Decreased availability of nitric oxide and hydrogen sulfide is a Hallmark of COVID-19

Dominic, Paari; Ahmad, Javaria; Bhandari, Ruchi; Pardue, Sibile; Solorzano, Juan; Jaisingh, Keerthish; Watts, Megan; Bailey, Steven R.; Orr, A. Wayne; Kevil, Christopher G.; Kolluru, Gopi K.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is involved in a global outbreak affecting millions of people who manifest a variety of symptoms. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is increasingly associated with cardiovascular complications requiring hospitalizations; however, the mechanisms underlying these complications remain unknown. Nitric oxide (NO) and hydrogen sulfide (H(2)S) are gasotransmitters that regulate key cardiovascular functions. METHODS: Blood samples were obtained from 68 COVID-19 patients and 33 controls and NO and H(2)S metabolites were assessed. H(2)S and NO levels were compared between cases and controls in the entire study population and subgroups based on race. The availability of gasotransmitters was examined based on severity and outcome of COVID-19 infection. The performance of H(2)S and NO levels in predicting COVID-19 infection was also analyzed. Multivariable regression analysis was performed to identify the effects of traditional determinants of gasotransmitters on NO and H(2)S levels in the patients with COVID-19 infection. RESULTS: Significantly reduced NO and H(2)S levels were observed in both Caucasian and African American COVID-19 patients compared to healthy controls. COVID-19 patients who died had significantly higher NO and H(2)S levels compared to COVID-19 patients who survived. Receiver-operating characteristic analysis of NO and H(2)S metabolites in the study population showed free sulfide levels to be highly predictive of COVID-19 infection based on reduced availability. Traditional determinants of gasotransmitters, namely age, race, sex, diabetes, and hypertension had no effect on NO and H(2)S levels in COVID-19 patients. CONCLUSION: These observations provide the first insight into the role of NO and H(2)S in COVID-19 infection, where their low availability may be a result of reduced synthesis secondary to endotheliitis, or increased consumption from scavenging of reactive oxygen species.