker, and pave the way for the identification of new therapeutic targets.