Immune Plasma for the Treatment of COVID-19: Lessons Learned so far

Abstract

COVID-19 convalescent plasma (CCP) has been explored as one of the treatment options for COVID-19. Results of many cohort studies and clinical trials have been recently published. At first glance, the results of the CCP studies appear to be inconsistent. However, it became clear that CCP is not beneficial if CCP with low anti-SARS-CoV-2 antibody concentrations is used, if it is administered late in advanced disease stages, and to patients who already mounted an antibody response against SARS-CoV-2 at the time of CCP transfusion. On the other hand, CCP may prevent progression to severe COVID-19 when very high-titer CCP is given early in vulnerable patients. Immune escape of new variants is a challenge for passive immunotherapy. While new variants of concern developed resistance to most clinically used monoclonal antibodies very rapidly, immune plasma from individuals immunized by both a natural SARS-CoV-2 infection and SARS-CoV-2 vaccination retained neutralizing activity against variants. This review briefly summarizes the evidence on CCP treatment to date and identifies further research needs. Ongoing research on passive immunotherapy is not only relevant for improving care for vulnerable patients in the ongoing SARS-CoV-2 pandemic, but even more as a model for passive immunotherapy in case of future pandemics with a newly evolving pathogen. Compared to other drugs, which must be newly developed in a pandemic (e.g., monoclonal antibodies, antiviral drugs), convalescent plasma is rapidly available, inexpensive to produce, and can be adaptive to viral evolution by selection of contemporary convalescent donors.

Convalescent Plasma for Critically-ill Covid-19 Patients

“…Among the immunomodulatory agents, passive antibody therapies including neutralizing monoclonal antibodies (mAbs), hyperimmunoglobulin and convalescent plasma (CP) have been early and successfully used [3]. In comparison with monocloncal antibodies, immune plasma from individuals immunized by both a natural SARS-CoV-2 infection and SARS-CoV-2 vaccination retained neutralizing activity against new variants [4].…”

Assessment of the impact of pathogen reduction technologies on the neutralizing activity of COVID-19 convalescent plasma.

“…It was also reported that the administration of high titer CCP in early stages of disease to outpatients significantly reduced disease progression and hospitalization rate [9] . Despite the development of therapeutic antibodies, CCP may be in case of newly emerging SARS-CoV-2 variants also an important future treatment option [10] , [11] . Since CCP-donors are like first-time donors with an elevated risk for window-period transmission of blood borne viruses, pathogen reduction treatment (PRT) may be a way mitigating such risk.…”

GTH 2023: The Patient as a Benchmark

“…COVID-19 remains a highly relevant topic, on which Schrezenmeier 3 et al provides an overview of the use of immune plasma to describe both the benefits of immune plasma in general and the use of reconvalescent plasma in COVID-19 in particular. His plenary lecture on convalescent plasma presents the studies on this topic.…”