In a recent study posted to the medRxiv* preprint server, researchers conducted a controlled, double-blinded Phase III trial to evaluate the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune globulin (COVIG) in immunocompromised, hospitalized coronavirus disease 2019 (COVID-19) patients.
To date, only three trials have tested the efficacy of COVIG among hospitalized COVID-19 patients. One phase I/II trial reported lower mortality in the COVIG treated patients; however, two Phase III trials did not confirm these findings. According to the authors, the current trial is one of the first randomized trials examining the effects of COVIG in severely immunocompromised patients with COVID-19.
About the study
In the present study, researchers enrolled severely immunocompromised hospitalized patients (within 72 hours of admission) who produced a positive reverse transcription-polymerase chain reaction (RT-PCR) report and had symptomatic COVID-19 for their double-blinded, controlled Phase III trial.
They randomly assigned the enrolled patients in a 1:1 ratio to the test and control groups. While the test group received 15 grams of COVIG, the control group received an equivalent dose of convalescent plasma (IVIG). The researchers and participants remained blinded to the allocated treatment until day 28 or till the attainment of the primary endpoint.
The researchers gathered baseline data, including demographics, medical history, vital parameters, and respiratory support of all the study participants using a web-based case report form. They collected nasal swabs at baseline and quantified SARS-CoV-2 ribonucleic acid (RNA) following treatment with SARS-CoV-2 antibodies.
They performed a SARS-CoV-2 trimeric spike (S) immunoglobulin G (IgG) assay, where S IgG >33·8 binding antibody units (BAU)/ml indicated a positive result.
The studys' primary endpoint was the occurrence of severe COVID-19, ascertained by any of the following - high-flow nasal oxygen, need for mechanical ventilation, lack of clinical improvement after seven days of treatment, or re-admission for RT-PCR-confirmed COVID-19 within 28 days.
The trial began in April 2021 and was terminated by July 29, 2021 (early), when monoclonal antibodies (mAbs) casirivimab/imdevimab became available for treating hospitalized COVID-19 patients. Accordingly, the study analysis was performed after the enrolment of 21% of the target population (small sample size), referred to as the intention-to-treat population.
The team performed Fisher’s exact test to compare proportions in both treatment groups in the primary endpoint analysis. They used a mixed-effects model for analyzing repeated measurements of viral decay. The model accounted for the linear effect of time, the interaction between time and treatment group, and random intercepts, and adjusted for age, vaccination status of the patients, and duration of symptoms at inclusion.
Using the regression coefficient of the interaction term between treatment and time group, the researchers quantified the average rate of change of viral decay in each treatment group.
The authors screened 37 patients during the study, of which 10 received COVIG and eight received conventional IVIG without SARS-CoV-2 antibodies.
At baseline, 11% of patients had SARS-CoV-2 IgG antibodies, and their median age was 58 years. The median Charlson Comorbidity Index (CCI), a mortality risk predictor for patients with several comorbid conditions, was 3, and oxygen supplementation was three L/min.
Based on the assumption that the high-risk patient population of the study had a 70% chance of reaching the primary endpoint of severe COVID-19, the researchers hypothesized a 30% reduction in hospitalization with COVIG treatment.
The study results showed that only 20% of patients had severe COVID-19 post-treatment with COVIG and zero death count, whereas, unfortunately, 88% developed severe COVID-19 in the control arm, and three out of eight patients died. Although 50% of patients had a severe adverse event (SAE), eight related to COVID-19, three deaths due to COVID-19 were reported only in the IVIG group.
Among 16 seronegative patients, 13% and 88% developed severe COVID-19 in the COVIG and IVIG arms, respectively. However, despite being treated with COVIG, one patient of the two seropositive patients developed severe COVID-19.
Interestingly, the median duration of hospital stay was similar in both groups, i.e., nine days; likewise, the authors observed the same viral decay rates in both groups.
Overall, COVIG averted the severe course of COVID-19 in severely immunocompromised patients, highlighting that the mAb dosage and timing of antibody-based treatment are less crucial in patients with hampered antibody production.
The current trial data add to the current evidence in favor of COVIG for severely immunocompromised patients infected with SARS-CoV-2. The COVIG treatment is significantly effective, particularly when mAbs are unavailable or new SARS-CoV-2 variants of concern emerge that are resistant to all clinically used mAbs.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.