Mental health outcomes in patients discharged after COVID-19 hospitalization: the case report of a male nurse in the context of occupational surveillance program of health care workers

This case study draws attention on mental health sequelae that emerged in the context of the COVID-19 outbreak after recovery from hospitalization, even in subjects without personal psychiatric history. The case involves a 65-year-old male shift nurse who took SARS-COV-2 infection through a co-worker and that had been hospitalized for interstitial pneumonia from April 6 to April 17. After recovery, he developed psychiatric symptoms overlapping between different dimensions of psychiatric disorders and started to be followed by the Occupational Health Department of a Major University Hospital in central Italy. He reported a score of 28 at the Peritraumatic Distress Inventory and of 39 at the Self-Rating Anxiety State. He was treated with a combination therapy of SSRI and NaSSA antidepressants with clinical remission. In this case study, authors discuss the possible overlapping role of post-traumatic stress and anxiety symptoms in patients discharged after COVID-19 hospitalization that may deserve appropriate classification, treatment and follow up with the future goal to refine clinical management of post and long COVID syndromes of subjects who present low abnormalities in other specialty investigations.Copyright © 2022 EDIZIONI MINERVA MEDICA.

P.0404 Rapid antidepressant response to first-line selective serotonin reuptake inhibitors in post-COVID-19 depression

Introduction: Depression was reported in 30–40% of patients at one, three, and six months following COVID-19 [1]. The host immune response to SARS-CoV-2 infection and related severe systemic inflammation seems to be the main mechanism contributing to the development of post-COVID depression. Emerging literature suggests anti-inflammatory and antiviral properties of antidepressants in the treatment of SARS-CoV-2 infection [2]. We hypothesized that post-COVID depression, triggered by infection and sustained by systemic inflammation, could particularly benefit from antidepressants. Thus, the present study aims to investigate the efficacy of SSRI in treating post-COVID depression. Methods: We included 58 adults patients who showed depressive episodes in the six months following COVID-19. We excluded patients if they showed: other psychiatric comorbidities, ongoing treatment with antidepressants or neuroleptics, somatic disease and medications known to affect mood. The severity of depression was rated at baseline and after for four weeks from the start of the treatment on the Hamilton Depression Rating Scale (HDRS) and response was considered when the patients achieved a 50% HDRS reduction after treatment. Statistical analyses to compare group means and frequencies (Student's t-test, Pearson χ2 test) were performed. To investigate changes in HDRS scores over time, repeated measures ANOVAs (according to sex, mood disorder history, and antidepressant molecule) were performed. Results: We found that 53 (91%) patients showed a clinical response to antidepressant treatment. Age, sex, mood disorder history, and hospitalization for COVID did not affect the response rate. Patients were treated with sertraline (n=26), citalopram (n=18), paroxetine (n=8), fluvoxamine (n=4), and fluoxetine (n=2). From baseline to follow-up, patients showed a significant decrease over time of HDRS score (F=618.90, p<0.001), irrespectively of sex (0.28, p=0.599), mood disorder history (F=0.04, p=0.834), and drug used (F=1.47, p=0.239). Discussion: Common knowledge highlights that among antidepressant-treated patients, response rates are moderate (40–60%). On the contrary, we observed a rapid response to the first-line antidepressants in more than 90% of patients irrespectively of clinical variables, thus suggesting a higher antidepressant response rate in post-COVID depression. The pathophysiology of post-COVID neuropsychiatric sequelae mainly entails severe systemic inflammation and subsequent neuroinflammation. In this context, we have previously found that one and three months after COVID-19, the severity of depression was predicted by the baseline systemic immune-inflammation index (SII) [3,4]. Furthermore, we found a protective effect of the IL-1β and IL-6 receptor antagonist against post-COVID depression possibly associated with their effect in dampening SII [5]. Mounting evidence suggests that antidepressants may a) decrease markers of inflammation;b) may inhibit acid sphingomyelinase preventing the infection of epithelial cells with SARS-CoV-2;c) may prevent the COVID-19 related cytokine storm by stimulating the σ-1 receptor;d) may exert antiviral effects via lysosomotropic properties;e) may inhibit platelets activation [2]. In conclusion, we hypothesized that post-COVID depression could particularly benefit from antidepressants since this molecules have anti-inflammatory and antiviral properties, pass the BBB and accumulate in the CNS, thus preventing the neuro-inflammation triggered by SARS-CoV-2 and associated with post-COVID depression. No conflict of interest

Advancing insights on ß-cyclodextrin inclusion complexes with SSRIs through lens of X-ray diffraction and DFT calculation.

Depression-the global crisis hastened by the coronavirus outbreak, can be efficaciously treated by the selective serotonin reuptake inhibitors (SSRIs). Cyclodextrin (CD) inclusion complexation is a method of choice for reducing side effects and improving bioavailability of drugs. Here, we investigate in-depth the ß-CD encapsulation of sertraline (STL) HCl (1) and fluoxetine (FXT) HCl (2) by single-crystal X-ray diffraction and DFT complete-geometry optimization, in comparison to the reported complex of paroxetine (PXT) base. X-ray analysis unveiled the 2:2 ß-CD-STL/FXT complexes with two drug molecules inserting their halogen-containing aromatic ring in the ß-CD dimeric cavity, which are stabilized by the interplay of intermolecular O2-H⋯N1-H⋯O3 H-bonds, C3/C5-H⋯π and halogen⋯halogen interactions. Similarly, the 1:1 ß-CD-tricyclic-antidepressant (TCA) complexes have an exclusive inclusion mode of the aromatic ring, which is maintained by C3/C5-H⋯π interactions. By contrast, the 2:1 ß-CD-PXT complex has a total inclusion that is stabilized by host-guest O6-H⋯N1-H⋯O5 H-bonds and C3-H⋯π interactions. The inherent stabilization energies of 1 and 2 evaluated using DFT calculation suggested that the improved thermodynamic stabilities via CD encapsulation facilitates the reduction of drug side effects. Moreover, the SSRI conformational flexibilities are thoroughly discussed for understanding of their pharmacoactivity.