SARS-CoV-2 hyperimmune globulin for severely immunocompromised patients with COVID-19: a randomised, controlled, double-blind, phase 3 trial

Abstract

SummaryBackgroundSeverely immunocompromised patients are at risk for severe COVID-19. Benefit from convalescent plasma in these patients is suggested but data from randomised trials are lacking. The aim of this study is to determine efficacy of SARS-CoV-2 hyperimmune globulin (“COVIG”) in treatment of severely immunocompromised, hospitalised COVID-19 patients.MethodsIn this randomised, controlled, double-blind, multicentre, phase 3 trial, severely immunocompromised patients who were hospitalised with symptomatic COVID-19 were randomly assigned (1:1) to receive 15 grams of COVIG or 15 grams of intravenous immunoglobulin without SARS-CoV-2 antibodies (IVIG, control). Patients included were solid organ transplant patients with three drugs from different immunosuppressive classes or patient with disease or treatment severely affecting B-cell function. Patients that required mechanical ventilation or high flow nasal oxygen were excluded. All investigators, research staff, and participants were masked to group allocation. The primary endpoint was occurrence of severe COVID-19 evaluated up until day 28 after treatment, defined as the need for mechanical ventilation, high-flow nasal oxygen, readmission for COVID-19 after hospital discharge or lack of clinical improvement on day seven or later. This trial is registered with Netherlands Trial Register (NL9436).FindingsFrom April, 2021, to July, 2021, 18 participants were enrolled at three sites in the Netherlands; 18 patients were analysed. Recruitment was halted prematurely when casirivimab/imdevimab became the recommended therapy in the Dutch COVID-19 treatment guideline for seronegative, hospitalised COVID-19 patients. Median age was 58 years and all but two were negative for SARS-CoV-2 spike IgG at baseline. Severe COVID-19 was observed in two out of ten (20%) patients treated with COVIG compared to seven of eight (88%) in the IVIG control group (p = 0·015, Fisher’s exact test).InterpretationCOVIG reduced the incidence of severe COVID-19 in severely immunocompromised patients, hospitalised with COVID-19. COVIG may be a valuable treatment in this patient group and can be used when no monoclonal antibody therapies are available.FundingThe Netherlands Organisation for Health Research and Development, Sanquin Blood Supply Foundation.

Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial

“…Indeed, it is very unfortunate that 2 years into the pandemic, data from large randomized trials on the value of CP in immunocompromised patients are still lacking completely. ( 21 ).…”

Dosing of convalescent plasma and hyperimmune anti-SARS-CoV-2 immunoglobulins: a phase I/II dose finding study

“…(13) COVIg is an intravenous immunoglobulin product produced from pooled plasma from more than 1000 donors and included ConvP donations. (14) The main advantage of ConvP is that it can be collected very early on in a pandemic, but its antiviral activity varies between each donor. In contrast, it takes several months to produce a first batch of COVIg, but it is more polyclonal than ConvP, the antibody content is constant in each vial of a batch, and ABO blood group matching is not required.…”