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The experience of individuals with Coronavirus Disease 2019 (COVID‐19) ranges from asymptomatic to life threatening multi‐organ dysfunction. Specific HLA alleles may affect the predisposition to severe COVID‐19 because of their role in presenting viral peptides to launch the adaptive immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In this population‐based case–control study in the midwestern United States, we performed high‐resolution HLA typing of 234 cases hospitalized for COVID‐19 in the St. Louis metropolitan area and compared their HLA allele frequencies with those of 22,000 matched controls from the National Marrow Donor Program (NMDP). We identified two predisposing alleles, HLA‐DRB1*08:02 in the Hispanic group (OR = 9.0, 95% confidence interval: 2.2–37.9; adjusted p = 0.03) and HLA‐A*30:02 in younger African Americans with ages below the median (OR = 2.2, 1.4–3.6; adjusted p = 0.01), and several candidate alleles with potential associations with COVID‐19 in African American, White, and Hispanic groups. We also detected risk‐associated amino acid residues in the peptide binding grooves of some of these alleles, suggesting the presence of functional associations. These findings support the notion that specific HLA alleles may be protective or predisposing factors to COVID‐19. Future consortium analysis of pooled cases and controls is warranted to validate and extend these findings, and correlation with viral peptide binding studies will provide additional evidence for the functional association between HLA alleles and COVID‐19. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose–response data using the Ortho VITROS IgG assay. The proliferation of severe acute respiratory syndrome coronavirus 2 serological assays and non‐uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between multiple serological assays. Methods: We compared the Ortho, Abbott, Roche, an anti‐spike (S) ELISA, and a virus neutralization assay. Relationships relative to FDA‐approved cutoffs under the CCP emergency use authorization were identified in convalescent plasma from a cohort of 79 donors from April 2020. Results: Relative to the neutralization assay, the spearman r value of the Ortho Clinical, Abbott, Roche, anti‐S ELISA assays was 0.65, 0.59, 0.45, and 0.76, respectively. The best correlative index for establishing high‐titer units was 3.87 signal‐to‐cutoff (S/C) for the Abbott, 13.82 cutoff index for the Roche, 1:1412 for the anti‐S ELISA, 1:219 by the neutralization assay, and 15.9 S/C by the Ortho Clinical assay. The overall agreement using derived cutoffs compared to a neutralizing titer of 1:250 was 78.5% for Abbott, 74.7% for Roche, 83.5% for the anti‐S ELISA, and 78.5% for Ortho Clinical. DISCUSSION: Assays based on antibodies against the nucleoprotein were positively associated with neutralizing titers and the Ortho assay, although their ability to distinguish FDA high‐titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

ABSTRACT: Obese and type 2 diabetic (T2D) patients have a fivefold increased rate of infection following placement of an indwelling orthopaedic device. Though implant infections are associated with inflammation, periosteal reactive bone formation, and osteolysis, the effect of obesity/T2D on these complicating factors has not been studied. To address this question, C57BL/6J mice were fed a high fat diet (60% Kcal from fat) to induce obesity/T2D, or a control diet (10% Kcal from fat) for 3 months, and challenged with a transtibial pin coated with a bioluminescent USA300 strain of S. aureus. In the resulting infected bone, obesity/T2D was associated with increased S. aureus proliferation and colony forming units. RNA sequencing of the infected tibiae on days 7 and 14 revealed an increase in 635 genes in obese/T2D mice relative to controls. Pathways associated with ossification, angiogenesis, and immunity were enriched. MicroCT and histology on days 21 and 35 demonstrated significant increased periosteal reactive bone formation in infected obese/T2D mice versus infected controls (p < 0.05). The enhanced periosteal bone formation was associated with increased osteoblastic activity and robust endochondral ossification, with persistant cartilage on day 21 that was only observed in infected obesity/T2D. Osteolysis and osteoclast numbers in obesity/T2D were also significantly increased versus infected controls (p < 0.05). Consistent with an up‐regulated immune transcriptome, macrophages were more abundant within both the periosteum and the new reactive bone of obese/T2D mice. In conclusion, we find that implant‐associated S. aureus osteomyelitis in obesity/T2D is associated with increased inflammation, reactive bone formation, and osteolysis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1614–1623, 2018. [ABSTRACT FROM AUTHOR]