Targeting acute immune responses and aberrant inflammation to improve the clinical outcome of elderly SARS-Cov-2 infected patients (IMMU-COV-AGING)
Progetto The recent outbreak of SARS-CoV-2 infection in Lombardy has forced an age-related rationing of ventilators, leaving medical treatment as the only option for the elderly, the most fragile cohort of patients showing the highest rates of morbidity and mortality. A better understanding of magnitude, specificity and kinetics of anti–SARS-CoV-2 immune response is key particularly because the disease progression can be either asymptomatic or develop life-threatening pneumonia and respiratory insufficiency. While the former appear to resolve spontaneously, the latter require hospitalization and the frequent use of mechanical ventilation in intensive care units. The reasons of this dichotomy is still unknown and must be somewhat linked to the different degrees of immunity response. Indeed, recent clinical and experimental evidence revealed that severe respiratory distress and high systemic inflammation are associated with the so-called cytokine release syndrome, a life-threatening condition characterized by high productions of pro-inflammatory cytokines. In this respect, treatment with anti-IL-1, anti-IL-6R, and JAK/STAT inhibitors have gained attention given their ability to interfere with the “cytokine storm” which features patients with the worst clinical outcomes of SARS-CoV-2 infection. However, the clinical benefit of biologic therapies is still unknown and a paucity of information exists on their impacts on innate and adaptive immune responses during SARS-CoV-2 infection.
The present proposal of translational immunology aims to disclose the impact of SARS-CoV-2 acute infections and of the related biologic treatments on the homeostasis of those immune cells naturally endowed with the highest antiviral activities: Neutrophils, Natural Killer (NK) and T lymphocytes. In particular, we will characterize their effector-functions in association with the clinical outcomes of SARS-CoV-2 acutely infected patients with different sex, ages and disease progression