SARS-CoV-2 at the human-animal interphase: A review.

Since its emergence in China in December 2019, COVID-19 remains the recent leading disease of concern drawing the public health attention globally. The disease is known of viral origin and zoonotic nature originating from animals. However, to date neither the source of the spillover nor the intermediate hosts are identified. Moreover, the public health situation is intermittently aggravated by identification of new animals susceptible to the SARS-CoV-2 infection, potentially replicating the virus and maintaining intra and interspecies spread of the disease. Although the role of a given animal and/or its produce is important to map the disease pattern, continuous efforts should be undertaken to further understand the epidemiology of SARS-CoV-2, a vital step to establish effective disease prevention and control strategy. This manuscript attempted to review updates regarding SARS-CoV-2 infection at the human-animal interface with consideration to postulations on the genetic relatedness and origin of the different SARS-CoV-2 variants isolated from different animal species. Also, the review addresses the possible role of different animal species and their produce in transmission of the disease. Also, the manuscript discussed the contamination potentiality of the virus and its environmental stability. Finally, we reviewed the currently instituted measures to prevent and manage the spread of SARS-CoV-2 infection. The manuscript suggested the One Health based control measures that could prove of value for the near future.

Molecular epidemiology of influenza, RSV, and other respiratory infections among children in Qatar: A six years report (2012-2017).

BACKGROUND: Studies on the etiology of respiratory infections among children in Qatar and surrounding countries are limited. OBJECTIVES: To describe the prevalence and seasonality of RSV, influenza, and other respiratory pathogens among children in Qatar. METHODS: We retrospectively collected and analyzed data of 33,404 children (<15 years) presented with influenza-like illness from 2012 to 2017. RESULTS: At least one respiratory pathogen was detected in 26,138 (78%) of patients. Together, human rhinoviruses (HRV), respiratory syncytial virus (RSV), and influenza viruses comprised nearly two-thirds of all cases, affecting 24%, 19.7%, and 18.5%, respectively. A prevalence of 5-10% was recorded for adenovirus, parainfluenza viruses (PIVs), human bocavirus (HboV), and human coronaviruses (HCoVs). Human metapneumovirus (HMPV), enteroviruses, M. pneumonia, and parechovirus had prevalences below 5%. While RSV, influenza, and HMPV exhibited strong seasonal activity in the winter, HRV was active during low RSV and influenza circulation. The burden of RSV exceeds that of influenza among young age groups, whereas influenza correlated positively with age. Further, HRV, adenovirus, influenza, and RSV infection rates varied significantly between male and females. CONCLUSION: This comprehensive multi-year study provides insights into the etiology of ILI among children in Qatar, which represents the Gulf region. Our results reinforce the significance of active surveillance of respiratory pathogens to improve infection prevention and control strategies, particularly among children.

Serologic Detection of Middle East Respiratory Syndrome Coronavirus Functional Antibodies.

We developed and validated 2 species-independent protein-based assays to detect Middle East respiratory syndrome coronavirus functional antibodies that can block virus receptor-binding or sialic acid-attachment. Antibody levels measured in both assays correlated strongly with virus-neutralizing antibody titers, proving their use for serologic confirmatory diagnosis of Middle East respiratory syndrome.

Inter- Versus Intra-Host Sequence Diversity of pH1N1 and Associated Clinical Outcomes.

The diversity of RNA viruses dictates their evolution in a particular host, community or environment. Here, we reported within- and between-host pH1N1virus diversity at consensus and sub-consensus levels over a three-year period (2015-2017) and its implications on disease severity. A total of 90 nasal samples positive for the pH1N1 virus were deep-sequenced and analyzed to detect low-frequency variants (LFVs) and haplotypes. Parallel evolution of LFVs was seen in the hemagglutinin (HA) gene across three scales: among patients (33%), across years (22%), and at global scale. Remarkably, investigating the emergence of LFVs at the consensus level demonstrated that within-host virus evolution recapitulates evolutionary dynamics seen at the global scale. Analysis of virus diversity at the HA haplotype level revealed the clustering of low-frequency haplotypes from early 2015 with dominant strains of 2016, indicating rapid haplotype evolution. Haplotype sharing was also noticed in all years, strongly suggesting haplotype transmission among patients infected during a specific influenza season. Finally, more than half of patients with severe symptoms harbored a larger number of haplotypes, mostly in patients under the age of five. Therefore, patient age, haplotype diversity, and the presence of certain LFVs should be considered when interpreting illness severity. In addition to its importance in understanding virus evolution, sub-consensus virus diversity together with whole genome sequencing is essential to explain variabilities in clinical outcomes that cannot be explained by either analysis alone.

Demographic and Clinical Characteristics of Early Travel-Associated COVID-19 Cases.

Background: SARS-CoV-2 continues to claim hundreds of thousands of people's lives. It mostly affects the elderly and those with chronic illness but can also be fatal in younger age groups. This article is the first comprehensive analysis of the epidemiological and clinical outcomes of the travel-associated SARS-CoV-2 cases until April 19, 2020. Methods: Demographic and clinical data of travel-associated SARS-CoV-2 cases were collected for the period between January 16, 2020 and April 19, 2020. More than one hundred and eighty databases were searched, including the World Health Organization (WHO) database, countries' ministries websites, and official media sites. Demographic and clinical data were extracted and analyzed. Results: A total of 1,186 cases from 144 countries meeting the inclusion criteria were reported and included in the analysis. The mean age of the cases was 44 years, with a male to female ratio of 1.6:1. Travel-associated cases originated from more than 40 countries, with China, Italy, and Iran reporting the highest numbers at 208, 225, and 155, respectively. Clinical symptoms varied between patients, with some reporting symptoms during the flights (117 cases; 9.87%). A total of 312 (26.31%) cases were hospitalized, of which 50 cases (4.22%) were fatal. Conclusion: Major gaps exist in the epidemiology and clinical spectrum of the COVID-19 travel-associated cases due to a lack of reporting and sharing data of many counties. The identification and implementation of methodologies for measuring traveler's risk to coronavirus would help in minimizing the spread of the virus, especially in the next waves.

Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections.

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein-based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43-positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.

An Evaluation of the National Brucellosis Surveillance System in Qatar, 2018.

Introduction Brucellosis is one of the most prevalent bacterial zoonoses and is considered an economically important infection that affects humans and livestock. The infection is usually transmitted to humans through direct contact with infected materials, such as the afterbirth, or indirectly through the ingestion of animal products. In addition, the consumption of raw milk represents a major source of the infection. In the Eastern Mediterranean region, the incidence of brucellosis ranges from one per 100,000 to 20 per 100,000; however, the actual figure is estimated at 20 to 25 times greater owing to the poor surveillance systems among countries in the region. For such reasons, this study is conducted to comprehensively evaluate the brucellosis surveillance system in Qatar, to identify potential strengths and limitations and, hence, inform decision-makers about future mitigation strategies. Methods A retrospective record review was conducted at the surveillance unit in the Ministry of Public Health (MoPH) to analyze all Brucella notification forms from January to November 2018 for the completeness of notification and timeliness of reporting. The principal investigators conducted data abstraction and analysis in November 2018. Results A total of 125 notification forms were analyzed. It was revealed that the internal completeness varied across the different data elements of the notification forms from 39% up to 100%. Also, the timeliness of the reporting ranged from one day for the T3 time point up to 16 days for the T1 time point. Conclusion Ultimately, the strengthening of the national Brucellosis surveillance system in Qatar demands the implementation of several strategies, including the establishment of veterinary surveillance, enforcement of livestock importation protocols, as well as routine compulsory vaccinations, devising a clear and sensitive case definition of the disease, and public education especially among high-risk groups (shepherds, slaughterhouse workers, and laboratory workers). In addition, continuous education of healthcare workers on the proper reporting of the disease and the electronization of the notification process are important steps to improve the surveillance system in the country.

Demographics and Epidemiology of Hepatitis B in the State of Qatar: A Five-Year Surveillance-Based Incidence Study.

Background: Expatriates represent >80% of Qatar's population, mostly arriving from countries in Africa and Asia that are endemic with many diseases. This increases the risk for introducing new pathogens into the country and provides a platform for maintenance of endemic pathogen circulation. Here, we report on the incidence and epidemiological characteristics of hepatitis B in Qatar between 2010 and 2014. Methods: We performed a retrospective epidemiological data analysis using the data available at the surveillance system of the Ministry of Public Health (MOPH) in Qatar. Data were collected from distinctive public and private incorporates around the nation. Reported cases of hepatitis B patients represent those who met the stringent case definition as per World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines and eventually reported to MOPH. Results: The annual incidence rates of hepatitis B cases were 30.0, 34.2, 30.5, 39.4, and 19.8 per 100,000 population in 2010, 2011, 2012, 2013, and 2014, respectively. There was no specific trend or seasonality for the reported cases. The incidence rates were higher in females compared to males between 2010 and 2012, but similar in 2013 and 2014. The highest incidence rates were reported among individuals between 25 and 34 years of age. No cases were reported in children younger than five years in 2013 and 2014. Rates of hepatitis B cases declined dramatically in 2014, in both Qataris and non-Qataris, as compared to the previous years. Conclusion: Our results indicate a dramatic decline of hepatitis B cases in Qatar but mandate improved surveillance and vaccination efforts in expatriates in the nation.

Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits.

Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary camels, thus resulting in a lack of viral transmission.

Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar.

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (n = 3/4) and IgM (n = 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (n = 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.

Evaluation of the Completeness and Timeliness of National Malaria Surveillance System in Qatar, 2016.

Background The high influx of migrant workers from malaria-endemic countries along with the presence of a malaria vector in Qatar has raised the alarm of the possible reintroduction of local transmission. Meanwhile, the Qatar Malaria Surveillance System aims to detect any local malaria transmission as well as to monitor trends in imported cases. Aim Evaluating the attributes of the Malaria Surveillance System in Qatar will help identify any gaps necessitating rectification. Method The completeness and timeliness of the malaria surveillance system were determined. The direct method was used to determine completeness. Timeliness was evaluated by calculating the time lag between the onset of disease and notification receipt by the surveillance team (T) or diagnosis (T1) and between the diagnosis and receipt of notification by the surveillance team (T2). Results The overall external completeness of Malaria surveillance system was yielded at 47% (219/493). The most frequently reported data fields were found to be age, gender, and nationality with a percentage of 99% or more. However, the least reported data components were found to be lab results, types of samples, sample collection, and travel destinations with percentages of 59%, 58%, 56%, and 41%, respectively.The overall median time lags was six days for T, four days for T1, and two days for T2. Conclusion Our study has identified several merits and areas of improvement in the National Malaria Surveillance System in Qatar. The attributes of evaluation, completeness and timeliness, need more quality improvement. Evaluation of other surveillance system attributes is highly recommended.

Knowledge, Attitude, and Practice Regarding Zika Among Travelers to Brazil: Qatar's Airport Study 2017.

Background The Zika virus has become an international health issue and poses a systematic risk for a growing number of travelers. Qatar is no exception to this status, where its Hamad International Airport (HIA) has become an important hub for many travelers to and from affected countries. Thus, it is a national necessity to determine the knowledge, attitude, and practice of travelers' regarding this emerging disease in the State of Qatar. Methods This was a cross-sectional study that employed a self-administered questionnaire (n=100) and was conducted at Hamad International Airport. Descriptive and inferential statistical tests were applied to analyze the data using the Statistical Package for the Social Sciences (SPSS) (IBM SPSS Statistics 21, IBM Corporation, Armonk, NY, USA, 2014). Results The majority of travelers (75%) reported hearing about the Zika disease prior to their current flight, mainly from the media (73%) and the internet (46%). The majority of participants (69%) knew about the vector-borne transmission and symptomatology of a Zika infection while more than half (54%) correctly identified effective methods to prevent infection. Regarding their attitude, less than two-thirds (58%) of the participants agreed that pregnant women must postpone their travel to any Zika-affected area. Regarding their practice, only a quarter of the sampled travelers (24%) sought pre-travel medical advice before going to Brazil. Comparing the knowledge score among different education levels, we found that high-school students scored significantly better than those with diplomas and bachelors, p=0.042 and p=0.012, respectively. Conclusion The survey findings revealed that the knowledge of Zika infection is low among travelers to Brazil. Thus, stronger efforts to educate travelers about Zika are recommended. It is also vital that travelers be encouraged to seek proper medical advice prior to travel.

How Do the First Days Count? A Case Study of Qatar Experience in Emergency Risk Communication during the MERS-CoV Outbreak.

This case study is the first to be developed in the Middle East region to document what happened during the response to the 2013 MERS outbreak in Qatar. It provides a description of key epidemiologic events and news released from a prime daily newspaper and main Emergency Risk Communication (ERC) actions that were undertaken by public health authorities. Using the Crisis and Emergency Risk Communication (CERC) theoretical framework, the study analyzes how the performed ERC strategies during the first days of the outbreak might have contributed to the outbreak management. METHODS: MERS-CoV related events were chronologically tracked, together with the relevant stories that were published in a major newspaper over the course of three distinct phases of the epidemic. The collected media stories were then assessed against the practiced emergency risk communication (ERC) activities during the same time frame. RESULTS: The Crisis & Emergency Risk Communication (CERC) framework was partially followed during the early days of the MERS-CoV epidemic, which were characterized by overwhelming uncertainty. The SCH's commitment to a proactive and open risk communication strategy since day one, contributed to creating the SCH's image as a credible source of information and allowed for the quick initiation of the overall response efforts. Yet, conflicting messages and over reassurance were among the observed pitfalls of the implemented ERC strategy. CONCLUSION: The adoption of CERC principles can help restore and maintain the credibility of responding agencies. Further work is needed to develop more rigorous and comprehensive research strategies that address sharing of information by mainstream as well as social media for a more accurate assessment of the impact of the ERC strategy.

Improving Influenza Vaccination Rate among Primary Healthcare Workers in Qatar.

The purpose of this study was to improve influenza vaccination, and determine factors influencing vaccine declination among health care workers (HCW) in Qatar. We launched an influenza vaccination campaign to vaccinate around 4700 HCW in 22 Primary Health Care Corporation (PHCC) centers in Qatar between 1st and 15th of November, 2015. Our target was to vaccinate 60% of all HCW. Vaccine was offered free of charge at all centers, and information about the campaign and the importance of influenza vaccination was provided to employees through direct communication, emails, and social media networks. Staff were reported as vaccinated or non-vaccinated using a declination form that included their occupation, place of work and reasons for declining the vaccine. Survey responses were summarized as proportional outcomes. We exceeded our goal, and vaccinated 77% of the target population. Only 9% declined to take the vaccine, and the remaining 14% were either on leave or had already been vaccinated. Vaccine uptake was highest among aides (98.1%), followed by technicians (95.2%), and was lowest amongst pharmacists (73.2%), preceded by physicians (84%). Of those that declined the vaccine, 34% provided no reason, 18% declined it due to behavioral issues, and 21% declined it due to medical reasons. Uptake of influenza vaccine significantly increased during the 2015 immunization campaign. This is attributed to good planning, preparation, a high level of communication, and providing awareness and training to HCW with proper supervision and monitoring.

Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Infection in Camel Workers in Qatar During 2013-2014: A Case-Control Study.

The transmission routes and risk factors for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infections are still unknown. We used the World Health Organization questionnaire for MERS-CoV case-control studies to assess risk factors for human MERS-CoV seropositivity at a farm complex in Qatar. Nine camel workers with MERS-CoV antibodies and 43 workers without antibodies were included. Some camel-related activities may pose a higher risk of MERS-CoV infection, as may cross-border movements of camels, poor hand hygiene, and overnight hospital stays with respiratory complaints. The risk factors identified in this study can be used to develop infection prevention and control measures for human MERS-CoV infections.

High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014.

Two of the earliest Middle East respiratory syndrome (MERS) cases were men who had visited the Doha central animal market and adjoining slaughterhouse in Qatar. We show that a high proportion of camels presenting for slaughter in Qatar show evidence for nasal MERS-CoV shedding (62/105). Sequence analysis showed the circulation of at least five different virus strains at these premises, suggesting that this location is a driver of MERS-CoV circulation and a high-risk area for human exposure. No correlation between RNA loads and levels of neutralizing antibodies was observed, suggesting limited immune protection and potential for reinfection despite previous exposure.

Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013-2014.

We determined the presence of neutralizing antibodies to Middle East respiratory syndrome coronavirus in persons in Qatar with and without dromedary contact. Antibodies were only detected in those with contact, suggesting dromedary exposure as a risk factor for infection. Findings also showed evidence for substantial underestimation of the infection in populations at risk in Qatar.

Reliable typing of MERS-CoV variants with a small genome fragment.

BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging pathogen that causes lower respiratory tract infection in humans. Camels are the likely animal source for zoonotic infection, although exact transmission modes remain to be determined. Human-to-human transmission occurs sporadically. The wide geographic distribution of MERS-CoV among dromedary camels and ongoing transmissions to humans provides concern for the evolution of a MERS-CoV variant with efficient human-to-human transmission capabilities. Phylogenetic analysis of MERS-CoV has occurred by analysis of full-length genomes or multiple concatenated genome fragments, which is time-consuming, costly and limited to high viral load samples. OBJECTIVE: To develop a simple, reliable MERS-CoV variant typing assay to facilitate monitoring of MERS-CoV diversity in animals and humans. STUDY DESIGN: Phylogenetic analysis of presently known full-length MERS-CoV genomes was performed to identify genomic regions with sufficient phylogenetic content to allow reliable MERS-CoV variant typing. RT-PCR assays targeting these regions were designed and optimized. RESULTS: A reverse-transcription PCR assay for MERS-CoV targeting a 615 bp spike fragment provides a phylogenetic clustering of MERS-CoV variants comparable to that of full-length genomes. The detection limit corresponds to a cycle treshold value of ∼ 35 with standard upE real time PCR assays on RNA isolated from MERS-CoV EMC. Nasal swabs from RT-PCR positive camels (Ct values 12.9-32.2) yielded reliable sequence information in 14 samples. CONCLUSIONS: We developed a simple, reliable MERS-CoV variant typing assay which is crucial in monitoring MERS-CoV circulation in real time with relatively little investment on location.