Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16⁺ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16⁺ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16⁺ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16⁺ cytotoxic T cells. Proportions of activated CD16⁺ T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. Procedures in adult patients (January 2011–June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011–2013, 2014–2017 and 2018–2020). Adverse event rates (AERs) were calculated and stratified into early phase (3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (3 months). In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3–2.6) years. The annual number of implants (range: 346–600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4–7: 23, 25 and 33%; P < 0.001) and in-hospital deaths (18.5, 17.2 and 11.2; P < 0.001) decreased significantly between eras. Overall, mortality, transplants and the probability of weaning were 55, 25 and 2% at 5 years after the implant, respectively. Major infections were mainly noted early after the implant occurred (AER_{<3 months}: 1.44 vs AER_{>3 months}: 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant. In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent.

With the exception of inactivated vaccines, all SARS-CoV-2 vaccines currently used for clinical application focus on the spike envelope glycoprotein as a virus-specific antigen. Compared to other SARS-CoV-2 genes, mutations in the spike protein gene are more rapidly selected and spread within the population, which carries the risk of impairing the efficacy of spike-based vaccines. It is unclear to what extent the loss of neutralizing antibody epitopes can be compensated by cellular immune responses, and whether the use of other SARS-CoV-2 antigens might cause a more diverse immune response and better long-term protection, particularly in light of the continued evolution towards new SARS-CoV-2 variants. To address this question, we explored immunogenicity and protective effects of adenoviral vectors encoding either the full-length spike protein (S), the nucleocapsid protein (N), the receptor binding domain (RBD) or a hybrid construct of RBD and the membrane protein (M) in a highly susceptible COVID-19 hamster model. All adenoviral vaccines provided life-saving protection against SARS-CoV-2-infection. The most efficient protection was achieved after exposure to full-length spike. However, the nucleocapsid protein, which triggered a robust T-cell response but did not facilitate the formation of neutralizing antibodies, controlled early virus replication efficiently and prevented severe pneumonia. Although the full-length spike protein is an excellent target for vaccines, it does not appear to be the only option for future vaccine design.

OBJECTIVES: Mitral regurgitation (MR) is frequently observed in patients undergoing left ventricular assist device implantation. We investigated the impact of preoperative MR on left ventricular assist device patients. METHODS: A retrospective propensity score-matched analysis of adult patients enrolled in the EUROMACS registry between 1 January 2011 and 30 November 2021 was performed. Patients were divided into 2 groups according to the grade of preoperative MR: none-to-mild (MR 0–II) or moderate-to-severe (MR III–IV). RESULTS: Following 1:1 propensity score matching, each group consisted of 914 patients. Incidence of postoperative temporary right ventricular support, reoperation for bleeding and dialysis was similar. MR III–IV demonstrated shorter median intensive care unit stay [14 days (6; 27.8) vs 10 days (5; 22), P = 0.004] and ventilation time [72 h (22, 320) vs 31 h (18, 150), P < 0.001]. Mortality was lower for MR III–IV patients [subdistribution hazard ratio: 0.66, 95% confidence interval (CI): 0.59–0.73, P < 0.001]. The 1-year survival was 68.1% (95% CI: 65.1–71.3%) in MR 0–II and 75% (95% CI: 72.1–78%) in MR III–IV. A lower incidence of total complications [odds ratio (OR): 0.93 (0.89–0.98), P = 0.003] and trend towards a lower risk of neurological dysfunction (subdistribution hazard ratio: 0.79; 95% CI: 0.61–1.01, P = 0.063) and sustained ventricular tachycardia [OR: 0.93 (0.54–1.03), P = 0.074] were demonstrated for MR III–IV. The risk of fatal stroke and pump thrombosis was similar. CONCLUSIONS: Moderate-to-severe MR in patients undergoing left ventricular assist device implantation is associated with better mid-term survival and lower incidence of total major adverse events and complications. The incidence of severe postoperative complications including fatal stroke and device thrombosis was similar.