We compared the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific antibodies to induce natural killer cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in patients with natural infection and vaccinated persons. Analyzing plasma samples from 39 coronavirus disease 2019 (COVID-19) patients and 11 vaccinated individuals, significant induction of ADCC could be observed over a period of more than 3 months in both vaccinated and recovered individuals. Although plasma antibody concentrations were lower in recovered patients, we found antibodies elicited by natural infection induced a significantly stronger ADCC response compared to those induced by vaccination, which may affect protection conferred by vaccination.

Background and Aims: Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers. Approach and Results: A total of 50 livers (nonfibrotic = 22, and fibrotic = 29) were analyzed and compared with colon and tonsil tissue (each N = 14) and peripheral blood (N = 32). Human intrahepatic ILCs were characterized ex vivo and on stimulation using flow cytometry and single-cell RNA sequencing. ILC differentiation and plasticity were analyzed by both bulk and clonal expansion experiments. Finally, the effects of ILC-derived cytokines on primary human HSteCs were studied. Unexpectedly, we found that an “unconventional” ILC3-like cell represented the major IL-13-producing liver ILC subset. IL-13⁺ ILC3-like cells were specifically enriched in the human liver, and increased frequencies of this cell type were found in fibrotic livers. ILC3-derived IL-13 production induced upregulation of proinflammatory genes in HSteCs, indicating a potential role in the regulation of hepatic fibrogenesis. Finally, we identified KLRG1-expressing ILC precursors as the potential progenitor of hepatic IL-13⁺ ILC3-like cells. Conclusions: We identified a formerly undescribed subset of IL-13–producing ILC3-like cells that is enriched in the human liver and may be involved in the modulation of chronic liver disease.

While the syndrome of inadequate antidiuresis (SIAD) is still the most common cause of hyponatremia in cancer patients, the rise in endocrine immune-related adverse events (irAEs) owing to immune checkpoint inhibitors (ICI) considerably shaped the differential diagnosis of electrolyte disorders in cancer patients. We report here 3 cases of different endocrine irAEs, first manifesting with new-onset hyponatremia under ICI therapy for malignant melanoma: one with primary adrenal insufficiency, one with hypophysitis, and one with autoimmune type 1 diabetes. Early diagnosis of endocrine toxicities can save lives but may be challenging and essentially delayed by subtle or nonspecific clinical presentation and a lack of readily available endocrinological laboratory evaluation in the primary care setting. This exemplary case series demonstrates the broad spectrum of endocrinopathies that physicians should be aware of under ICI therapy and emphasizes new-onset hyponatremia as a possibly early, simple, and low-cost biomarker of irAEs, which may be considered as a red flag in patients receiving checkpoint blockade. As ICI-induced endocrinopathies are still under-represented in clinical practice guidelines, we here propose an updated algorithm for diagnosis of cancer-related hyponatremia, highlighting the important diagnostic steps to be considered before making the diagnosis of SIAD.

Goals and Background: International guidelines recommend prioritized treatment initiation in hepatitis C virus (HCV)-infected patients with advanced liver disease. We aimed to evaluate whether the widespread usage of direct acting antivirals (DAAs) has led to a decrease in late presentation for care. Study: Data derived from the multicenter German Hepatitis C Cohort (GECCO) was analyzed. Treatment naive HCV-infected patients initiating DAA-based treatment between January 2014 and September 2017 were included. Advanced liver disease was defined by aspartate aminotransferase to platelet ratio index score ≥1.5, METAVIR≥F3, or FibroScan ≥9.5 kPa. Period prevalence and risk factors for late presentation were evaluated. Results: Six hundred fifty-three HCV-monoinfected and 210 HIV/HCV-coinfected patients (mean age, 48.6±12.7 y; 65.5% male) were included. Overall 32.5% of patients had advanced liver disease. In 2014 39.4% of patients presented with advanced liver disease, decreasing to 30.1%, 34.4%, and 26.4% in the years 2015, 2016, and 2017 (P=0.057), respectively. Patients with and without advanced liver disease differed in age (P<0.0001), CD4⁺ ≤350/µL (P=0.027), genotype (P=0.005), transmission route (P=0.047), body mass index (P2 years ago were positively and HCV transmission through men who have sex with men was negatively associated with advanced liver disease. Conclusions: Overall 32.5% of patients presented with advanced liver disease. We observed a trend toward a lower proportion of patients starting treatment late. GT3, age, years since HCV diagnosis and HCV transmission route were identified as risk factors for presentation with advanced liver disease.