Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2). So far, viral targets of cellular immunity and factors determining successful mounting of T cell responses are poorly defined. We therefore analyzed cellular responses to membrane, nucleocapsid, and spike proteins in individuals suffering from moderate or severe infection and in individuals who recovered from mild disease. We demonstrate that the CoV-2–specific CD4⁺ T helper cell response is directed against all 3 proteins with comparable magnitude, ex vivo proliferation, and portions of responding patients. However, individuals who died were more likely to have not mounted a cellular response to the proteins. Higher patient age and comorbidity index correlated with increased frequencies of CoV-2–specific CD4⁺ T cells, harboring higher portions of IL-2–secreting, but lower portions of IFN-γ–secreting, cells. Diminished frequencies of membrane protein–reactive IFN-γ⁺ T cells were particularly associated with higher acute physiology and chronic health evaluation II scores in patients admitted to intensive care. CoV-2–specific T cells exhibited elevated PD-1 expression in patients with active disease as compared with those individuals who recovered from previous mild disease. In summary, our data suggest a link between individual patient predisposition with respect to age and comorbidity and impairment of CoV-2–specific Th1-type cellular immunity, thereby supporting a concept of altered T cell function in at-risk patients.

Studies from multiple countries have shown that acute kidney injury (AKI) in hospitalized patients is associated with mortality and morbidity. There are no reliable data at present on the incidence and mortality of AKI episodes among hospitalized patients in Germany. The utility of administrative codings of AKI for the identification of AKI episodes is also unclear. In an exploratory approach, we retrospectively analyzed all episodes of AKI over a period of 3.5 years (2014-2017) on the basis of routinely obtained serum creatinine measurements in 103 161 patients whose creatinine had been measured at least twice and who had been in the hospital for at least two days. We used the "Kidney Disease: Improving Global Outcomes" (KDIGO) criteria for AKI. In parallel, we assessed the administrative coding of discharge diagnoses of the same patients with codes from the International Classification of Diseases (ICD-10-GM). Among 185 760 hospitalizations, stage 1 AKI occurred in 25 417 cases (13.7%), stage 2 in 8503 cases (4.6%), and stage 3 in 5881 cases (3.1%). AKI cases were associated with length of hospital stay, renal morbidity, and overall mortality, and this association was stage-dependent. The in-hospital mortality was 5.1% for patients with stage 1 AKI, 13.7% for patients with stage 2 AKI, and 24.8% for patients with stage 3 AKI. An administrative coding for acute kidney injury (N17) was present in only 28.8% (11 481) of the AKI cases that were identified by creatinine criteria. Like the AKI cases overall, those that were identified by creatinine criteria but were not coded as AKI had significantly higher mortality, and this association was stage-dependent. AKI episodes are common among hospitalized patients and are associated with considerable morbidity and mortality, yet they are inadequately documented and probably often escape the attention of the treating physicians.

The Eurotransplant Senior Program (ESP) neglects HLA matching for elderly (≥65 years) kidney transplant recipients (KTR). Few data regarding the influence of DR matching on clinical and immunologic outcome in elderly KTR exist. This retrospective long-term observational study included 244 elderly out of n = 972 adult KTR between 2004 and 2014. Data analysis included patient and graft survival, biopsy-proven rejections [T-cell-mediated rejections (TCMR) and antibody-mediated rejections] and development of de novo donor-specific HLA antibodies (DSA). Outcome data were assessed over a maximum period of 10 years. Due to the nature of the ESP, elderly KTR showed significantly more HLA mismatches, shorter time on dialysis and shorter cold ischaemia time. Elderly KTR had significantly worse graft and patient survival, and after 7 years, the rate of de novo DSA (33 versus 25%, P = 0.034) and TCMR (39 versus 27%, P < 0.001) was significantly higher compared with younger KTR. Multivariate analysis identified donor age, delayed graft function and HLA-DR mismatches as independent risk factors for TCMR. Within the group of elderly KTR, HLA-DR mismatches were associated with a significantly higher incidence of TCMR and development of de novo DSA. Occurrence of TCMR and de novo DSA in elderly KTR resulted in significantly worse graft survival. In elderly KTR, HLA-DR mismatches are independent risk factors for TCMR and the development of all classes of de novo DSA, both of which significantly impair graft survival. Introduction of HLA-DR matching in elderly KTR might significantly improve immunologic and overall outcome.

Background: De-novo malignancies after kidney transplantation represent one major cause for mortality after transplantation. However, most of the studies are limited due to small sample size, short follow-up or lack of information about cancer specific mortality.Methods: This long-term retrospective analysis included all adult patients with complete follow-up that underwent kidney transplantation between 1995 and 2016 at our centre. All patients with diagnosis of malignancy excluding non-melanoma skin cancer (NMSC) were identified and a matched control group was assigned to the kidney transplant recipients with post-transplant malignancies.Results: 1417 patients matched the inclusion criteria. 179 malignancies posttransplant were diagnosed in 154 patients (n = 21 with two, n = 2 patients with three different malignancies). Mean age at cancer diagnosis was 60.3±13.3 years. Overall incidence of de-novo malignancies except NMSC was 1% per year posttransplant. Renal cell carcinoma was the most common entity (n = 49, incidence 4.20 per 1000 patient years; cancer specific mortality 12%), followed by cancer of the gastro-intestinal tract (n = 30, 2.57; 50%), urinary system (n = 24, 2.06; 13%), respiratory system (n = 18, 1.54; 89%), female reproductive system (n = 15, 1.29; 13%), posttransplant lymphoproliferative disorders and haematological tumours (n = 14, 1.20; 21%), cancers of unknown primary (n = 7, 0.60 100%) and others (n = 22, 1.89; 27%). Male sex, re-transplantation and time on dialysis were associated with de-novo malignancies after transplantation.Conclusion: De-novo malignancies continue to be a serious problem after kidney transplantation. To improve long-term outcome after Kidney transplantation, prevention and cancer screening should be more tailored and intensified.