Depressed man with protective mask in self-isolation quarantine during virus outbreak pandemic, adult male standing by the window

After three weeks of treatments, I was healing from COVID, at home, had no fever, and just a little cough. But sometimes at night, my breath could go away all of a sudden, making me feel as if I was to die. I knew what it was because I had suffered from panic attacks in the past. It was terrible. Panic made me suffer more than COVID.”

This is the report of a COVID-19 survivor at the one-month follow-up psychiatric interview. Not only cough, fever, dyspnea, and pain but also depression, anxiety, and insomnia were found to be associated with COVID-19 infection.

In our study, published in Brain Behaviour and Immunity (July 2020), we found that in a cohort of 402 adults a significant proportion of patients self-rated in the psychopathological range: 31% for depression, 42% for anxiety, 28% for PTSD and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Consistent with the known gender effect, we found that females suffered more for both anxiety and depression. Positive previous psychiatric history was also found to be associated with increased scores on most psychopathological measures.

According to the current insights on inflammation in psychiatry, we found that the baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on lymphocyte, neutrophil, and platelet counts, was positively associated with scores of depression and anxiety. This evidence suggests that worse inflammation leads to worse depression. Persistent low-grade inflammation is known to be implicated in the pathophysiology of mood disorders. Furthermore, the Benedetti group has found that high peripheral inflammation is associated with a lack of response to antidepressant treatment, brain abnormalities affecting both white and grey matter, and cognitive impairment. Interestingly, Raymond W. Lam and colleagues, of the Unversity of British Columbia, have found increased systemic inflammatory response in seasonal affective disorder, with normalization of immune functions and depressive symptoms after light therapy. Hypothetically, COVID-19 could create, out of season, the same pathogenetic conditions which we observe in seasonal affective disorder.

In light of the alarming impact of COVID-19 infection on mental health, we now suggest assessing, diagnosing, and treating the psychopathology of COVID-19 survivors, to deepen research on inflammatory biomarkers. This approach may allow us to identify new specific targets for the treatment of inflammation-related neuropsychiatric conditions, and consider the potential immunomodulatory role of light therapy in COVID-19 psychiatric sequelae.

We are now seeing and testing survivors at three months follow-up, with clinical and neuropsychological assessment. We will also analyze inflammatory serology using a broad cytokine panel, to better understand how the immune-inflammatory response translates into psychiatric illness.

We suggest that investigators of the clinical chronobiology of mood disorders investigate neuroinflammation as a potential pathogenic mechanism of illness.


Mario G. Mazza and Francesco Benedetti, Departments of Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute IRCCS, Ospedale San Raffaele, and Vita-Salute University, Milano, Italy