Inflammatory pathways and potential therapies for COVID-19: A mini review

Abstract

The public health crisis of the novel coronavirus disease (COVID-19) is alarming since January 2020. COVID-19 genome (SARS-CoV-2) is related to other highly pathogenic coronaviruses SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus). Amino acid substitutions in some of SARS-CoV-2 proteins resulted in mutations proposing more virulent and contagious properties for this novel virus. Coronavirus penetrates the host cell via endocytosis and once infected, immune responses are triggered to fight against the pathogen. Innate immune response activates major transcription factors to secrete proinflammatory cytokines and type 1 interferon response (T1INF) to induce antiviral immunity. While adaptive immunity initiates cascade of B-cells antibody mediated and T-cells cellular mediate immunities, several mechanisms are raised by SARS-CoV-2 to evade host immune response. Consequently, a surge of proinflammatory cytokines, known as cytokine storm (CS) are released. Failure to manage CS results in several pathological complications as acute respiratory distress syndrome (ARDS). Although researches have not discovered an effective treatment against SARS-CoV-2, recent therapeutic approaches recommending the use of anti-inflammatories in combination with antivirals and some repurposed drugs for COVID-19 patients. Future medications should be designed to target essential hallmarks in the CS to improve clinical outcomes.

Serum cytokine/chemokine profile and clinical/paraclinical data in COVID-19 deceased and recovered patients

“…Previous studies have suggested that IL-1β and IL-6 are key pro-inflammatory biomarkers in initiation of the acute phase response, resulting in a broad range of local and systemic events such as fever and recruitment of leukocytes. 18 , 19 Increased IL-17 in patients with COVID-19 pneumonia has been observed in other studies, 40 and Th-17 cells contribute in the cytokine storm triggered by SARS-CoV-2. 41 Further, elevations of IL-2, IL-4 and IL-17 levels are observed in COVID-19 patients’ serums with prominent lung damage.…”

“… 17 As declared, the intense and uncontrolled inflammation induced by SARS-CoV-2 leads to severe disease, increased morbidity, and mortality, so dampening and downregulating the inflammatory response and reducing its intensity could be a promising therapy. 18 , 19 Exploring broad with patients in different geographical areas and ethnical groups might pave the way toward controlling SARS-CoV-2 immunopathogenesis. 20 The challenges would be to increase knowledge and understand the physiopathology of COVID-19 and emerging mutants.…”

Screening of Natural Products Inhibitors of SARS-CoV-2 Entry

“…The anti-inflammatory activity of both species has been identified in rat and mouse inflammation models [ 28 , 29 ]. Recent therapeutic approaches for COVID-19 patients recommend the use of anti-inflammatories in combination with antivirals [ 30 ]. Since Stachytarpheta cayennensis extract has anti-inflammatory activity in addition to antiviral activity, it could also be used in the inflammatory stages of COVID-19.…”

Endotheliitis, Shunts, and Ventilation–Perfusion Mismatch in Coronavirus Disease 2019: A Literature Review of Disease Mechanisms

“…The immune response is responsible for inflammation and lung injury when the virus fights. Apoptosis of infected cells releases new viral particles [ 34 , 35 ]. Repetitive injury, together with viral replication, leads to the loss of type 1 and 2 pneumocytes, which generates diffuse alveolar damage that ultimately culminates in acute respiratory distress syndrome (ARDS) [ 34 , 35 ].…”