The purpose of this study is to investigate if receiving doses of arginine (a protein inthe body) will improve mitochondria function in children with COVID-19.The study will be performed in Children's Healthcare of Atlanta, Egleston campus.Patients will be randomized to receive one of three doses of arginine three times a dayfor five days or at discharge whichever comes first.
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.
Drug: Arginine Hydrochloride
Arginine will be infused based on the manufacturer's instructions (R-Gene 10, Pfizer),
over 30 minutes. However, rates may be slowed to over 60 minutes for patients
experiencing symptoms of flushing, nausea, vomiting, or headache at the research team's
discretion. Pediatric doses will be drawn up by the pharmacy.
Other Name: L-arginine
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
Children's Healthcare of Atlanta (CHOA), Egleston
Atlanta, Georgia, United States
Investigator: Claudia R Morris, MD
Contact: 404-727-5500
claudia.morris@choa.org
Investigator: Caludia R Morris, MD
Claudia R. Morris, MD
404 727-5500
claudia.r.morris@emory.edu
Dunia Hatabah, MD
470-6626706
dunia.hatabah@emory.edu
Claudia R. Morris, MD, Principal Investigator
Emory University