ABSTRACT
BackgroundOrgan transplant recipients are at high risk of viral infections but show lower humoral vaccine responsiveness than immunocompetent individuals. HLA evolutionary divergence (HED) quantifies the sequence differences between homologous HLA alleles and reflects the breadth of the immunopeptidome presented to T lymphocytes. MethodsWe retrospectively investigated the impact of HED on humoral response to SARS-CoV-2 mRNA vaccine in 310 liver transplant recipients (undetectable anti-spike IgG titers considered as no response, [≤]250 BAU/mL as moderate response, >250 BAU/mL as strong response) and to Hepatitis B virus (HBV) vaccine in 424 liver transplant candidates (anti-HBs IgG <10 mIU/mL considered as no response, 10-100 mIU/mL as moderate reponse, [≥]100 mIU/mL as strong response). HED between aligned allele pairs at HLA-A, -B, -DRB1 and- DQB1 loci were measured as a continuous metric using the Grantham distance. The impact of HED on vaccine responses was analyzed through ordinal logistic regression and inverse probability weighting approach based on generalised propensity scores. FindingsFor both vaccines, HED at the DQB1 locus, but not at other loci, was significantly higher in responders than in others, independent of covariates associated to the response (age, time since transplant, hemoglobin levels, combined graft, immunosuppression with steroids or mycophenolate for SARS-CoV-2 vaccine; age, gender, and liver disease for HBV vaccine). InterpretationDQB1 HED is a critical determinant of humoral response to vaccines in liver transplant recipients. This metric could guide the design of future vaccines as it predicts the magnitude of the repertoire of vaccine-derived peptides presented to CD4 helper T cells. FundingInstitut National de la Sante et de la Recherche Medicale (INSERM)
ABSTRACT
Numerous SARS-CoV-2 rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially-available SARS-CoV-2 rapid serological tests using the STARD methodology (Standards for Reporting of Diagnostic Accuracy Studies). 250 sera from 159 PCR-confirmed SARS-CoV-2 patients (collected from 0 to 32 days after onset of symptoms) were tested with rapid serological tests. Control sera (N=254) were retrieved from pre-COVID periods from patients with other coronavirus infections (N=11), positive rheumatoid factors (N=3), IgG/IgM hyperglobulinemia (N=9), malaria (n=5), or no documented viral infection (N=226). All samples were tested using rapid lateral flow immunoassays (LFIA) from ten manufacturers. Only four tests achieved [≥]98% specificity, with other tests ranging from 75.7%-99.2%. Sensitivities varied by the day of sample collection, from 31.7%-55.4% (Days 0-9), 65.9%-92.9% (Days 10-14), and 81.0%-95.2% (>14 days) after the onset of symptoms, respectively. Only three tests evaluated met French Health Authorities' thresholds for SARS-CoV-2 serological tests ([≥]90% sensitivity + [≥]98% specificity). Overall, the performances between tests varied greatly, with only a third meeting acceptable specificity and sensitivity thresholds. Knowing the analytical performance of these tests will allow clinicians to use them with more confidence, could help determine the general population's immunological status, and may diagnose some patients with false-negative RT-PCR results.
