Can Cytokine Blocking Prevent Depression in COVID-19 Survivors?
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LETTER TO THE EDITOR
Can Cytokine Blocking Prevent Depression in COVID-19 Survivors? Francesco Benedetti 1,2 & Mario Mazza 1,2 & Giulio Cavalli 2,3 & Fabio Ciceri 2,4 & Lorenzo Dagna 2,3 & Patrizia Rovere-Querini 2,4 Received: 18 October 2020 / Accepted: 22 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Current insight on inflammation in psychiatry suggests that infection-triggered perturbation of immune homeostasis could foster psychopathology (Miller and Raison 2016). High rates of psychiatric disorders have been reported during and after coronavirus infection (Rogers et al. 2020). We also observed a psychopathological impact of COVID-19, with emergent depression and post-traumatic stress disorder (PTSD) after COVID-19 associated to systemic inflammation index (SII) during the acute illness (Mazza et al. 2020): 31% of patients self-rated in the psychopathological range for depression and 28% for PTSD, one month after hospital discharge, complete viral clearance and clinical recovery. Studies revealed persistent low-grade inflammation in mood disorders, and pointed at interleukin (IL)-1β and IL-6 as inflammatory cytokines implicated in major depression and its detrimental outcomes(Arteaga-Henríquez et al. 2019). Severe COVID-19 induces a ‘cytokine storm’ involving massive release of IL-1β and IL-6. Pharmacological blockade of both cytokines was explored and we reported benefits on hyper-inflammation and progression to respiratory failure with high-dose anakinra (Cavalli et al. 2020), a recombinant version of the human IL-1β receptor antagonist, and less clear effects with tocilizumab (Campochiaro et al. 2020), a monoclonal antibody targeting the IL-6 receptor. Given the central
* Francesco Benedetti [email protected] 1
Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS Scientific Institute Ospedale San Raffaele, Milano, Italy
2
University Vita-Salute San Raffaele, Milano, Italy
3
Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS Scientific Institute Ospedale San Raffaele, Milano, Italy
4
Department of Medicine, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Scientific Institute Ospedale San Raffaele, Milano, Italy
role of IL-1 and IL-6 in depression, we hypothesize that depressive symptoms should be lower in COVID-19 survivors treated with cytokine-blocking agents. We now prospectively evaluated the severity of depressive symptoms (Zung Self-rating Depression Scale, ZSDS) and PTSD (revised Impact of Event Scale, IES-R), one and three months after discharge, in 84 male COVID-19 survivors who during hospitalization had received the best available medical treatment at the time, including hydroxychloroquine, lopinavir/ritonavir, and respiratory support, alone or combined with anakinra (5 mg/Kg/day twice daily until clinical benefit, defined as sustained improvement of respiratory parameters and 75% reduction of serum C-reactive protein, CRP), or tocilizumab (single i.v. dose of 400 mg, followed by a secon
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