ABSTRACT
Purpose: To define the burden of morbidity and mortality arising from COVID-19 in individuals with primary (PID) and secondary immunodeficiency (SID) in the United Kingdom. Methods In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. Anonymised demographic data, pre-SARS-CoV-2 infection lymphocyte counts, co-morbidities, targeted treatments and outcomes were collected. Three groups were analysed in further detail: individuals with common variable immunodeficiency (CVID), individuals with any PID, including CVID, receiving immunoglobulin replacement therapy (IgRT) and individuals with secondary immunodeficiency. Results A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID, had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Conclusion Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.
Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Common Variable ImmunodeficiencyABSTRACT
Severe 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 optimization studies are required to evaluate the performance characteristics of these assays which could facilitate widescale sero-epidemiological surveillance.