Severe acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain, 2018–2022

Background Severe acute respiratory tract infections (SARI) pose a health threat to children and adults worldwide. The SARI surveillance program was initiated in 2018 in Bahrain to monitor the activity of respiratory pathogens. Salmaniya Medical Complex (SMC) was chosen as the sentinel site for the SARI surveillance program. This study aimed to describe the epidemiology of SARI patients admitted to SMC from 2018 to 2022. Methods Patients meeting the World Health Organization definition of SARI and presenting with cough and fever within the last 10 days and admitted to SMC from January 2018 until December 2022 were included in the study. Epidemiological data on SARI cases were collected from SARI surveillance data and analyzed using SPSS version 25 and Excel. Results A total of 1362 SARI cases were enrolled from January 2018 to the end of December 2022; the majority were males (57.7%, n = 786). The highest SARI incidence rates were recorded among individuals over 65 years old (155.5 per 100,000) in 2021 and among those under 5 years old (887 per 100,000) in 2020. About half of the patients had at least one comorbidity (54.0%, n = 735), with diabetes (23.0%, n = 313) and hypertension (17.2%, n = 234) being the most common. The highest number of cases was observed in 2021 (27%, n = 373), followed by 2018 (20%, n = 267). A viral pathogen was detected in 30.7% (n = 418) of the SARI patients. The most prevalent pathogen was influenza A (11.5%, n = 156), followed by SARS-CoV-2 (9.7%, n = 132), respiratory syncytial virus (RSV) (5.1%, n = 69), and influenza B (3.9%, n = 53). The highest percentage of SARI cases was recorded in the winter months, mainly January (17%, n = 236). The percentages of influenza A and RSV cases were highest in December, at 22% (n = 39) and 14% (n = 25), respectively. Influenza B cases were recorded predominantly in March (9%, n = 11). Conclusion The incidence of SARI was highest among patients above 65 years old. The majority had comorbidities. Influenza and respiratory syncytial viruses were the most frequent causes of SARI, with influenza A being the most prevalent. December and January were the months with the highest SARI cases and viral detection rates. Promoting vaccination, timely testing, and prompt treatment, especially for the elderly and those with comorbidities, is key to reducing SARI-related morbidity and mortality, especially during peak seasons.


INTRODUCTION
Influenza refers to both a viral respiratory illness that is characterized by fever, malaise, and myalgia and the causative single-strand negative sense RNA orthomyxoviruses.Influenza viruses include types A, B, C, and D. Influenza A and B are the most known to cause seasonal epidemics. 1Further influenza A is known to cause some of the deadliest pandemics in human history, which is attributed to the genetic variation occurring each season.3][4] In 2009, the estimated number of deaths during the H1N1 pandemic ranged from 150,000 to 575,000 deaths. 5he term "influenza" is also broadly used to describe any viral respiratory illness. 6It is important to distinguish influenza from other viral respiratory infections due to its systemic symptoms, its tendency to cause winter epidemics, and its ability to spread quickly among close contacts. 7Influenza viruses circulate around the world, causing seasonal influenza outbreaks.
The threat of acute respiratory tract infections is one of the largest in the world.It is estimated that influenza viruses in the United States alone cause 12,000-61,000 deaths each year. 8Globally, influenza viruses are estimated to cause 291,000-645,000 deaths annually. 9e incubation period of influenza viruses ranges from 1 to 4 days, 10 with a serial interval of 3-5 days. 11A characteristically uncomplicated influenza illness starts with the acute onset of fever, cough, and body pain. 12Depending on the virus type and the patient's characteristics, a complicated illness and poor outcomes could occur.
Hence, influenza surveillance programs are needed to provide valuable information to public health authorities and policymakers to inform appropriate prevention and control strategies.Since 1952, the Global Influenza Surveillance and Response System (GISRS) has been monitoring the circulation of influenza viruses.In 2011, the World Health Organization adopted the new Pandemic Influenza Preparedness Framework. 13fluenza surveillance programs are used to create baseline data on virus activity, detect locally circulating virus strains, identify the seasonality of viruses, estimate the disease burden, evaluate the effectiveness of vaccines and antivirals, and spot unusual events that may herald novel viruses.
Global public health relies heavily on severe acute respiratory tract infections (SARI) surveillance to monitor and respond to severe respiratory infections.The process involves integrating surveillance systems, standardized case definitions, and laboratory diagnostics in order to detect and track outbreaks of respiratory diseases.Global collaboration and data sharing through global networks such as the GISRS enable early detection of pathogens and establish the basis for health interventions.SARI surveillance data are utilized to estimate disease burden and severity, lead vaccine development, and outline health policies.Through an enhanced understanding of respiratory disease trends and coordinated responses, SARI surveillance contributes to global respiratory health prevention and control. 14Further SARI surveillance programs generate baseline data to which emerging pandemics could be compared. 15evere acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain Bahrain is a small archipelago with about 1.5 million inhabitants. 15In Bahrain, the SARI surveillance program was updated in 2018 to be aligned with the recent WHO recommendations.The provision of secondary and tertiary care in Bahrain is carried out through three governmental hospitals: Salmaniya Medical Complex (SMC), Bahrain Defense Force (BDF) Hospital, and King Hamad University Hospital (KHUH).Both BDF and KHUH provide care mainly to the Ministry of Defense and Interior personnel and their families. 16MC, being the main and largest secondary hospital in Bahrain, was selected as the sentinel surveillance site. 17SMC provides emergency, outpatient, secondary, and tertiary care to the entire population of Bahrain, making it the most representative site for effective surveillance. 18everal studies documented the epidemiological and virological variance in SARI patients, between influenza seasons.A study conducted in Central America found that the most common viruses circulating were respiratory syncytial virus (RSV) and influenza A virus.All cases of viral co-infection occurred in children less than 5 years old.RSV and influenza virus were respectively identified mainly during July-November and May-July. 19In Congo, influenza A virus was the most common virus; the majority of cases were children under 5e years old and occurred during the rainy season. 19In the Eastern Mediterranean Region, influenza A (H1N1) pdm09 and RSV were found to be the most common respiratory infections circulating, with most cases also occurring in children under 5 years old. 20here were no published studies that described the epidemiology, distribution, and seasonality of influenza viruses among SARI patients in the Kingdom of Bahrain.This study aims to describe the epidemiology, distribution, and seasonality of circulating viruses among SARI patients admitted to a sentinel site in Bahrain from 2018 to 2022.

Study design and study setting
This is an epidemiological analysis of collected SARI surveillance data from January 2018 through December 2022 in the Kingdom of Bahrain.The SARI surveillance program was updated in 2018 to adopt the latest definitions and measures recommended by the WHO SARI surveillance program, and SMC was chosen as the sentinel site for surveillance.Epidemiological and virological data were collected on a daily basis from SARI patients admitted to the SMC.Data were then uploaded to the WHO Eastern Mediterranean Flu Network (EMFLU) website.

Study population
SARI is defined by the WHO as any patient with an acute respiratory infection, presenting with cough, a history of fever, or a measured temperature ≥38°C in the last 10 days that required hospital admission. 21This definition was used in the SARI surveillance program conducted in Bahrain.All patients who met the SARI definition and were admitted to SMC from January 2018 to December 2022 were included in the study.

Data collection
An assigned public health specialist from the public health directorate was responsible for collecting the data from patients fitting the SARI criteria.Collected data included: patient's age, sex, address, influenza vaccination status, symptoms onset date, reporting date, date of collection of nasopharyngeal specimens, reverse transcriptionpolymerase chain reaction (RT-PCR) for influenza test result, date of hospital admission, date of discharge, outcome status as dead or alive, intensive care unit (ICU) admission during the stay, the requirement of mechanical ventilation, administration of antiviral medication, and medical comorbidities.Demographic data of Bahrain were obtained from Bahrain's Open Data Portal. 22

Ethical approval
The study adhered to the Helsinki Declaration guidelines and received ethical approval from the Ministry of Health's Health Research Committee in the Kingdom of Bahrain (AUPH-2024-00060).The data, anonymized prior to receipt, were obtained by the research team from the influenza surveillance team.

Specimen collection and testing
All enrolled patients fitting the SARI criteria underwent RT-PCR tests to identify the causative VOL.2024 / ART. 25   Severe acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain

Statistical analysis
The data for the patients were initially retrieved from the EMFLU database.The refined data were then analyzed in SPSS version 25, which enabled in-depth analyses of rates, trends, patterns, and relationships, revealing insights into patient characteristics and outcomes.Additionally, Microsoft Excel was utilized as a complementary tool to create clear and informative visualizations.
The mean and standard deviations were reported for the quantitative variables, whereas the qualitative variables were summarized with counts and percentages.Incidence rates specific to different age groups were computed using midyear population statistics.

Total SARI
A total of 1,362 patients were registered during the surveillance period between 2018 and 2022.
Male patients constituted most of the study population: 786 patients (57.7%).The average overall incidence of SARI was highest among patients aged above 65 years and those aged below 5 years, with incidences of 93 and 63 cases per 100,000 individuals, respectively (Figure 1).
Over half of the patients presented with at least one comorbidity 735 (54%), and 346 (25%) had two or more comorbidities.The most frequently observed diseases were diabetes in 313 patients (25%) and heart disease in 234 patients (18%) (Table 1).Among the enrolled patients, 199 (14.6%) patients were admitted to the ICU, 124 (9%) required mechanical ventilation, and 87 (6.3%) patients died (  1).In relation to influenza A seasonality, the percentage of positive influenza A samples peaked between October and December, with 22% (25), 16% (25), and 22% (39), respectively.The lowest Severe acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain those below 5 years accounting for 3.7 and 2.3 cases per 100,000, respectively.In 2018, the incidence rate peaked in those aged above 65 years, with 12 cases per 100,000.The year 2019 saw an equivalent incidence in patients above 65 years old and those less than 5 years old, with rates of 4.5 and 4.8, respectively.In 2020, the incidence rate for patients under 5 years old remained relatively constant at approximately four cases per 100,000, while no cases were reported among those above 65 years old.In 2022, the incidence rate approached zero across all age groups (Figure 1).
Seasonal trends in influenza B demonstrated peaks in January and March, with the percentages of positive samples reaching 6% ( 14) and 9% (11), respectively (Figure 2).Outcomes for influenza B in SARI patients indicated that 13.2% (7) were admitted to the ICU, 3.8% (2) required mechanical ventilation, and a mortality rate of 5.6% (3) was recorded.A proportion of 43% ( 23) of influenza B patients presented with comorbidities, with asthma emerging as the most prevalent associated condition (Table 1).

RSV
In the observational period, 68 cases of RSV, accounting for 5% of total SARI cases, were reported.The year 2018 witnessed 19% (13) of RSV cases, which increased to 30.8% (21) of the cases in 2019, marking the highest occurrence during the surveillance period.Subsequently, the cases decreased to a 5-year low in 2020, recording percentages were recorded between June and August, with respective percentages of 4% (2), 4% (3), and 2% (1) (Figure 2).Of the influenza A positive cases, the majority of the samples were un-subtyped (50.6%, 70), with H1N1 strains constituting 44.2% (69) and H3N2 strains making up 5.1% ( 8) of the cases.With respect to clinical outcomes, 21.8% (34) of the patients were admitted to the ICU, 11.5% (18)  required mechanical ventilation, and mortality was observed in 7.7% (12) of influenza A SARI patients.

Influenza B
Fifty-three patients were diagnosed with influenza B, constituting  Severe acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain 7.3% (5) of the total cases.However, in 2021 and 2022, the numbers began to increase, reporting 17.6% (12) and 25% (17), respectively.Among the RSV patients, most were males, accounting for 57.3% (39) (Table 1).
The average incidence of RSV was highest among children below 5 years old, approximating 10 cases per 100,000 individuals.Specifically, the incidence among children under 5 was 8 cases per 100,000 in 2018, increasing to 16 cases per 100,000 in 2019.A decline was noticed in 2020 and 2021, with the rate dropping to around 5 cases per 100,000.However, in 2022, the incidence rate picked up to reach 14 cases per 100,000 (Figure 1).
Assessing the seasonality of RSV, the percentage of positive samples peaked between October and December, with proportions of 9% (11), 8% (12), and 14% (25), respectively.Conversely, the period from April to July recorded the lowest number of cases, with no RSV cases detected (Figure 2).
Regarding comorbidities, the majority of RSV patients did not exhibit any underlying diseases, with only 27.9% ( 19) having associated conditions.Asthma was the most prevalent comorbidity, accounting for eight of these cases.Concerning patient outcomes, 17.9% (12) were admitted to the ICU, the same percentage required mechanical ventilation, and a mortality rate of 6% (4) was recorded (Table 1).

DISCUSSION
SARI poses a huge burden on healthcare systems globally, with influenza viruses causing the most severe infections.The novel H1N1 influenza virus in 2009 sparked a pandemic that touched 74 nations on 6 continents and killed hundreds of thousands of people. 25thorough understanding of the seasonality of influenza viruses is the first step in being prepared for the prevention and management of influenza outbreaks as well as unforeseen pandemics.
Additionally, the detection of circulating influenza viruses aids vaccine producers in determining the components of the seasonal influenza vaccine.Furthermore, SARI surveillance enhances the understanding of influenza seasonality in our region and aids in optimizing vaccination timing to avoid significant outbreaks.A seasonal trend in SARI cases was evident, as the highest percentage of SARI cases were recorded in the winter months.This peak of SARI was driven mainly by influenza A and RSV cases which increased in December.While influenza B cases were recorded predominantly in March.This is in line with findings from both regional and global studies.A study conducted in the Eastern Mediterranean Region, also found that SARI cases surged in winter. 27An epidemiological study in Egypt also confirms that their influenza season peaks during the winter months. 28Furthermore, a study in Tunisia reported a peak in SARI cases among ICU patients during the winter. 29Similarly, studies conducted in Vietnam and Shanghai reported a surge in SARI cases caused by influenza during the winter season. 30,31However, in South America, the patterns exhibited some variations.A study in Chile recorded a peak in SARI cases during the winter (March-May) and autumn (June-August) months, while a study from Suriname did not identify any seasonal pattern for the occurrence of SARI cases. 32,335][36] It is Severe acute respiratory infections: An epidemiological analysis of surveillance data in Bahrain million and SMC as the main secondary hospital, admitting all age groups across all four governorates enhances the study's relevance and generalizability of the results to Bahrain and similar settings. 17,18,41

CONCLUSION
From 2018 to 2022, the surveillance data showed a significant increase in the incidence of SARI among individuals aged over 65 years and those with comorbidities.Influenza A and RSV were the primary detected causative agents in SARI cases, with influenza A being the predominant pathogen identified.A seasonal pattern was observed in the occurrence of SARI, with the winter months of December and January being the peak months.These findings highlight the importance of vaccination, timely testing, and prompt treatment of patients presenting with symptoms suggestive of influenza, especially for the elderly, and people with comorbid conditions, given their heightened risk of severe outcomes.Furthermore, intensifying vaccine promotion efforts before the peak of the influenza season is essential to boost immunity in the vulnerable, thus reducing infection and hospitalization rates.

AUTHORS' CONTRIBUTIONS
AA and AMM were the main contributors to the study design, literature review, data analysis, drafting of the manuscript, oversight for all phases of the project, and final approval of the version to be published.BAA, EM, and WHF were responsible for the literature review, data collection, data analysis, and drafting of the manuscript.QA was responsible for the data collection and revision of the manuscript.AKAA and MSY were responsible for the literature review and drafting of the manuscript.BA and EM were responsible for editing and reviewing the final manuscript.All the authors have read and approved the final manuscript.

ACKNOWLEDGMENTS
The authors gratefully acknowledge all medical staff working at the Pediatric and Medical more likely that people will spend more time indoors during winter, which can lead to respiratory illnesses spreading more easily. 28ur study found that the incidence of SARIs was highest in children under the age of 5 years and in individuals over the age of 65 years, which is consistent with a study carried out in Pakistan. 37tudies conducted in Arizona and Chile revealed that ages above 65 years were the most affected. 32,38In contrast, the study conducted in Egypt found that children under 5 years of age were the most frequently admitted for SARI. 28nother study in Morocco found that most SARI patients were below the age of 15 years. 39Due to their increased susceptibility to influenza viruses, children suffer from more severe cases of influenza than other age groups. 40However, it is possible that parents' commitment to seek care for their children may justify the higher number of children less than 5 years old at the SARI sentinel site in Bahrain.Additionally, unlike young children, adults can generally take over-the-counter medications instead of visiting a hospital for treatment.
The study had some limitations, as it was based on surveillance data.One of which was underreporting, where not every case fitting the definition is reported in a timely manner.Another is the lack of comprehensive data, where not all aspects of SARI are collected, such as presenting symptoms.While influenza A predominated during the surveillance period, most of the samples were reported without the subtype, as the subtype is usually done at a later stage.The surveillance period included the period of the COVID-19 pandemic, which laid an unprecedented strain on health care systems including that of the Kingdom of Bahrain.This may lead to a decline in the accuracy and quality of the reported data.
Nonetheless, this study has several strengths.It is the first study to describe the epidemiology of SARI in patients from Bahrain, encompassing 5 years of surveillance data.In our study, viral pathogens were assessed in each patient reported in the surveillance program via RT-PCR.Furthermore, selecting SMC as the sentinel site for Bahrain's surveillance program carries substantial implications for the generalizability of the study's findings.Given Bahrain's small population of about 1.5

Figure 1 .
Figure 1.Age-specific incidence rates of SARI cases per 100,000 from 2018 to 2022 in the Kingdom of Bahrain.

Figure 2 .
Figure 2. The percentage of positive SARI cases in the period from 2018 to 2022 in the Kingdom of Bahrain.

Table 1 . SARI patients' demographics, outcomes, and comorbidities by lab results for the period from 2018 to 2022 in the Kingdom of Bahrain.
*Others: SARS-CoV-2, adenovirus, rhinovirus, negative results.