Convalescent plasma therapy in COVID-19: Unravelling the data using the principles of antibody therapy

ABSTRACT

Introduction

When the COVID-19 pandemic struck no specific therapies were available and many turned to COVID-19 convalescent plasma (CCP), a form of antibody therapy. The literature provides mixed evidence for CCP efficacy.

Areas covered

PubMed was searched using the words COVID-19 and convalescent plasma and individual study designs were evaluated for adherence to the three principles of antibody therapy, i.e. that plasma 1) contain specific antibody; 2) have enough specific antibody to mediate a biological effect; and 3) be administered early in the course of disease. Using this approach, a diverse and seemingly contradictory collection of clinical findings was distilled into a consistent picture whereby CCP was effective when used according to the above principles of antibody therapy. In addition, CCP therapy in immunocompromised patients is useful at any time in the course of disease.

Expert opinion

CCP is safe and effective when used appropriately. Today, most of humanity has some immunity to SARS-CoV-2 from vaccines and infection, which has lessened the need for CCP in the general population. However, COVID-19 in immunocompromised patients is a major therapeutic challenge, and with the deauthorization of all SARS-CoV-2-spike protein-directed monoclonal antibodies, CCP is the only antibody therapy available for this population.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• convalescent plasma
• antibody
• immune therapy

Article highlights

• Evidence from over a century of experience with antibody therapies demonstrates that the success of this modality requires that the antibody preparation contain antibody specific to the infectious agent in question in sufficient quantity and be administered early in the course of disease.

• The literature on CCP is now voluminous. Although cursory reviews of CCP efficacy may yield mixed results, an analysis based on biological plausibility that considers the principles of antibody therapy reveals that early in the pandemic when COVID-19 had high mortality CCP reduced mortality when used early in disease and when administered using units of CCP that contained a high concentration of specific antibody. The CCP use case in immunocompromised patients is especially compelling.

• With much of the population having immunity to SARS-CoV-2 from vaccination and natural infection, the usefulness of CCP in immunocompetent persons has lessened. However, CCP retains a vital role in the treatment of COVID-19 in immunocompromised patients who often respond poorly to vaccines and infection.

• The experience with COVID-19 teaches us how to use convalescent plasma effectively in future infectious disease emergencies.

Declaration of interest

A Casadevall is on the scientific advisory board for SAB Therapeutics. S Shoham recieved research grants from F2G and Ansun Biopharma; consulted for Immunome and Karius; has stock options with Immunome.

Reviewer disclosures

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.