Convalescent Plasma Reduced Mortality in Immunocompromised COVID-19 Patients

The continued mutating of COVID-19 has exacerbated the need for new treatments. While vaccines and antivirals like Paxlovid remain effective, this efficacy is significantly weakened by Omicron and its subvariants.

This week, the Centers for Disease Control and Prevention (CDC) estimated that the emerging XBB.1.5 Omicron subvariant is now responsible for 43% of new infections in the US.

In the past, neutralizing anti-spike monoclonal antibody treatments have been utilized to treat COVID-19. Now, COVID-19 variants have increasingly displayed monoclonal antibody resistance, as well as increased virulence and transmissibility. Thus, COVID-19 patients, and especially immunocompromised individuals, need new agents that will reduce morbidity and mortality.

A new study, published in JAMA, assessed the safety and efficacy of COVID-19 convalescent plasma transfusion for improving disease outcomes in immunocompromised patients. The study authors noted that immunocompromised individuals have an increased risk of COVID-19 morbidity and mortality, due to a common inability to mount antibody responses to COVID-19 vaccination.

Convalescent plasma, a blood product collected from recovered COVID-19 patients, is an increasingly attractive treatment due to the hypothesis that the plasma contains therapeutic COVID-19 antibodies that can be passively transferred to immunocompromised patients.

The investigators conducted a systematic review and meta-analysis of 125 case reports, 13 uncontrolled large case studies, 5 matched cohort studies, and 3 randomized clinical trials. Keywords and terms included in the search were: (COVID-19 OR SARS-CoV-2 OR coronavirus disease 2019) AND (convalescent plasma OR immune plasma OR hyperimmune plasma) AND (immunosuppression OR immunodeficiency OR immunocompromised OR cancer OR transplant OR malignancy OR hematological OR oncologic OR lymphoma OR leukemia OR myeloma OR agammaglobulinemia OR hypogammaglobulinemia OR common variable immunodeficiency OR autoimmune disorder).

Eligible patients had a primary (inherited) or secondary (hematological or solid cancers, autoimmune disorders, or organ transplants) immunosuppression and a confirmed COVID-19 diagnosis. They were given a transfusion with COVID-19 convalescent plasma in any dosage. The control groups were treated with standard-of-care according to local treatment guidelines, both with and without placebo.

The review and analysis followed the Cochrane Handbook for Systematic Review of Interventions and reported findings according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The reports were collected on August 12, 2022, and were published beginning on January 1, 2020.

The principal outcome of interest was all-cause mortality after COVID-19 convalescent plasma transfusion in immunosuppressed patients, and the analysis showed transfusion of convalescent plasma was positively associated with a mortality reduction in immunocompromised COVID-19 patients.

Separate meta-analyses suggested COVID-19 convalescent plasma transfusion decreased mortality rates (compared to control cohorts) across both randomized clinical trials and matched cohort studies, with a pooled risk ratio of 0.63.

The study authors noted that, due to the continued rapid mutating of COVID-19, the studies reviewed here reflect different variants than those previously dominant. Thus, a significant benefit of COVID-19 convalescent plasma in reducing mortality in immunocompromised patients cannot be definitively assumed. However, these data are a strong support for the hypothesis.

The investigators concluded that these findings encourage the use of COVID-19 convalescent plasma in immunocompromised persons, and certainly merit further investigation.