Abstract
To date, no vaccines or effective drugs have been approved to prevent or treat COVID-19 and the current standard care relies on supportive treatments. Therefore, based on the fast and global spread of the virus, urgent investigations are warranted in order to develop preventive and therapeutic drugs. In this regard, treatments addressing the immunopathology of SARS-CoV-2 infection have become a major focus. Notably, while a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and impaired adaptive host immune defense may lead to tissue damage both at the site of virus entry and at systemic level. Several studies highlight relevant changes occurring both in innate and adaptive immune system in COVID-19 patients. In particular, the massive cytokine and chemokine release, the so-called “cytokine storm”, clearly reflects a widespread uncontrolled dysregulation of the host immune defense. Although the prospective of counteracting cytokine storm is compelling, a major limitation relies on the limited understanding of the immune signaling pathways triggered by SARS-CoV-2 infection. The identification of signaling pathways altered during viral infections may help to unravel the most relevant molecular cascades implicated in biological processes mediating viral infections and to unveil key molecular players that may be targeted. Thus, given the key role of the immune system in COVID-19, a deeper understanding of the mechanism behind the immune dysregulation might give us clues for the clinical management of the severe cases and for preventing the transition from mild to severe stages.
Highlights
The outbreak of the novel coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), firstly found in Wuhan, in the Hubei province of China, in December 2019, has rapidly spread worldwide, becoming a global public health emergency
While a rapid and well-coordinated immune response represents the first line of defense against viral infection, excessive inflammatory innate response and dysregulated adaptive host immune defense may cause harmful tissue damage at both at the site of virus entry and at systemic level
Based on this anti-inflammatory effect, they are likely to be effective against the consequences of the elevated levels of cytokines typically observed in patients with COVID-19.80 Among them, baricitinib, a selective inhibitor of JAK 1 and 2, has been predicted by crystallographic studies to inhibit two members of the numb-associated kinase family, such as AP2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK), hindering viral endocytosis into lung cells, at the concentration approved for the treatment of arthritis rheumatoid.[86]
Summary
The outbreak of the novel coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), firstly found in Wuhan, in the Hubei province of China, in December 2019, has rapidly spread worldwide, becoming a global public health emergency.
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