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

Abstract

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: Twenty of 21 patients demonstrated improvement inblood oxygenation. The improvement in patients on ECOM was similar to that seen in patients treated with conventional mechanical ventilation. Available data from blood gases showed stark increases in PaO2:FiO2 ratio after the 2nd dose (Median increase = 92.5, IQR = 74) and at 24 hours after the 3rd dose (Median increase over baseline 84.5, IQR = 110). No patient showed deterioration of oxygenation below baseline during subsequent measurements. A mean 292% increase in PaO2:FiO2 ratio was seen with full or partial resolution of the “ground glass” parenchymal changes associated with COVID-19 pneumonitis in 19 patients.A laboratory panel of inflammatory markers, including LDH, troponin, C-reactive protein, ferritin, D-Dimer, and interleukin-6 was obtained prior to and post treatment with aviptadil. In all patients, improvement can be seen on each of the inflammatory markers. The largest average percent decrease was seen in C-reactive protein (76% ±3%) and interleukin-6 (75% ±3%). No patient demonstrated an increase in any of the inflammatory markers.Clinically and statistically significant improvement was seen on the WHO Ordinal Scale, where zero represents discharge to home with no need for further therapy and 10 represents death can be seen in both ventilated and ECMOtreated patients. The median improvement was 4 points (mean 2.5 points;p<0.001).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. .