Genetic and virological characteristics of a reassortant avian influenza A H6N1 virus isolated from wild birds at a live-bird market in Egypt.

The first detection of a human infection with avian influenza A/H6N1 virus in Taiwan in 2013 has raised concerns about this virus. During our routine surveillance of avian influenza viruses (AIVs) in live-bird markets in Egypt, an H6N1 virus was isolated from a garganey duck and was characterized. Phylogenetic analysis indicated that the Egyptian H6N1 strain A/Garganey/Egypt/20869C/2022(H6N1) has a unique genomic constellation, with gene segments inherited from different subtypes (H5N1, H3N8, H7N3, H6N1, and H10N1) that have been detected previously in AIVs from Egypt and some Eurasian countries. We examined the replication of kinetics of this virus in different mammalian cell lines (A549, MDCK, and Vero cells) and compared its pathogenicity to that of the ancestral H6N1 virus A/Quail/HK/421/2002(H6N1). The Egyptian H6N1 virus replicated efficiently in C57BL/6 mice without prior adaptation and grew faster and reached higher titers than in A549 cells than the ancestral strain. These results show that reassortant H6 AIVs might pose a potential threat to human health and highlight the need to continue surveillance of H6 AIVs circulating in nature.

Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E.

Repurposing vitamins as antiviral supporting agents is a rapid approach used to control emerging viral infections. Although there is considerable evidence supporting the use of vitamin supplementation in viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the specific role of each vitamin in defending against coronaviruses remains unclear. Antiviral activities of available vitamins on the infectivity and replication of human coronaviruses, namely, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus 229E (HCoV-229E), were investigated using in silico and in vitro studies. We identified potential broad-spectrum inhibitor effects of Hydroxocobalamin and Methylcobalamin against the three tested CoVs. Cyanocobalamin could selectively affect SARS-CoV-2 but not MERS-CoV and HCoV-229E. Methylcobalamin showed significantly higher inhibition values on SARS-CoV-2 compared with Hydroxocobalamin and Cyanocobalamin, while Hydroxocobalamin showed the highest potent antiviral activity against MERS-CoV and Cyanocobalamin against HCoV-229E. Furthermore, in silico studies were performed for these promising vitamins to investigate their interaction with SARS-CoV-2, MERS-CoV, and HCoV-229E viral-specific cell receptors (ACE2, DPP4, and hAPN protein, respectively) and viral proteins (S-RBD, 3CL pro, RdRp), suggesting that Hydroxocobalamin, Methylcobalamin, and Cyanocobalamin may have significant binding affinity to these proteins. These results show that Methylcobalamin may have potential benefits for coronavirus-infected patients.

Comparison of SARS-Cov-2 omicron variant with the previously identified SARS-Cov-2 variants in Egypt, 2020-2022: insight into SARS-Cov-2 genome evolution and its impact on epidemiology, clinical picture, disease severity, and mortality.

BACKGROUND: The o severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has killed millions of people and caused widespread concern around the world. Multiple genetic variants of SARS-CoV-2 have been identified as the pandemic continues. Concerns have been raised about high transmissibility and lower vaccine efficacy against omicron. There is an urgent need to better describe how omicron will impact clinical presentation and vaccine efficacy. This study aims at comparing the epidemiologic, clinical, and genomic characteristics of the omicron variant prevalent during the fifth wave with those of other VOCs between May 2020 and April 2022. METHODS: Epidemiological data were obtained from the National Electronic Diseases Surveillance System. Secondary data analysis was performed on all confirmed COVID-19 patients. Descriptive data analysis was performed for demographics and patient outcome and the incidence of COVID-19 was calculated as the proportion of SARS-CoV-2 confirmed patients out of the total population of Egypt. Incidence and characteristics of the omicron cohort from January- April 2022, were compared to those confirmed from May 2020-December 2021. We performed the whole-genome sequencing of SARS-CoV-2 on 1590 specimens using Illumina sequencing to describe the circulation of the virus lineages in Egypt. RESULTS: A total of 502,629 patients enrolled, including 60,665 (12.1%) reported in the fifth wave. The incidence rate of omicron was significantly lower than the mean of incidences in the previous subperiod (60.1 vs. 86.3/100,000 population, p < 0.001). Symptoms were reported less often in the omicron cohort than in patients with other variants, with omicron having a lower hospitalization rate and overall case fatality rate as well. The omicron cohort tended to stay fewer days at the hospital than did those with other variants. We analyzed sequences of 2433 (1590 in this study and 843 were obtained from GISAID platform) Egyptian SARS-CoV-2 full genomes. The first wave that occurred before the emergence of global variants of concern belonged to the B.1 clade. The second and third waves were associated with C.36. Waves 4 and 5 included B.1.617.2 and BA.1 clades, respectively. CONCLUSIONS: The study indicated that Omicron-infected patients had milder symptoms and were less likely to be hospitalized; however, patients hospitalized with omicron had a more severe course and higher fatality rates than those hospitalized with other variants. Our findings demonstrate the importance of combining epidemiological data and genomic analysis to generate actionable information for public health decision-making.

Double-antibody-based nano-biosensing system for the onsite monitoring of SARS-CoV-2 variants.

The fast and reliable diagnosis of COVID-19 is the foremost priority for promoting public health interventions. Therefore, double-antibody-based immunobiosensor chips were designed, constructed, and exploited for clinical diagnosis. Gold nanoparticles/tungsten oxide/carbon nanotubes (AuNPs/WO3/CNTs) were used as the active working sensor surface to support the chemical immobilization of a mixture of SARS-CoV-2 antibodies (anti-RBD-S and anti-RBD-S-anti-Llama monoclonal antibodies). The morphology and chemical functionalization of the fabricated disposable immunochips was characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). After full assay optimization, the immunobiosensor showed a high sensitivity to detect SARS-CoV-2-S protein with limits of detection and quantification of 1.8 and 5.6 pg/mL, respectively. On the other hand, for the SARS-CoV-2 whole virus particle analysis, the detection and quantification limits were determined to be 5.7 and 17 pg/mL, respectively. The biosensor showed a highly selective response toward SARS-CoV-2, even in the presence of influenza, nontargeting human coronaviruses, and Middle East respiratory syndrome coronavirus (MERS-CoV). The immunochips exhibited distinct responses toward the variants of concern: B.1>C.36.3>Omicron> Delta> Alpha coronavirus variants. For biosensor validation, twenty-nine clinical specimens were analyzed, and the impedimetric responses were positively detected for two Delta samples, eighteen Omicron samples, and six B.1-type samples in addition to three negative samples. Eventually, the immunobiosensor was fabricated in the form of ready-to-use chips capable of sensitive detection of virus variants, especially variants of concern (VOC) and interest, in a specimen within 15 min. The chips provided instantaneous detection with the direct application of clinical samples and are considered a point-of-care device that could be used in public places and hot spots.

Whole-Genome Sequence of a Human Monkeypox Virus Strain Detected in Egypt.

Monkeypox virus has recently been detected in multiple countries. Two cases of monkeypox virus were reported in Egypt as part of an ongoing international outbreak. We report the whole-genome sequence of a monkeypox virus that was retrieved from the first confirmed case in Egypt. The virus was fully sequenced on the Illumina platform, and phylogenetic analysis demonstrated that the current monkeypox strain is closely related to clade IIb, which caused recent multicountry outbreaks.

Molecular identification and virological characteristics of highly pathogenic avian influenza A/H5N5 virus in wild birds in Egypt.

Multiple incursions of different subtypes of highly pathogenic avian influenza (HPAI) A/H5NX viruses have caused widely considerable outbreaks in poultry and hundreds of human infections. Extensive reassortment events associated with currently circulating clade 2.3.4.4b of A/H5NX viruses have been widely recorded. Wild migratory birds contribute to the spillover of diverse viruses throughout their migration flyways. During our active surveillance of avian influenza in Egypt, we successfully isolated and fully characterized HPAI A/H5N5 virus of clade 2.3.4.4b that was detected in a healthy purple heron. The Egyptian H5N5 virus is genotypically similar with the same subtype that was detected in the far east of Russia and several European countries. The antigenic analysis showed that the Egyptian H5N5 virus is distinct from HPAI A(H5N8) viruses in Egypt. The virus preferentially binds to avian-like receptors rather than human-like receptors. Our results showed that the virus caused 100% and 60% lethality in chicken and mice respectively. Increasing active surveillance efforts, monitoring the dynamics of emerging AIVs, and risk assessment implementation should be globally applied especially in hot spot regions like Egypt.

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.

Robust antiviral activity of commonly prescribed antidepressants against emerging coronaviruses: in vitro and in silico drug repurposing studies.

During the current coronavirus disease 2019 (COVID-19) pandemic, symptoms of depression are commonly documented among both symptomatic and asymptomatic quarantined COVID-19 patients. Despite that many of the FDA-approved drugs have been showed anti-SARS-CoV-2 activity in vitro and remarkable efficacy against COVID-19 in clinical trials, no pharmaceutical products have yet been declared to be fully effective for treating COVID-19. Antidepressants comprise five major drug classes for the treatment of depression, neuralgia, migraine prophylaxis, and eating disorders which are frequently reported symptoms in COVID-19 patients. Herein, the efficacy of eight frequently prescribed FDA-approved antidepressants on the inhibition of both SARS-CoV-2 and MERS-CoV was assessed. Additionally, the in vitro anti-SARS-CoV-2 and anti-MERS-CoV activities were evaluated. Furthermore, molecular docking studies have been performed for these drugs against the spike (S) and main protease (Mpro) pockets of both SARS-CoV-2 and MERS-CoV. Results showed that Amitriptyline, Imipramine, Paroxetine, and Sertraline had potential anti-viral activities. Our findings suggested that the aforementioned drugs deserve more in vitro and in vivo studies targeting COVID-19 especially for those patients suffering from depression.

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.

Antiviral activity of chitosan nanoparticles encapsulating silymarin (Sil-CNPs) against SARS-CoV-2 (in silico and in vitro study).

To develop a specific treatment against COVID-19, we investigated silymarin-chitosan nanoparticles (Sil-CNPs) as an antiviral agent against SARS-CoV-2 using in silico and in vitro approaches. Docking of Sil and CNPs was carried out against SARS-CoV-2 spike protein using AutoDock Vina. CNPs and Sil-CNPs were prepared by the ionic gelation method and characterized by TEM, FT-IR, zeta analysis, and the membrane diffusion method to determine the drug release profile. Cytotoxicity was tested on both Vero and Vero E6 cell lines using the MTT assay. Minimum binding energies with spike protein and ACE2 were -6.6, and -8.0 kcal mol-1 for CNPs, and -8.9, and -9.7 kcal mol-1 for Sil, respectively, compared to -6.6 and -8.4 kcal mol-1 respectively for remdesivir (RMV). CNPs and Sil-CNPs were prepared at sizes of 29 nm and 82 nm. The CC50 was 135, 35, and 110 µg mL-1 for CNPs, Sil, and Sil-CNPs, respectively, on Vero E6. The IC50 was determined at concentrations of 0.9, 12 and 0.8 µg mL-1 in virucidal/replication assays for CNPs, Sil, and Sil-CNPs respectively using crystal violet. These results indicate antiviral activity of Sil-CNPs against SARS-CoV-2.

Prevalence and determinants of SARS-CoV-2 neutralizing antibodies in Lebanon.

According to the Lebanese Ministry of Public Health, more than 1,053,000 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been confirmed in Lebanon so far. The actual number of cases is likely to be higher. We conducted a serological study from October 2020 to April 2021 to estimate the prevalence of SARS-CoV-2 neutralizing antibodies and identify associated factors. Serum samples as well as demographic, health, and behavioral data were collected from 2,783 subjects. Sera were tested by microneutralization assay. Neutralizing antibodies were detected in 58.9% of the study population. The positivity rate increased over the study period. It was highest among the group who remained at work during the COVID-19 pandemic and in peri-urban areas with limited adherence to preventive measures. Sex and age were associated with positivity. Reported previous COVID-19, exposure to a COVID-19 patient in the family, and attending gatherings were associated with increased prevalence. Not taking any precautionary measures against COVID-19 was a risk factor, whereas precautionary measures such as working from home and washing hands were protective. The high neutralizing antibody seroprevalence rates detected in this study emphasize the high transmission rate of SARS-CoV-2 infection in the community. Adherence to preventive measures and non-pharmaceutical interventions imposed by the government is recommended.

Incidence and seroprevalence of seasonal influenza a viruses in Egypt: Results of a community-based cohort study.

BACKGROUND: H1N1 and H3N2 influenza A viruses circulate in people as seasonal influenza viruses. Data on influenza infection rates and circulation in demographic subpopulations in Egypt are limited. In this study, we aimed to determine the incidence and seroprevalence of seasonal influenza A virus infections in a cohort of rural Egyptians between 2017 and 2020. METHODS: A total of 2383 subjects were enrolled from 390 households in five study sites in Northern Egypt. Informed consents were obtained. Sera were collected from participants on an annual basis (Baseline: 2016-2017, Follow up 1: 2017-2018, Follow up 2: 2018-2019, and Follow up 3: 2019-2020) to determine seroprevalence of antibodies against H1N1 and H3N2 viruses by hemagglutination inhibition assay and to estimate incidence based on seroconversion. RESULTS: Seropositivity against H1N1 was over 40% and over 60% against H3N2. The high seroprevalence was due to natural infection because participants were mostly unvaccinated. Seropositive participants were younger than seronegative participants indicating that the infection rate is higher in children. Incidence of both viruses ranged from 4% to 28% depending on study year. The incidence and seroprevalence of H3N2 and H1N1 infections at Follow up 1, 2, and 3 showed an increase at Follow up 2 observed for all age categories corresponding to season 2018-2019, at which the vaccine efficacy was the lowest worldwide compared with preceding and following seasons. CONCLUSIONS: This cohort study provided estimates of influenza A infection rates among rural Egyptians. We recommend updating influenza vaccination programs to focus on such populations.

Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b in Wild Birds and Live Bird Markets, Egypt.

Clade 2.3.4.4 H5Nx influenza viruses have further diversified into several subclades. Sub-clade 2.3.4.4b H5N1 viruses have been widely circulating in wild birds and detected in Europe, Africa, Asia, and North America since October 2020. In this study, we report the first detection of highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses in wild birds and domestic ducks from live bird markets in Egypt. Phylogenetic analysis revealed that the Egyptian H5N1 virus retained the genomic composition of Eurasian strains. Mutations in the viral proteins associated with zoonotic potential and pathogenicity were detected in Egyptian isolates. Egypt is considered a hot spot for the evolution of the influenza virus, so active surveillance of avian influenza viruses in Egypt is warranted.

SARS-CoV-2-Impedimetric Biosensor: Virus-Imprinted Chips for Early and Rapid Diagnosis.

Due to the current global SARS-CoV-2 pandemic, rapid and accurate diagnostic tools are needed to prevent the spread of COVID-19 across the globe. An electrochemical sensing platform was constructed using CNTs/WO3-screen printed electrodes for imprinting the complete virus particles (SARS-CoV-2 particles) within the polymeric matrix to create viral complementary binding sites. The sensor provided high selectivity toward the target virus over other tested human corona and influenza respiratory interference viruses. The sensitivity performance of the sensor chips was evaluated using different viral concentrations, while the limits of detection and quantification were 57 and 175 pg/mL, respectively. Reaching this satisfied low detection limit (almost 27-fold more sensitive than the RT-PCR), the sensor was applied in clinical specimens obtained from SARS-CoV-2 suspected cases. Thus, dealing directly with clinical samples on the chip could be provided as a portable device for instantaneous and simple point of care in hospitals, airports, and hotspots.

Delineating a potent antiviral activity of Cuphea ignea extract loaded nano-formulation against SARS-CoV-2: In silico and in vitro studies.

The outbreak of coronavirus disease-2019, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a worldwide emerging crisis. Polyphenols are a class of herbal metabolites with a broad-spectrum antiviral activity. However, most polyphenols encounter limited efficacy due to their poor solubility and degradation in neutral and basic environments. Thus, the effectiveness of their pharmaceutical application is critically dependent on the delivery systems to overcome the aforementioned drawbacks. Herein, Polyphenols-rich Cuphea ignea extract was prepared and its constituents were identified and quantified. Molecular docking was conducted for 15 compounds in the extract against SARS-CoV-2 main protease, among which rutin, myricetin-3-O-rhamnoside and rosmarinic acid depicted the most promising antiviral activity. Further, a self-nanoemulsifying formulation, composed of 10% oleic acid, 40% tween 20 and propylene glycol 50%, was prepared to improve the solubility of the extract components and enable its concurrent delivery permitting combined potency. Upon dilution with aqueous phases, the formulation rapidly Formsnanoemulsion of good stability and excellent dissolution profile in acidic pH when compared to the crude extract. It inhibited SARS-CoV-2 completely in vitro at a concentration as low as 5.87 µg/mL presenting a promising antiviral remedy for SARS-CoV-2, which may be attributed to the possible synergism between the extract components.

Determinants of having severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in Egypt.

BACKGROUND: Reported laboratory-confirmed COVID-19 cases underestimate the true burden of disease as cases without laboratory confirmation, and asymptomatic and mild cases are missed by local surveillance systems. Population-based seroprevalence studies can provide better estimates of burden of disease by taking into account infections that were missed by surveillance systems. Additionally, little is known about the determinants of seroconversion in community settings. METHODS: We conducted a cross-sectional serologic survey among 888 participants in Egypt. RESULTS: Neutralizing antibodies were detected in 30% of study volunteers. Age and educational level were associated with being seropositive as people older than 70 years and people with graduate degrees had lower seroprevalence. Self-reporting cases having COVID-19-related symptoms such as fever, malaise, headache, dyspnea, dry cough, chest pain, diarrhea, and loss of taste or smell were all associated with having antibodies. Fever and loss of taste or smell were strong predictors with odds ratios of 2.1 (95% confidence interval: 1.3-3.5) and 4.5 (95% confidence interval: 2.6-7.8), respectively. CONCLUSIONS: Our results can guide COVID-19 prevention and control policies and assist in determining the immunity level in some Egyptian communities.

Sinapic Acid Suppresses SARS CoV-2 Replication by Targeting Its Envelope Protein.

SARS CoV-2 is still considered a global health issue, and its threat keeps growing with the emergence of newly evolved strains. Despite the success in developing some vaccines as a protective measure, finding cost-effective treatments is urgent. Accordingly, we screened a number of phenolic natural compounds for their in vitro anti-SARS CoV-2 activity. We found sinapic acid (SA) selectively inhibited the viral replication in vitro with an half-maximal inhibitory concentration (IC50) value of 2.69 µg/mL with significantly low cytotoxicity (CC50 = 189.3 µg/mL). Subsequently, we virtually screened all currently available molecular targets using a multistep in silico protocol to find out the most probable molecular target that mediates this compound's antiviral activity. As a result, the viral envelope protein (E-protein) was suggested as the most possible hit for SA. Further in-depth molecular dynamic simulation-based investigation revealed the essential structural features of SA antiviral activity and its binding mode with E-protein. The structural and experimental results presented in this study strongly recommend SA as a promising structural motif for anti-SARS CoV-2 agent development.

Immunogenicity and Safety of an Inactivated SARS-CoV-2 Vaccine: Preclinical Studies.

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world's population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.

Incidence, household transmission, and neutralizing antibody seroprevalence of Coronavirus Disease 2019 in Egypt: Results of a community-based cohort.

SARS-CoV-2 virus is transmitted in closed settings to people in contact with COVID-19 patients such as healthcare workers and household contacts. However, household person-to-person transmission studies are limited. Households participating in an ongoing cohort study of influenza incidence and prevalence in rural Egypt were followed. Baseline enrollment was done from August 2015 to March 2017. The study protocol was amended in April 2020 to allow COVID-19 incidence and seroprevalence studies. A total of 290 households including 1598 participants were enrolled and followed from April to October 2020 in four study sites. When a participant showed respiratory illness symptoms, a serum sample and a nasal and an oropharyngeal swab were obtained. Swabs were tested by RT-PCR for SARS-CoV-2 infection. If positive, the subject was followed and swabs collected on days three, six, nine, and 14 after the first swab day and a serum sample obtained on day 14. All subjects residing with the index case were swabbed following the same sampling schedule. Sera were collected from cohort participants in October 2020 to assess seroprevalence. Swabs were tested by RT-PCR. Sera were tested by Microneutralization Assay to measure the neutralizing antibody titer. Incidence of COVID-19, household secondary attack rate, and seroprevalence in the cohort were determined. The incidence of COVID-19 was 6.9% and the household secondary attack rate was 89.8%. Transmission within households occurred within two-days of confirming the index case. Infections were asymptomatic or mild with symptoms resolving within 10 days. The majority developed a neutralizing antibody titer by day 14 post onset. The overall seroprevalence among cohort participants was 34.8%. These results suggest that within-household transmission is high in Egypt. Asymptomatic or mild illness is common. Most infections seroconvert and have a durable neutralizing antibody titer.