Treatment of COVID-19 with special consideration of liver diseases.

Patients with chronic liver disease (CLD), especially cirrhosis, and immunosuppressed post-liver transplant patients generally appear to be at increased risk of infection, resulting in increased mortality. This is also evident in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, where patients with cirrhosis in particular are at high risk for coronavirus disease 2019 (COVID-19). Prevention and treatment of SARS-CoV-2 infection are therefore important measures to protect this vulnerable group of patients from the consequences of COVID-19. The recent SARS-CoV-2 pandemic has led to exceptionally rapid development of vaccines, prophylactic and therapeutic antibodies, as well as testing of new drugs and drugs already approved for other indications. In this article, we summarize therapeutic approaches with special consideration of patients with chronic liver disease and patients after liver transplantation.Copyright © 2023, The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

Antiviral T-cell frequencies in a healthy population: Reference values for evaluating antiviral immune cell profiles in immunocompromised patients and their application during the SARS-CoV-2 pandemic

Background: Viral infections and reactivations (e.g. cytomegalovirus (CMV)) are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and in patients with immunodeficiencies. Here, antiviral drugs are the mainstay of treatment, but they have side effects and cannot achieve complete viral clearance without prior reconstitution of functional virus-specific T cells (VSTs). Method(s): We performed serological testing and measured VST frequencies against 23 viral protein-derived peptide pools of 11 clinically relevant human viruses by Interferon-gamma (IFN-gamma) ELISpot assay in a cohort of healthy donors (n=151). Moreover, we performed in-depth immune profiling in patients actively infected with SARS-CoV-2 (n=92) and in unvaccinated, recovered COVID-19 patients (n=204) by ELISA, ELISpot, multicolor flow cytometry and multiplex analysis. Result(s): Based on serological testing, IFN-gamma ELISpot results, age and sex, we established normal ranges for VST frequencies in healthy donors for better interpretation of VST frequencies observed in immunocompromised patients. While in SARS-CoV-2 recovered patients, the antiviral immune response was characterized by a broad specificity, significantly lower T-cell responses were observed during active infection. Comparison with the previously established reference values for VST frequencies revealed an overall reduced T-cell functionality based on the lack of CMV-pp65-reactive T cells in CMV-seropositive COVID-19 patients, which was associated with an inflammatory milieu, expression of inhibitory molecules, and effector caspase activity in T cells. Conclusion(s): The established reference values are an invaluable tool for immune response assessment, therapeutic agent intensity and decision making in immunocompromised patients. Further, we provide evidence that the low T-cell response observed during SARS-CoV-2 infection is not exclusively due to lymphopenia, but rather due to checkpoint- and cell death-associated mechanisms, suggesting that these patients may benefit from SARS-CoV-2-specific T-cell therapy.