Happy Hypoxia: Higher NO in red blood cells of COVID 19 patients

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has spread to almost 100 countries, infected over 10M patients and resulted in 505K deaths worldwide as of 30th June 2020. The major clinical feature of severe COVID-19 requiring ventilation is acute Respiratory Distress Syndrome (ARDS) with multi-functional failure as a result of a cytokine storm with increased serum levels of cytokines. The pathogenesis of the respiratory failure in COVID-19 is yet unknown, but diffuse alveolar damage with interstitial thickening leading to compromised gas exchange is a plausible mechanism. Hypoxia has been seen in the COVID-19 patients however, patients present with a distinct phenotype. Intracellular levels of NO playing important role in the vasodilation of small vessels.Objectives: To elucidate the intracellular levels of NO inside of RBCs in COVID-19 patients compared with that of healthy control subjects.Methods: We recruited 14 COVID-19 infected cases who had pulmonary involvement of their disease, 4 non-COVID-19 healthy controls (without pulmonary involvement and were not hypoxic) and 2 hypoxic non-COVID-19 patients subjects who presented at the Masih Daneshvari Hospital of Tehran, Iran between March-May 2020. Whole blood samples were harvested from patients and intracellular levels of NO in 1 million red blood cells (RBC) was measured by DAF staining using flow cytometry (FACS Calibour, BD, CA, USA).Results: The Mean florescent of intensity for NO was significantly enhanced in COVID-19 patients compared with healthy control subjects (P≤0.05). As a further control for whether hypoxia induced this higher intracellular NO, we evaluated the levels of NO inside RBC of hypoxic patients. No significant differences in NO levels were seen between the hypoxic and non-hypoxic control group.Conclusions: This pilot study demonstrates increased levels of intracellular NO in RBCs from COVID-19 patients. Future studies should examine whether intracellular NO would be increased in large number of COVID-19 patients for usage of possible NO therapy in severe patients.