Abstract
Since the onset of the COVID-19 pandemic in the fall of 2019 over 4 million people have been infected and over 280,000 have died (1). Information about the SARS-CoV2 virus is evolving rapidly. At this time there are no interventions proven to be effective for cases infected with SARS-CoV2. Current knowledge about the clinical and laboratory manifestations of COVID-19 infection is reviewed and combined with knowledge about the immunopathogenic mechanisms of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV1) and Middle East Respiratory Syndrome (MERS) to formulate theories and suggest possible therapeutic interventions. SARS-CoV2 immunopathogenic mechanisms vary from immunosuppression that initially enables viral escape to a hyperinflammatory immune response. Ultimately therapeutic intervention will be phase dependent.
Highlights
Since the onset of the COVID-19 pandemic in the fall of 2019 over 4 million people have been infected and over 280,000 have died [1]
C5a blockade was shown to be protective in the MERSCoV and H5N1 influenza virus induced acute lung injury mice models [15,16,17]
In direct sepsis induced Acute Respiratory Distress Syndrome (ARDS), pulmonary pathogens activate a robust innate immune response in epithelial cells and alveolar macrophages followed by neutrophil infiltration and monocyte recruitment [18]
Summary
Since the onset of the COVID-19 pandemic in the fall of 2019 over 4 million people have been infected and over 280,000 have died [1]. SARS-CoV2 infected patients with poor clinical evolution demonstrate a marked reduction in CD4+ and CD8+ T cells along with a significant degree of T cell PD1 and TIM3 overexpression, indicative of T cell exhaustion Both lymphopenia and T cell exhaustion were directly correlated with the increase in the levels of IL-6, IL-10, and TNF alpha and with disease severity. SARS-CoV1 and MERS have evolved defenses to evade the immune system such as using double membrane vesicles which lack pattern recognition receptors, impairing early production of interferon type 1 and its downstream signaling, increasing early production of inhibitory cytokines such as IL-10 and overexpressing PD-L1 receptors on hematopoietic and non-hematopoietic cells and PD1 on T cells These viruses can downregulate antigen presentation by MHC class I and II which diminishes T cell activation and shifts the Th1 response to a Th2 cytokine profile and promotes a T cell exhaustion phenotype [11,12,13]. C5a blockade was shown to be protective in the MERSCoV and H5N1 influenza virus induced acute lung injury mice models [15,16,17]
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