Longitudinal evaluation of the impact of immunosuppressive regimen on immune responses to COVID-19 vaccination in kidney transplant recipients.

International audienceImmunocompromised patients have a high risk of death from SARS-CoV-2 infection. Vaccination with an mRNA vaccine may protect these patients against severe COVID-19. Several studies have evaluated the impact of immune-suppressive drug regimens on cellular and humoral responses to SARS-CoV-2 variants of concern in this context. We performed a prospective longitudinal study assessing specific humoral (binding and neutralizing antibodies against spike (S) and T-lymphocyte (cytokine secretion and polyfunctionality) immune responses to anti-COVID-19 vaccination with at least two doses of BNT162b2 mRNA vaccine in stable kidney transplant recipients (KTR) on calcineurin inhibitor (CNI)- or belatacept-based treatment regimens. Fifty-two KTR−31 receiving CNI and 21 receiving belatacept—were enrolled in this study. After two doses of vaccine, 46.9% of patients developed anti-S IgG. Anti-spike IgG antibodies were produced in only 21.4% of the patients in the belatacept group, vs. 83.3% of those in the CNI group. The Beta and Delta variants and, more importantly, the Omicron variant, were less well neutralized than the Wuhan strain. T-cell functions were also much weaker in the belatacept group than in the CNI group. Renal transplant patients have an impaired humoral response to BNT162b2 vaccination. Belatacept-based regimens severely weaken both humoral and cellular vaccine responses. Clinically, careful evaluations of at least binding IgG responses, and prophylactic or post-exposure strategies are strongly recommended for transplant recipients on belatacept-based regimens

CD177, a specific marker of neutrophil activation, is associated with coronavirus disease 2019 severity and death

International audienceThe identification of patients with coronavirus disease 2019 and high risk of severe disease is a challenge in routine care. We performed cell phenotypic, serum, and RNA sequencing gene expression analyses in severe hospitalized patients (n = 61). Relative to healthy donors, results showed abnormalities of 27 cell populations and an elevation of 42 cytokines, neutrophil chemo-attractants, and inflammatory components in patients. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. Higher levels were confirmed in a second cohort and in intensive care unit (ICU) than non-ICU patients (P < 0.001). Longitudinal measurements discriminated between patients with the worst prognosis, leading to death, and those who recovered (P = 0.01). These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care