Psychotropic drug repurposing for COVID-19: a systematic review

Introduction: Recently, several antidepressants, mood stabilizers, and antipsychotics have been suggested to have favorable effects in the treatment of COVID-19. Objective(s): The aim of this systematic review was to collect evidence from preclinical and clinical studies concerning the scientific evidence for the repurposing of psychotropic drugs in COVID-19 treatment. Method(s): Two independent authors searched PubMed-MEDLINE, Scopus, PsycInfo, Clinical Trial Registration Site US (ClinicalTrials. gov) databases, and reviewed the reference lists of articles for eligible articles published up to May 31st, 2021. All preclinical and clinical studies on the effect of any psychotropic drug on Sars-CoV-2 or patients with COVID-19 were included. The Newcastle-Ottawa scale was used for the quality assessment of clinical studies. This systematic review adheres to the PRISMA guidelines. Result(s): 22 studies were included in the synthesis: 9 clinical studies, 9 preclinical studies, and 4 computational studies. The use of antidepressants, both SSRI and non-SSRI, was associated with a reduced risk of severe complications of COVID-19. Several antipsychotics showed an increased risk for both Sars-CoV-2 infection and severe complications during COVID-19. Conclusion(s): The current evidence supports a potential anti- SARS-CoV-2 role for several antidepressants, while the evidence on mood stabilizers or antipsychotics remains controversial. Drug repurposing proved highly successful in response to the current pandemic and psychotropic medications are widely used in clinical practice with well-known safety and tolerability profiles, showing antiviral, immunomodulatory, and anti-inflammatory properties, being perfect candidates for possible treatment of COVID-19. Further research will deliver optimized and specific therapeutic tools that will increase the preparedness of health systems for possible future epidemics.

Strong ACE-2 expression in the choroidal vessels: do high choroid plexuses serve as a gateway for SARS-CoV-2 infection on the human brain?

OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2.  The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a  strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.

Fetal programming of COVID-19: may the barker hypothesis explain the susceptibility of a subset of young adults to develop severe disease?

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARS-COV-2 infection, irrespectively of his/her age.