Rapid Recovery from Critical COVID-19 Respiratory Failure after treatment with VIP

Abstract

Background: Vasoactive Intestinal Peptide (VIP) blocks replication of the SARS-CoV-2 virus, inhibits cytokine synthesis, prevents cytopathy, and upregulates surfactant production in human pulmonary cells. RLF-100™ (aviptadil), is currently in phase 2/3 trials with FDA Fast Track designation for treating Critical COVID-19 with Respiratory Failure. Methods: Case series of 21 consecutive with Critical COVID-19 and multiple co-morbidities, treated with intravenous aviptadil (synthetic VIP). Sixteen patients were treated with ventilation alone 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 2.5-fold increase in PaO2:FiO2 ratio was seen (P<0.0001) 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. Four of 5 patients on ECMO have been decannulated, and thus far three 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 3 point reduction (mean 2.7; P<0.001) in the WHO Ordinal Scale was observed (P<.001). Comment: The short term outcome in these 21 patients represent a dramatic response in patients whose comorbidities precluded their randomization in all other trials of COVID therapeutics and who were previously treated with remdesivir, tocilizumab, or convalescent plasma. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect