Vaccine‐induced SARS‐CoV‐2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS‐CoV‐2 vaccine doses increase anti‐spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti‐spike IgG, pseudoneutralization (ACE2 blocking), and live‐virus neutralization (nAb) against VOCs before and after a third SARS‐CoV‐2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti‐spike IgG assays and focused on thresholds associated with neutralization. A third SARS‐CoV‐2 vaccine dose increased median total anti‐spike (1.6‐fold), pseudoneutralization against VOCs (2.5‐fold vs. Delta), and neutralizing antibodies (1.4‐fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti‐spike IgG >4 Log10(AU/ml) on the Euroimmun ELISA and >4 Log10(AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.

Immunocompromised populations are at high risk for severe COVID-19. Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs), and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses may increase anti-spike antibody titers in some SOTRs, but whether this results in enhanced neutralizing capability, especially versus novel variants of concern (VOCs) that exhibit immune escape and higher infectivity (e.g., the Delta variant), is unclear. Here, we report that a third dose of a SARS-CoV-2 vaccine increases anti-SARS-CoV-2 spike and RBD IgG levels as well as plasma neutralizing capability versus VOCs, including Delta, in some SOTRs. However, anti-spike IgG and neutralizing capability remained significantly reduced compared to fully vaccinated healthy controls. These findings highlight the need for continued study of strategies to improve protection from COVID-19 in immunosuppressed populations as more SARS-CoV-2 VOCs emerge.

Background The efficacy of COVID-19 convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-SARS-CoV-2 antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors. Methods A cross-sectional study was conducted among 20 pre-pandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n=35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percent detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher’s exact and Wilcoxon rank-sum tests, respectively. Results Among CCP donors (n=140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days(interquartile range=38-50) and 9%(n=12) were hospitalized due to COVID-19. Compared to healthy blood donor controls, CCP donors had significantly higher plasma levels of IFN-γ, IL-10, IL-15, IL-21 and MCP-1, but lower levels of IL-1RA, IL-8, IL-16, and VEGF-A(P&lt;0.0014). Significant differences were also observed in plasma levels of IL-8, IL-15 and IP-10 between CCP donors with low(&lt;40) vs. high(≥160) anti-SARS-CoV-2 neutralizing antibody titers(P&lt;0.0014). The median levels of IL-6, IL-8, TNF-α, IL-12/IL23p40, MDC were significantly higher among CCP donors who were hospitalized vs. non-hospitalized(P&lt;0.05). Conclusion Heterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors as compared to SARS-CoV-2 naïve, healthy blood donors.