The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia–reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin–angiotensin–aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes.

Kidney transplantation is unquestionably the most advantageous and preferred treatment when patients with end-stage renal disease are considered. It does have a substantially positive influence on both the quality and expectancy of their lives. Thus, it is quintessential to extend the survival rate of kidney grafts. On account of T-cell-focused treatment, this is being exponentially achieved. The kynurenine pathway, as an immunosuppressive apparatus, and indoleamine 2,3-dioxygenase (IDO1), as its main regulator, are yet to be exhaustively explored. This review presents the recognised role of IDO1 and its influence on the kynurenine pathway, with emphasis on immunosuppression in kidney transplant protection.

Background: Diabetes mellitus is among the most frequent comorbidities worsening COVID-19 outcome. Nevertheless, there are no data regarding the optimal risk stratification of patients with diabetes and COVID-19. Since individual C₂HEST components reflect the comorbidities, we assumed that the score could predict COVID-19 outcomes. Material and Methods: A total of 2184 medical records of patients hospitalized for COVID-19 at the medical university center were analyzed, including 473 diabetic patients and 1666 patients without any glucose or metabolic abnormalities. The variables of patients’ baseline characteristics were retrieved to calculate the C₂HEST score and subsequently the diabetic and non-diabetic subjects were assigned to the following categories: low-, medium- or high-risk. The measured outcomes included: in-hospital mortality; 3-month and 6-month all-cause mortality; non-fatal end of hospitalization (discharged home/sudden-deterioration/rehabilitation) and adverse in-hospital clinical events. Results: A total of 194 deaths (41%) were reported in the diabetic cohort, including 115 in-hospital deaths (24.3%). The 3-month and 6-month in-hospital mortality was highest in the high-risk C₂HEST stratum. The C₂HEST score revealed to be more sensitive in non-diabetic-group. The estimated six-month survival probability for high-risk subjects reached 0.4 in both cohorts whereas for the low-risk group, the six-month survival probability was 0.7 in the diabetic vs. 0.85 in the non-diabetic group—levels which were maintained during whole observation period. In both cohorts, receiver operating characteristics revealed that C₂HEST predicts the following: cardiogenic shock; acute heart failure; myocardial injury; and in-hospital acute kidney injury. Conclusions: We demonstrated the usefulness and performance of the C₂HEST score in predicting the adverse COVID-19 outcomes in hospitalized diabetic subjects.