It's Easy to Miss Mis-a: A Case Series of Multi-inflammatory Syndrome in Adults Associated with Sars-Cov-2 Infection and Cardiogenic Shock Managed with Mechanical Circulatory Support

Study: The main clinical manifestation of severe COVID-19 is hypoxemia that fulfills the criteria of acute respiratory distress syndrome (ARDS). The "cytokine storm" driven in large part by reactive oxygen species (ROS) during an excessive immune response to SARS-CoV-2 infection leads to ARDS aggravation and multi-organ failure (MOF). Other complications include massive endothelial dysfunction and widespread coagulopathy. Despite all efforts there is no effective therapy available yet. The efficacy of vaccines could be threatened by viral mutations. Since HBOCs are intended to reverse hypoxemia, this study examined their hypothetical therapeutic potential for COVID-19. Methods: There are several types of HBOCs under development: human, bovine or worm Hb-based;cross-linked, conjugated, polymerized or encapsulated;low or high oxygen affinity (P50);oxygenated or carbonylated (CO);pharmacologically modified. The most common conjugation methods are PEGylation, nitroxylation or antioxidant enzymes. Glutaraldehyde is still being used as a polymerization agent. Pharmacologic modification includes cross-linking with o-ATP, polymerization with o-adenosine and conjugation with GSH. This analysis was based on HBOCs published pre-clinical/clinical performance vis-a-vis severe COVID-19 pathophysiology. Results: HBOCs with low P50 can yield insufficient oxygen delivery and with high P50 will be unable to be properly oxygenated. CO-HBOCs can deepen hypoxemia. HBOCs with uncontrolled redox potential will be a source of ROS/ferryl Hb, thus augmenting "cytokine storm," endothelial injury and MOF. HBOCs not catabolized physiologically will lead to iron overload, increasing susceptibility to bacterial infections. Conclusions: It seems that only oxygenated HBOCs with moderate P50, controlled redox chemistry and anti-inflammatory properties, without procoagulant activity and catabolized physiologically could be considered for future studies to establish their therapeutic value in COVID-19.