Whole blood-based measurement of SARS-CoV-2-specific T cell responses reveals asymptomatic infection and vaccine efficacy in healthy subjects and patients with solid organ cancers (preprint)

Accurate assessment of SARS-CoV-2 immunity in the population is critical to evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T cell responses are a critical feature of the immune response that will likely form a key correlate of protection against COVID-19. Here, we developed and optimised a high-throughput whole blood-based assay to determine the T cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 156 healthy donors and 67 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were harvested and analysed for Th1-type effector cytokines (IFN-{gamma} and IL-2). Amongst healthy donors, highly significant differential IFN-{gamma}+/IL-2+ SARS-CoV-2-specific T cell responses were seen amongst vaccinated or previously infected COVID-19-positive individuals in comparison to unknown/naive individuals (P < 0.0001). IL-2 production from T cells in response to SARS-CoV-2 derived antigens was a highly predictive diagnostic assay (P < 0.0001; 96.0% sensitivity, 93.9% specificity); measurement of IFN-{gamma}+ SARS-CoV-2 specific T cell responses was equally effective at identifying asymptomatic (antibody and T cell positive) participants. A single dose of COVID-19 vaccine induced IFN-{gamma} and/or IL-2 SARS-CoV-2-specific T cell responses in 28/29 (96.6%) of healthy donors, reducing significantly to 27/56 (48.2%) when measured in cancer patients (P = 0.0003). Overall, this cost-effective standardisable test ensures accurate and comparable assessments of SARS-CoV-2-specific T cell responses amenable to widespread population immunity testing.

Hospital-Based Donor Recruitment and Pre-Donation Serologic Testing for COVID-19 Convalescent Plasma (preprint)

BackgroundMajor blood centers perform serologic testing on potential COVID-19 convalescent plasma donors retrospectively after blood donation. A hospital-based recruitment program for COVID-19 convalescent plasma (CCP) donors may be an efficient way to prospectively identify potential donors. Study Design and MethodsPatients who recovered from known or suspected COVID-19 were identified and recruited through medical record searches and public appeals. Participants were screened with a modified donor history questionnaire (DHQ), and if eligible, were consented and tested for SARS-CoV-2 antibodies (IgG and IgM). Participants who were positive for SARS-CoV-2 IgG were referred to a local blood center for convalescent plasma collection. ResultsOf 179 individuals screened, 128 completed serologic testing and 89 were referred for convalescent plasma donation to a local blood center (49.7% of those screened). IgG antibodies to SARS-CoV-2 were detected in 23/51 (45.1%) of participants with suspected COVID-19 and in 66/77 (85.7%) of participants with self-reported PCR-confirmed COVID-19. Testing was performed at a median of 38 days since last symptoms. Participant age positively correlated with anti-SARS-CoV-2 IgG and IgM levels. Time since last symptoms did not correlate with IgG or IgM levels. A wide range of SARS-CoV-2 IgG levels were observed. ConclusionA hospital based CCP donor recruitment program can prospectively identify potential CCP donors. Variability in SARS-CoV-2 IgG levels has implications for selection of CCP units for transfusion.