Post-acute sequelae of COVID-19 include several neuropsychiatric disorders. Little is known about the relationship between post-COVID-19 syndrome and suicidality. The aim of the study was to investigate the risk of suicide in subjects with persistent post-COVID-19 syndrome. One-thousand five-hundred eighty-eight subjects were assessed in the Post-Acute Care Service at the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS of Rome. Assessment included: (a) sociodemographic characteristics; (b) symptoms during and after COVID-19; (c) psychopathological evaluation. Participants were divided in those with (SUI) or without (NON SUI) suicide risk according to the Mini International Neuropsychiatric Interview. Additionally, subjects with SUI were split into those with high (HIGH SUI) and low (LOW SUI) suicide risk. Between-group comparisons were made with t-tests for continuous variables and χ2 tests for categorical variables. SUI showed greater percentages of physical complaints during and after COVID-19, greater percentages of psychiatric history and presence of psychiatric history in relatives, greater percentages of subjects previously undergoing psychopharmacotherapy, and greater levels of anxiety, mixed depressive symptoms, general psychopathology than NON SUI. HIGH SUI showed greater number of symptoms during and after COVID-19 and higher levels of mixed depressive symptoms than LOW SUI. Percentages of subjects undergoing psychotherapy was higher in LOW SUI than HIGH SUI. Greater levels of physical complaints and psychopathology during post-COVID-syndrome might enhance the risk of committing suicide. Treatment of physical complaints and psychotherapy might reduce suicide risk.

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR “mood disord*”[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR “eating disorder*”[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR “attention-deficit”[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2–HO-1, BDNF–TrkB, and cyclic AMP–CREB pathways, could protect from depression, while glycogen synthase kinase-3β and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.

The relationship between depression and post-COVID-19 disease syndrome (post-COVID-19 syndrome) is established. Nevertheless, few studies have investigated the association between post-COVID-19 syndrome and mixed depression, i.e., a specific sub-form of depression characterized by high level of excitatory symptoms. Aims of the present study are: (a) to compare the post-COVID-19 syndrome’s burden in depressed and non-depressed patients, and (b) to investigate the correlation between post-COVID-19 syndrome’s burden and the severity of mixed depression. One thousand and forty six (n = 1460) subjects with post-COVID-19 syndrome were assessed. Subjects were divided into those with (DEP) or without (CONT) depression. Sociodemographically, post-COVID-19 syndrome’s symptoms number and type were compared. In DEP, association between levels of excitatory symptoms and the presence of post-COVID-19 syndrome’s symptoms were additionally assessed. DEP showed greater percentages of family history of psychiatric disorders than CONT. DEP showed higher percentages of post-COVID-19 symptoms than CONT. A greater level of excitatory symptoms were associated to higher frequencies of post-COVID-19 syndrome’ symptoms. Higher levels of post-COVID-19 syndrome’s symptoms in DEP corroborate the evidence of a common pathway between these two syndromes. Presence of excitatory symptoms seem to additionally add a greater illness burden. Such findings might help clinicians choose the appropriate treatment for such states. More specifically, therapies aimed to treat excitatory symptoms, such as antipsychotics and mood stabilizers, might help reduce the illness burden in post-COVID-19 patients with mixed depression.

COVID-19 affects brain function, as deduced by the “brain fog” that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR “deep gray matter” OR “cortical thickness” OR caudate OR striatum OR accumbens OR putamen OR “regions of interest” OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Brief Psychiatric Rating Scale (BPRS). Dependent variables include: (a) respiratory parameters, i.e., partial pressure of oxygen in arterial blood (PaO2), oxygen saturation (SpO2), ratio between arterial partial pressure of oxygen (PaO2), and fraction of inspired oxygen (PaO2/FiO2); (b) outcome parameters, i.e., duration of hospitalization and number of pharmacological treatments used during the hospitalization. We investigated between-group differences and the relationships between severity of delirium/depression and the dependent variables. Duration of hospitalization was longer for DEL than for either DEP or CONT and for DEP compared to CONT. NEECHAM and HAM-D scores predicted lower PaO2 and PaO2/FiO2 levels in the DEL and DEP groups, respectively. In DEP, BPRS scores positively correlated with duration of hospitalization. Delirium impacted the course of COVID-19 more severely than depression. The mechanisms by which delirium and depression worsen respiratory parameters differ.