COVID-19 Immunobiology: Lessons Learned, New Questions Arise

Abstract

There is strong evidence that COVID-19 pathophysiology is mainly driven by a spatiotemporal immune deregulation. Both its phenotypic heterogeneity, spanning from asymptomatic to severe disease/death, and its associated mortality, are dictated by and linked to maladaptive innate and adaptive immune responses against SARS-CoV-2, the etiologic factor of the disease. Deregulated interferon and cytokine responses, with the contribution of immune and cellular stress-response mediators (like cellular senescence or uncontrolled inflammatory cell death), result in innate and adaptive immune system malfunction, endothelial activation and inflammation (endothelitis), as well as immunothrombosis (with enhanced platelet activation, NET production/release and complement hyper-activation). All these factors play key roles in the development of severe COVID-19. Interestingly, another consequence of this immune deregulation, is the production of autoantibodies and the subsequent development of autoimmune phenomena observed in some COVID-19 patients with severe disease. These new aspects of the disease that are now emerging (like autoimmunity and cellular senescence), could offer us new opportunities in the field of disease prevention and treatment. Simultaneously, lessons already learned from the immunobiology of COVID-19 could offer new insights, not only for this disease, but also for a variety of chronic inflammatory responses observed in autoimmune and (auto)inflammatory diseases.

Inflammation and Platelet Activation After COVID-19 Vaccines - Possible Mechanisms Behind Vaccine-Induced Immune Thrombocytopenia and Thrombosis

“…The AZ and mRNA vaccines both enhanced inflammation, platelet activation and vascular endothelial activation, a notable finding given that COVID-19 itself is also associated with extensive inflammation and platelet activation with e.g. high circulating proinflammatory cytokine levels, enhanced P-selectin expression and high soluble levels and extensive widespread vascular endothelial activation (29)(30)(31)(32)(33). Several studies of COVID-19 associated platelet activation or vascular endothelial activation have included advanced OMICS analyses, and despite the few biomarkers in common with our study, it is difficult to directly compare the COVID-19 vaccine and SARS-CoV-2 infection/COVID-19 induced changes.…”

Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure

“…Deterioration of respiratory function in COVID-19 seems to be associated with a profound deregulation of immune response [ 7 ]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects predominantly alveolar epithelial cells, triggering aberrant inflammatory responses leading to acute respiratory distress syndrome (ARDS) [ 8 , 9 ].…”

COVID-19 Specific Immune Markers Revealed by Single Cell Phenotypic Profiling

“…The achievement of an adequate immune cell response as well as immune regulatory molecules and neutralizing antibodies could guarantee the elimination of the SARS-CoV-2 viral threat [ 10 , 11 ]. Conversely, the impairment of the adaptive immune machinery at this stage, coupled with immunochemical hyperactivation, can cause severe disease symptoms in COVID-19 patients [ 12 , 13 , 14 ]. A major risk of multiorgan failure has indeed been reported together with lung inflammation [ 15 , 16 , 17 , 18 ] and represents the main manifestation of life-threatening respiratory distress at the severe stage [ 18 ].…”