COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions' disorders, and Guillain-Barre syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.

https://www.mdpi.com/1422-0067/22/8/4081/pdf

Neurological Complications of COVID-19: Underlying Mechanisms and Management.

The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for SARS-CoV-2 infections.

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro.

As the global burden of mortality from COVID-19 continues to rise, an understanding of who is most at risk of adverse outcomes is of paramount importance. Pre-existing cardiometabolic, renal and respiratory diseases as well as old age are well-established risk factors associated with disease severity and mortality among patients with COVID-19. However, mounting evidence also indicates an increased susceptibility to, and risk of adverse outcomes from COVID-19 in people with schizophrenia, independent of age and comorbidity. Therefore, elucidating the underlying pathophysiological mechanisms which may increase the risk of poor outcomes in people with schizophrenia is of crucial importance. Here, we provide a narrative on the current understanding of COVID-19 in patients with schizophrenia and propose potential mechanisms which may link schizophrenia with an increased susceptibility to, and greater risk of adverse outcomes from COVID-19. Given the existing knowledge gaps, robust clinical and biological studies are required to further our understanding of some of these underlying mechanisms, so that effective prevention and treatment strategies for COVID-19 in patients with schizophrenia can be developed.

/pdf/covid-19-in-people-with-schizophrenia-potential-mechanisms-4eutf3wiu0.pdf

COVID-19 in People With Schizophrenia: Potential Mechanisms Linking Schizophrenia to Poor Prognosis

This Review discusses the potential drug interactions risk between Drugs used in treating COVID-19 infection and Drugs used in treating comorbid conditions (Diabetes, hypertension, cardiovascular illness).Six Databases were consulted a) Micromedex drug interaction b) Medicine complete.com c) Liverpool Drug Interaction Group for COVID-19 therapies d) Epocrates e) Medscape f) drugs.com. To acquire information on possible interaction effects between drugs used for COVID-19 treatment such as atazanavir, lopinavir/ritonavir, remdesivir, molnupiravir, paxlovid(nirmatrelvir/ritonavir), dexamethasone, azithromycin, chloroquine, and FDA approved monoclonal antibodies with primarily used antidiabetic drugs, antihypertensive drugs, and drugs acting on the cardiovascular system.Potential interaction effects such as worsening glycemic control were prominent with lopinavir/ritonavir and the primarily used antidiabetic drugs, which needs dosage adjustment and close monitoring. The risk of hypotension and irregular heart rhythm is the potential interaction effects with concomitant use of drugs for COVID-19 treatment and antihypertensive drugs. Caution is advised with drugs such as atazanavir and lopinavir/ritonavir when concomitantly used in treating comorbid conditions. Drugs such as remdesivir, molnupiravir, and some monoclonal antibodies are safer in use with drugs used in treating the comorbid condition.Drug-drug interaction remains one of the significant factors in altering the therapeutic efficacy. Drugs used to manage comorbid conditions may influence the COVID-19 treatment with potential interaction effects. These enhance the view on safety concerns about the drug interaction risk in managing COVID-19 infection in patients with comorbid conditions. This primary evidence may concern preventing potential or unintentional effects resulting from Drug-drug interaction, Improving patient quality of life. 

https://doi.org/10.1016/j.dsx.2022.102451

Drug interaction risk between cardioprotective drugs and drugs used in treatment of COVID-19: A evidence-based review from six databases

Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro

Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted. The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone. Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety

/pdf/drug-drug-interactions-between-covid-19-treatments-and-2hidv9o886.pdf

Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review.

Introduction The SARS-CoV-2 pandemic with psychiatric comorbidities leads to a scenario in which the use of psychotropic drugs may be required. This requires the support of evidence-based medicine to take into account possible interactions between antidepressants, mood stabilizers, benzodiazepines, and coronavirus infection treatments. Methods Three databases were consulted: (a) Lexicomp Drug Interactions, (b) Micromedex Solutions Drugs Interactions, (c)Liverpool Drug Interaction Group for COVID-19 therapies. The CredibleMeds QTDrugs List was also queried. Hydroxychloroquine, chloroquine, azithromycin, lopinavir-ritonavir, remdesivir, favipiravir, tocilizumab, baricitinib, anakinra, and dexamethasone – drugs used for SARS-CoV-2 – were analyzed, and consensus recommendations are made. Results The potential interactions of agomelatine, desvenlafaxine, duloxetine, milnacipran, and vortioxetine with COVID-19 treatments shall be considered less risky. Antidepressant interactions with hydroxychloroquine, chloroquine, and azithromycin enhance the risk of QT prolongation, and ECG monitoring is advised for most antidepressants. Antidepressants with lopinavir/ritonavir involve multiple CYP enzyme interactions (except with milnacipran). Gabapentin, oxcarbazepine, pregabalin, topiramate, and zonisamide are safe treatment options that have no significant interactions with COVID-19 treatments. Lithium is contraindicated with hydroxychloroquine, chloroquine, and azithromycin. Precaution should be taken in using valproic acid with lopinavir-ritonavir. The use of benzodiazepines does not present a risk of drug interaction with COVID-19 treatments, except lopinavir/ritonavir. Conclusions Clinicians prescribing antidepressants, mood stabilizers/anticonvulsants, and benzodiazepines, should be aware of the probable risk of drug-drug interaction with COVID-19 medications and may benefit from heeding these recommendations for use to ensure patient safety.

Drug-drug Interactions between COVID-19 Treatments and Antidepressants, Mood Stabilizers/Anticonvulsants, and Benzodiazepines: Integrated Evidence from 3 Databases.

Ana Rubio-García

Papers

Drug-drug interactions between COVID-19 treatments and antipsychotics drugs: integrated evidence from 4 databases and a systematic review.

Drug-drug Interactions between COVID-19 Treatments and Antidepressants, Mood Stabilizers/Anticonvulsants, and Benzodiazepines: Integrated Evidence from 3 Databases.

The role of antipsychotics against COVID-19: A topic for debate.