In a recent study posted to the medRxiv* preprint server, researchers reviewed various randomized clinical trials and cohort studies to evaluate the decrease in mortality rates among coronavirus disease 2019 (COVID-19) patients treated with COVID-19 convalescent plasma.
Transfusion of COVID-19 convalescent plasma was one of the earlier methods adopted to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before monoclonal antibodies and effective antivirals were developed.
With the emergence of immune evasive SARS-CoV-2 variants, such as Omicron, challenging the efficacy of existing monoclonal antibodies, there is renewed interest in plasma transfusion therapy.
However, there have been differing results regarding the effectiveness of COVID-19 convalescent plasma transfusion therapy, despite its widespread availability and use. Factors such as the biologically diverse nature of convalescent plasma, the non-standard therapy protocols, as well as the use of convalescent therapy for anything from prophylactic treatment to last resort therapy for patients with multiorgan failure could be causing ambiguity about its success.
With the reawakening of interest in COVID-19 convalescent plasma transfusion therapy, it is important to understand its benefits in decreasing mortality rates among COVID-19 patients.
About the study
In the present study, the researchers conducted a systematic review and meta-analysis of pooled data from various randomized clinical trials and cohort studies that used COVID-19 convalescent plasma transfusion to treat hospitalized COVID-19 patients. They considered studies on hospitalized COVID-19 patients treated with COVID-19 convalescent plasma, irrespective of the dosage.
The primary outcome measured was all-cause mortality during hospitalization. A subgroup analysis focusing on the differences among COVID-19 patients treated with convalescent plasma transfusion was also conducted. The analyzed data included demographic characteristics such as age, sex, and whether they required mechanical ventilation during COVID-19 convalescent plasma treatment. The volume and antibody type of the COVID-19 convalescent plasma transfusion and the time of transfusion were also obtained.
To determine the effectiveness of COVID-19 convalescent plasma therapy in reducing mortality rates among hospitalized COVID-19 patients, the researchers compared the observed mortality among the plasma transfusion patients with the expected number of deaths if all the patients were at equal risk. Additional subgroup analyses evaluated the mortality rates among patients receiving COVID-19 convalescent plasma therapy based on the timing of the transfusion and the antibody concentration of the plasma.
The results reported that the use of COVID-19 convalescent plasma transfusion for treating hospitalized COVID-19 patients significantly reduced the mortality rates compared to control cohorts in randomized control trials and matched cohort studies. The review analyzed 39 randomized control trial studies and 70 matched cohort studies with 21,529 and 50,160 patients enrolled, respectively.
The meta-analysis of randomized control trials indicated that COVID-19 convalescent plasma transfusion was associated with a 13% decrease in mortality rates compared to patients who received standard care. In comparison, the analysis of cohort studies suggested a 23% reduction in mortality rates.
The subgroup analyses, which examined the change in mortality associated with early and late treatments and high and low antibody concentrations in plasma, reported that early treatment with high antibody concentrations in convalescent plasma resulted in a significant decrease in mortality rates as compared to treatments that were initiated later during the disease or had lower antibody concentrations. Higher antibody levels in the COVID-19 convalescent plasma were associated with a 15% reduction in mortality rates, while initiating the transfusion treatment early in the course of the disease was linked to 37% lower mortality rates.
Additionally, in an exploratory analysis of COVID-19 outpatients treated with COVID-19 convalescent plasma transfusion, a 35% reduction in hospitalization rates was observed, but no benefits were associated with mortality rates. A review of reports and case series from the United States that evaluated the mortality risks associated with COVID-19 convalescent plasma treatment indicated a 25% mortality risk.
Overall, the results indicated that treatment of hospitalized COVID-19 patients with convalescent plasma transfusions reduced the mortality rates by 13%. Initiating the transfusion earlier during the SARS-CoV-2 infection and administering plasma with high antibody concentrations were associated with a greater reduction in mortality rates.
The authors believe that these results support the administration of convalescent plasma as an effective treatment method until more effective therapies have been developed in the case of future pandemics.
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.