Cytokine storm induced new onset depression in patients with COVID-19. A new look into the association between depression and cytokines -two case reports

Abstract

Background Depression appears to be a common complication in patients during and post–COVID-19 infection. Understanding the mechanism of action of cytokines such as interleukin-6, interleukin-10 and others in depression and in cytokine storm syndrome, the core component of COVID- 19, could shine a new light on future treatment options for both disorders. Objective This review demonstrates the role of interleukins in COVID-19 pathogenesis and their role in depression. Results We described cases we have treated as an example for the dual role interleukins have in COVID-19 infection and depression and reviewed approximately 70 articles focusing on the role of interleukins in cytokine storm syndrome and depression. Conclusion This review highlights the key features of cytokines in both diseases. As the scientific community has more time to recover and process the effect of the current pandemic, we believe that additional research will pave the way to diverse pathways to treat depression in these patient and others.

On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

“…Alpert et al (2020) described two cases of COVID-19 patients with elevated amounts of IL-6 (25 pg/mL and 26.7 pg/mL respectively) who were diagnosed with major depressive disorder (according to the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5)) during COVID 19 infection. Both patients' depressive symptoms subsided about 6 weeks after initiation of anti-depressant pharmacotherapy and normalization of the inflammatory cytokines [192]. The authors concluded that lower cytokine activity ameliorates depressive symptoms as normalization of IL-6 plasma levels decreased depression with or without antidepressants [192].…”

“…The world-wide effect of the coronavirus disease 2019 (COVID-19) pandemic is enormous and is not solely limited to the increased mortality and morbidity rates, but also extends into the mental health of the global population [191]. Considerable amount of clinical data is emerging regarding the manifestation of depression in patients during [192][193][194] and post-COVID 19 infection [192][193][194][195]. It is estimated that about 48% of confirmed COVID-19 cases displayed overt psychological symptoms such as depression and often expressed feelings of regret, loneliness, helplessness, and irritation [196].…”

“…There is growing body of literature regarding dual role of IL-6 in COVID-19 infection and depression [192]. Normal plasma levels of IL-6 in adults range between 1 and 10 pg/ml; whereas in a systemic inflammation this amount increases to several ng/ml [197] and even higher concentrations were reported in COVID-19 patients [198].…”

“…Normal plasma levels of IL-6 in adults range between 1 and 10 pg/ml; whereas in a systemic inflammation this amount increases to several ng/ml [197] and even higher concentrations were reported in COVID-19 patients [198]. Indeed, cytokine release syndrome (CRS) is common in COVID-19 patients and increased levels of serum IL-6 have been identified to be significantly associated with acute respiratory distress syndrome (ARDS), respiratory failure, and poor disease outcome in numerous studies [192,[199][200][201]. Studies suggest that new onset depression is most probably caused by inflammation initiated during the active phase of the infection leading to a cytokine surge [202].…”

“…Both patients' depressive symptoms subsided about 6 weeks after initiation of anti-depressant pharmacotherapy and normalization of the inflammatory cytokines [192]. The authors concluded that lower cytokine activity ameliorates depressive symptoms as normalization of IL-6 plasma levels decreased depression with or without antidepressants [192]. Moreover, Benedett et al (2020) studied effects of treatment with cytokine-blocking agents on the psychopathological status of the patients with COVID-19 infection.…”