Influenza infection, SARS, MERS and COVID-19: Cytokine storm - The common denominator and the lessons to be learned

Abstract

The outbreak of COVID-19 reminds us that the emerging and reemerging respiratory virus infections pose a continuing threat to human life. Cytokine storm syndromes of viral origin seem to have a common pathogenesis of the imbalanced immune response with the exaggerated inflammatory reaction combined with the reduction and functional exhaustion of T cells. Immunomodulatory therapy is gaining interest in COVID-19, but this strategy has received less attention in other respiratory viral infections than it deserved. In this review we suggest that based on the similarities of the immune dysfunction in the severe cases of different respiratory viral infections, some lessons from the immunomodulatory therapy of COVID-19 (particularly regarding the choice of an immunomodulatory drug, the selection of patients and optimal time window for this kind of therapy) could be applied for some cases of severe influenza infection and probably for some future outbreaks of novel severe respiratory viral infections.

Keywords: COVID-19; Cytokine storm; IL-6; Immunotherapy; Influenza; SARS.

Fig. 1

The range of clinical conditions, associated with an excessive systemic action of the inflammatory autacoids termed “cytokine storm syndrome”, is very wide and includes both infectious and non-infectious diseases. While distinct etiology implies the important differences in the treatment strategies of these medical conditions, some lessons (both for diagnosis and therapy) have been recently learned from non-infectious cytokine storm syndromes for the similar hyperinflammatory phenotype in COVID-19. Therefore, we suggest that some lessons from COVID-19 could be implemented for other respiratory viral infections, including widespread influenza infection and possible future outbreaks of novel respiratory viruses. These lessons concern taking into account the complex immunopathology underlying cytokine storm syndrome in this context, prompt diagnosis of this phenotype and judicious application of anti-inflammatory therapy (particularly regarding the selection of patients for this kind of therapy, optimal time window for this therapy and the choice of an immunomodulatory drug). CRP C-reactive protein; CRS cytokine release syndrome; MAS macrophage activation syndrome; MERS Middle East respiratory syndrome; pHLH primary hemophagocytic lymphohistiocytosis; SARS severe acute respiratory syndrome.