HLA B53 is associated with a poor outcome in black COVID-19 patients.

A disproportionate incidence of death has occurred in African Americans (Blacks) in the United States due to COVID-19. The reason for this disparity is likely to be multi-factorial and may involve genetic predisposition. The association of human leukocyte antigens (HLA) with severe COVID-19 was examined in a hospitalized population (89% Black, n = 36) and compared to HLA typed non-hospitalized individuals (20% Black, n = 40) who had recovered from mild disease. For additional comparison, HLA typing data was available from kidney transplant recipients and deceased donors. Hospitalized patients were followed for 45 days after admission to our medical center with death as the primary end-point. One HLA allele, B53, appeared to be more prevalent in the hospitalized COVID-19 patients (percent of positive subjects, 30.5) compared to national data in US Black populations (percent of positive subjects, 24.5). The percent B53 positive in non-hospitalized COVID-19 patients was 2.6, significantly less than the percent positive in the hospitalized COVID-19 patients (p = 0.001, Fisher's exact test) and less than the 8 percent positive listed in national data bases for US Caucasian populations. Significantly greater deaths (73 percent) were observed in HLA B53 positive hospitalized COVID-19 patients compared to hospitalized COVID-19 patients who were B53 negative (40 percent). Multi-variate analysis indicated that HLA B53 positive Black hospitalized COVID-19 patients were at a 7.4 fold greater risk of death than Black COVID-19 patients who were B53 negative. Consideration for accelerated vaccination and treatment should be given to HLA B53 positive Black COVID19 patients.

Correlation of Automated Chemiluminescent Method with Enzyme-Linked Immunosorbent Assay (ELISA) Antibody Titers in Convalescent COVID-19 Plasma Samples: Development of Rapid, Cost-Effective Semi-Quantitative Diagnostic Methods.

BACKGROUND: We investigated the utility of an automated chemiluminescent SARS-CoV-2 IgG antibody assay platform in quantifying the amount of binding antibodies present in donated convalescent plasma. METHODS: A total of 179 convalescent plasma units were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Beckman-Coulter chemiluminescent immunoassay (CLIA) platform. The equipment-derived numerical values (S/Co ratio) were recorded. Aliquots from the same units were subjected to enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 S1 protein. The relationship between ELISA titers and CLIA S/Co values was analyzed using linear regression and receiver operating characteristics (ROC) curve. RESULTS: Twenty-one samples (11.7%) had S/Co values of less than 1.0 and were deemed negative for antibodies and convalescent plasma had S/Co values between >1.0 and 5.0 (70/179, 39.1%). Fifteen units (8.4%) had negative ELISA titer. The majority of the units (95/179. 53.1%) had titers ≥1:1024. The sensitivities of ELISA to CLIA were comparable (90.5% vs 88.3%, respectively; p=0.18). There was positive linear correlation between CLIA S/Co values and ELISA IgG titer (Rho = 0.75; Spearman's rank = 0.82, p-value = <0.0001). The agreement between the two methods was fair, with a κ index of 0.2741. Using the ROC analysis, we identified a CLIA S/Co cutoff value of 8.2, which gives a sensitivity of 90% and a specificity of 82% in predicting a titer dilution of ≥1:1024. CONCLUSION: The utility of automated antibody detection systems can be extended from simply a screening method to a semi-quantitative and quantitative functional antibody analysis. CLIA S/Co values can be used to reliably estimate the ELISA antibody titer. Incorporation of chemiluminescent-based methods can provide rapid, cost-effective means of identifying anti-SARS-CoV-2 antibody titers in donated plasma for use in the treatment of COVID-19 infection.

Administration of high titer convalescent anti-SARS-CoV-2 plasma: From donor selection to monitoring recipient outcomes.

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.