Development, Implementation, Pharmacokinetic and Safety Evaluation of an Immunotherapeutic Treatment for COVID-19: Double-blind Randomized Placebo-controlled Trial.

Abstract

Passive immunotherapy has been evaluated in many infections. The present study aims to evaluate purified F(ab')2 fraction of equine hyperimmune IgG (anti-SARS-CoV-2) in the treatment of coronavirus lung disease. Patients with coronavirus disease of 2019 (COVID-19) with World Health Organization (WHO) score 3, 4 or 5 up to 72 hours of evolution from the onset of symptoms were included. They were randomly assigned to anti-SARS-CoV-2 or placebo. Follow-up was performed for 28 days to assess efficacy, safety, pharmacokinetics, detection of anti-horse antibodies, circulating cytokines and determination of anti-SARS neutralizing activity. The 20 initial patients (44±14 years) were included. On the third day of treatment there was an improvement (P=0.02) in arterial saturation (95±1.6 vs. 93±2.5%) with increasing differences over time between treatments (day 8: 97±0.1 vs. 94±0.3%). The length of oxygen therapy treatment was 2±0.8 vs. 3±0.9 (0.048) in patients falling within WHO 5 category (no difference to WHO 4). Mean hospitalization was 13±2.5 vs. 14±0.8 days (P=0.095) and time to clinical improvement was 2±0.5 vs. 3±0.9 days (P=0.048) in patients with initial 5 WHO category, with no differences to patients who started with WHO stage 4. The time to nasal swab negativization was 10±2.1 vs. 12±0 day (P=0.015). No adverse reactions or intercurrences were detected. All patients presented heterophile antibodies without clinical correlate. The new treatment shows improvement in arterial saturation (days 3 to 12), and a decrease on detectable viral RNA (days 8 to 11) with good pharmacokinetic and safety profile.