Mortality reduction in 46 severe Covid-19 patients treated with hyperimmune plasma. A proof of concept single arm multicenter interventional trial

Abstract

BACKGROUND Hyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19. METHODS We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety. RESULTS The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, 30 on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related). CONCLUSIONS Hyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.

Evidence favouring the efficacy of convalescent plasma for COVID-19 therapy

“…25 Wisconsin, USA 27 Forest plot illustrating odds ratios (OR) and 95% confidence intervals for controlled studies and aggregate fixed effect models. Fixed effect ORs for Duan et al 26 , Rasheed et al 19 , Perotti et al 23 , Hegerova et al 21 , Zeng et al 9 , Donato et al 10 , Liu et al 22 , Salazar et al 11 , Gharbharan et al 8 , Xia et al 12 , Abolghasemi et al 24 , and Li et al 7 are represented in blue. The aggregate fixed effect model OR is represented in shaded blue.…”

Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study

“…To date, published clinical data regarding convalescent plasma transfusions as treatment for COVID-19 include single-arm, observational studies from China, the United States, Italy 5,7,[14][15][16] and, most recently, two randomized open-label trials that were terminated before full enrollment 17,18 . In respiratory infections specifically, the strongest evidence suggests that the benefit of passive antibody transfer is most demonstrable in patients who were treated within days of symptom onset 11,[19][20][21] .…”

Antivirals for COVID-19 in Solid Organ Transplant Recipients

“…In a matched control trial of 39 patients classified as having severe to life-threatening COVID-19 treated with CP, plasma recipients had greater likelihood of stable or improved oxygen requirements with an adjusted analysis showing a survival benefit with CP in non-intubated patients (HR 0.19, p = 0.015), but not for intubated patients [47•]. In an observational study of 46 patients with moderate-to-severe ARDS and need for mechanical ventilation or continuous positive airway pressure treated with CP, there was a decrease in mortality at 7 days compared to a match cohort [48]. In an open-label, multicenter, randomized trial of 103 patients with severe or life-threatening COVID-19 at 7 centers in Wuhan, China, comparing standard care plus CP versus standard care alone, CP was associated with lower 28-day mortality (24% vs. 16%), greater likelihood of discharge by 28 days (36% vs. 51%), and faster clinical improvement [49•].…”