ABSTRACT
ObjectiveSARS-CoV-2 vaccinations have demonstrated vaccine immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. Subsequently, there is an urgent need to address the impact of immunosuppression on vaccine immunogenicity. MethodsSerological, T-cell ELISpot, cytokines and immunophenotyping investigations were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n=13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n=12), unvaccinated (UNVACC, n=11) and infection-naive unvaccinated (HC, n=3) cohorts. All participants, except HC, had prior COVID-19 infection. ResultsT-cell responses were identical between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n=3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. Furthermore, both VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS. ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.
ABSTRACT
PurposeSARS-CoV-2 serology testing is key for assessing seroprevalence and antibody response post-vaccination in immunocompromised patients. Evaluation of current SARS-CoV-2 serological assays have been performed on samples from severe COVID-19 hospitalised patients. However, robust assay development requires assessment in asymptomatic and non-hospitalised individuals to determine if serological assays are sensitive to detect waning and mild antibody responses. Our study evaluated the performance characteristics between two high-throughput SARS-CoV-2 IgG nucleocapsid assays (Abbott and Roche) and The binding site (TBS) Anti-Spike IgG/A/M ELISA kit in healthcare workers. Methods236 samples were collected from Portsmouth Hospital University NHS Trust (PHU) and The Dudley Group NHS Trust and analysed for SARS-CoV-2 serology. We derived concordance, agreement and assay performance as well as using receiver operating characteristic (ROC) curves to redefine the assay threshold of the Abbott assay. ResultsResult concordance between the Abbott and TBS was 66%. Discrepant samples were analysed using the Roche assay which showed 100% agreement with the TBS assay. In samples analysed >58 days post-PCR, the sensitivity of Abbott and Roche was 100%. In samples analysed >100 days post-PCR the sensitivity of the Abbott assay dropped to 77.2% but remained at 100% for the Roche assay. A redefined Abbott threshold of 0.64 increased the sensitivity to 90% giving results similar to Roche and TBS assays ConclusionThis study demonstrated Abbott assay had a lower sensitivity in comparison to TBS and Roche. Furthermore, TBS can be implemented as a viable alternative for SARS-CoV-2 serology testing where high-throughput assays are not available on site. Trial registration number and date of registration Not applicable. Trial registration number, date of registration followed by "retrospectively registered" Not applicable. AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology testing is key for assessing seroprevalence and antibody response post-vaccination in immunocompromised patients. Here we performed a comparison between two high-throughput nucleocapsid assays (Abbott SARS-CoV-2 IgG and Roche Elecsys Anti-SARS-CoV-2) and The Binding Site (TBS) anti-Spike IgG/A/M-SARS-CoV-2 ELISA kit. 236 samples were collected across 2 sites, Portsmouth Hospital University NHS Trust (PHU) and The Dudley Group NHS Trust. We derived concordance, agreement and assay performance as well as using receiver operating characteristic (ROC) curves to redefine the assay threshold of the Abbott assay. Result concordance between the Abbott and TBS was 66%. Discrepant samples were analysed using the Roche assay which showed 100% agreement with the TBS assay. In samples analysed >58 days post-PCR, the sensitivity of Abbott and Roche was 100%. In samples analysed >100 days post-PCR the sensitivity of the Abbott assay dropped to 77.2% but remained at 100% for the Roche assay. A redefined Abbott threshold of 0.64 increased the sensitivity to 90% giving results similar to the Roche and TBS assays. In conclusion, this study demonstrated Abbott assay had a lower sensitivity in comparison to TBS and Roche. This study established TBS can be implemented as a viable alternative for SARS-CoV-2 serology testing where high-throughput assays are not available on site. Furthermore, anti-spike assays, such as TBS, could be used to monitor vaccination responses to deduce SARS-CoV-2 population-immunity. Further optimisation studies are required to evaluate the performance characteristics of these assays which could facilitate widescale sero-epidemiological surveillance.
