COVID 19 severity is associated with the presence of lung derived cfDNA in plasma

Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies

“…The DAMP most frequently reported for COVID-19 is lactate dehydrogenase, a central enzyme of anaerobic glycolysis that is present in virtually all cells and that, therefore, reliably indicates cell death when occurring at high concentrations in the extracellular space ( 200 – 202 ). Other DAMPs which have been observed at elevated levels in the blood or plasma of patients with severe COVID-19 comprise high-mobility group box protein (HMGB)1 ( 51 , 110 , 111 , 202 – 206 ), S100 proteins ( 108 , 110 , 202 , 207 – 209 ), plasma hyaluronan ( 210 ), extracellular (e)ATP ( 211 , 212 ), the antimicrobial peptide LL-37 ( 213 , 214 ), histones (e.g ( 215 – 217 ), reviewed in ( 218 , 219 ) and circulating self-DNA, including nDNA ( 13 , 20 , 21 , 42 , 46 , 47 ), mtDNA ( 13 , 18 , 21 , 42 , 43 , 48 , 49 ), NET-associated cfDNA ( 201 , 215 , 220 – 222 ), histone-DNA complexes ( 219 ), and cfDNA of non-specified subcellular origin ( 45 , 48 , 50 – 54 ). As recently reviewed for sepsis ( 72 ), most of these studies reported a positive correlation of the plasma levels of at least some of the beforementioned DAMPs with the degree of disease severity (e.g., mild versus severe cases, COVID-19 patients at ICU admission versus healthy controls, ICU-admitted cases with fatal outcomes versus surviving patients, poor oxygenation status, patients with acute respiratory distress syndrome or with multisystem inflammatory syndrome in children, etc.).…”

“…Elevated concentrations of cell-free (cf) self-DNA in blood or plasma of COVID-19 patients have been reported repeatedly and in most cases, cfDNA levels correlated with disease severity ( 13 , 18 – 21 , 42 – 56 ). This finding should not come as a surprise, because during pyroptosis, pro-inflammatory cytokines are released together with cellular content, including self-DNA and other damage-associated molecular patterns (DAMPs) ( 6 , 13 , 14 , 46 , 54 , 57 , 58 ). DAMPs (or alarmins) are endogenous molecules that adopt the additional function of signalling danger when their fragmentation or translocation to the ‘wrong space’ indicates damage to self ( 59 – 61 ).…”