Resurgence of influenza and respiratory syncytial virus in Egypt following two years of decline during the COVID-19 pandemic: outpatient clinic survey of infants and children, October 2022.

INTRODUCTION: Two years after unprecedented low rates of circulation of most common respiratory viruses (SARS-CoV-2), the Egyptian ARI surveillance system detected an increase in acute respiratory infections (ARIs) with a reduced circulation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially among school children. A national survey was conducted to estimate the burden and identify the viral causes of ARIs among children < 16 years of age. METHODS: A one-day survey was carried out in 98 governmental outpatient clinics distributed all over Egypt 26 governorates. The four largest referral hospitals in each governorate where most influenza-like illness (ILI) patients seek care were selected. Using the WHO case definition, the first five patients < 16 years of age with ILI symptoms visiting the selected outpatient clinics on the survey day were enrolled. Basic demographic and clinical data of patients were collected using a linelist. Patients were swabbed and tested for SARS-CoV-2, influenza, and Respiratory Syncytial virus (RSV) by RT-PCR at the Central Laboratory in Cairo. RESULTS: Overall, 530 patients enrolled, their mean age was 5.8 ± 4.2, 57.1% were males, and 70.2% reside in rural or semi-rural areas. Of all patients, 134 (25.3%) had influenza, 111 (20.9%) RSV, and 14 (2.8%) coinfections. Influenza-positive children were older compared to RSV, (7.2 ± 4.1, 4.3 ± 4.1, p < 0.001), with more than half of them (53.0%) being school students. Dyspnea was reported in RSV more than in influenza (62.2% vs. 49.3%, p < 0.05). Among RSV patients, children < 2 years had a higher rate of dyspnea than others (86.7% vs. 53.1%, < 0.001). CONCLUSIONS: A resurgence of influenza and RSV was detected in Egypt in the 2022-2023 winter season. Influenza caused a higher rate of infection than RSV, while RSV caused more severe symptoms than influenza. Monitoring a broader range of respiratory pathogens is recommended to estimate the ARI burden and risky groups for severe disease in Egypt.

Adapting an integrated acute respiratory infections sentinel surveillance to the COVID-19 pandemic requirements, Egypt, 2020-2022.

Objectives: In Egypt, an integrated surveillance for acute respiratory infections (ARIs) was established in 2016 to identify the causes of ARIs. The surveillance system includes 19 governmental hospitals. In response to the coronavirus disease 2019 (COVID-19) pandemic, the World Health Organisation (WHO) requested surveillance adaptation to address the emerging challenges. This study aims to describe the experience in Egypt of adapting ARI surveillance to the COVID-19 pandemic. Methods: WHO case definitions were used to identify patients with ARIs. Nasopharyngeal/oropharyngeal swabs were collected for SARS-CoV-2 and influenza testing. Demographic and clinical information were obtained by interviewing patients at the hospitals. During the COVID-19 pandemic, the first two outpatients daily and every fifth admitted patient were enrolled in the study. To determine the status of ARIs in Egypt during the pandemic, patient demographic, clinical and laboratory data from 2020 to 2022 were obtained and descriptive analyses were performed. Results: Overall, 18,160 patients were enrolled in the study, including 7923 (43.6%) seen at outpatient clinics and 10,237 (56.4%) inpatients. Of the study participants, 6453 (35.5%) tested positive for ARIs, including 5620 (87.1%) for SARS-CoV-2, 781 (12.1%) for influenza and 52 (0.8%) for SARS-CoV-2/influenza coinfection. SARS-CoV-2 was the cause for 95.3% of admitted patients and 65.4% of outpatients. Influenza subtypes included A/H3 (55.7%), Influenza-B (29.1%) and H1/pdm09 (14.2%). Compared with influenza, SARS-CoV-2 tended to infect the elderly, in warm weather and in urban governorates, and resulted in more hospitalisations, longer hospital stays and higher case fatalities (16.3% vs 6.6%, p < 0.001). Conclusions: ARI surveillance in Egypt was successfully adapted to the COVID-19 pandemic and effectively described the clinical characteristics and severity of circulating viruses. Surveillance reported the re-emergence of influenza with a severe course and high fatality. Surveillance is essential for monitoring the activity of respiratory viruses with the aim of guiding clinical management, including preventative and control measures.

Coinfection With SARS-CoV-2 and Influenza A(H1N1) in a Patient Seen at an Influenza-like Illness Surveillance Site in Egypt: Case Report.

BACKGROUND: Sentinel surveillance of influenza-like illness (ILI) in Egypt started in 2000 at 8 sentinel sites geographically distributed all over the country. In response to the COVID-19 pandemic, SARS-CoV-2 was added to the panel of viral testing by polymerase chain reaction for the first 2 patients with ILI seen at one of the sentinel sites. We report the first SARS-CoV-2 and influenza A(H1N1) virus co-infection with mild symptoms detected through routine ILI surveillance in Egypt. OBJECTIVE: This report aims to describe how the case was identified and the demographic and clinical characteristics and outcomes of the patient. METHODS: The case was identified by Central Public Health Laboratory staff, who contacted the ILI sentinel surveillance officer at the Ministry of Health. The case patient was contacted through a telephone call. Detailed information about the patient's clinical picture, course of disease, and outcome was obtained. The contacts of the patient were investigated for acute respiratory symptoms, disease confirmation, and outcomes. RESULTS: Among 510 specimens collected from patients with ILI symptoms from October 2019 to August 2020, 61 (12.0%) were COVID-19-positive and 29 (5.7%) tested positive for influenza, including 15 (51.7%) A(H1N1), 11 (38.0%) A(H3N2), and 3 (10.3%) influenza B specimens. A 21-year-old woman was confirmed to have SARS-CoV-2 and influenza A(H1N1) virus coinfection. She had a high fever of 40.2 °C and mild respiratory symptoms that resolved within 2 days with symptomatic treatment. All five of her family contacts had mild respiratory symptoms 2-3 days after exposure to the confirmed case, and their symptoms resolved without treatment or investigation. CONCLUSIONS: This case highlights the possible occurrence of SARS-CoV-2/influenza A(H1N1) coinfection in younger and healthy people, who may resolve the infection rapidly. We emphasize the usefulness of the surveillance system for detection of viral causative agents of ILI and recommend broadening of the testing panel, especially if it can guide case management.

Epidemiology, Disease Severity and Outcome of Severe Acute Respiratory Syndrome Coronavirus 2 and Influenza Viruses Coinfection Seen at Egypt Integrated Acute Respiratory Infections Surveillance, 2020-2022.

Background: Cocirculation of influenza (Flu) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (SARS-CoV-2/Flu) represent a public health concern as it may worsen the severity and increase fatality from coronavirus disease 2019. An increase in the number of patients with coinfection was recently reported. We studied epidemiology, severity, and outcome of patients with SARS-CoV-2/Flu coinfection seen at Egypt's integrated acute respiratory infections surveillance to better describe disease impact and guide effective preventive measures. Methods: The first two outpatients were seen daily, and every fifth patient admitted to 19 sentinel hospitals with respiratory symptoms was enrolled. Patients were interviewed using a standardized questionnaire and provided nasopharyngeal swabs to be tested for SARS-CoV-2 and influenza by real-time polymerase chain reaction at the central laboratory. Data from all patients with coinfection were obtained, and descriptive data analysis was performed for patients' demographics, clinical course, and outcome. Results: The total number of patients enrolled between January 2020 and April 2022 was 18,160 and 6,453 (35.5%) tested positive for viruses, including 52 (0.8%) coinfection. Of them, 36 (69.2%) were coinfected with Flu A/H3, 9 (17.3%) Flu-B, and 7 (13.5%) Flu A/H1. Patients' mean age was 33.2 ± 21, 55.8% were males, and 20 (38.5%) were hospitalized, with mean hospital days 6.7 ± 6. At the hospital, 14 (70.0%) developed pneumonia, 6 (30.0%) ICU admitted, and 4 (20.0%) died. The hospitalization rate among patients coinfected with Flu-B and Flu A/H3 was 55.6 and 41.7%, with mean hospital days (8.0 ± 6 and 6.4 ± 6), pneumonia infection (40.0 and 80.0%), ICU admission (40.0 and 26.7%), and death (20.0% for both), while no patients hospitalized with A/H1. Conclusions: The recent increase in the number of SARS-CoV-2/Flu coinfections was identified in Egypt. The disease could have a severe course and high fatality, especially in those coinfected with Flu-B and Flu A/H3. Monitoring disease severity and impact is required to guide preventive strategy.

Incidence, risk factors, and whole-genome sequence of SARs-CoV-2 and influenza virus among the Egyptian pilgrims returning from Umrah mass gathering in Saudi Arabia, April-May 2022.

BACKGROUND: Ramadan Umrah is the second largest Islamic pilgrimage with 2.75 million pilgrims allowed in 2022. This report presents the results of a survey among Egyptian pilgrims returning from Ramadan Umrah to monitor SARS-CoV-2 and influenza activity and identify prevalent SARS-CoV-2 variants after this mass gathering. METHODS: Cross-sectional survey conducted at Cairo airport from 30th April 2022-5 th May 2022. Pilgrims were invited to participate voluntarily. After consenting, participants interviewed using questionnaire including demographics, health status, and vaccination information and asked to provide NP/OP swabs for SARS-CoV-2 and influenza testing by RT-PCR. Whole-genome sequencing performed for 29 SARS-CoV-2 isolates. Incidence calculated, descriptive data analysis performed, and SARS-CoV-2 patients were compared to negatively tested participants using chi2 and p value< 0.05. RESULTS: Overall, 1003 subjects participated, their mean age 50.9 ± 13 years, 594 (59.2%) were males. Of them, 76(7.6%) tested positive including 67(6.7%) SARS-CoV-2, 7(0.7%) influenza and 2(0.2%) SARS-CoV-2/influenza coinfection. Omicron sublineage BA.2 was the prevalent variant with no difference in severity identified between BA.1 and BA.2. No difference was identified between COVID-19 incidence among receivers of different vaccine types or between fully vaccinated and booster dose receivers. CONCLUSIONS: Survey indicated a low incidence of SARs-CoV-2 and influenza among Egyptian pilgrims returning from Ramadan Umrah. Patients had mild or no symptoms with no hospitalization or deaths reported. Full vaccination and booster doses of COVID-19 vaccines proved equally effective. Enhancing COVID-19 and influenza vaccination before mass gatherings and close monitoring of respiratory viruses among pilgrims returning from Hajj and Umrah are crucial for outbreak early detection and mitigation.

SARS-CoV-2 Genetic Diversity and Lineage Dynamics in Egypt during the First 18 Months of the Pandemic.

COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages.

Insight into Genetic Characteristics of Identified SARS-CoV-2 Variants in Egypt from March 2020 to May 2021.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in Egypt in February 2020. Data about the prevalence rates of the SARS-CoV-2 lineages are relatively scarce. To understand the genetic characteristics of SARS-CoV-2 in Egypt during several waves of the pandemic, we analyzed sequences of 1256 Egyptian SARS-CoV-2 full genomes from March 2020 to May 2021. From one wave to the next, dominant strains have been observed to be replaced by other dominant strains. We detected an emerging lineage of SARS-CoV-2 in Egypt that shares mutations with the variant of concern (VOC). The neutralizing capacity of sera collected from cases infected with C.36.3 against dominant strains detected in Egypt showed a higher cross reactivity of sera with C.36.3 compared to other strains. Using in silico tools, mutations in the spike of SARS-CoV-2 induced a difference in binding affinity to the viral receptor. The C.36 lineage is the most dominant SARS-CoV-2 lineage in Egypt, and the heterotrophic antigenicity of SARS-CoV-2 variants is asymmetric. These results highlight the value of genetic and antigenic analyses of circulating strains in regions where published sequences are limited.

Induced humoral immunity of different types of vaccines against most common variants of SARS-CoV-2 in Egypt prior to Omicron outbreak.

The diversity of SARS-CoV-2 continues to lead to the emergence of new SARS-CoV-2 variants. SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic by determining the neutralizing antibody response. This study aims to investigate vaccine-induced antibodies against most common variants of SARS-CoV-2 in Egypt. Sera samples were collected from vaccinated participants and neutralizing activity against the SARS-CoV-2 variants was determined using microneutralization assay. Our results show that the BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCov-19 (AstraZeneca), and Ad26.COV2.S COVID-19 (Janssen) vaccines elicited neutralizing antibody responses more than the BBIBP-CorV vaccine (Sinopharm) against B.1, C.36.3, and AY.32 (Delta) variants. While vaccines remain highly effective in managing the COVID-19 pandemic, ongoing monitoring of vaccine effectiveness is needed.

Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibodies in Egyptian Convalescent Plasma Donors.

Using convalescent plasma as immunotherapy is an old method for treatment of infectious diseases. Several countries have recently allowed the use of such therapy for the treatment of COVID-19 patients especially those who are critically ill. A similar program is currently being tested in Egypt. Here, we tested 227 plasma samples from convalescent donors in Egypt for neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a microneutralization (MN) assay. A third of the tested samples did not have antibody titers and 58% had titers between 1:10 and 1:80. Only 12% had titers >1:160. We also compared MN assays using different virus concentrations, plaque reduction neutralization (PRNT) assays, and a chemiluminescence assay that measures immunoglobulin G (IgG) binding to N and S proteins of SARS-CoV-2. Our results indicated that a MN assay using 100 TCID50/ml provides comparable results to PRNT and allows for high throughput testing.

EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2.

Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kß p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kß/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kß pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.