Emergence of a New Zoonotic COVID-19 that Creates a Pandemic: Update on Current Pharmacotherapeutics and Future Prospective of Plasma Therapy

The current decade started on an unexpected note, with almost the entire world grappling with a newly arisen pandemic. A novel coronavirus, tracing its first human host to a Chinese province, has spread to all geographical areas with human populations. The virus, named SARS-CoV-2, infects the lower respiratory tract, much like other coronaviruses, that caused the 2002 epidemic, to which it is eponymous. The severity of infection is seen in individuals with comorbidities like diabetes, cardiovascular disorders, chronic respiratory problems, hypertension, cancer, etc. This virus represents another incidence of zoonosis to humans and has infected over eighteen million people since December 2019, of its first human transmission. All the currently employed therapies are either aimed at alleviating the severity of the symptoms or being administered on a trial basis. This review attempts to summarize brief aetiology of the virus, epidemiology of the outbreak, clinical symptoms of the disease with a postulated mechanism of pathogenesis and several existing and approved drugs and therapeutics along with plasma therapy, which are being clinically reviewed for their activity, as well as safety, against the disease;none of which are approved yet. A few promising vaccine candidates, as per in vivo studies, are also underway, but their evaluation might take a year at least. Meanwhile, experts have come up with the concept of "social distancing" to stem the viral spread, as the medical research fraternity of the world strives hard to find a safe, successful and effective cure for it.Copyright © 2021 Bentham Science Publishers.

Drug utilization in patients with SARS-CoV-2 in an intensive care unit

Context: Prescription indication studies allow identifying the problems that arise during the use of the drug. Aims: To evaluate the treatments used in patients diagnosed with SARS-CoV-2 infection hospitalized in critical care service, through a prescription indication study.Methods: A longitudinal observational study of medication use of the indication-prescription type with elements of the therapeutic scheme and practical consequences was carried out. The sample was characterized from the sociodemographic, clinical, and pharmacotherapeutic points of view. The prescription was evaluated through the indicators: indication, therapeutic scheme, treatment individualization, and drug combinations. The detected adverse reactions were classified according to their causality by the Naranjo Algorithm, their severity, their clinical significance, and according to their mechanism by Rawlins and Thompson.Results: In the sample (n = 77), the male gender predominated (79%) between 27-59 years old (64%), alcohol consumer (62%), hypertensive (33%) with long hospital stay (51%). A total of 417 medications were analyzed, being antibiotics (50.6%) the most prescribed. 73.4% of the therapeutic schemes were correct;however, 26.6% had problems with the therapeutic schemes due to incorrect doses, intervals, duration of treatment, and risky interactions. According to Rawlins and Thompson, two probable adverse reactions were detected, mild, non-serious, and type A and B.Conclusions: The results obtained will allow the pharmaceutical professional to create risk matrices that guarantee a timely intervention in the health team to contribute to the rational and safe use of medicines in patients infected with SARS-CoV-2.

Mental Health Symptom Reduction Using Digital Therapeutics Care Informed by Genomic SNPs and Gut Microbiome Signatures.

Neuropsychiatric diseases and obesity are major components of morbidity and health care costs, with genetic, lifestyle, and gut microbiome factors linked to their etiology. Dietary and weight-loss interventions can help improve mental health, but there is conflicting evidence regarding their efficacy; and moreover, there is substantial interindividual heterogeneity that needs to be understood. We aimed to identify genetic and gut microbiome factors that explain interindividual differences in mental health improvement after a dietary and lifestyle intervention for weight loss. We recruited 369 individuals participating in Digbi Health's personalized digital therapeutics care program and evaluated the association of 23 genetic scores, the abundance of 178 gut microbial genera, and 42 bacterial pathways with mental health. We studied the presence/absence of anxiety or depression, or sleep problems at baseline and improvement on anxiety, depression, and insomnia after losing at least 2% body weight. Participants lost on average 5.4% body weight and >95% reported improving mental health symptom intensity. There were statistically significant correlations between: (a) genetic scores with anxiety or depression at baseline, gut microbial functions with sleep problems at baseline, and (b) genetic scores and gut microbial taxa and functions with anxiety, depression, and insomnia improvement. Our results are concordant with previous findings, including the association between anxiety or depression at baseline with genetic scores for alcohol use disorder and major depressive disorder. As well, our results uncovered new associations in line with previous epidemiological literature. As evident from previous literature, we also observed associations of gut microbial signatures with mental health including short-chain fatty acids and bacterial neurotoxic metabolites specifically with depression. Our results also show that microbiome and genetic factors explain self-reported mental health status and improvement better than demographic variables independently. The genetic and microbiome factors identified in this study provide the basis for designing and personalizing dietary interventions to improve mental health.

Hospitalized COVID-19 Patients with Severe Acute Respiratory Syndrome: A Population-Based Registry Analysis to Assess Clinical Findings, Pharmacological Treatment and Survival.

Background and Objectives: One of the most serious clinical outcomes in hospitalized patients with COVID-19 is severe acute respiratory syndrome (SARS). The aim is to analyze pharmacological treatment, survival and the main mortality predictors. Materials and Methods: A real-world data study from COVID-19-hospitalized patients with SARS from 1 March to 31 May 2020 has been carried out. Variables such as hospital length of stay, ventilation type and clinical outcomes have been taken into account. Results: In Castile and Leon, 14.03% of the 7307 in-hospital COVID-19 patients developed SARS, with a mortality rate of 42.53%. SARS prevalence was doubled in males compared to females, and 78.54% had an age of 65 years or more. The most commonly used medicines were antibiotics (89.27%), antimalarials (68.1%) and corticosteroids (55.9%). Survival of patients developing SARS was lower compared to patients without this complication (12 vs. 13 days). The main death predictors were disseminated intravascular coagulation (DIC) (OR: 13.87) and age (>65 years) (OR: 7.35). Conclusions: Patients older than 65 years who develop DIC have a higher probability of hospital death. Tocilizumab and steroids have been linked to a lower incidence of hospital death, being the main treatment for COVID-19 hospitalized patients with SARS.

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.

The Impact of the COVID-19 Pandemic on Diagnosing and Treating Attention Deficit Hyperactivity Disorder: New Challenges on Initializing and Optimizing Pharmacological Treatment.

Introduction: COVID-19 has been causing huge disruptions in mental healthcare services worldwide, including those related to ADHD. Some consequences of the pandemic, such as virtual schooling and remote work, as well as increased telemedicine, have posed new challenges for ADHD diagnosis and treatment. In this narrative review, we summarize existing COVID-19 and ADHD literature especially focusing on ADHD diagnostic during the pandemic and treatment adherence. Methods: The databases searched were: PubMed, PsycINFO, EMBASE, Google Scholar and medRxiv. We included all English language articles and preprints that reported on medication/pharmacological treatment among the terms "ADHD" and "COVID-19" resulting in a total of 546 articles. The final search was done on Dec-23 2021. We selected fifteen articles focusing on the challenges of ADHD diagnostic during COVID-19 pandemic. Results: Of the fifteen studies included, most were cross-sectional and perspective pieces. Most of them discussed that individuals with ADHD present risk factors that may make them more vulnerable to health negative consequences of the pandemic, which in turn may have an impact on treatment efficacy and adherence. Telemedicine is also addressed as a potential powerful instrument on monitoring ADHD treatment. Conclusion: Despite the challenges posed by the pandemic on monitoring ADHD treatment, the available literature stressed that the current scenario also may offer new opportunities that could lead to the development of individualized treatment interventions, such as the remote monitoring of symptoms.

COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends.

AIMS: The novel Coronavirus disease 2019 (COVID-19) has caused great distress worldwide. Acute respiratory distress syndrome (ARDS) is well familiar but when it happens as part of COVID-19 it has discrete features which are unmanageable. Numerous pharmacological treatments have been evaluated in clinical trials to control the clinical effects of CARDS, but there is no assurance of their effectiveness. MATERIALS AND METHODS: A systematic review of the literature of the Medline, Scopus, Bentham, PubMed, and EMBASE (Elsevier) databases was examined to understand the novel therapeutic approaches used in COVID-19-Associated Acute Respiratory Distress Syndrome and their outcomes. KEY FINDINGS: Current therapeutic options may not be enough to manage COVID-19-associated ARDS complications in group of patients and therefore, the current review has discussed the pathophysiological mechanism of COVID-19-associated ARDS, potential pharmacological treatment and the emerging molecular drug targets. SIGNIFICANCE: The rationale of this review is to talk about the pathophysiology of CARDS, potential pharmacological treatment and the emerging molecular drug targets. Currently accessible treatment focuses on modulating immune responses, rendering antiviral effects, anti-thrombosis or anti-coagulant effects. It is expected that considerable number of studies conducting globally may help to discover effective therapies to decrease mortality and morbidity occurring due to CARDS. Attention should be also given on molecular drug targets that possibly will help to develop efficient cure for COVID-19-associated ARDS.

Pharmacological Treatments against COVID-19 in Pregnant Women.

The recent respiratory virus known as SARS-CoV-2 has caused millions of deaths worldwide, causing great uncertainty due to the lack of a specific treatment, which has been mitigated by the use of various drugs traditionally used against other types of pathologies. Pregnancy presents special physiological conditions that expose the pregnant woman and the foetus to greater risk. Pregnant women are often excluded from trials due to possible risk of toxicity or side effects, resulting in a lack of knowledge about the use of drugs and treatments during pregnancy. The main objective of this review was to compile existing knowledge about currently available drug treatments for COVID-19 in pregnant women. The review report met the criteria of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) review protocol and was registered with the registration number CRD42021251036. The electronic databases searched were Scopus, PubMed, CINAHL and SciELO. Finally, 22 articles were included, resulting in an analysis of drugs with an acceptable safety profile in the treatment of pregnant women with COVID-19.

Pharmacological therapy for Tourette syndrome: What medicine can do and cannot do.

Tourette syndrome (TS) is a frequently observed developmental neuropsychological disorder occurring in children. The pathophysiology involves both genetic and environmental factors. In this review, clinical characteristics, pathophysiology, and treatment approaches based on the pathophysiology of TS are presented. The pathophysiology is the acceleration of developmental decrement of dopamine (DA) activity at the terminal of nigro-striatal (NS)-DA system causing DA D2 receptor up-ward regulation. Serotonergic neurons involving in development of the biphasic sleep-wake-rhythm, and locomotion may be involved. Pharmacological treatments constitute an important part in managing TS. Small dose of levodopa and aripiprazole showed the good effect controlling the tics, without side effects. Intervention with enhancing the day time activity and keeping the regular sleep-wake-rhythm, and encouraging locomotion are important. The data from Yoshiko Nomura Neurological Clinic for Children regarding the clinical features and outcomes, medication effects, and OCD and outcomes are shown. To discuss about the environmental factor, how the COVID-19 pandemic affected the TS patients is also presented.

Effectiveness of a Family Support Intervention on Caregiving Burden in Family of Elderly Patients With Cognitive Decline After the COVID-19 Lockdown.

Background: The coronavirus disease 2019 (COVID-19) pandemic had a great impact on patients with cognitive decline or dementia. The lockdown period may exacerbate behavioral disorders and worsen distress of caregivers. The aim of this study is to evaluate the effectiveness of a family support intervention on the negative effects that the COVID-19 lockdown may have on patients and related caregivers. Methods: We recruited patients whose related caregivers had attended a family support course before the COVID-19 lockdown. The course was for family members of patients with cognitive decline or dementia and consisted in eight meetings during which the participants received information about the disease, the management of neuropsychiatric symptoms, and community resources and services available for patients with dementia. Data on cognitive decline, neuropsychiatric symptoms, and functional status had been collected before the course with the Mini-Mental State Examination (MMSE), the Neuropsychiatric Inventory (NPI), and the Instrumental (IADL) and Basic (BADL) Activities of Daily Living scales, respectively. The caregiving burden had been evaluated at the end of the course by means of the Zarit Burden Interview (ZBI). After the COVID-19 lockdown, a phone interview was made to compare neuropsychiatric symptoms, functional status, and caregiver's burden with the previous evaluation. Results: There were no significant changes before and after the COVID-19 lockdown in the mean NPI score. The IADL, BADL, and ZBI scores were significantly lower after lockdown than before. The BADL scores were inversely associated with ZBI scores. Thus, despite a worsening of patients' functional status, the caregivers' burden decreased significantly probably due to the positive effect of the family support intervention. Conclusions: Our study demonstrated that a complete family support intervention for caregivers of patients with cognitive decline or dementia can reduce the burden of care even in a particular negative period, such as the COVID-19 lockdown.

The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment.

The recent outbreak of the corona virus disease (COVID-19) has had major global impact. The relationship between severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and psychiatric diseases is of great concern, with an evident link between corona virus infections and various central and peripheral nervous system manifestations. Unmitigated neuro-inflammation has been noted to underlie not only the severe respiratory complications of the disease but is also present in a range of neuro-psychiatric illnesses. Several neurological and psychiatric disorders are characterized by immune-inflammatory states, while treatments for these disorders have distinct anti-inflammatory properties and effects. With inflammation being a common contributing factor in SARS-CoV-2, as well as psychiatric disorders, treatment of either condition may affect disease progression of the other or alter response to pharmacological treatment. In this review, we elucidate how viral infections could affect pre-existing psychiatric conditions and how pharmacological treatments of these conditions may affect overall progress and outcome in the treatment of SARS-CoV-2. We address whether any treatment-induced benefits and potential adverse effects may ultimately affect the overall treatment approach, considering the underlying dysregulated neuro-inflammatory processes and potential drug interactions. Finally, we suggest adjunctive treatment options for SARS-CoV-2-associated neuro-psychiatric symptoms.

Risk of pre-term births and major birth defects resulting from paternal intake of COVID-19 medications prior to conception.

OBJECTIVE: With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the 3 months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone. RESULTS: For azithromycin and naproxen, large numbers of offspring were exposed (> 1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~ 900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (< 300 offspring). Our evidence suggests that azithromycin and naproxen are safe with respect to pre-term birth and birth defects. For the other drugs investigated larger exposures are needed for conclusive statements.

Medical Management of COVID-19: Evidence and Experience.

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and this infectious disease is termed COVID-19 in short. On a global scale, as of June 1, 2020, the World Health Organization (WHO) published statistics of 6,057,853 infected patients and 371,166 deaths worldwide. Despite reported observational data about the experimental use of certain drugs, there is no conclusively proven curative therapy for COVID-19 as of now; however, remdesivir received emergency use authorization (EUA) by the Food and Drug Administration (FDA) recently for use in patients hospitalized with COVID-19. There are several ongoing clinical trials related to the pharmacological choices of therapy for COVID-19 patients; however, drug trials related to observational studies so far have yielded mixed results and therefore have created a sense of confusion among healthcare professionals (HCPs). In this review article, we seek to collate and provide a summary of treatment strategies for COVID-19 patients with a variable degree of illness and discuss pharmacologic and other therapies intended to be used either as experimental medicine/therapy or as part of supportive care in complicated cases of COVID-19.