Cytokine storm:
It is well observed clinically that one of the main causes of deterioration of patients’ clinical conditions is the significant increase of proinflammatory cytokines levels in their sera suggesting the importance of this immune defense mechanism in the pathological processes of this disease(27). This huge increase in cytokines levels or what is known clinically with cytokine storm, could lead to serious pathologic findings including increased vascular permeability, increased blood viscosity, deteriorated pulmonary functions which could be associated with multiple organ failure and death(63).
A study which compared COVID-19 patients who were admitted to ICU units with clinically stable patients and normal controls found that there was noticeable increase in serum levels of certain cytokines including IL-1β, IL-1ra, IL-7, IL-8, IL-9, IL-10, basic FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, TNFα, and VEGF in ICU and stable patients in relation to the third group. In specific, IL-2, IL-7, IL-10, G-CSF, IP-10, MCP-1, MIP-1α, and TNFα were even higher in those admitted to ICU compared with the clinically stable patients highlighting the role of the cytokine storm in worsening the patients’ clinical conditions(64). Another study showed similar findings suggesting the relation between the increase in proinflammatory cytokines levels and the occurrence of serious lung pathology (65).
The cytokine storm has been proposed to be in part due to abnormal GIT microbiota features which have normally important role in maintaining a balanced host immune response. In a study which involved 366 study subjects, it was found a significant correlation between microbiota disturbance and uncontrolled production of inflammatory cytokines suggesting a relation between COVID-19 cytokine storm and microbiota patterns. Examples of these microbiota are Bacteroides genus, Streptococcus genus and Clostridiales which had negative correlation with the measured proinflammatory cytokines while Ruminococcus genus, Blautia genus and Lactobacillus genus had positive correlation (66).