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.

Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents.

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

The species coalescent indicates possible bat and pangolin origins of the COVID-19 pandemic.

A consensus species tree is reconstructed from 11 gene trees for human, bat, and pangolin beta coronaviruses from samples taken early in the pandemic (prior to April 1, 2020). Using coalescent theory, the shallow (short branches relative to the hosts) consensus species tree provides evidence of recent gene flow events between bat and pangolin beta coronaviruses predating the zoonotic transfer to humans. The consensus species tree was also used to reconstruct the ancestral sequence of human SARS-CoV-2, which was 2 nucleotides different from the Wuhan sequence. The time to most recent common ancestor was estimated to be Dec 8, 2019 with a bat origin. Some human, bat, and pangolin coronavirus lineages found in China are phylogenetically distinct, a rare example of a class II phylogeography pattern (Avise et al. in Ann Rev Eco Syst 18:489-422, 1987). The consensus species tree is a product of evolutionary factors, providing evidence of repeated zoonotic transfers between bat and pangolin as a reservoir for future zoonotic transfers to humans.

Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents.

The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 is less pathogenic in animal models than previously circulating variants of concern1-4. Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here we have evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters and hACE2 transgenic mice. We have observed no obvious differences among BA.2, BA.4 and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2.

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.

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

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.

Plaque-neutralizing antibody to BA.2.12.1, BA.4 and BA.5 in individuals with three doses of BioNTech or CoronaVac vaccines, natural infection and breakthrough infection.

BACKGROUND: BA.2.12.1, BA.4 and BA.5 subvariants of SARS-CoV-2 variant-of-concern (VOC) Omicron (B.1.1.529) are spreading globally. They demonstrate higher transmissibility and immune escape. OBJECTIVES: Determine BA.2.12.1, BA.4 and BA.5 virus plaque reduction neutralization test (PRNT) antibody titres in individuals recently vaccinated with BNT162b2 (n = 20) or CoronaVac (n = 20) vaccines or those convalescent from ancestral wild- type (WT) SARS-CoV-2 (n = 20) or BA.2 infections with (n = 17) or without (n = 7) prior vaccination. RESULTS: Relative to neutralization of the WT virus, those vaccinated with BNT162b2 had 4.8, 3.4, 4.6, 11.3 and 15.5-fold reductions of geometric mean antibody titres (GMT) to BA.1, BA.2, BA.2.12.1, BA.4 and BA.5 viruses, respectively. Similarly, those vaccinated with CoronaVac had 8.0, 7.0, 11.8, 12.0 and 12.0 fold GMT reductions and those with two doses of CoronaVac boosted by BNT162b2 had 6.1, 6.7, 6,3, 13.0 and 21.2 fold GMT reductions to these viruses, respectively. Vaccinated individuals with BA.2 breakthrough infections had higher GMT antibody levels vs. BA.4 (36.9) and BA.5 (36.9) than unvaccinated individuals with BA.2 infections (BA.4 GMT 8.2; BA.5 GMT 11.0). CONCLUSIONS: BA.4 and BA.5 subvariants were less susceptible to BNT162b2 or CoronaVac vaccine elicited antibody neutralization than subvariants BA.1, BA.2 and BA.2.12.1. Nevertheless, three doses BNT162b2 or booster of BNT162b2 following two doses of CoronaVac elicited detectable BA.4 and BA.5 neutralizing antibody responses while those vaccinated with three doses of CoronaVac largely fail to do so. BA.2 infections in vaccinated individuals led to higher levels of BA.4 or BA.5 neutralizing antibody compared to those who were vaccine-naive.

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.

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.

Lebanese SARS-CoV-2 genomics: 24 months of the pandemic.

The COVID-19 pandemic continues to pose a global health concern, despite the ongoing vaccination campaigns, due to the emergence and rapid spread of new variants of the causative agent SARS-CoV-2. These variants are identified and tracked via the marker mutations they carry, and the classification system put in place following tremendous sequencing efforts. In this study, the genomes of 1,230 Lebanese SARS-CoV-2 strains collected throughout 2 years of the outbreak in Lebanon were analyzed, 115 of which sequenced within this project. Strains were classified into seven GISAID clades, the major one being GRY, and 36 Pango lineages, with three variants of concern identified: alpha, delta and omicron. A time course distribution of GISAID clades allowed the visualization of change throughout the two years of the Lebanese outbreak, in conjunction with major events and measures in the country. Subsequent phylogenetic analysis showed the clustering of strains belonging to the same clades. In addition, a mutational survey showed the presence of mutations in the structural, non-structural and accessory proteins. Twenty five (25) mutations were labeled as major, i.e. present in more than 30% of the strains, such as the common Spike_D614G and NSP3_T183I. Whereas 635 were labeled as uncommon, i.e. found in very few of the analyzed strains as well as GISAID records, such as NSP2_I349V. Distribution of these mutations differed between 2020, and the first and the second half of 2021. In summary, this study highlights key genomic aspects of the Lebanese SARS-CoV-2 strains collected in 2020, the first year of the outbreak in Lebanon, versus those collected in 2021, the second year of COVID-19 in Lebanon.

Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra05268c

Six compounds namely, tanshinone IIA (1), carnosic acid (2), rosmarinic acid (3), salvianolic acid B (4), baicalein (5), and glycyrrhetinic acid (6) were screened for their anti-SARS-CoV-2 activities against both the spike (S) and main protease (Mpro) receptors using molecular docking studies. Molecular docking recommended the superior affinities of both salvianolic acid B (4) and glycyrrhetinic acid (6) as the common results from the previously published computational articles. On the other hand, their actual anti-SARS-CoV-2 activities were tested in vitro using plaque reduction assay to calculate their IC50 values after measuring their CC50 values using MTT assay on Vero E6 cells. Surprisingly, tanshinone IIA (1) was the most promising member with IC50 equals 4.08 ng μl−1. Also, both carnosic acid (2) and rosmarinic acid (3) showed promising IC50 values of 15.37 and 25.47 ng μl−1, respectively. However, salvianolic acid (4) showed a weak anti-SARS-CoV-2 activity with an IC50 value equals 58.29 ng μl−1. Furthermore, molecular dynamics simulations for 100 ns were performed for the most active compound from the computational point of view (salvianolic acid 4), besides, the most active one biologically (tanshinone IIA 1) on both the S and Mpro complexes of them (four different molecular dynamics processes) to confirm the docking results and give more insights regarding the stability of both compounds inside the SARS-CoV-2 mentioned receptors, respectively. Also, to understand the mechanism of action for the tested compounds towards SARS-CoV-2 inhibition it was necessary to examine the mode of action for the most two promising compounds, tanshinone IIA (1) and carnosic acid (2). Both compounds (1 and 2) showed very promising virucidal activity with a most prominent inhibitory effect on viral adsorption rather than its replication. This recommended the predicted activity of the two compounds against the S protein of SARS-CoV-2 rather than its Mpro protein. Our results could be very promising to rearrange the previously mentioned compounds based on their actual inhibitory activities towards SARS-CoV-2 and to search for the reasons behind the great differences between their in silico and in vitro results against SARS-CoV-2. Finally, we recommend further advanced preclinical and clinical studies especially for tanshinone IIA (1) to be rapidly applied in COVID-19 management either alone or in combination with carnosic acid (2), rosmarinic acid (3), and/or salvianolic acid (4). Tanshinone IIA shows the most promising anti-SARS-CoV-2 biological activity: molecular docking, molecular dynamics, in vitro, and SAR studies.

Prevalence of viral pathogens in a sample of hospitalized Egyptian children with acute lower respiratory tract infections: a two-year prospective study.

Background: Viral pneumonias are a major cause of childhood mortality. Proper management needs early and accurate diagnosis. This study objective is to investigate the viral etiologies of pneumonia in children. Results: This prospective study enrolled 158 and 101 patients in the first and second year, respectively, and their mean age was 4.72 ± 2.89. Nasopharyngeal swabs were collected and subjected to virus diagnosis by reverse transcription polymerase chain reaction (RT-PCR). Viral etiologies of pneumonia were evidenced in 59.5% of the samples in the first year, all of them were affirmative for influenza A, 2 samples were affirmative for Human coronavirus NL63, and one for Human coronavirus HKU1. In the second year, 87% of patients had a viral illness. The most prevalent agents are human metapneumovirus which was detected in 44 patients (43.6%) followed by human rhinovirus in 35 patients (34.7%) and then parainfluenza-3 viruses in 33 patients (32.7%), while 14 patients had a confirmed diagnosis for both Pan coronavirus and Flu-B virus. Conclusions: Viral infection is prevalent in the childhood period; however, the real magnitude of viral pneumonia in children is underestimated. The reverse transcriptase polymerase chain reaction has to be a vital tool for epidemiological research and is able to clear the gaps in-between clinical pictures and final diagnoses.

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS-CoV-2.

Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-based small molecules. A series of pyrazine conjugates was synthesized by microwave-assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine-triazole conjugates (5 d-g) and (S)-N-(1-(benzo[d]thiazol-2-yl)-2-phenylethyl)pyrazine-2-carboxamide 12 i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).

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.

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2.

Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC50 close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.

New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2.

At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-e) by incorporating 1,2,3-triazole were synthesized via a modified microwave-assisted click chemistry technique. Among the synthesized conjugates, 4-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-fluoro-2-(trifluoromethyl)quinoline (10g) and 6-fluoro-4-(2-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)ethoxy)-2-(trifluoromethyl)quinoline (12c) show high potency against SARS-CoV-2. The selectivity index (SI) of compounds 10g and 12c also indicates the significant efficacy compared to the reference drugs.