Severe COVID-19: what have we learned with the immunopathogenesis?

Abstract

The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself. Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena. Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment – A narrative review

“…Another investigation identified advanced age, male gender, underlying comorbidities, including hypertension, diabetes, obesity, chronic obstructive lung disease, cardiac, hepatic and/or renal disease, malignancy, immunodeficiency, and pregnancy as key risk factors for the progression of COVID-19 to severe, i.e., critical disease [ 27 ]. In particular, the presence of any iatrogenic and/or “acquired” immunosuppression (as in injury-associated immunosuppression [ 28 ]) may be important in the context of disease progression [ [29] , [30] , [31] , [32] , [33] , [34] ] and we could recently demonstrate that e.g., cellular immunosuppression of first in line key immune cells can be observed in severe, but not in nonsevere cases [ 35 ].…”

COVID-19 in Children With Liver Disease

“…TMPRSS2, transmembrane serine protease 2, helps to prime the spike protein and promotes entry. Once inside the host cell, viral replication takes place, releasing virions which infect other ACE2 expressing cells (15)(16)(17).…”

“…To begin with, the lymphopenia and high neutrophil to lymphocyte ratio described in adults with severe COVID-19 infection are not observed in children (20,21). Lymphopenia is found in up to 80% of adults, and affects all lymphocyte subsets including T cells, B cells and natural killer cells (NK), but chiefly affects cellular immunity with T cell suppression (16,(20)(21)(22). The suppression is not only in numbers but in expression of cell exhaustion and inhibition markers such as PD-1, LAG-3 and TIM3 (16,22).…”

“…Lymphopenia is found in up to 80% of adults, and affects all lymphocyte subsets including T cells, B cells and natural killer cells (NK), but chiefly affects cellular immunity with T cell suppression (16,(20)(21)(22). The suppression is not only in numbers but in expression of cell exhaustion and inhibition markers such as PD-1, LAG-3 and TIM3 (16,22). Children with COVID-19 appear to have preserved CD8+ cytotoxic responses except in the most severe of cases (4,19,21).…”

Severe Acute Respiratory Syndrome Coronavirus-2 Induces Cytokine Storm and Inflammation During Coronavirus Disease 19: Perspectives and Possible Therapeutic Approaches

“…Therefore, lung damage and inflammation primarily start following the specifying binding to ACE2, but probably it is not the only viral mechanism ( Behl et al, 2020 ; Bordallo et al, 2020 ; Verdecchia et al, 2020 ). The exuberant inflammation may certainly be considered as one of the main causes of severity and mortality during SARS-CoV-2 infection.…”