Immunogenicity of the BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis Is Associated with Medical Conditions.

BACKGROUND AND OBJECTIVES: Patients undergoing maintenance hemodialysis have an attenuated immune response to vaccination. The aim of our study was to determine the predictive factors for humoral response to vaccination with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In this retrospective, single-center study, we included patients on maintenance hemodialysis already vaccinated with two doses of the BNT162b2 vaccine (Pfizer-BioNTech) and with a post-vaccination serological follow-up. RESULTS: 252 patients were included for study with a mean age of 71.9 (±14.4) years. Twelve patients (4.7%) were under immunosuppressive therapy (calcineurin inhibitors: n = 4; chemotherapy for myeloma: n = 3; last infusion of rituximab over the previous 4 years: n = 2; abatacept: n = 2; adalimumab n = 1). Three of these patients were under immunosuppressive therapy for nonrenal solid organ transplantation. Multivariate analysis identified immunosuppressive therapy (OR 4.73 [1.38-16.17], p = 0.013) and lower baseline albumin levels (OR 1.23 [1.09-1.38], p < 0.001) as independent predictive factors of nonresponse to vaccination. Older age (ß = -0.59 ± 0.21, p = 0.006) and immunosuppressive therapy (ß = 40.33 ± 13.33, p = 0.003) were significantly associated with lower humoral response to vaccination. CONCLUSIONS: Approximately 90% of patients under maintenance hemodialysis developed specific antibodies to the BNT162b2 mRNA vaccine. Immunosuppressive therapy, malnutrition, and older age were associated with a higher risk of nonseroconversion or lower humoral response to mRNA-based vaccination against SARS-CoV-2. We strongly recommend serological monitoring after vaccination to determine booster timing, especially for patients with malnutrition or on immunosuppressive therapy.

Expression of Exhaustion Markers on CD8+ T-Cell Patterns Predict Outcomes in Septic Patients Admitted to the ICU.

RATIONALE: There is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis. DESIGN: Observational prospective study. SETTING: Two ICUs in a teaching hospital (France). PATIENTS: Eighty patients with sepsis admitted to the ICU. INTERVENTIONS: Quantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ). MEASUREMENTS AND MAIN RESULTS: Using unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes. CONCLUSIONS: Easy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.

Pulmonary mucormycosis following autologous hematopoietic stem cell transplantation for rapidly progressive diffuse cutaneous systemic sclerosis: A case report.

RATIONALE: The use of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases has become the first indication for transplant in nonmalignant disease. Mucormycosis is a rare invasive infection with increasing incidence in patients treated with AHSCT. We report the first case of pulmonary mucormycosis following AHSCT for systemic sclerosis (SSc). PATIENT CONCERNS: A 24-year-old woman with rapidly progressive diffuse cutaneous SSc presented with an acute respiratory distress syndrome 6 days after AHSCT. DIAGNOSES: The results of clinical and computed tomography scan were consistent with pulmonary mucormycosis and the diagnosis was confirmed by a positive Mucorales Polymerase Chain Reaction on a peripheral blood sample. INTERVENTIONS AND OUTCOMES: Early antifungal therapy by intravenous amphotericin B provided rapid improvement within 4 days and sustained recovery after 2 years of follow-up. LESSONS: With the progressively increasing use of AHSCT and other stem cell therapy for treatment of severe SSc and other autoimmune diseases, the potential onset of rare post-transplant fungal infections, such as mucormycosis, requires careful patient monitoring and better awareness of early initiation of adequate therapy.

Outcomes of kidney transplant recipients admitted to the intensive care unit: a retrospective study of 200 patients.

BACKGROUND: Risk of over-immunosuppression or immunization may mitigate the overall and long-term renal outcomes of kidney transplant recipients (KTR) admitted to the ICU in the modern era but remain poorly described. Thus, there is an unmet need to better characterize the survival of KTR admitted to the ICU, but also the renal and immunological outcomes of survivors. METHODS: Retrospective observational study that included 200 KTR admitted between 2010 and 2016 to the ICU of a teaching hospital (median age 61 years [IQR 50.7-68]; time from transplantation 41 months [IQR 5-119]). Survival curves were compared using the Log-rank test. RESULTS: Mortality rates following admission to the ICU was low (26.5% at month-6), mainly related to early mortality (20% in-hospital), and predicted by the severity of the acute condition (SAPS2 score) but also by Epstein Barr Virus proliferation in the weeks preceding the admission to the ICU. Acute kidney injury (AKI) was highly prevalent (85.1%). Progression toward chronic kidney disease (CKD) was observed in 45.1% of survivors. 15.1% of survivors developed new anti-HLA antibodies (donor-specific antibodies 9.2% of cases) that may impact the long-term renal transplantation function. CONCLUSIONS: Notwithstanding the potential biases related to the retrospective and monocentric nature of this study, our findings obtained in a large cohort of KTR suggest that survival of KTR admitted in ICU is good but in-ICU management of these patients may alter both survival and AKI to CKD transition, as well as HLA immunization. Further interventional studies, including systematic characterization of the Epstein Barr virus proliferation at the admission (i.e., a potential surrogate marker of an underlying immune paralysis and frailty) will need to address the optimal management of immunosuppressive regimen in ICU to improve survival but also renal and immunological outcomes.

Short- and long-term outcomes of AL amyloidosis patients admitted into intensive care units.

Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs. 60%, P = 0·03; 71% vs. 45%, P = 0·02, respectively). In AL patients, the simplified Index of Gravity Score (IGS2) was the only independent predictive factor for death by day 28, whereas the Mayo-Clinic classification stage had no influence. In Cox's multivariate regression model, only cardiac arrest and on-going chemotherapy at ICU admission significantly predicted death at 6 months. Short-term outcomes of AL patients admitted into an ICU were mainly related to the severity of the acute medical condition, whereas on-going chemotherapy for active amyloidosis impacted on long-term outcomes.

Hepatitis E Virus-Induced Cryoglobulinemic Glomerulonephritis in a Nonimmunocompromised Person.

Hepatitis E virus (HEV)-related kidney disease and symptomatic cryoglobulinemia have been observed in solid-organ transplant recipients. However, HEV RNA in the cryoprecipitate has not yet been assessed. We report what to our knowledge is the first documented case of autochthonous HEV-induced cryoglobulinemic crescentic and membranoproliferative glomerulonephritis in an immunocompetent man with no notable medical history. He presented with edema, hypertension, increased serum creatinine level, and nephrotic syndrome. Type II cryoglobulinemia with monoclonal immunoglobulin G (IgG) κ light chain was detected. Anti-HEV IgG and IgM, as well as HEV RNA, were detected in serum and cryoprecipitate. Histologic analysis of a kidney biopsy specimen revealed features of crescentic and membranoproliferative glomerulonephritis. After HEV clearance, kidney and liver parameters improved and HEV RNA and cryoglobulinemia were undetectable. Hence, we conclude that HEV can cause severe kidney disease and should be considered in cases of unexplained glomerular disease.