Arginine Replacement Therapy in COVID-19

In the early stages of COVID-19, it was believed that children were immune or had very mild disease. Given the unfolding pandemic, children's cases are exhibiting an increasing global trend and are associated with some serious complications in addition to more long-term complications such as multisystem inflammatory syndrome in children (MIS-C) and "Long Covid". A significant number of hospitalized and critically ill pediatric patients have now been documented, in addition to a high number of emergency department (ED) visits despite previous reports suggesting rare or mild disease in children. The research team and others have shown that severe COVID-19 and MIS-C are associated with acute arginine deficiency in both adults and children. There has been increased evidence of the role of the endothelium associated with severe inflammation in COVID-19. Low plasma arginine bioavailability has been implicated in endothelial dysfunction, immune regulation, and hypercoagulation. The research team also identified high sPLA2 levels in COVID-19 and MIS-C, an observation previously made in children with Kawasaki's Disease. Subsequent studies have shown that sPLA2 is associated with the pathobiology leading to COVID-19 mortality, with enzyme levels 10-fold higher in people who died vs. mild disease and is also associated with Mito dysfunction. Not only could sPLA2 represent a prognostic indicator of disease severity, but it also represents a mechanism with potential therapeutic targets.

Information learned from the Mito activity in COVID-19 can contribute to further understanding of severe acute respiratory syndrome by coronavirus (SARS-CoV-2) infection. This data may help guide future treatment targets and strategies.

Inclusion criteria

• Established diagnosis of COVID-19 requiring admission to the hospital for treatment of COVID-19 infection
• Age 3 years - 21 years of age

Exclusion criteria

• Severe hepatic dysfunction: ALT> 6 x Upper limit of normal
• Renal dysfunction: Creatinine > 1.5 x upper limit of normal or on dialysis
• Acute Stroke
• Pregnancy
• Allergy to arginine
• Past history of severe cardiac disease or significant cardiac surgery [minor procedures like ventricular septal defect (VSD) repair are not an exclusion]
• History of significant pulmonary disease [Cystic Fibrosis, sickle cell disease (SCD)]
• History of organ transplant
• History of metabolic or mitochondrial disease (including Diabetes)
• History of severe neurocognitive delays (severe cerebral palsy, anoxic brain injury)
• History of ventriculoperitoneal (VP) shunt or hydrocephalus
• PI discretion that the patient is not an ideal candidate for the study
• History of HIV of immune compromise