Presence and short‐term persistence of SARS‐CoV‐2 neutralizing antibodies in COVID‐19 convalescent plasma donors

Background In March 2020, the Food and Drug Administration (FDA) approved use of COVID‐19 convalescent plasma (CCP) as an investigational new drug for treatment of COVID‐19. Since then, collection of CCP from COVID‐19–recovered patients has been implemented in donor centers nationwide. Childrenʼs Hospital Colorado rapidly put into practice a CCP collection protocol, necessitating development and implementation of assays to evaluate SARS‐CoV‐2 antibodies in CCP units. Study Design and Methods We evaluated 87 units of CCP collected from 36 donors over two to four sequential donations using both antigen‐binding assays for SARS‐CoV‐2 nucleoprotein and spike antigens and a live virus focus reduction neutralization test (FRNT50). Results Our data show that the majority of donors (83%) had a FRNT50 titer of at least 80, and 61% had a titer of at least 160, which met the FDAʼs criteria for acceptable CCP units. Additionally, our data indicate that analysis of antibodies to a single SARS‐CoV‐2 antigen is likely to miss a percentage of seroconverters; however, these individuals tend to have neutralizing antibody titers of less than 80. There was considerable variability in the short‐term, sustained antibody response, measured by neutralizing antibody titers, among our donor population. Conclusion The correlation of neutralizing activity and antigen‐binding assays is necessary to qualify CCP for therapeutic use. Since SARS‐CoV‐2 antibody levels decline in a percentage of donors, and such a decline is not detectable by current qualitative assays implemented in many laboratories, robust, quantitative assays are necessary to evaluate CCP units best suited for therapeutic infusion in COVID‐19 patients.