Trials of the Pfizer-BioNTech BNT162b2 mRNA vaccine showed 95% efficacy in preventing symptomatic disease; however, the trials excluded immunocompromised patients (ICPs). We aim at analyzing antibody response in ICPs. A prospective cohort study was conducted at Sheba Medical Center, Israel, between January and April 2020, in 1274 participants who received the vaccine, including 1002 ICPs and 272 immunocompetent healthcare workers (HCWs). Antibodies were measured two-four weeks after vaccination by SARS-CoV-2 anti–receptor binding domain IgG antibodies (RBD IgG) and pseudo-virus neutralization assays. Multivariable logistic regression analyses were used to identify factors associated with vaccine-induced antibody response. Adverse events (AEs) were monitored. RBD-IgG antibodies were detected in 154/156 (98.7%) of patients with HIV, 75/90 (83.3%) with solid malignancies, 149/187 (79.7%) with myeloma, 83/111 (74.8%) following hematopoietic stem cell transplants, 25/36 (69.4%) following liver transplantation, 26/43 (60.5%) with myelodysplastic syndrome, 96/188 (51.0%) with chronic lymphocytic leukemia/non-Hodgkin's lymphoma, 50/110 (45.5%) following kidney transplantation, 15/80 (18.8%) following heart transplantation, and 269/272 (98.9%) in controls. There was a significant correlation r = 0.74 (95%CI 0.69,0.78) between RBD-binding IgG and neutralizing antibodies in all groups. Multivariate logistic regression analysis showed that age > 65 years (OR 0.41,95%CI 0.30,0.57) and underlying immunosuppression (OR 0.02,95%CI 0.01,0.07) were significantly associated with a non-reactive response of IgG antibodies. HIV patients showed a similar immunological response as healthy adults. The vaccine was safe without any episodes of rejection, graft-versus-host disease (GVHD) or allergy. Immunocompetent HCWs experienced significantly more AEs than ICPs. Antibody response to the Pfizer-BioNTech vaccine was highly variable among different ICPs; thus, individual recommendations should be provided for the different immunosuppression states.

BACKGROUND. The goal of antiretroviral therapy (ART) is to suppress HIV-1 replication and reconstitute CD4 ⁺ T cells. Here, we report on HIV-infected individuals who had a paradoxical decline in CD4 ⁺ T cells despite ART-mediated suppression of plasma HIV-1 load (pVL). We defined such an immunological outcome as extreme immune decline (EXID). METHODS. EXID’s clinical and immunological characteristics were compared to immunological responders (IRs), immunological nonresponders (INRs), healthy controls (HCs), and idiopathic CD4 ⁺ lymphopenia (ICL) patients. T cell immunophenotyping and assembly/activation of inflammasomes were evaluated by flow cytometry. PBMC transcriptome analysis and genetic screening for pathogenic variants were performed. Levels of cytokines/chemokines were measured by electrochemiluminescence. Luciferase immunoprecipitation system and NK-mediated antibody-dependent cellular cytotoxicity (ADCC) assays were used to identify anti-lymphocyte autoantibodies. RESULTS. EXIDs were infected with non-B HIV-1 subtypes and after 192 weeks of consistent ART-mediated pVL suppression had a median CD4 ⁺ decrease of 157 cells/ μ l, compared with CD4 ⁺ increases of 193 cells/ μ l and 427 cells/ μ l in INR and IR, respectively. EXID had reduced naive CD4 ⁺ T cells, but similar proportions of cycling CD4 ⁺ T cells and HLA-DR ⁺ CD38 ⁺ CD8 ⁺ T cells compared with IR and INR. Levels of inflammatory cytokines were also similar in EXID and INR, but the IL-7 axis was profoundly perturbed compared with HC, IR, INR, and ICL. Genes involved in T cell and monocyte/macrophage function, autophagy, and cell migration were differentially expressed in EXID. Two of the 5 EXIDs had autoantibodies causing ADCC, while 2 different EXIDs had an increased inflammasome/caspase-1 activation despite consistently ART-suppressed pVL. CONCLUSIONS. EXID is a distinct immunological outcome compared with previously described INR. Anti–CD4 ⁺ T cell autoantibodies and aberrant inflammasome/caspase-1 activation despite suppressed HIV-1 viremia are among the mechanisms responsible for EXID.

Sexually transmitted diseases (STDs), mainly lymphogranuloma venereum (LGV), induce colorectal symptoms that may be misdiagnosed as inflammatory bowel disease (IBD). This study describes patients who presented with STDs masquerading as IBD in order to improve understanding of missed diagnosis of colorectal STDs and their association with LGV in Israel. This retrospective, descriptive study characterized the clinical, endoscopic, and pathological findings of 16 patients who were diagnosed with a colorectal STD after erroneously being diagnosed with IBD. Molecular genotyping was used to characterize some of the Chlamydia trachomatis isolates. All patients were men who have sex with men (MSM), mostly HIV-1-positive, and had clinical and endoscopic findings compatible with IBD. The STD was diagnosed 1-36 months after the initial diagnosis: 14 were positive for Chlamydia trachomatis, of which three were of the LGV2b (ST58) serotype and one was ST 108 serotype. Five were positive for gonorrhea and four were positive for syphilis. Several pathogens were diagnosed in six episodes. Colorectal STDs may resemble IBD and therefore their diagnosis may be delayed. IBD symptoms in MSM who engage in non-protected anal sex should prompt at least syphilis and anal PCR for STD testing. If C. trachomatis is diagnosed but LGV subtyping cannot be done, doxycycline 100mg twice daily for 21days should be recommended.