Cytokine and Chemokine Levels in Coronavirus Disease 2019 Convalescent Plasma

Abstract

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<0.0014). Significant differences were also observed in plasma levels of IL-8, IL-15 and IP-10 between CCP donors with low(<40) vs. high(≥160) anti-SARS-CoV-2 neutralizing antibody titers(P<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<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.

SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals

“…For example, those later in the convalescent period exhibited T cell maturation with effector cells remaining, possibly to clear residual infection. This is consistent with the cytokine data, demonstrating a time effect since diagnosis (32).…”

“…Highly sensitive, multiplexed sandwich immunoassays using MULTI-ARRAY electrochemiluminescence detection technology (MesoScale Discovery) were used for the quantitative evaluation of 35 different human cytokines and chemokines in plasma samples from eligible CCP donors (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A, Eotaxin, MIP-1β, Eotaxin-3, TARC, IP-10, MIP-1α, MCP-1, MDC, MCP-4, IL-18, IL-1RA, G-CSF [CSF3], IFN-2a, IL-33, and IL-21), as previously described (32). Cytokine and chemokine concentrations were calculated per manufacturer protocol (MSD Discovery Workbench analysis software) and were considered detectable if both runs of each sample had a signal greater than the analyte-and plate-specific lower limit of detection (LLOD) (i.e., 2.5 SDs of the plate-specific blank).…”

Rapid implementation of a cohort for the study of post-acute sequelae of SARS-CoV-2 infection/COVID-19

“…Furthermore, the pathogenesis of PASC is entirely unknown. Some studies have detected biologic abnormalities but have not yet linked them to clinical phenotypes [13][14][15][16][17][18]. As millions of individuals worldwide continue to become infected with SARS-CoV-2, the public health implications of PASC and the need to uncover interventions to prevent or treat it are self-evident.…”

Coronavirus Disease 2019 Convalescent Plasma and the Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Titer

“…As Girardin and colleagues have demonstrated in the current study [ 1 ], studying CCP continues to provide invaluable insight into the immunopathogenesis of SARS-CoV-2 [ 21 , 22 ]. While their findings suggest potential modification of CCP donation, refined practice may be impractical.…”