Effective Convalescent Plasma IgG Ratios Greater Than 18.45 to Ensure High Neutralizing Capacity

Researchers from the New York State Department of Health found that current COVID-19 convalescent plasma (CCP) guidelines may be allowing for sera with low neutralizing capacity to be administered. These findings were published in the Journal of Infectious Diseases.

Blood donations (N=981) from individuals who have been symptom-free of COVID-19 for at least 2 weeks were assessed for this study. Test sera was serially diluted and mixed with 100 ml of 200 plaque forming units of SARS-CoV-2 and seeded on agar plates.

Plaques were assessed after incubation, and the titers where the plaque reduction neutralization test (PRNT) was 50% (PRNT₅₀) or 90% (PRNT₉₀) were recorded. A 10% subset of repeat donor serum was assessed for SARS-CoV-2 immunoglobulin (Ig)G antibodies. Study authors compared ratios of IgG across donations.

Blood donors were 61.1% men aged mean age of 48 years. Men had higher mean PRNT₅₀ titers (263.8) compared with women (171.5; P <.0001) and age was positively correlated (PRNT₅₀: Spearman r, 0.2129; P <.0001 vs PRNT₉₀: Spearman r, 0.1988; P <.0001).

PRNT titers were at least 1:80 among 73.0% of PRNT₅₀ and 25.8% of PRNT₉₀ samples, and at least 1:160 among 51.4% of PRNT₉₀ and 9.5% of PRNT₉₀ samples.

Participants had been ill with COVID-19 14 to 35 days previously (n=45), 36 to 60 days (n=27), 61 to 75 days (n=55), or greater than 75 days (n=69). Stratified by their time since infection, average PRNT₅₀ neutralizing titers decreased with time (P <.0001) and a 6-week window was observed as the optimal time for maximizing higher titer samples. This pattern was not observed for PRNT₉₀ (P =.0661).

IgG ratios were observed to decline over time, although not significantly. Sera with IgG ratios less than 12 had significantly lower PRNT₅₀ and PRNT₉₀ levels compared against sera with ratios of at least 12 (P <.0001). Similarly, samples with ratios greater than 18.45 had significantly higher PRNT₅₀ and PRNT₉₀ titers (P <.0001).

Among the samples with IgG ratios greater than 18.45, the mean PRNT₅₀ titer was 1:523.5 and PRNT₉₀ titer was 1:190.4.

An area under the curve analysis determined the ideal cut off for diagnostic use was PRNT of at least 1:80 for both 50% (sensitivity, 91.9%; specificity, 93.1%) and 90% (sensitivity, 89.7%; specificity, 90.3%).

This study may have been limited by including only time since recovery from COVID-19 instead of time since symptom onset as stratification.

These data indicated the current guidelines for using CCP with IgG ratios of at least 12 may result in the inclusion of plasma with low neutralizing capacity. The study authors instead recommended that CCP should have ratios greater than 18.45, as these samples were more likely to have PRNT₅₀ titers of at least 1:640 and/or PRNT₉₀ titers of at least 1:80.

Reference

Girardin RC, Dupuis II AP, Payne AF, et al. Temporal analysis of serial donations reveals decrease in neutralizing capacity and justifies revised qualifying criteria for COVID-19 convalescent plasma. J Infect Dis. 2021;jiaa803. doi:10.1093/infdis/jiaa803.