Impact of HLA divergence on humoral response to SARS-CoV-2 and HBV vaccines in the liver transplantation setting (preprint)

Background. Organ 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. Methods: We 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. Findings: For 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). Interpretation: DQB1 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. Funding: Institut National de la Sante et de la Recherche Medicale (INSERM)

Oculomotor nerve palsy in an asymptomatic child with COVID-19.

We report the case of a 2-year-old girl with acute-onset divergent strabismus and ptosis in the right eye. She had an exotropia of 45Δ for near, eyelid ptosis affecting the visual axis, adduction, limitations of up- and downgaze, and a discrete mydriasis in the right eye. Neurological conditions were ruled out. Serology was positive for SARS-CoV-2 antibodies. The patient was managed conservatively with ocular physiotherapy and close visual acuity monitoring. On follow-up examination at 1 month, there was marked improvement of the exotropia (25Δ for near), adduction, ptosis, and mydriasis.