Circulating levels of PADs and citrullinated histone H3 in SARS-CoV-2 infection: Influence of genetic polymorphisms.

BACKGROUND

Peptidyl arginine deiminases (PADs) and citrullinated H3 histone (H3Cit) play a crucial role in the inflammatory response. These components determine various clinical situations in COVID-2019 associated pneumonia. Single nucleotide polymorphisms (SNPs) in the genes PADI2 and PADI4 may influence the outcome of poorer patient outcomes. We analyze the association of circulating levels NETs biomarkers (PAD2, PAD4, and H3Cit) and the SNPs on PADI2 (rs1005753 and rs2235926) and PADI4 (rs11203366, rs11203367, and rs874881) in hospitalized patients with severe acute respiratory distress syndrome (ARDs) by SARS-CoV-2 pneumonia.

METHODS

A cross-sectional study in 160 hospitalized patients with ARDs by SARS-CoV-2 pneumonia. The plasma levels of PAD2, PAD4, and H3Cit were determined by ELISA method. The SNPs were determined by qPCR using TaqMan probes. Logistic regression models and receiver operating characteristics (ROC) curve were used to assess the association and predictive value of PAD2, PAD4, and H3Cit plasma levels in outcome by ARDs by SARS-CoV-2 pneumonia.

RESULTS

PAD2, PAD4, and H3Cit concentrations were predictors of invasive mechanical ventilation (IMV) requirement and non-survival. PAD2 were associated with non-survival, while PAD4 and H3Cit were associated with requirement IMV. In addition, PAD2 and PAD4 concentrations were related with inflammation markers such as NLR, MLR, dNLR, SII, SIRI, AISI, and NHL. In the carriers of TT genotype of rs1005753 of PADI2 were associated with increased of H3Cit, while, the carriers of GTG/GTG haplotype of PADI4 was related to the presence of increased of PAD4 circulating levels.

CONCLUSION

SNPs in PADI2 and PADI4 have a significant influence on concentrations of PAD2, PAD4, and H3Cit, which are predictor markers of requirement IMV and non-survival in severe ARDS by SARS-CoV-2 pneumonia.