Exploring the management approaches of cytokines including viral infection and neuroinflammation for neurological disorders.

Considerable evidence supports that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in various neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. The purpose of this study is to discuss the recent research on treating cytokine storm and amyloids, including stroke, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's condition, Multi-sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS). Neuroinflammation observed in neurological disorders has a pivotal role in exacerbating Aß burden and tau hyperphosphorylation, suggesting that stimulating cytokines in response to an undesirable external response could be a checkpoint for treating neurological disorders. Furthermore, the pro-inflammatory cytokines help our immune system through a neuroprotective mechanism in clearing viral infection by recruiting mononuclear cells. This study reveals that cytokine applications may play a vital role in providing novel regulation and methods for the therapeutic approach to neurological disorders and the causes of the deregulation, which is responsible for neuroinflammation and viral infection. However, it needs to be further investigated to clarify better the mechanisms of cytokine release in response to various stimuli, which could be the central point for treating neurological disorders.

The Adverse Reactions of Pfizer BioNTech COVID-19 Vaccine Booster Dose are Mild and Similar to the Second Dose Responses: A Retrospective Cross-Sectional Study.

Background: Like other vaccines, Pfizer BioNTech's COVID-19 vaccine efficacy against SARS-CoV-2 virus infections begins to decline within a few months after the 2nd dose. On August 12, 2021, the FDA allowed additional Pfizer BioNTch's COVID-19 vaccine dose (3rd or booster dose) for individuals with weakened immunity. This study aimed to evaluate the short-term adverse reactions (ADRs) of the 2nd and the 3rd doses of the Pfizer BioNTech COVID-19 vaccine. Methods: Information for this study was collected by Google Form questionnaire (online survey). The results included responses from 442 people, the majority from Saudi Arabia. Results: The most common local ADRs following the 3rd dose were injection site pain, injection site hypersensitivity, and axillary lymph node swelling. The most common systemic ADRs were fatigue, muscle pain, bone pain, headache, and fever less than 38ºC. Less common systemic ADRs were shivering, fever more than 38ºC, nasal congestion and rhinorrhea, arrhythmia, cough, abdominal pain, chest tightness, nausea, diarrhea, vomiting, and tachypnea. Rare systemic ADRs were constipation, dizziness and vertigo, lack of concentration, sore throat, excessive hair loss, dysmenorrhea and heavy menstruation, and Bell's palsy. Severe allergic reactions were reported by 2.6% of participants after the 2nd dose, compared with none after the 3rd dose. Nasal congestion and runny nose are more frequent after the 3rd dose. The ADRs of the 2nd and 3rd doses were significantly more prevalent in females. 12% of participants reported ADRs lasting more than one week after the 3rd dose compared to 5% after the 2nd dose. People ≤ 60 years were more affected by the vaccine ADRs. Conclusion: Most of the ADRs reported after the 3rd vaccine dose were consistent with the Pfizer vaccine information sheet and similar to the 2nd dose ADRs.

Repurposing food molecules as a potential BACE1 inhibitor for Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain that manifests as dementia, disorientation, difficulty in speech, and progressive cognitive and behavioral impairment. The emerging therapeutic approach to AD management is the inhibition of ß-site APP cleaving enzyme-1 (BACE1), known to be one of the two aspartyl proteases that cleave ß-amyloid precursor protein (APP). Studies confirmed the association of high BACE1 activity with the proficiency in the formation of ß-amyloid-containing neurotic plaques, the characteristics of AD. Only a few FDA-approved BACE1 inhibitors are available in the market, but their adverse off-target effects limit their usage. In this paper, we have used both ligand-based and target-based approaches for drug design. The QSAR study entails creating a multivariate GA-MLR (Genetic Algorithm-Multilinear Regression) model using 552 molecules with acceptable statistical performance (R 2 = 0.82, Q 2 loo = 0.81). According to the QSAR study, the activity has a strong link with various atoms such as aromatic carbons and ring Sulfur, acceptor atoms, sp2-hybridized oxygen, etc. Following that, a database of 26,467 food compounds was primarily used for QSAR-based virtual screening accompanied by the application of the Lipinski rule of five; the elimination of duplicates, salts, and metal derivatives resulted in a truncated dataset of 8,453 molecules. The molecular descriptor was calculated and a well-validated 6-parametric version of the QSAR model was used to predict the bioactivity of the 8,453 food compounds. Following this, the food compounds whose predicted activity (pKi) was observed above 7.0 M were further docked into the BACE1 receptor which gave rise to the Identification of 4-(3,4-Dihydroxyphenyl)-2-hydroxy-1H-phenalen-1-one (PubChem I.D: 4468; Food I.D: FDB017657) as a hit molecule (Binding Affinity = -8.9 kcal/mol, pKi = 7.97 nM, Ki = 10.715 M). Furthermore, molecular dynamics simulation for 150 ns and molecular mechanics generalized born and surface area (MMGBSA) study aided in identifying structural motifs involved in interactions with the BACE1 enzyme. Molecular docking and QSAR yielded complementary and congruent results. The validated analyses can be used to improve a drug/lead candidate's inhibitory efficacy against the BACE1. Thus, our approach is expected to widen the field of study of repurposing nutraceuticals into neuroprotective as well as anti-cancer and anti-viral therapeutic interventions.

Psychological Distress During COVID-19 Curfews and Social Distancing in Saudi Arabia: A Cross-Sectional Study.

Background: Coronavirus disease 2019 (COVID-19) has spread to over 150 countries worldwide. Since the first case of COVID-19 was confirmed in Saudi Arabia, cases have continued to escalate exponentially. The COVID-19 outbreak has had a negative effect on mental health and well-being. The study aimed to investigate the effects of the strict national regulations associated with the COVID-19 pandemic on mental health. Methods: This was a cross-sectional study of a convenience sample of Saudi residents. Saudi residents aged 18 years or older were invited to complete an online questionnaire after one month of a nationwide 24-h curfew between May 6, 2020 and May 13, 2020. We measured psychological distress using the Depression, Anxiety, and Stress Scale-21 (DASS-21). We ran binary logistic regression analyses to detect variables that significantly predicted DASS-21 scores. Results: A sample of 2252 participants was recruited from the general population of Saudi Arabia. The DASS-21 score means and standard deviations for depression and anxiety for the whole sample (10.73 ± 10.29 and 6.98 ± 8.30, respectively) were in the range of mild depression and anxiety. In contrast, the mean DASS-21 stress score was within the normal range (11.97 ± 10.80). The mean stress score for healthcare workers was within the normal range (13.70 ± 10.68) but was significantly higher than the mean score for the public (11.56 ± 10.89; P = 0.0006). Several variables (e.g., age, gender, and history of contact with confirmed COVID-19 cases) were significantly associated with higher DASS-21 scores. Conclusions: The COVID-19 pandemic has created a psychological burden. Therefore, there is an urgent need to implement emergency public health interventions that ameliorate the risk perception of COVID-19 through the dissemination of adequate and targeted health information that could be a successful measure to mitigate the psychological impact of the Covid-19 pandemic.

Minor to Moderate Side Effects of Pfizer-BioNTech COVID-19 Vaccine Among Saudi Residents: A Retrospective Cross-Sectional Study.

BACKGROUND: The Pfizer-BioNTech COVID-19 vaccine has recently received emergency approval from the US FDA. The mRNA technology was used to manufacture the Pfizer vaccine; however, as a pioneering technology that has never been used in the manufacture of vaccines, many people have concerns about the vaccine's side effects. Thus, the current study aimed to track the short-term side effects of the vaccine. METHODS: The information in this study was gathered by a Google Form-questionnaire (online survey). The results included the responses of 455 individuals, all of whom are Saudi Arabia inhabitants. Adverse effects of the vaccine were reported after the first and the second doses. RESULTS: The most common symptoms were injection site pain, headaches, flu-like symptoms, fever, and tiredness. Less common side effects were a fast heartbeat, whole body aches, difficulty breathing, joint pain, chills, and drowsiness. Rare side effects include Bell's palsy and lymph nodes swelling and tenderness. Flu-like symptoms were more common among those under 60 years of age, while injection site pain was more frequent among recipients who were 60 years and older. The study revealed a significant increase in the number of females who suffered from the vaccine side effects compared to males. Difficulty of breathing was more reported among recipients who had been previously infected with the coronavirus compared to those who had not been previously infected. CONCLUSION: Most of the side effects reported in this study were consistent with Pfizer's fact sheet for recipients and caregivers. Further studies are required to determine the long-term side effects.

Relationship Between Public Mental Health and Immune Status During the COVID-19 Pandemic: Cross-Sectional Data from Saudi Arabia.

PURPOSE: Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic and continues to escalate exponentially in many countries across the globe. Recently, higher rates of psychological distress have been reported in several countries during the pandemic. Accordingly, the study aim was to investigate the relationship between public mental health and immune status during the COVID-19 pandemic. METHODS: Participants of this cross-sectional study were 2252 national and foreign residents of Saudi Arabia. We used a web-based self-rated questionnaire to measure the association between psychological distress (Depression, Anxiety and Stress Scales [DASS-21]) and immune status (Immune Status Questionnaire [ISQ]) during the COVID-19 pandemic. We also investigated predictors of reduced immune status using binary logistic regression analyses. RESULTS: Data from 1721 respondents showed that 17.5% of participants scored below the immune status cutoff (ISQ ˂ 6). Mean (± standard deviation) depression, anxiety, and stress scores in the reduced immune status group (ISQ ˂ 6) indicated moderate depression, anxiety, and stress (19.1 ± 11.4; 15.0 ± 9.6; 21.8 ± 11.2, respectively) and were significantly higher than scores in the normal immune status group (ISQ ≥ 6) (8.6 ± 9.1, P ˂ 0.0001; 5.0 ± 6.7, P ˂ 0.0001; 9.3 ± 9.3, P ˂ 0.0001, respectively). The regression analysis showed that age, anxiety, and stress were the only factors that significantly predicted the presence of reduced immune status. CONCLUSION: There is an association between mental health problems during the COVID-19 pandemic and immune response in the public, especially in elderly people.

Health Literacy, Perceived Threat, and Posttraumatic Stress Disorder During the COVID-19 Pandemic in Saudi Arabia.

PURPOSE: This study aimed to investigate the prevalence of and factors associated with posttraumatic stress disorder (PTSD) during the COVID-19 pandemic in Saudi Arabia. MATERIALS AND METHODS: This was a cross-sectional online survey that targeted adults over the age of 18 residing in Saudi Arabia. The data collection began June 1, 2020 and continued for four weeks. The Posttraumatic Stress Disorder Checklist-Specific, the Brief Illness Perception Questionnaire version BIP-Q5, and a 9-item health literacy measure were used. RESULTS: There were 1249 participants, of which 62.21% were under the age of 34. The prevalence of PTSD was 19.5% among all participants. The results showed that both the perception of threat (OR =1.17, 95% CI = 1.13-1.19) and health literacy (OR =0.97, 95% CI = 0.95-0.99) were associated with PTSD symptoms. CONCLUSION: This study highlights important findings that the level of an individual's perception of threat and health literacy is associated with symptoms of PTSD. Thus, an understanding of these constructs in the target population will enable the development of better measures designed to reduce the psychological impact of the COVID-19 pandemic.

Prevalence of post-traumatic stress disorder during the COVID-19 pandemic in Saudi Arabia.

BACKGROUND: The coronavirus diseases of 2019 (COVID-19) pandemic was classified as one of the worst pandemics in the 21st century. Its rapid transmission, unpredicted mortality rate, and the uncertainty surrounding its transmission method have evoked additional fear and anxiety. Nonetheless, to the best of our knowledge, no prior study has explored PTSD prevalence three months after the start of the quarantine procedures in Saudi Arabia nor has examined PTSD prevalence by three different methods. OBJECTIVE: This observational cross-sectional study aimed to identify the prevalence, severity, and influencing factors of PTSD in different regions of Saudi Arabia three months after the onset of the quarantine procedures related to the COVID-19 pandemic. METHODS: Through the month of June 2020, 1374 people (49.05% men and 50.95% women) completed a 35-item, 10-minute online. The prevalence of PTSD was measured using PCL-S (specific for COVID-19) that assesses the 17 symptoms of PTSD. Resilience was measured using 2-items Arabic version of the Connor-Davidson Resilience Scale 2 (CD-RISC 2). RESULTS: We calculated the prevalence by three methods, namely, PTSD cut-off score, criteria, and combined, and the prevalence was 22.63%, 24.8%, and 19.6%, respectively. Female participants showed higher prevalence than male. As well, participants who were either tested positive or suspected of having been infected with COVID-19 showed higher PTSD prevalence. Higher resilience was associated with lower PTSD prevalence. CONCLUSIONS: This was the first study to report PTSD prevalence by three differential methods three months after the onset of the quarantine procedures related to the COVID-19 pandemic in Saudi Arabia. We observed a significant impact of the COVID-19 pandemic in the Saudi population; therefore, great attention should be performed in implementing new procedures that deal with the highlighted risk factors, especially in vulnerable groups, to overcome the psychological impact of the COVID-19 pandemic.

Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review.

The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.