Evaluation of the Most Visible Symptoms Associated with COVID-19 Vaccines Among the Residents of Makkah, Saudi Arabia: An Observational, Cross-Sectional Study.

Background: This research evaluated the most visible symptoms associated with coronavirus (COVID-19) vaccines among residents in Makkah of Saudi Arabia. Methods: A cross-sectional study was conducted in 2021 among a representative sample of residents receiving COVID-19 vaccination at King Abdullah Medical City, Al Ukayshiyyah, and Umm Al-Qura University vaccination centers. A total of 805 participants selected by a census sampling method were included. Data regarding characteristics, medical history, and post-vaccination symptoms were obtained with an interview-based questionnaire. Results: The participants' mean age was 25.20 ± 15.5 years. Of them, 61.7% and 38.3% received one and two doses of the COVID-19 vaccine, respectively. 2.2% have an allergic reaction to the COVID-19 vaccine. 25.3% were infected with COVID-19, 23% were infected before the first dose, and only 1.6% were infected after the first dose. Significant statistical associations were found between males and females in smoking status, age, body mass index, history of diabetes mellitus, and types of COVID-19 vaccines (P-value < 0.05). After adjustment for confounding variables, male participants had lower odds of having swelling, redness, or pain at the injection site, muscle or joint pain, headache, dizziness, and nausea compared to female participants [OR = 0.596, 95% CI = (0.388-0.916)], [OR = 0.272, 95% CI = (0.149-0.495)], [OR = 0.529, 95% CI = (0.338-0.828)], [OR = 0.263, 95% CI = (0.125-0.554)], and [OR = 0.145, 95% CI = (0.31-0.679), P < 0.05 for all], respectively. Conclusion: The female participants may have a higher risk of post-COVID-19 vaccination symptoms than males among Makkah residents of Saudi Arabia.

Lack of Evidence on Association between Iron Deficiency and COVID-19 Vaccine-Induced Neutralizing Humoral Immunity.

Iron is a crucial micronutrient for immunity induction in response to infections and vaccinations. This study aimed to investigate the effect of iron deficiency on COVID-19-vaccine-induced humoral immunity. We investigated the effectiveness of COVID-19 vaccines (BNT162b2, mRNA-1273, and ChAdOx nCov-2019) in iron-deficient individuals (n = 63) and provide a side-by-side comparison to healthy controls (n = 67). The presence of anti-SARS-CoV-2 spike (S) and anti-nucleocapsid (NP) IgG were assessed using in-house S- and NP-based ELISA followed by serum neutralization test (SNT). High concordance between S-based ELISA and SNT results was observed. The prevalence of neutralizing antibodies was 95.24% (60/63) in the study group and 95.52% (64/67) in the controls with no significant difference. The presence/absence of past infection, period since vaccination, vaccine type, and being iron-deficient or having iron-deficiency anemia did not exert any significant effect on the prevalence or titer of anti-SARS-CoV-2 neutralizing antibodies. NP-based ELISA identified individuals unaware of exposure to SARS-CoV-2. Moreover, absence of anti-NP IgG was noted in participants who were previously diagnosed with COVID-19 suggesting the unpredictability of after-infection immunity. To sum up, this study demonstrated an initial lack of evidence on the association between iron deficiency and the effectiveness of COVID-19-vaccine-induced neutralizing humoral immunity. Similar studies with larger sample size remain necessary to obtain comprehensive conclusions about the effect or lack of effect of iron on COVID-19-vaccine effectiveness.

In silico identification of microRNAs targeting the PPARα/γ: promising therapeutics for SARS-CoV­2 infection.

The SARS-CoV-2 lifecycle is dependent on the host metabolism machinery. It upregulates the PPARα and PPARγ genes in lipid metabolism, which supports the essential viral replication complex including lipid rafts and palmitoylation of viral protein. The use of PPAR ligands in SARS-CoV-2 infection may have positive effects by preventing cytokine storm and the ensuing inflammatory cascade. The inhibition of PPARα and PPARγ genes may alter the metabolism and may disrupt the lifecycle of SARS-CoV-2 and COVID-19 progression. In the present work, we have identified possible miRNAs targeting PPARα and PPARγ in search of modulators of PPARα and PPARγ genes expression. The identified miRNAs could possibly be viewed as new therapeutic targets against COVID-19 infection.

Energetic and frustration analysis of SARS-CoV-2 nucleocapsid protein mutations.

The ongoing COVID-19 spreads worldwide with the ability to evolve in diverse human populations. The nucleocapsid (N) protein is one of the mutational hotspots in the SARS-CoV-2 genome. The N protein is an abundant RNA-binding protein critical for viral genome packaging. It comprises two large domains including the N-terminal domain (NTD) and the C-terminal domain (CTD) linked by the centrally located linker region. Mutations in N protein have been reported to increase the severity of disease by modulating viral transmissibility, replication efficiency as well as virulence properties of the virus in different parts of the world. To study the effect of N protein missense mutations on protein stability, function, and pathogenicity, we analyzed 228 mutations from each domain of N protein. Further, we have studied the effect of mutations on local residual frustration changes in N protein. Out of 228 mutations, 11 mutations were predicted to be deleterious and destabilized. Among these mutations, R32C, R191C, and R203 M mutations fall into disordered regions and show significant change in frustration state. Overall, this work reveals that by altering the energetics and residual frustration, N protein mutations might affect the stability, function, and pathogenicity of the SARS-CoV-2.

A potential association between obesity and reduced effectiveness of COVID-19 vaccine-induced neutralizing humoral immunity.

Due to the adverse effects of obesity on host immunity, this study investigated the effectiveness of COVID-19 vaccines (BNT162b2, ChAdOx-nCov-2019, and mRNA-1273) in inducing anti-SARS-CoV-2 Spike (S) neutralizing antibodies among individuals with various obesity classes (class I, II, III, and super obesity). Sera from vaccinated obese individuals (n = 73) and normal BMI controls (n = 46) were subjected to S-based enzyme-linked immunosorbent assay (ELISA) and serum-neutralization test (SNT) to determine the prevalence and titer of anti-SARS-CoV-2 neutralizing antibodies. Nucleocapsid-ELISA was also utilized to distinguish between immunity acquired via vaccination only versus vaccination plus recovery from infection. Data were linked to participant demographics including age, gender, past COVID-19 diagnosis, and COVID-19 vaccination profile. S-based ELISA demonstrated high seroprevalence rates (>97%) in the study and control groups whether samples with evidence of past infection were included or excluded. Interestingly, however, SNT demonstrated a slightly significant reduction in both the rate and titer of anti-SARS-CoV-2 neutralizing antibodies among vaccinated obese individuals (60/73; 82.19%) compared to controls (45/46; 97.83%). The observed reduction in COVID-19 vaccine-induced neutralizing humoral immunity among obese individuals occurs independently of gender, recovery from past infection, and period from last vaccination. Our data suggest that COVID-19 vaccines are highly effective in inducing protective humoral immunity. This effectiveness, however, is potentially reduced among obese individuals which highlight the importance of booster doses to improve their neutralizing immunity. Further investigations on larger sample size remain necessary to comprehensively conclude about the effect of obesity on COVID-19 vaccine effectiveness on humoral immunity induction.

Effect of the COVID-19 Vaccine on the Menstrual Cycle among Females in Saudi Arabia.

Background: The number of reports of menstrual changes after COVID-19 vaccination in the Saudi population is still unknown. Therefore, this study aimed to assess the effect of the COVID-19 vaccine(Pfizer, AstraZeneca, and Moderna) on the menstrual cycle among females in Saudi Arabia. Methods: This descriptive cross-sectional study was conducted in Saudi Arabia at Umm Al-Qura University (UQU) from August 2021 to February 2022. Data was collected through a previously validated online questionnaire. Results: A total of 2338 participants who received the first dose of the COVID-19 vaccine participated in this study; 1606 (68.7%) of them received the second dose in addition to the first. The mean age of the study participants was 35.4±9.5 years. No significant associations were found between the type of COVID-19 vaccine and the impact on the menstrual cycle, either for the first or second dose (P-values > 0.05). A significant association was found only between the first dose vaccination day and the impact on the menstrual cycle in the second question of "After receiving the COVID-19 vaccine, your next period was" (P-value ≤ 0.05). Significant associations were found between the second dose vaccination day and the impact on the menstrual cycle in the first and second questions of "After receiving the COVID-19 vaccine, your next period was", and "After receiving the first dose, your next period was," respectively (P-values ≤ 0.05). Conclusion: The study found a potential association between the COVID-19 vaccine and menstrual cycle irregularities, which could impact females' quality of life.

Knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people and the level of HIV/AIDS awareness among the general population in the kingdom of Saudi Arabia: A cross-sectional study.

Introduction: The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (HIV/AIDS) are worldwide public health issues. Since Saudi Arabia is growing more accessible to the outside world, it is critical to analyze the general population's knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people, and the level of HIV/AIDS awareness. Therefore, this study aimed to assess the knowledge of HIV/AIDS transmission modes and attitudes toward HIV/AIDS infected people, as well as the level of HIV/AIDS awareness among the general population in the Kingdom of Saudi Arabia. Methods: The current online community-based cross-sectional descriptive study was conducted among the general population of the Kingdom of Saudi Arabia using a self-administrated electronic questionnaire between October 2017 and February 2018. A score <3 was considered a negative response. In contrast, scores of 3 and 4 were considered positive responses. The sum score of each outcome was evaluated according to Bloom's cutoff point. The scores for knowledge and attitude were transformed into mean percentage scores by dividing the sum scores obtained by the respondents by the number of items multiplied by 100. Consequently, the overall mean percentage of scores for each category of knowledge and attitude at 60% and above was considered a good level, whereas <60% was deemed a poor level. Results: A total of 2,081 subjects residing in the Kingdom of Saudi Arabia participated in this survey. The mean score of the participant's responses to knowledge items on HIV/AIDS transmission modes was 84.2 ± 15.8%. The mean score of the participant's responses to attitude items toward HIV/AIDS infected people was 50.1 ± 49.9%. The mean score of the participant's responses to attitude items toward the level of HIV/AIDS awareness in Saudi Arabia was 55.7 ± 3.6%. Many socio-demographic variables were significantly associated with mean scores of knowledge of HIV/AIDS transmission modes, mean scores of attitude toward HIV/AIDS infected people, and mean scores of attitude toward the level of HIV/AIDS awareness (P-value ≤ 0.05). The Spearman rank correlation explained significant negative linear correlations between knowledge of HIV/AIDS transmission modes-attitudes toward HIV/AIDS infected people and knowledge of HIV/AIDS transmission modes-attitudes toward the level of HIV/AIDS awareness of r = -0.040 and r = -0.070, respectively (P-value ≤ 0.05). Otherwise, there was a positive linear correlation between attitudes toward HIV/AIDS infected people-attitudes toward the level of HIV/AIDS awareness (r = 0.080, P-value = 0.072). Conclusions: The study showed that a high percentage of the respondents had good knowledge of HIV/AIDS transmission modes. However, a low rate of the study respondents had positive attitudes toward HIV/AIDS infected people and the level of HIV/AIDS awareness among the general population in Saudi Arabia. Therefore, there is a dire need for advocacy campaigns and policies to help reduce HIV stigmatization levels.

Human Mastadenovirus Infections in Children: A Review of the Current Status in the Arab World in the Middle East and North Africa.

Human mastadenovirus (HAdV) is a non-enveloped icosahedral virus with double-stranded DNA genomes. The mortality rate of HAdV infections can reach 35.5%, while gastroenteritis HAdV infections, HAdV pneumonia, and disseminated disease tend to show a worse outcome, with rates ranging from 44.2% to 50%. In addition, HAdV can cause infections at any age but most commonly in the pediatric population, especially in young children and infants. Therefore, this review aims to assess the current status of HAdV infections among children in the Arab World, particularly in the Middle East and North Africa. Web of Science, Scopus, PubMed, EMBASE, and Google Scholar databases for publications in English were searched up to July 2022 for relevant articles. The literature search yielded a total of 21 studies, which were included in this review. Studies reporting HAdV infections in children were conducted in 17 out of the 22 countries. The average prevalence rate of HAdV infections in children was 12.7%, with average prevalence rates of 12.82% and 12.58% in the Middle East and North African countries, respectively. The highest prevalence rate (28.3%) was reported in Egypt, whereas the lowest prevalence (1.5%) was reported in Sudan. The included studies presented children with signs and symptoms of gastroenteritis, acute respiratory infection, acute diarrhea, and acute hemorrhagic conjunctivitis. In conclusion, the average prevalence rate of HAdV infections in children was 12.7%, with average prevalence rates of 12.82% and 12.58% in the Middle East and North African countries, respectively. Finding the precise prevalence rate of this virus is crucial because it will guide future planning for effective disease control and the selection of particular treatment options during epidemics and special seasons.

Low Prevalence of Syndromic Respiratory Tract Infections among Returning Hajj Pilgrims Amidst the COVID-19 Pandemic: A Post-Hajj Survey.

This study estimates the point prevalence of symptomatic respiratory tract infections (RTIs) among returned Hajj pilgrims and their contacts in 2021. Using the computer-assisted telephone interview (CATI) technique, domestic pilgrims were invited to participate in this cross-sectional survey two weeks after their home return from Hajj. Of 600 pilgrims approached, 79.3% agreed to participate and completed the survey. Syndromic definitions were used to clinically diagnose possible influenza-like illnesses (ILI) and COVID-19. Median with range was applied to summarise the continuous data, and frequencies and proportions were used to present the categorical variables. Simple logistic regression was carried out to assess the correlations of potential factors with the prevalence of RTIs. The majority of pilgrims (88.7%) reported receiving at least two doses of the COVID-19 vaccine before Hajj. Eleven (2.3%) pilgrims reported respiratory symptoms with the estimated prevalence of possible ILI being 0.2%, and of possible COVID-19 being 0.4%. Among those who were symptomatic, five (45.5%) reported that one or more of their close contacts had developed similar RTI symptoms after the pilgrims' home return. The prevalence of RTIs among pilgrims who returned home after attending the Hajj 2021 was lower compared with those reported in the pre-pandemic studies; however, the risk of spread of infection among contacts following Hajj is still a concern.

Prevalence and Association of Transfusion Transmitted Infections with ABO and Rh Blood Groups among Blood Donors in the Western Region of Saudi Arabia: A 7-Year Retrospective Analysis.

This study was aimed at determining the prevalence estimate and association of transfusion-transmitted infections (TTIs) with ABO and Rh blood groups among blood donors at the King Faisal Specialist Hospital and Research Center (KFSH & RC) in the western region of Saudi Arabia. A retrospective study was conducted at the blood bank center of KFSH and RC from 1 January 2013 to 31 December 2019. Data on ABO and Rh blood group testing, serological testing, molecular investigations, serological assays, nucleic acid testing (NATs), and socio-demographic information were gathered. During the study period, there were 959,431 blood donors at the KFSH and RC. The overall 7-year cumulative prevalence estimate of blood transfusion-transmitted infections among blood donors was low at 7.93%, with an average prevalence estimate of 0.66%. Donors with the O blood group, the O RhD +ve blood group, in particular, were more at risk of developing TTIs, whereas donors with the AB blood group, the AB RhD -ve blood group, in particular, were at the lowest risk of developing TTIs. In total, 96.9% of the blood donors were males (n = 916,567). Almost half of the blood donors belong to the O blood group (49.4%). A total of 861,279 (91.0%) donors were found to be RhD positive. The percentages of TTIs were found to be higher in RhD +ve donors compared with RhD -ve donors. The prevalence estimate of the hemoglobin C (HbC) infection was the most common TTI among the blood donors being 3.97%, followed by malaria being 2.21%. The least prevalence estimate of TTI in the present study was for NAT HIV being 0.02%. Significant associations were observed between RhD +ve and RhD -ve among the malaria-infected donors (A: χ2 = 26.618, p = 0.001; AB: χ2 = 23.540, p = 0.001; B: χ2 = 5.419, p = 0.020; O: χ2 = 68.701, p = 0.001). The current 7-year retrospective study showed a low level of TTIs among blood donors. However, we urge that more research encompassing the entire country be conducted in order to obtain more representative results in terms of the prevalence estimate and association of transfusion-transmitted infections with ABO and Rh blood groups in communities.

Seroprevalence of Hepatitis E Virus Infection in Middle Eastern Countries: A Systematic Review and Meta-Analysis.

Hepatitis E virus (HEV) is a hepatotropic virus that is a major public health concern worldwide. Autochthonous HEV is spread through oral feces in unsanitary environments, as well as vertical and, occasionally, blood transfusion. HEV is more common in developing countries, but it has recently become more widespread in developed countries as well. The Middle East (ME) has long been an endemic location for HEV infection. Therefore, the aim of this systematic review and meta-analysis was to assess the seroprevalence of anti-HEV antibodies in ME countries. The author systematically searched five databases, namely ScienceDirect, EMBASE, Scopus, PubMed, and Google Scholar, to identify English-language articles published on or before 25 April 2022. Comprehensive meta-analysis software was used for all statistical analyses (CMA, version 3, BioStat, Englewood, CO, USA). After quality control and exclusion of irrelevant studies, 80 studies were included in the qualitative synthesis and meta-analysis. A forest plot showed that the overall pooled seroprevalence of HEV infection in ME countries in the fixed-effect and random-effect models were 21.3% (95% CI: 0.209-0.216) and 11.8% (95% CI: 0.099-0.144), respectively. Furthermore, the findings showed a high level of heterogeneity (I2 = 98.733%) among the included studies. In both fixed-effect and random-effect models, the seroprevalence of HEV infection by country was high in Egypt as compared to other regions, at 35.0% (95% CI: 0.342-0.359), and 34.7% (95% CI: 0.153-0.611), respectively. The seroprevalence of HEV infection by country was high among pregnant women, at 47.9% (95% CI: 0.459-0.499) in the fixed-effect model, and in renal transplant recipients, at 30.8% (95% CI: 0.222-0.410) in the random-effect model. The seroprevalence of HEV infection varies by country and study population in the Middle East. More research is needed to determine the disease's incidence, morbidity, and mortality in the region, where it is prevalent.

Syndromic surveillance of respiratory-tract infections and hand hygiene practice among pilgrims attended Hajj in 2021: a cohort study.

BACKGROUND: The risk of transmission of viral respiratory tract infections (RTIs) is high in mass gatherings including Hajj. This cohort study estimated the incidence of symptomatic RTIs and hand hygiene compliance with its impact among Hajj pilgrims during the COVID-19 pandemic. METHODS: During the week of Hajj rituals in 2021, domestic pilgrims were recruited by phone and asked to complete a baseline questionnaire. Pilgrims were followed up after seven days using a questionnaire about the development of symptoms, and practices of hand hygiene. Syndromic definitions were used to clinically diagnose 'possible' influenza-like illnesses (ILI) and COVID-19 infection. RESULTS: A total of 510 pilgrims aged between 18 and 69 (median of 50) years completed the questionnaire, 280 (54.9%) of whom were female, and all of them (except for one) were vaccinated against COVID-19 with at least one dose. The mean (± SD) of pilgrims' hand hygiene knowledge score (on a scale of 0 to 6) was 4.15 (± 1.22), and a higher level of knowledge was correlated with a higher frequency of handwashing using soap and water. Among those 445 pilgrims who completed the follow-up form, 21 (4.7%) developed one or more respiratory symptoms, of which sore throat and cough were the commonest (respectively 76.2% and 42.8%); 'possible ILI' and 'possible COVID-19' were present in 1.1% and 0.9% of pilgrims. Obesity was found to be a significant factor associated with the risk of developing RTIs (odds ratio = 4.45, 95% confidence interval 1.15-17.13). CONCLUSIONS: Hajj pilgrims are still at risk of respiratory infections. Further larger and controlled investigations are needed to assess the efficacy of hand hygiene during Hajj.

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach.

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (-8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (-8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins-the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.

Genetic Structure of Cucumber Mosaic Virus From Natural Hosts in Nigeria Reveals High Diversity and Occurrence of Putative Novel Recombinant Strains.

Cucumber mosaic virus (CMV, Bromoviridae: Cucummovirus), one of the most widespread plant viruses with several hosts, causes huge losses in yield quality and quantity. The occurrence of various CMV strains and high genetic diversity within the virus complicate its management. We describe the population structure of CMV in Nigeria using partial RNA1 and RNA3 gene sequences from three natural hosts: pepper (Capsicum annuum), tomato (Solanum lycopersicum), and watermelon (Citrullus lanatus). One hundred and six leaf samples were obtained from 16 locations across Nigeria, and specific primers were used to amplify the two gene fragments using PCR. Twenty-four samples tested positive for CMV using RNA1 primers, and amplicons were sequenced from 12 isolates, revealing 82.94-99.80% nucleotide and 85.42-100% amino acid sequence similarities within the population. The partial RNA3 fragment, corresponding to the complete coat protein (CP) gene, was sequenced from seven isolates, with 95.79-97.90% and 98.62-100% nucleotide and amino acid intrapopulation similarities, respectively. The isolates belonged to subgroup IB and formed distinct phylogenetic clusters in both gene sets, indicating putative novel strains. Recombination signals, supported by phylogenetic inferences, were detected within the RNA1 dataset (P ≤ 0.05) and identified a recombinant isolate within the Nigerian sequences. No recombination was detected within the CP genes. Population genetics parameters established high diversity within the Nigerian population compared to other isolates worldwide, while selection pressure estimates revealed the existence of negative selection in both gene sets. Although CMV subgroup IB strains were postulated to originate from Asia, this study reveals their prevalence across several hosts from different locations in Nigeria. To our knowledge, this is the first comprehensive description of a recombinant CMV subgroup IB isolate from West Africa, which has implications for its robust detection and overall management.

Lack of Antibodies to SARS-CoV-2 among Blood Donors during COVID-19 Lockdown: A Study from Saudi Arabia.

In response to the coronavirus disease 2019 (COVID-19), Saudi Arabia have imposed timely restrictions to minimize the infection spread, lower the risk for vulnerable groups, and reduce the pressure on healthcare services. The effectiveness of these measures has not been assessed comprehensively and, thereby, remains uncertain. Besides monitoring the number of COVID-19 cases diagnosed by molecular assays, the seroprevalence can serve as an indicator for the incidence rate among the general population. This study aimed to evaluate seroprevalence status of all healthy blood donors who attended one of the main largest hospital located in the western region of Saudi Arabia from 1 January to 31 May 2020. The study period covered two months prior to reporting the first COVID-19 case in the country on 2 March 2020. Importantly, it covered the period when "lock-down type" measures have been enforced. Samples were subjected to in-house enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CLIA), and microneutralization (MN). The sero statuses of all samples were confirmed negative, demonstrating the lack of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among blood donors during COVID-19 lockdown period. This study supports the hypothesis that COVID-19 restrictions have potential for limiting the extent of the infection.

Evaluation of Antimicrobial Stewardship Programs (ASPs) and their perceived level of success at Makkah region hospitals, Kingdom of Saudi Arabia.

Antimicrobial stewardship programs (ASPs) are collaborative efforts to optimize antimicrobial use in healthcare institutions through evidence-based quality improvement strategies. The general administration of pharmaceutical care in the Saudi ministry of health (MOH) is putting outstanding efforts in implementing antimicrobial stewardship in Saudi health care settings. Several surveys have been conducted globally and reported many types of antimicrobial stewardship strategies in health institutions and their effectiveness. This study aims to identify ASPs in Makkah region hospitals and their perceived level of success. We administered a regional survey to explore current progress and issues related to the implementation of ASPs in Makkah region hospitals at the pharmacy level (n = 25). Among responding hospitals, 19 (76%) hospitals, the most commonly reported ASP were as following: formulary restrictions (90%) for broad-spectrum antimicrobials and use of prospective feedback on antimicrobial prescribing (68%), use of clinical guidelines and pathways (100%), and use of automatic stop orders (68%) to limit inappropriate antimicrobial therapy. The study outcomes will also be of pivotal importance to devise policies and strategies for antimicrobial stewardship implementation in other non-MOH settings in the Makkah region. Based on our results, all reported institutions have at least one antimicrobial stewardship program in a process with a high success rate. A multidisciplinary ASP approach, active involvement of drug & therapeutic committee, formulary restrictions, and availability of education & training of pharmacists and physicians on ASP are the primary elements for perceived successful antimicrobial stewardship programs in the Makkah region hospitals.

Adenovirus E1B 55-Kilodalton Protein Targets SMARCAL1 for Degradation during Infection and Modulates Cellular DNA Replication.

Here, we show that the cellular DNA replication protein and ATR substrate SMARCAL1 is recruited to viral replication centers early during adenovirus infection and is then targeted in an E1B-55K/E4orf6- and cullin RING ligase-dependent manner for proteasomal degradation. In this regard, we have determined that SMARCAL1 is phosphorylated at S123, S129, and S173 early during infection in an ATR- and CDK-dependent manner, and that pharmacological inhibition of ATR and CDK activities attenuates SMARCAL1 degradation. SMARCAL1 recruitment to viral replication centers was shown to be largely dependent upon SMARCAL1 association with the RPA complex, while Ad-induced SMARCAL1 phosphorylation also contributed to SMARCAL1 recruitment to viral replication centers, albeit to a limited extent. SMARCAL1 was found associated with E1B-55K in adenovirus E1-transformed cells. Consistent with its ability to target SMARCAL1, we determined that E1B-55K modulates cellular DNA replication. As such, E1B-55K expression initially enhances cellular DNA replication fork speed but ultimately leads to increased replication fork stalling and the attenuation of cellular DNA replication. Therefore, we propose that adenovirus targets SMARCAL1 for degradation during infection to inhibit cellular DNA replication and promote viral replication.IMPORTANCE Viruses have evolved to inhibit cellular DNA damage response pathways that possess antiviral activities and utilize DNA damage response pathways that possess proviral activities. Adenovirus has evolved, primarily, to inhibit DNA damage response pathways by engaging with the ubiquitin-proteasome system and promoting the degradation of key cellular proteins. Adenovirus differentially regulates ATR DNA damage response signaling pathways during infection. The cellular adenovirus E1B-55K binding protein E1B-AP5 participates in ATR signaling pathways activated during infection, while adenovirus 12 E4orf6 negates Chk1 activation by promoting the proteasome-dependent degradation of the ATR activator TOPBP1. The studies detailed here indicate that adenovirus utilizes ATR kinase and CDKs during infection to promote the degradation of SMARCAL1 to attenuate normal cellular DNA replication. These studies further our understanding of the relationship between adenovirus and DNA damage and cell cycle signaling pathways during infection and establish new roles for E1B-55K in the modulation of cellular DNA replication.