Abstract

INTRODUCTION
LDH is released by cytokine-mediated tissue damage, reflecting injury and possible organ dysfunction. It is associated with severity and mortality in patients with Covid-19. Circulating free DNA (cfDNA) is a marker of tissue damage, released by the nucleus and mitochondria after cell destruction. Recent studies have showed its possible role as a marker of tissue damage in Covid-19.

METHODS
Prospective, observational, longitudinal study of 91 hospitalized patients with different degrees of severity. The evolution distinguished viral, early inflammatory and late inflammatory phases. Clinical data, immune cells, proinflammatory cytokine levels(TNF-a,IL-1ß,IL-8,IL-6,INF-?,IL-17A andG-CSF),serum inflammatory markers (CRP,PCT,D-dimer,ferritin) and tissue damage markers (LDH and cfDNA) were included.

RESULTS
LDH levels increased in parallel with severity, but did not discriminate mortality in the first sample and only showed significantly higher levels in critically ill patients. The IL-6/LDH correlation was close and significant in all degrees of severity and at all stages of the disease. The cfDNA value was higher in more severe and patients who died, and was the only biomarker that remained higher in these patients during the 3 phases of the disease. The multivariate study showed that cfDNA, and not IL-6, was an independent risk factor for critical status and ICU admission.

CONCLUSIONS
cfDNA is an excellent marker of tissue damage, severity and mortality in Covid-19 disease, better than LDH. The IL-6/LDH association seems to reflect better timely inflammation, and cfDNA probably reflects better the extent of tissue damage.