Combined blockade of programmed death-1 and activation of CD137 increase responses of human liver T cells against HBV, but not HCV

In patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, antiviral functions of T cells are impaired; these might be increased by blocking T-cell co-inhibitory pathways, such as preventing interaction between the receptor programmed death (PD)-1 and its ligand, PD-L1. We attempted to optimize the restoration of T-cell functions in patients with chronic HBV or HCV infection with a combination of reagents that block PD-1 interaction with PD-L1 and stimulate T-cell signaling via CD137, a member of the tumor necrosis factor-receptor family

Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection

Dysfunctional CD8(+) T cells present in chronic virus infections can express programmed death 1 (PD-1) molecules, and the inhibition of the engagement of PD-1 with its ligand (PD-L1) has been reported to enhance the antiviral function of these T cells. We took advantage of the wide fluctuations in levels of viremia which are typical of chronic hepatitis B virus (HBV) infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T-cell dysfunction and on its reversibility through the blocking of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T-cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in samples from patients with chronic infection, in contrast to those from patients with acute HBV infection. In chronic HBV infection, virus-specific T cells were detected mainly in patients with lower levels of viremia. These HBV-specific CD8(+) T cells expressed PD-1, and their function was improved by the blocking of PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection and this spectrum is proportional to HBV replication levels and can be improved by blocking the PD-1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available antiviral therapies

Severe COVID-19 pneumonia in Piacenza, Italy — A cohort study of the first pandemic wave

International audienceBackground: Piacenza is the closest city to the first coronavirus disease 2019 (COVID-19) cluster in Italyand has the highest national COVID-19 death rates per population. The objective of this study is to presentcharacteristics and outcomes of patients admitted to medical departments of the Hospital of Piacenzaduring the first wave of the epidemic.Methods: A total of 218 patients with confirmed or suspect COVID-19 and severe pneumonia wereincluded from February 21st to May 15th, 2020. Routinely-collected clinical and laboratory data were ret-rospectively retrieved from electronic medical files. A Cox proportional-hazards model was fit to assessthe association of treatment and other variables with death.Results: Median age of patients was 68 years; 150 patients (69%) had comorbidities, mainly hypertension(107, 49%). Overall, 185 (85%) patients had acute respiratory distress syndrome (ARDS) on admission,including 103 (47%) with moderate or severe ARDS. Chest computed tomography scan showed bilateraldisease in 201 (98%) and extensive lung involvement in 79 (50%) patients. Most patients received antiviraltreatment (187, 86%) and corticosteroids (134, 61%). All patients received respiratory support and 64 (29%)were admitted to intensive care unit. As of June 30th, 100 patients (46%) died, 109 patients (50%) weredischarged, and 9 patients (4%) were still hospitalized. In multivariable Cox analysis, age above 65 years,having more than one comorbidity, severe ARDS, low platelet counts, and high LDH levels at admissionwere associated with mortality, while having diarrhea at admission was associated with survival. Theuse of antivirals or corticosteroids was not associated with surviva

Treatment for COVID-19—a cohort study from Northern Italy

International audienceMulticentre, retrospective cohort study with multivariable Cox proportional-hazards modelling and survival-time inverse-probability-weighting, evaluating the impact of different treatments on survival of proven COVID-19 patients admitted to two Hospitals in the province of Piacenza, Italy. Use of tocilizumab and of high doses of low molecular weight heparin, but not of antivirals (either alone or in combination), azithromycin, and any corticosteroid, was independently associated with lower mortality. Our results support further clinical evaluation of high doses of low molecular weight heparin and tocilizumab as COVID-19 therapeutics

Case Report: B Lymphocyte Disorders Under COVID-19 Inflammatory Pressure

Members of the COVID-Piacenza Group Daniela Aschieri, Mario Barbera, Carlo Cagnoni, Luigi Cavanna, Cosimo Franco, Chiara Gorrini, Andrea Magnacavallo, Massimo Nolli, Massimo Piepoli, Roberta Schiavo, Matteo Silva, Marco Stabile, Angela Rossi, Giovanni Vadacca. Affiliations for all members is: “Guglielmo da Saliceto” Piacenza Hospital, Via Taverna 49, 29121 Piacenza, ItalySevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects humans through the angiotensin converting enzyme-2 (ACE-2) receptor expressed on many cells, including lymphocytes. In Covid-19 patients IL-6 is overexpressed, and hyperactivated plasmacytoid lymphocytes are detected in peripheral blood film. We hypothesize that, due to the unpredictable interaction between the new virus and the B cell lineage of infected patients, a cascade of out of control events can ensue, capable of determining unexpected pathologic disorders involving such lineage. Here we report two cases of autoimmune hemolytic anemia (AIHA) and two cases of B-cell hematological malignancies developed or reactivated during acute SARS-CoV-2 infection. The temporal relationship of the events may suggest a potential causal relationship between SARS-CoV-2 infection and the hematopoietic disorders. We suggest that special attention should be paid to COVID-19 patients with underlining B cell lineage disorders.Peer reviewe