A disorder clinically resembling cystic fibrosis caused by biallelic variants in the AGR2 gene.

PURPOSE: We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause. METHODS: Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed. RESULTS: We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant AGR2 transcripts caused by an intronic variant and complete absence of AGR2 transcripts caused by the large gene deletion, resulting in loss of function (LoF). Furthermore, transcriptome analysis identified significant downregulation of components of the mucociliary machinery (intraciliary transport, cilium organisation), as well as upregulation of immune processes. CONCLUSION: We describe a previously unrecognised autosomal recessive disorder caused by AGR2 variants. AGR2-related disease should be considered as a differential diagnosis in patients presenting a CF-like phenotype. This has implications for the molecular diagnosis and management of these patients. AGR2 LoF is likely the disease mechanism, with consequent impairment of the mucociliary defence machinery. Future studies should aim to establish a better understanding of the disease pathophysiology and to identify potential drug targets.

Aspiration of superabsorbent polymer beads resulting in focal lung damage: a case report.

BACKGROUND: Concerns have recently been raised about reported incidents of intestinal obstruction following ingestion of Superabsorbent polymer (SAP) beads. Texas Poison Centers reported 110 cases of superabsorbent polymer bead ingestions between 2011 and 2016 (Pediatr Emerg Care 35:426-7, 2019). Furthermore, cases of related auditory complications following the placement of SAP beads into the external auditory canal have also been reported. Here, we report the first case of significant airway damage secondary to the ingestion of a SAP bead (Orbeez), which was aspirated and then overlooked. Further, we hypothesized that the capability of the bead to expand in size once exposed to water from the respiratory mucous may contribute to airway damage. CASE PRESENTATION: A 3-year-old boy presented to our hospital with persistent cough and recurrent hospitalizations to the general ward and intensive care unit. The boy was diagnosed with focal lung bronchiectasis in the left lower lobe, which occurred after the patient aspirated an Orbeez bead before a year. The bead was removed using flexible bronchoscopy and a retrieval basket. CONCLUSION: Orbeez beads are commonly ingested by young children resulting in gastrointestinal obstruction. The beads can easily be aspirated by children and overlooked by their caregivers and physicians for long periods of time due to their small size. The bead can cause significant airway damage after multiplying in size when coming into contact with respiratory mucus which consists of 95% water.

Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.

Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

Rs37972 and rs37973 single-nucleotide polymorphisms in the glucocorticoid-inducible 1 gene are not associated with asthma risk in a Saudi Arabian population.

OBJECTIVE: Rs37972 and rs37973 variants in the glucocorticoid-induced transcript 1 gene have been associated with inhaled glucocorticosteroid responsiveness in asthmatics; however, some discrepancies have been also reported. This study aims to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in Saudi Arabian asthmatics. METHODS: Two-hundred seventy-one diagnosed asthmatics (3-65 years old) and 387 healthy control subjects of equivalent age were recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and rs37973 SNPs was performed by PCR amplification of segments of interest, followed by Sanger sequencing. RESULTS: The global frequencies of the minor (risk) alleles were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi-square (χ(2)) tests revealed significant differences between asthmatic and healthy groups, in allele frequencies for rs37973 SNP only (χ(2) = 3.98, Yates' p value = 0.046). Regarding genotype frequencies, a significant difference between asthmatic and healthy groups was observed for variant rs37972 only (χ(2) = 8.19, Yates' p value = 0.016). To determine a possible association of the minor "T" and "G" alleles with asthma, both the recessive and dominant genetic models were tested. For rs37973, none of the genotypes were significantly associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus C/C) indicated a significant "protective" association with asthma, in which C/T + T/T individuals had lower odds of being asthmatics than C/C individuals (OR = 0.67; 95% CI = 0.48-0.94; p = 0.019*). CONCLUSIONS: The minor alleles "T" and "G" of rs37972 and rs37973 SNPs, respectively, were not significantly associated with increased asthma risk in asthma patients from Saudi Arabia.

Prevalence of pulmonary arteriovenous malformations in children versus adults with hereditary hemorrhagic telangiectasia.

It is unclear whether pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia develop later in life or are preformed in childhood. We show that the prevalence of PAVMs in children is similar to that in their parents, providing evidence against de novo PAVM formation in hereditary hemorrhagic telangiectasia.

A Case of a Gastric Stent Complication Presenting With a Gastrojujenal Fistula.

Laparoscopic sleeve gastrectomy (SG) is a widely performed bariatric procedure known for its safety and efficacy, yet complications, particularly postoperative leaks, remain a concern. Endoscopic stenting is one of the approaches for leak management that has some complications such as the rare fistula with adjacent organs. Here, we present a unique case of a 56-year-old diabetic female who developed a gastroenteric fistula following endoscopic stent placement for a post-SG leak. The patient had a delayed stent removal, and three weeks later she presented with dysphagia and vomiting in a follow-up appointment. Esophagogastroduodenoscopy (EGD) showed an esophageal stricture and a large gastroenteric fistula that was confirmed by imaging to be a fistula between the pylorus and proximal small bowel. The patient's symptoms improved gradually with conservative management, and imaging showed the resolution of the fistula and associated esophageal stricture. This case highlights the importance of timely stent removal (ideally within 6-8 weeks) and close follow-up with EGD and CT to detect and manage potential complications, while emphasizing the need for further research on optimal stent placement duration.

Studying the Association Between Knowledge of Professionalism and Demographic Characteristics in King Saud University Medical Students.

Objectives To study the association between the level of knowledge regarding professionalism and demographic characteristics among medical students from years three to five at King Saud University, Riyadh, Saudi Arabia. Methods Data for this quantitative observational cross-sectional study were collected using stratified random sampling. The participants included male and female students from years three to five studying at the College of Medicine, King Saud University. Data were collected using a self-administered questionnaire and analyzed using the Student's t-test and a one-way ANOVA test. Results The study comprised 112 female (52%) and 103 male (48%) students who completed 215 questionnaires. The mean percentage values of correct answers by females and males were 59.99% and 59.31%, respectively. Statistical analysis revealed no significant difference between the mean percentage of correct answers given by males and females (p=0.684). The mean percentage of correct answers among the 3rd, 4th, and 5th-year medical students was 59.27%, 56.56%, and 62.72%, respectively. Statistical analysis revealed significant differences between the academic year groups (p<0.05), and the grade point average (GPA) groups showed significant differences (p<0.05). Conclusion A highly significant association was found between knowledge of professionalism and both academic level and performance among medical students. This suggests that professional perception evolves parallel to acquiring basic science and clinical knowledge.

Hospital Length of Stay and Related Factors for COVID-19 Inpatients Among the Four Southern Regions Under the Proposed Southern Business Unit of Saudi Arabia.

Objective: To assess the length of stay (LoS) variation for COVID-19 inpatients among the four regions of the Southern Business Unit (SBU). Methods: This is a comparative retrospective study of the LoS of COVID-19 inpatients in the four regions of the SBU in the KSA. Data was collected from the Ministry of Health (MoH) in all hospitals in the SBU. Participants were all patients admitted with confirmed COVID-19 between March 2020 and February 2021. Variables included region (variable of interest), demographics, comorbidities, and complications. Multilinear regression was performed to control for any factors that might have had an association with LoS. Results: The mean LoS of the total sample was 10 days and Bisha (the reference) was 7 days. Compared to Bisha, LoS in Jazan was 34% longer, in Najran 62% longer, and Aseer 40% longer. We observed that other factors also had an association with LoS, compared to Bisha, compared to the references, Saudi patients had a 15% shorter stay; admission to ICU increased LoS by 57%; patients who died during hospitalization had a 39% shorter LoS; the complications from COVID-19 of acute kidney injury and ARDS increased LoS by 22% and 48% respectively. Conclusion: After statistically controlling for confounders, this study reveals that LoS was significantly impacted by region in the SBU in the KSA. We recommend that further study be conducted to illuminate the underlying causes of this variation which may be organizational or structural to ensure high quality of care, access to care, and equity of resources throughout all regions of the SBU in accordance with the new Model of Care in Vision 2030.

Characteristics of Hospitalized COVID-19 Patients in the Four Southern Regions Under the Proposed Southern Business Unit of Saudi Arabia.

Background: This is the first descriptive and comparative study conducted of COVID-19 inpatients from multi-centers in the four administrative southern regions and proposed Southern Business Unit (Jazan, Najran, Bisha, and Aseer) of the Kingdom of Saudi Arabia (KSA). Methods: Participants were 809 randomly selected patients admitted to the eight sampled hospitals with confirmed COVID-19 between March 2020 and February 2021. We assessed and compared socio-demographics, clinical characteristics, and clinical outcomes of the four regions. Results: Socio-demographic and clinical characteristics of the participants are a mean age of 60 ± 17.7 years, 70% Saudi male, the prevalence of diabetes (DM2) 58%, hypertension (HTN) 48%, obesity 43%, cardiac diseases 15%, and immunity or cancer diseases almost 1%. The prevalence of complications during admission were bacterial pneumonia 65%, acquired respiratory distress syndrome (ARDS) 32%, sepsis 20%, multi-organ failure 18%, acute kidney diseases 15%, and arrhythmia 4%. Clinical outcomes were: admitted to intensive care unit (ICU) 52%, mortality rate 25%, referred to other facilities 9%, and mean length of stay (LOS) was 11± 9.5 days. We observed statistically significant variation in many variables among the four regions. Najran and Aseer had a higher prevalence of risk factors for severity including age and comorbidities accompanied by higher rates of complications, ICU admissions, LOS, and mortality. Bisha and Jazan had lower prevalence of risk factors and LOS with lower rates of complications, ICU admissions, and mortality. Conclusion: This study reveals that the geographic region in which the patient was cared for was related to the severity and outcome of COVID-19 infection. Policy makers should search for solutions to regional differences in underlying health conditions such as DM2, HTN, and obesity to plan for improvements in preventive care as well as resource distribution to ensure quality for all Saudi citizens. This study will serve as guidance to begin to form strategies for these improvements as envisioned in the future New Model of Care.

Parental perceptions and the 5C psychological antecedents of COVID-19 vaccination during the first month of omicron variant surge: A large-scale cross-sectional survey in Saudi Arabia.

Background: With the rapid surge of SARS-CoV-2 Omicron variant, we aimed to assess parents' perceptions of the COVID-19 vaccines and the psychological antecedents of vaccinations during the first month of the Omicron spread. Methods: A cross-sectional online survey in Saudi Arabia was conducted (December 20, 2021-January 7, 2022). Convenience sampling was used to invite participants through several social media platforms, including WhatsApp, Twitter, and email lists. We utilized the validated 5C Scale, which evaluates five psychological factors influencing vaccination intention and behavior: confidence, complacency, constraints, calculation, and collective responsibility. Results: Of the 1,340 respondents, 61.3% received two doses of the COVID-19 vaccine, while 35% received an additional booster dose. Fify four percentage were unwilling to vaccinate their children aged 5-11, and 57.2% were unwilling to give the additional booster vaccine to children aged 12-18. Respondents had higher scores on the construct of collective responsibility, followed by calculation, confidence, complacency, and finally constraints. Confidence in vaccines was associated with willingness to vaccinate children and positively correlated with collective responsibility (p < 0.010). Complacency about COVID-19 was associated with unwillingness to vaccinate older children (12-18 years) and with increased constraints and calculation scores (p < 0.010). While increasing constraints scores did not correlate with decreased willingness to vaccinate children (p = 0.140), they did correlate negatively with confidence and collective responsibility (p < 0.010). Conclusions: The findings demonstrate the relationship between the five antecedents of vaccination, the importance of confidence in vaccines, and a sense of collective responsibility in parents' intention to vaccinate their children. Campaigns addressing constraints and collective responsibility could help influence the public's vaccination behavior.

Healthcare Workers' SARS-CoV-2 Omicron Variant Uncertainty-Related Stress, Resilience, and Coping Strategies during the First Week of the World Health Organization's Alert.

BACKGROUND: As the SARS-CoV-2 Omicron variant emerged and spread globally at an alarming speed, healthcare workers' (HCWs) uncertainties, worries, resilience, and coping strategies warranted assessment. The COVID-19 pandemic had a severe psychological impact on HCWs, including the development of Post-Traumatic Stress symptoms. Specific subgroups of HCWs, such as front-line and female workers, were more prone to poor mental health outcomes and difficulties facing stress. METHODS: The responses to an online questionnaire among HCWs in the Kingdom of Saudi Arabia (KSA) were collected from 1 December 2021 to 6 December 2021, aiming to assess their uncertainties, worries, resilience, and coping strategies regarding the Omicron variant. Three validated instruments were used to achieve the study's goals: the Brief Resilient Coping Scale (BRCS), the Standard Stress Scale (SSS), and the Intolerance of Uncertainty Scale (IUS)-Short Form. RESULTS: The online survey was completed by 1285 HCWs. Females made up the majority of the participants (64%). A total of 1285 HCW's completed the online survey from all regions in KSA. Resilient coping scored by the BRCS was negatively and significantly correlated with stress as scored by the SSS (r = -0.313, p < 0.010). Moreover, intolerance of uncertainty scored by the IUS positively and significantly correlated with stress (r = 0.326, p < 0.010). Increased stress levels were linked to a considerable drop in resilient coping scores. Furthermore, being a Saudi HCW or a nurse was linked to a significant reduction in resilient coping ratings. Coping by following healthcare authorities' preventative instructions and using the WHO website as a source of information was linked to a considerable rise in resilient coping. CONCLUSIONS: The negative association between resilient coping and stress was clearly shown, as well as how underlying intolerance of uncertainty is linked to higher stress among HCWs quickly following the development of a new infectious threat. The study provides early insights into developing and promoting coping strategies for emerging SARS-CoV-2 variants.

SARS-CoV-2 Omicron Variant: Exploring Healthcare Workers' Awareness and Perception of Vaccine Effectiveness: A National Survey During the First Week of WHO Variant Alert.

Background: As the SARS-CoV-2 Omicron variant spreads in several countries, healthcare workers' (HCWs) perceptions and worries regarding vaccine effectiveness and boosters warrant reassessment. Methods: An online questionnaire among HCWs in Saudi Arabia (KSA) was distributed from Dec 1st-6th 2021 to assess their perceptions, vaccine advocacy to the Omicron variant, and their perception of the effectiveness of infection prevention measures and vaccination to prevent its spread, their Omicron variant related worries in comparison to the other variants, and their agreement with mandatory vaccination in general for adults. Results: Among the 1,285 HCW participants, two-thirds were female, 49.8 % were nurses, 46.4% were physicians, and 50.0% worked in tertiary care hospitals. 66.9% considered vaccination to be the most effective way to prevent the spread of the Omicron variant and future variants. The respondents however perceived social distancing (78.0%), universal masking (77.8%), and avoiding unnecessary travel (71.4%) as slightly superior to vaccination to prevent the spread of SARS-CoV-2 variants. HCWs aging 55 or older agreed significantly with vaccine ineffectiveness to control Omicron spread, while those who believed in non-pharmacological infection prevention measures agreed significantly with vaccination for that purpose. Male HCWs had a significant agreement with mandatory vaccination of all eligible adult populations. On the other hand, unwilling HCWs to receive the vaccine had strong disagreements with mandatory vaccination. Conclusions: The current study in the first week of Omicron showed that only two-thirds of HCWs felt that vaccination was the best option to prevent the spread of the Omicron variant, indicating the need for further motivation campaigns for vaccination and booster dose. HCWs had a strong belief in infection prevention measures to contain the spread of SARS-CoV-2 variants that should be encouraged and augmented.

Did the National Lockdown in Saudi Arabia Reduce Lower Respiratory Illnesses in Children?

Objectives: This study aims to explore the effect of lockdown and early precautionary measures implemented in Saudi Arabia on number of pediatric hospitalizations due to lower respiratory illnesses (bronchiolitis, asthma, and pneumonia). Methods: This is a retrospective cross-sectional study aims to review patients from four major hospitals in Saudi Arabia. All pediatric hospitalizations secondary to asthma, bronchiolitis, and pneumonia during the months of the lockdown (March, April, and May) in 2020 were documented. Then, they were compared to the previous 2 years. Variables like number of hospitalizations, oxygen requirement, mechanical ventilation, admission to the intensive care unit (ICU), length of stay, and results of viral studies were collected. Results: We included 1,003 children from four different centers. Males were slightly higher than females (55.8% vs. 44.2%). Total number of hospitalizations in 2020 was 201, significantly lower than 399 and 403 hospitalizations in 2019 and 2018, respectively (P < 0.01). The major drop happened on the months of April and May. Although bronchiolitis hospitalizations' dropped by more than half in 2020 compared to the previous 2 years, it was not statistically significant (P = 0.07). But, asthma hospitalizations were significantly less in 2020 compared to the previous 2 years (49-65% reduction, P = 0.003). Number of pneumonia cases were lowered in 2020 compared to the previous 2 years. However, proportion of pneumonia diagnosis to total hospitalizations increased in 2020 (55% compared to 50% and 35%). There was a surge of viral testing during a period of uncertainty in the early phase of the pandemic. This total reduction in hospitalization was not associated with higher oxygen requirements, mechanical ventilation, ICU admissions or longer hospital stay. Conclusions: Lockdown and precautionary measures executed during the early phase of COVID-19 pandemic helped decrease the number of hospitalizations due to lower respiratory illnesses in Saudi Arabia. Reduction in hospitalizations seems less likely to be secondary to hospital avoidance or delayed presentations as number of ICU admission and oxygen requirements did not increase. The post pandemic pattern of respiratory illnesses among children needs further research.

Faculty Members' Perspective on Virtual Interviews for Medical Residency Matching during the COVID-19 Crisis: A National Survey.

During the COVID-19 pandemic, conducting face-to-face medical residency interviews was challenging due to infection prevention precautions, social distancing, and travel restrictions. Virtual interviews were implemented by the Saudi Commission for Health Specialties (SCFHS) as an alternative process for residency matching while striving to maintain the same quality standards. This national survey was conducted to assess the satisfaction and perceptions of faculty members' virtual interview performance in the assessment for the medical training residency programs. Among the participating 173 faculty members, 34.1% did not have previous experience with video-conferencing. The Zoom application was the most commonly used platform (65.9%). Most (89.6%) of the faculty perceived virtual interviews as "adequate" platforms on which the candidates could express themselves, while almost half of the faculty (53.8%) agreed that virtual interviews allowed them to accurately reach an impression about the candidates. Overall, 73.4% of faculty felt comfortable ranking the virtually interviewed candidates. We conclude that the acceptance of participating faculty members in the first Saudi medical residency training matching cycle virtual interviewing event was well-perceived. This study provides evidence for future application and research of virtual interviews in residency candidates' assessment, especially after the pandemic crisis resolves.

Awareness of Sudden Infant Death Syndrome Among Saudi Arabian Women in 2019: A Cross-Sectional Study.

Introduction Studies on sudden infant death syndrome (SIDS) in Saudi Arabia are limited due to strict religious faith-related observances. The aim of this study was to assess Saudi mothers' awareness about SIDS. Methodology A cross-sectional online electronic survey was administered in different Saudi regions. A self-reported validated Arabic questionnaire was used for collecting data. The study sample included 363 respondents from 384 sample members. Results The final sample consisted of 363 (94.8%) respondents, a reduction in size due to 21 non-responders from the total 384 sample members. Two-hundred and thirty-two (63.9%) of the 363 respondents reported not having heard of any SIDS prevention messages, while 36.1% of them had received such messages. Most of the respondents (53.2%) correctly reported that babies should be laid on their backs while putting them to sleep, and only 5.5% reported that babies should be laid in their stomachs when being put to rest. Participants > 50 years, of urban residence, and with primary education had higher knowledge levels. Participants with an age of 18 to 29 years and those with higher education had higher knowledge levels about the correct baby position. Participants with an age between 30 and 39 years, of urban residence, and those with a primary educational level had a higher prevalence of receiving messages about SIDS. Conclusion A very good understanding of the proper way to put a baby to sleep among the participants was found, and most of them thought that messages about SIDS were not useful. This study suggests that health education messages regarding SIDS should be directed to all pregnant mothers.

A Novel Biallelic STING1 Gene Variant Causing SAVI in Two Siblings.

STING-associated vasculopathy of infantile-onset (SAVI) is one of the newly identified types of interferonopathies. SAVI is caused by heterozygous gain-of-function mutations in the STING1. We herein report for the first time a homozygous variant in the STING1 gene in two siblings that resulted in constitutive activation of STING gene and the SAVI phenotype. Exome sequencing revealed a novel homozygous NM_198282.3: c.841C>T; p.(Arg281Trp) variant in exon 7 of the STING1 gene. The variant segregated in the family to be homozygous in all affected and either heterozygous or wild type in all healthy. Computational structural analysis of the mutants revealed changes in the STING protein structure/function. Elevated serum beta-interferon levels were observed in the patients compared to the control family members. Treatment with Janus kinase inhibitor (JAK-I) Ruxolitinib suppressed the inflammatory process, decreased beta-interferon levels, and stopped the progression of the disease.

Herbs use in Saudi children with acute respiratory illnesses.

The current study aims to evaluate the prevalence of the utilization of various herbal remedies in children hospitalized with lower respiratory illnesses and assess the different herbal products which are most commonly used. Moreover, the indications of usage and the route and frequency of administration are also highlighted. All children who were hospitalized in three centers, through the period of 18 months, due to acute bronchiolitis, pneumonia, or bronchial asthma were included in this study. Any caregivers who were present during the hospitalization of such children were asked if they could respond to a questionnaire that included the names of any herbal products that they used, the indications which warranted their usage, and the frequency and route of administration. A total of 155 patients with acute lower respiratory illnesses were included. The overall prevalence of herbal medicine use was found to be 59.3%. The highest percentage of use was amongst children with bronchiolitis. Around 24 herbal products were used; the most common ones being sesame oil, fenugreek, olive oil, and dates. The most common indications of use were in order to relieve cough and abnormal breathing. The oral route was the main route of administration (95.7%) followed by nasal administration (4.3%). The median number of frequency of administration was two times. In conclusion, the use of herbal medicine in Saudi children with acute lower respiratory illnesses is very common. Further studies to assess the safety profile and possible benefits of these products are needed.

The Saudi Thoracic Society guidelines for influenza vaccinations.

Influenza viruses are responsible for the influenza outbreaks that lead to significant burden and cause significant morbidity and mortality worldwide. Based on the core proteins, influenza viruses are classified into three types, A, B, and C, of which only A and B cause significant human disease and so the vaccine is directed against these two subtypes only. The effectiveness of the vaccine depends on boosting the immune system against the serotypes included within it. As influenza viruses undergo periodic changes in their antigen, the vaccine is modified annually to ensure susceptibility. In contrast to other countries, Saudi Arabia faces a unique and challenging situation due to Hajj and Umrah seasons, when millions of people gather at the holy places in Mecca and Madinah, during which influenza outbreaks are commonly found. Such challenges making the adoption of strict vaccination strategy in Saudi Arabia is of great importance. All efforts were made to develop this guideline in an easy-to-read form, making it very handy and easy to use by health care workers. The guideline was designed to provide recommendations for problems frequently encountered in real life, with special consideration for special situations such as Hajj and Umrah seasons and pregnancy.