Rapid Recovery from COVID-19 Respiratory Failure with Comorbidity in 21 Patients Treated with Vasoactive Intestinal Peptide

Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect Alveolar Type II cells by blocking replication of the SARS-CoV-2 virus, inhibiting cytokine synthesis, preventing cytopathy, and upregulating surfactant production. RLF-100™ (aviptadil), a synthetic form of VIP has been granted Fast Track Designation for treating Critical COVID-19 with Respiratory Failure and is currently in phase 2/3 placebo-controlled trials. Methods: Case series of 21 consecutive patients with Acute Respiratory Failure in Critical COVID-19 and multiple co-morbidities, treated with intravenous VIP. Sixteen patients were treated with mechanical ventilation and five with extracorporeal membrane oxygenation (ECMO). Results: So far, 19 of 21 patients have survived. Improved radiographic appearance was seen in both lungs of 17 patients and in one lung of 2 patients. A mean 292% increase in PaO2:FiO2 ratio was seen with complete remission from respiratory failure in 9 patients and ongoing improvement in 10. Seven patients were discharged from the hospital, 7 sent to intermediate care, and 5 remain in the ICU. Three of 5 patients on ECMO have been decannulated and two have been discharged. A 75% (95% CI±3%: P<.001) reduction in IL-6 was seen with corresponding decrease in C-reactive protein. A median 4 point reduction in the NIAID Ordinal Scale was observed (P<.01). Comment: The short term outcomes in these 21 patients represent a dramatic response in patients who are excluded from all other trials of COVID therapeutics. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.Trial Registration: Expanded Access Protocol (EAP), NCT04453839.Funding Statement: Research support was provided by the Cavendish Impact Foundation and Princeton Alumni Angels. Clinical trial funding was provided by Relief Therapeutics Holdings, AG, Geneva and NeuroRx, Inc. Declaration of Interests: Author JCJ is employed by NeuroRx, Inc., a pharmaceutical company that is currently conducting clinical trials of RLF-100 in patients with COVID-19 and is Vice Chairman Elect of Relief Therapeutics, all other authors have no declaration to declare. Ethics Approval Statement: Human subjects’ protection was overseen by Advarra IRB, the Institutional Review Board (IRB) of the Houston Methodist Hospital, and by an independent Data Monitoring Committee.