Co-creating an educational resource to promote the uptake of Skin-to-Skin Contact in Saudi Arabia.

AIM: This paper focuses on the co-creation approach to develop culturally and linguistically appropriate educational interventions to promote the uptake of skin-to-skin contact. BACKGROUND: Skin-to-skin contact is beneficial to mothers and newborns, but it is rarely practised in Saudi Arabia. Co-creation involving service users to develop evidence-based resources about skin-to-skin contact relevant to the target population is an approach increasingly used to improve health outcomes. METHOD: A three-step method was used to develop the educational intervention including: (1) a systematic scoping review to identify the evidence-based information for education regarding skin-to-skin contact between mother and baby post-birth; (2) Co-creation of the resources using the Knowledge to Action Framework. The resource was developed collaboratively with academic staff from Australia and health care staff from Saudi hospital; and (3) Finalisation of the educational materials through a consensus development conference and Implementation. FINDINGS: The systematic scoping review generated useful information about the gaps in knowledge and barriers to skin-to-skin practice. Information was tailored and translated according to the needs of the Saudi population. A variety of educational materials including pamphlets, a PowerPoint presentation and a short video were co-created with the help of the stakeholders. Consensus was reached when 93% (87-100%) of the participants agreed about the mode of delivery and appropriateness of the PowerPoint and 100% agreed on the e-pamphlets and video. DISCUSSION: The skin-to-skin online educational resource was created by integrating co-creation principles and the Knowledge to Action framework with the aim of developing and customizing a culturally appropriate intervention using the best available evidence. By engaging in co-creation stakeholders gained a sense of ownership and were more willing to adopt and implement the intervention.

Psychogenetic, genetic and epigenetic mechanisms in Candida auris: Role in drug resistance.

In recent years, we are facing the challenge of drug resistance emergence in fungi. The availability of limited antifungals and development of multi-drug resistance in fungal pathogens has become a serious concern in the past years in the health sector. Although several cellular, molecular, and genetic mechanisms have been proposed to explain the drug resistance mechanism in fungi, but a complete understanding of the molecular and genetic mechanisms is still lacking. Besides the genetic mechanism, epigenetic mechanisms are pivotal in the fungal lifecycle and disease biology. However, very little is understood about the role of epigenetic mechanisms in the emergence of multi-drug resistance in fungi, especially in Candida auris (C. auris). The current narrative review summaries the clinical characteristics, genomic organization, and molecular/genetic/epigenetic mechanisms underlying the emergence of drug resistance in C. auris. A very few studies have attempted to evaluate the role of epigenetic mechanisms in C. auris. Furthermore, advanced genetic tools such as the CRISP-Cas9 system can be utilized to elucidate the epigenetic mechanisms and their role in the emergence of multi-drug resistance in C. auris.

Global emerging Omicron variant of SARS-CoV-2: Impacts, challenges and strategies.

Newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously posing high global public health concerns and panic resulting in waves of coronavirus disease 2019 (COVID-19) pandemic. Depending on the extent of genomic variations, mutations and adaptation, few of the variants gain the ability to spread quickly across many countries, acquire higher virulency and ability to cause severe disease, morbidity and mortality. These variants have been implicated in lessening the efficacy of the current COVID-19 vaccines and immunotherapies resulting in break-through viral infections in vaccinated individuals and recovered patients. Altogether, these could hinder the protective herd immunity to be achieved through the ongoing progressive COVID-19 vaccination. Currently, the only variant of interest of SARS-CoV-2 is Omicron that was first identified in South Africa. In this review, we present the overview on the emerging SARS-CoV-2 variants with a special focus on the Omicron variant, its lineages and hybrid variants. We discuss the hypotheses of the origin, genetic change and underlying molecular mechanism behind higher transmissibility and immune escape of Omicron variant. Major concerns related to Omicron including the efficacy of the current available immunotherapeutics and vaccines, transmissibility, disease severity, and mortality are discussed. In the last part, challenges and strategies to counter Omicron variant, its lineages and hybrid variants amid the ongoing COVID-19 pandemic are presented.

Saudi Women's Breastfeeding Knowledge, Attitude, and Practices: A Systematic Review and Meta-analysis.

INTRODUCTION: Despite the health benefits of breastfeeding, Saudi women do not exclusively breastfeed their babies. The purpose of this article was to synthesize Saudi women's breastfeeding knowledge, attitude, and practices and identify the factors that women reported for their breastfeeding cessation. METHODOLOGY: A systematic review and meta-analysis of randomized clinical trials and cross-sectional studies was undertaken. RESULTS: Saudi women reported poor knowledge in managing breastfeeding challenges and had a positive attitude toward formula feeding. Giving premade formula and sugar water was a common practice. The breastfeeding initiation rate (31.5%, 95% confidence interval [CI]: [22%, 41.8%]) and exclusive breastfeeding at 6 months were low (15.15, 95% CI: [8%, 24%]). Perceived low milk supply, returning to work, and using contraception were the main reasons for early breastfeeding cessation. DISCUSSION: The integration of Islamic, political, and economic cultures in Saudi Arabia can influence women's breastfeeding practices. There is a need for culturally appropriate breastfeeding educational programs for Saudi women.

Genetic Variants and Protective Immunity against SARS-CoV-2.

The novel coronavirus-19 (SARS-CoV-2), has infected numerous individuals worldwide, resulting in millions of fatalities. The pandemic spread with high mortality rates in multiple waves, leaving others with moderate to severe symptoms. Co-morbidity variables, including hypertension, diabetes, and immunosuppression, have exacerbated the severity of COVID-19. In addition, numerous efforts have been made to comprehend the pathogenic and host variables that contribute to COVID-19 susceptibility and pathogenesis. One of these endeavours is understanding the host genetic factors predisposing an individual to COVID-19. Genome-Wide Association Studies (GWAS) have demonstrated the host predisposition factors in different populations. These factors are involved in the appropriate immune response, their imbalance influences susceptibility or resistance to viral infection. This review investigated the host genetic components implicated at the various stages of viral pathogenesis, including viral entry, pathophysiological alterations, and immunological responses. In addition, the recent and most updated genetic variations associated with multiple host factors affecting COVID-19 pathogenesis are described in the study.

An Overview on Phenotypic and Genotypic Characterisation of Carbapenem-Resistant Enterobacterales.

Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.

Artificial Intelligence for Clinical Diagnosis and Treatment of Prostate Cancer.

As medical science and technology progress towards the era of "big data", a multi-dimensional dataset pertaining to medical diagnosis and treatment is becoming accessible for mathematical modelling. However, these datasets are frequently inconsistent, noisy, and often characterized by a significant degree of redundancy. Thus, extensive data processing is widely advised to clean the dataset before feeding it into the mathematical model. In this context, Artificial intelligence (AI) techniques, including machine learning (ML) and deep learning (DL) algorithms based on artificial neural networks (ANNs) and their types, are being used to produce a precise and cross-sectional illustration of clinical data. For prostate cancer patients, datasets derived from the prostate-specific antigen (PSA), MRI-guided biopsies, genetic biomarkers, and the Gleason grading are primarily used for diagnosis, risk stratification, and patient monitoring. However, recording diagnoses and further stratifying risks based on such diagnostic data frequently involves much subjectivity. Thus, implementing an AI algorithm on a PC's diagnostic data can reduce the subjectivity of the process and assist in decision making. In addition, AI is used to cut down the processing time and help with early detection, which provides a superior outcome in critical cases of prostate cancer. Furthermore, this also facilitates offering the service at a lower cost by reducing the amount of human labor. Herein, the prime objective of this review is to provide a deep analysis encompassing the existing AI algorithms that are being deployed in the field of prostate cancer (PC) for diagnosis and treatment. Based on the available literature, AI-powered technology has the potential for extensive growth and penetration in PC diagnosis and treatment to ease and expedite the existing medical process.

Tools to Alleviate the Drug Resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), an acid-fast bacillus that causes Tuberculosis (TB), is a pathogen that caused 1.5 million deaths in 2020. As per WHO estimates, another 4.1 million people are suffering from latent TB, either asymptomatic or not diagnosed, and the frequency of drug resistance is increasing due to intrinsically linked factors from both host and bacterium. For instance, poor access to TB diagnosis and reduced treatment in the era of the COVID-19 pandemic has resulted in more TB deaths and an 18% reduction in newly diagnosed cases of TB. Additionally, the detection of Mtb isolates exhibiting resistance to multiple drugs (MDR, XDR, and TDR) has complicated the scenario in the pathogen's favour. Moreover, the conventional methods to detect drug resistance may miss mutations, making it challenging to decide on the treatment regimen. However, owing to collaborative initiatives, the last two decades have witnessed several advancements in both the detection methods and drug discovery against drug-resistant isolates. The majority of them belong to nucleic acid detection techniques. In this review, we highlight and summarize the molecular mechanism underlying drug resistance in Mtb, the recent advancements in resistance detection methods, and the newer drugs used against drug-resistant TB.

Global Prevalence of Colistin Resistance in Klebsiella pneumoniae from Bloodstream Infection: A Systematic Review and Meta-Analysis.

Background: Among gram-negative bacteria, Klebsiella pneumoniae is one of the most common causes of healthcare-related infection. Bloodstream infections (BSIs) caused by Klebsiella pneumoniae are notorious for being difficult to treat due to resistance to commonly used antimicrobials. Klebsiella pneumoniae isolates from bloodstream infections are becoming increasingly resistant to carbapenems. In the fight against carbapenem-resistant Klebsiella pneumoniae, colistin [polymyxin E] is the antimicrobial of choice and is thus widely used. Objective: This study aimed to determine the global prevalence of colistin resistance amongst Klebsiella pneumoniae isolates from bloodstream infections. Methods: PubMed, Medline, Scopus, and the Cochrane Library were searched for published articles without restricting the search period. Studies meeting the predefined inclusion and exclusion criteria were included, and quality was assessed using Joanna Briggs Institute Checklist. We used a statistical random effect model to analyze data with substantial heterogeneity (I2 > 50%) in the meta-analysis. Results: A total of 10 studies out of 2873 search results that met the inclusion criteria were included in the final synthesis for this study. A pooled prevalence of colistin resistance was 3.1%, 95% CI (1.5−4.7%). The highest colistin resistance pooled prevalence was recorded in isolates studied in 2020 and beyond 12.90% (4/31), while Klebsiella pneumoniae isolates studied in 2015 and before and in 2016−2019 showed a pooled colistin resistance rate of 2.89% (48/1661) and 2.95% (28/948), respectively. The highest colistin resistance was found in Klebsiella pneumoniae isolates from Thailand (19.2%), while the least pooled resistance was in Klebsiella pneumoniae from South Korea (0.8%). The pooled prevalence of the multidrug-resistant (MDR) of Klebsiella pneumoniae from bloodstream infection ranged from 80.1%, 95% CI (65.0−95.2%), and the resistance prevalence of other antibiotics by Klebsiella pneumoniae from bloodstream infections were as follows; ciprofloxacin (45.3%), ertapenem (44.4%), meropenem (36.1%), imipenem (35.2%), gentamicin (33.3%), amikacin (25.4%) and tigecycline (5.1%). Klebsiella pneumoniae recovered from the intensive care unit (ICU) showed higher colistin resistance, 11.5% (9/781%), while non-ICU patients showed 3.03% (80/2604) pooled colistin resistance. Conclusion: This study showed low colistin resistance in Klebsiella pneumoniae isolates from global bloodstream infections. However, significant colistin resistance was observed in isolates collected from 2020 and beyond. Significant colistin resistance was also observed in Klebsiella pneumoniae isolates in bloodstream infections from the intensive care unit (ICU) compared to those from non-ICUs. As a result, there is a need to institute colistin administration stewardship in the ICU in clinical settings.

A Comprehensive Review on the Current Vaccines and Their Efficacies to Combat SARS-CoV-2 Variants.

Since the first case of Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, SARS-CoV-2 infection has affected many individuals worldwide. Eventually, some highly infectious mutants-caused by frequent genetic recombination-have been reported for SARS-CoV-2 that can potentially escape from the immune responses and induce long-term immunity, linked with a high mortality rate. In addition, several reports stated that vaccines designed for the SARS-CoV-2 wild-type variant have mixed responses against the variants of concern (VOCs) and variants of interest (VOIs) in the human population. These results advocate the designing and development of a panvaccine with the potential to neutralize all the possible emerging variants of SARS-CoV-2. In this context, recent discoveries suggest the design of SARS-CoV-2 panvaccines using nanotechnology, siRNA, antibodies or CRISPR-Cas platforms. Thereof, the present comprehensive review summarizes the current vaccine design approaches against SARS-CoV-2 infection, the role of genetic mutations in the emergence of new viral variants, the efficacy of existing vaccines in limiting the infection of emerging SARS-CoV-2 variants, and efforts or challenges in designing SARS panvaccines.

Promising Antimycobacterial Activities of Flavonoids against Mycobacterium sp. Drug Targets: A Comprehensive Review.

Tuberculosis (TB) caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb) remains a threat to mankind, with over a billion of deaths in the last two centuries. Recent advancements in science have contributed to an understanding of Mtb pathogenesis and developed effective control tools, including effective drugs to control the global pandemic. However, the emergence of drug resistant Mtb strains has seriously affected the TB eradication program around the world. There is, therefore, an urgent need to develop new drugs for TB treatment, which has grown researchers' interest in small molecule-based drug designing and development. The small molecules-based treatments hold significant potential to overcome drug resistance and even provide opportunities for multimodal therapy. In this context, various natural and synthetic flavonoids were reported for the effective treatment of TB. In this review, we have summarized the recent advancement in the understanding of Mtb pathogenesis and the importance of both natural and synthetic flavonoids against Mtb infection studied using in vitro and in silico methods. We have also included flavonoids that are able to inhibit the growth of non-tubercular mycobacterial organisms. Hence, understanding the therapeutic properties of flavonoids can be useful for the future treatment of TB.

The SARS-CoV-2 Antibodies, Their Diagnostic Utility, and Their Potential for Vaccine Development.

Antibodies (Abs) are important immune mediators and powerful diagnostic markers in a wide range of infectious diseases. Understanding the humoral immunity or the development of effective antibodies against SARS-CoV-2 is a prerequisite for limiting disease burden in the community and aids in the development of new diagnostic, therapeutic, and vaccination options. Accordingly, the role of antiviral antibodies in the resistance to and diagnosis of SARS-CoV-2 infection was explored. Antibody testing showed the potential in adding important diagnostic value to the routine diagnosis and clinical management of COVID-19. They could also play a critical role in COVID-19 surveillance, allowing for a better understanding of the full scope of the disease. The development of several vaccines and the success of passive immunotherapy suggest that anti-SARS-CoV-2 antibodies have the potential to be used in the treatment and prevention of SARS-CoV-2 infection. In this review, we highlight the role of antibodies in the diagnosis of SARS-CoV-2 infection and provide an update on their protective roles in controlling SARS-CoV-2 infection as well as vaccine development.

Global Prevalence and Potential Influencing Factors of COVID-19 Vaccination Hesitancy: A Meta-Analysis.

Countries worldwide have deployed mass COVID-19 vaccination drives, but there are people who are hesitant to receive the vaccine. Studies assessing the factors associated with COVID-19 vaccination hesitancy are inconclusive. This study aimed to assess the global prevalence of COVID-19 vaccination hesitancy and determine the potential factors associated with such hesitancy. We performed an organized search for relevant articles in PubMed, Scopus, and Web of Science. Extraction of the required information was performed for each study. A single-arm meta-analysis was performed to determine the global prevalence of COVID-19 vaccination hesitancy; the potential factors related to vaccine hesitancy were analyzed using a Z-test. A total of 56 articles were included in our analysis. We found that the global prevalence of COVID-19 vaccination hesitancy was 25%. Being a woman, being a 50-year-old or younger, being single, being unemployed, living in a household with five or more individuals, having an educational attainment lower than an undergraduate degree, having a non-healthcare-related job and considering COVID-19 vaccines to be unsafe were associated with a higher risk of vaccination hesitancy. In contrast, living with children at home, maintaining physical distancing norms, having ever tested for COVID-19, and having a history of influenza vaccination in the past few years were associated with a lower risk of hesitancy to COVID-19 vaccination. Our study provides valuable information on COVID-19 vaccination hesitancy, and we recommend special interventions in the sub-populations with increased risk to reduce COVID-19 vaccine hesitancy.

Systematic Review on Pathophysiological Complications in Severe COVID-19 among the Non-Vaccinated and Vaccinated Population.

COVID-19, caused by SARS-CoV-2, is one of the longest viral pandemics in the history of mankind, which have caused millions of deaths globally and induced severe deformities in the survivals. For instance, fibrosis and cavities in the infected lungs of COVID-19 are some of the complications observed in infected patients post COVID-19 recovery. These health abnormalities, including is multiple organ failure-the most striking pathological features of COVID-19-have been linked with diverse distribution of ACE2 receptor. Additionally, several health complications reports were reported after administration of COVID-19 vaccines in healthy individuals, but clinical or molecular pathways causing such complications are not yet studied in detail. Thus, the present systematic review established the comparison of health complication noted in vaccinated and non-vaccinated individuals (COVID-19 infected patients) to identify the association between vaccination and the multiorgan failure based on the data obtained from case studies, research articles, clinical trials/Cohort based studies and review articles published between 2020-2022. This review also includes the biological rationale behind the COVID-19 infection and its subsequent symptoms and effects including multiorgan failure. In addition, multisystem inflammatory syndrome (MIS) has been informed in individuals post vaccination that resulted in multiorgan failure but, no direct correlation of vaccination with MIS has been established. Similarly, hemophagocytic lymphohistiocytosis (HLH) also noted to cause multiorgan failure in some individuals following full vaccination. Furthermore, severe complications were recorded in elderly patients (+40 years of age), indicates that older age individuals are higher risk by COVID-19 and post vaccination, but available literature is not sufficient to comply with any conclusive statements on relationship between vaccination and multiorgan failure.

Application of Artificial Intelligence in Combating High Antimicrobial Resistance Rates.

Artificial intelligence (AI) is a branch of science and engineering that focuses on the computational understanding of intelligent behavior. Many human professions, including clinical diagnosis and prognosis, are greatly useful from AI. Antimicrobial resistance (AMR) is among the most critical challenges facing Pakistan and the rest of the world. The rising incidence of AMR has become a significant issue, and authorities must take measures to combat the overuse and incorrect use of antibiotics in order to combat rising resistance rates. The widespread use of antibiotics in clinical practice has not only resulted in drug resistance but has also increased the threat of super-resistant bacteria emergence. As AMR rises, clinicians find it more difficult to treat many bacterial infections in a timely manner, and therapy becomes prohibitively costly for patients. To combat the rise in AMR rates, it is critical to implement an institutional antibiotic stewardship program that monitors correct antibiotic use, controls antibiotics, and generates antibiograms. Furthermore, these types of tools may aid in the treatment of patients in the event of a medical emergency in which a physician is unable to wait for bacterial culture results. AI's applications in healthcare might be unlimited, reducing the time it takes to discover new antimicrobial drugs, improving diagnostic and treatment accuracy, and lowering expenses at the same time. The majority of suggested AI solutions for AMR are meant to supplement rather than replace a doctor's prescription or opinion, but rather to serve as a valuable tool for making their work easier. When it comes to infectious diseases, AI has the potential to be a game-changer in the battle against antibiotic resistance. Finally, when selecting antibiotic therapy for infections, data from local antibiotic stewardship programs are critical to ensuring that these bacteria are treated quickly and effectively. Furthermore, organizations such as the World Health Organization (WHO) have underlined the necessity of selecting the appropriate antibiotic and treating for the shortest time feasible to minimize the spread of resistant and invasive resistant bacterial strains.

Updates on Measles Incidence and Eradication: Emphasis on the Immunological Aspects of Measles Infection.

Measles is an RNA virus infectious disease mainly seen in children. Despite the availability of an effective vaccine against measles, it remains a health issue in children. Although it is a self-limiting disease, it becomes severe in undernourished and immune-compromised individuals. Measles infection is associated with secondary infections by opportunistic bacteria due to the immunosuppressive effects of the measles virus. Recent reports highlight that measles infection erases the already existing immune memory of various pathogens. This review covers the incidence, pathogenesis, measles variants, clinical presentations, secondary infections, elimination of measles virus on a global scale, and especially the immune responses related to measles infection.

Household COVID-19 secondary attack rate and associated determinants in Pakistan; A retrospective cohort study.

BACKGROUND: COVID-19 household transmissibility remains unclear in Pakistan. To understand the dynamics of Severe Acute Respiratory Syndrome Coronavirus disease epidemiology, this study estimated Secondary Attack Rate (SAR) among household and close contacts of index cases in Pakistan using a statistical transmission model. METHODOLOGY: A retrospective cohort study was conducted using an inclusive contact tracing dataset from the provinces of Punjab and Khyber-Pakhtunkhwa to estimate SAR. We considered the probability of an infected person transmitting the infection to close contacts regardless of residential addresses. This means that close contacts were identified irrespective of their relationship with the index case. We assessed demographic determinants of COVID-19 infectivity and transmissibility. For this purpose based on evolving evidence, and as CDC recommends fully vaccinated people get tested 5-7 days after close contact with a person with suspected or confirmed COVID-19. Therefore we followed the same procedure in the close contacts for secondary infection. FINDINGS: During the study period from 15th May 2020 to 15th Jan 2021, a total of 339 (33.9%) index cases were studied from 1000 cases initially notified. Among close contact groups (n = 739), households were identified with an assumed mean incubation period of 8.2+4.3 days and a maximum incubation period of 15 days. SAR estimated here is among the household contacts. 117 secondary cases from 739 household contacts, with SAR 11.1% (95% CI 9.0-13.6). All together (240) SAR achieved was 32.48% (95% CI; 29.12-37.87) for symptomatic and confirmed cases. The potential risk factors for SAR identified here included; old age group (>45 years of age), male (gender), household members >5, and residency in urban areas and for index cases high age group. Overall local reproductive number (R) based on the observed household contact frequencies for index/primary cases was 0.9 (95% CI 0.47-1.21) in Khyber Pakhtunkhwa and 1.3 (95% CI 0.73-1.56) in Punjab. CONCLUSIONS: SAR estimated here was high especially in the second phase of the COVID-19 pandemic in Pakistan. The results highlight the need to adopt rigorous preventive measures to cut the chain of viral transmission and prevent another wave of COVID-19.

Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders - Advances and challenges.

Autoimmune diseases are caused when immune cells act against self-protein. This biological self-non-self-discrimination phenomenon is controlled by a distinct group of lymphocytes known as regulatory T cells (Tregs), which are key inflammatory response regulators and play a pivotal role in immune tolerance and homeostasis. Treg-mediated robust immunosuppression provides self-tolerance and protection against autoimmune diseases. However, once this system fails to operate or poorly operate, it leads to an extreme situation where immune system reacts against self-antigens and destroys host organs, thus causing autoimmune diseases. Tregs can target both innate and adaptive immunity via modulating multiple immune cells such as neutrophils, monocytes, antigen-presenting cells, B cells, and T cells. This review highlights the Treg-mediated immunosuppression, role of several markers and their interplay during Treg development and differentiation, and advances in therapeutic aspects of Treg cells to reduce severity of autoimmunity-related conditions along with emphasizing limitations and challenges of their usages.

Prophylactic and therapeutic insights into trained immunity: A renewed concept of innate immune memory.

Trained immunity is a renewed concept of innate immune memory that facilitates the innate immune system to have the capacity to remember and train cells via metabolic and transcriptional events to enable them to provide nonspecific defense against the subsequent encounters with a range of pathogens and acquire a quicker and more robust immune response, but different from the adaptive immune memory. Reversing the epigenetic changes or targeting the immunological pathways may be considered potential therapeutic approaches to counteract the hyper-responsive or hypo-responsive state of trained immunity. The efficient regulation of immune homeostasis and promotion or inhibition of immune responses is required for a balanced response. Trained immunity-based vaccines can serve as potent immune stimuli and help in the clearance of pathogens in the body through multiple or heterologous effects and confer protection against nonspecific and specific pathogens. This review highlights various features of trained immunity and its applications in developing novel therapeutics and vaccines, along with certain detrimental effects, challenges as well as future perspectives.

Overview of clinical outcome and therapeutic effectiveness of Favipiravir in patients with COVID-19 admitted to intensive care unit, Riyadh, Saudi Arabia.

BACKGROUND: Prior to the availability of the current COVID-19 vaccine, the need to control the pandemic worldwide was focused on management of the disease using previously approved antivirals, including Favipiravir which inhibits viral replication through the RNA dependent RNA polymerase enzyme. Favipiravir's efficacy against different viral infections has made it a potential treatment for COVID-19. We are aiming in this study to assess the therapeutic efficacy and safety of Favipiravir in treating critically ill patients admitted with COVID-19 to Intensive Care Units (ICUs). METHODS: This is a retrospective cohort study was conducted in five tertiary hospitals in Riyadh, Kingdom of Saudi Arabia (KSA). The studied sample was randomized from a huge pool of data collected primarily for critically ill COVID-19 patients admitted to (ICUs) during the period between April 2020 to March 2021. Two groups of patients matched 1: 1 for age and body mass index (BMI) was enrolled in the study; one group received Favipiravir and another comparison group received other antimicrobial medications, not including Favipiravir. RESULTS: A total data of 538 COVID-19 patients were analyzed, 269 (50.%) received Favipiravir and 269 (50%) the control group received different treatments. More than two-thirds 201 (74.7%) were Saudi citizens, the majority 177 (65.8%) were males and the mean age and (BMI) were; (57.23 ± 15.16) years and (31.61 ± 7.33) kg/m2 respectively. The most frequent symptoms of presentation were shortness of breath (SOB), fever, and cough, and the most frequent comorbidity was diabetes mellitus, hypertension, and ischemic heart disease. In the supplemental therapy, corticosteroid, tocilizumab and chloroquine were statistically significant (P = 0.001) when combined in the FVP group more than in the comparison group. Severe acute respiratory distress syndrome (ARDS) was more frequent among Favipiravir group, while the overall mortality rate among the Favipiravir group was not statistically significant (p-value 0.4). CONCLUSION: According to the study's results revealing FVP is not superior to other antivirals, patients who received Favipiravir presented with more severe symptoms, more comorbidities, more complications, and is not effective in controlling the cytokine storm which negatively impact the efficacy of Favipiravir. FVP therapy had no influence on ICU and hospital length of stay in comparison with the control group as well as in the overall mortality rate among the FVP group was not statistically significant. further research is needed to understand how FVP along with other treatments can improve the length of stay among COVID-19 patients admitted to the ICU.