Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis (preprint)

BackgroundAntipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID19-related immunological parameters. MethodsDifferential gene expression profiles of non-COVID versus COVID RNA-Seq samples (CRA002390 project in GSA database) and drug-naive patients with psychosis at baseline and after three months of aripiprazole treatment was identified. An integrative analysis between COVID and aripiprazole immunomodulatory antagonist effects was performed. Findings82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fishers Exact Test, two tail; P value=3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated schizophrenia patients (P adj<0.05). The most significant pathways were associated to the immune system such as the "inflammatory bowel disease (IBD)" (the most significant pathway with a P adj of 0.00021), "Th1 and Th2 cell differentiation" and "B cell receptor signaling pathway", all three related to the defense against infections. InterpretationThis exploratory investigation may provide further support to the notion that protective effect is exerted by phenylpiperazine by modulating the immunological dysregulation associated to COVID-19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.

Short-term emotional impact of COVID-19 pandemic on Spaniard health workers.

BACKGROUND: The aims of this study were to evaluate the short-term impact of 2019-nCoV outbreak on the mental/psychological state of Spaniard health care workers (HCWs) and to explore the influencing factors, including organizational factors. METHODS: A web-based survey (Google forms questionnaire) spread via professional and scientific associations, professional WhatsApp and email lists, following a snowball technique was used. Data were collected from May 11th and May 31st, 2020 RESULTS: : A total of 1407 subjects were included in final analyses. 24.7% (348 out of 1407) of HCWs reported symptoms of acute stress (SARS-Q measurement) and 53.6% (754 out of 1407) reported symptoms related to poorer general health (GHQ-28 measurement). A higher risk of having an acute stress disorder was associated to being female, not having access to protective material, and several subjects´ perceived risks. Additionally, poorer overall general health (GHQ>24) was related to being female, working in a geographical area with a high incidence of infection, not being listened to by your co-workers, having a greater perception of stress at work and being able to transmit the infection to others. LIMITATIONS: We must consider a likely memory bias. CONCLUSION: The high prevalence of affective and general health symptoms among the HCWs and the critical influence of organizational issues and subjects´ perceived risk should lead health authorities to design future strategies to protect health professional force for facing a potential upcoming epidemiological crisis.

Drug-Drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review (preprint)

RelevanceManagement of symptoms like anxiety, delirium and agitation cannot be neglected in COVID-19 patients. Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored ObjectiveTo systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Evidence ReviewThree databases were consulted: (a) Lexicomp(R) Drug Interactions, (b) Micromedex(R) Solutions Drugs Interactions, (c) Liverpool (C) Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and TdP, the CredibleMeds(R) QTDrugs List was searched. Based on the information collected, the authors made a recommendation agreed to by consensus. In addition, a systematic review was conducted to find the clinical outcomes of drug-drug interactions between COVID-19 treatments and antipsychotics ResultsThe main interaction between COVID-19 drugs and antipsychotics are the risk of QT prolongation and TdP, and CYP interactions. Remdesivir, favipiravir, baricinitib, and anakinra can be used concomitantly with antipsychotics with no risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Tocilizumab is rather safe to use in combination with antipsychotics, although it can restore the activity of CYP3A4 and therefore its substrate metabolism may increase. The most demanding COVID-19 treatments for co-administration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin (all prolong QT interval) and lopinavir / ritonavir (CYP interaction and risk of QT prolongation). ConclusionsWe urge to development of evidence-based guidelines that can help clinicians decide the safest treatment combination and monitoring necessary for each particular patient. The selection of concomitant COVID-19 medications and antipsychotics should be evidence-based and closely monitored.