Developing a mortality risk prediction model using data of 3663 hospitalized COVID-19 patients: a retrospective cohort study in an Egyptian University Hospital.

PURPOSE: Since the declaration of COVID-19 as a pandemic, a wide between-country variation was observed regarding in-hospital mortality and its predictors. Given the scarcity of local research and the need to prioritize the provision of care, this study was conducted aiming to measure the incidence of in-hospital COVID-19 mortality and to develop a simple and clinically applicable model for its prediction. METHODS: COVID-19-confirmed patients admitted to the designated isolation areas of Ain-Shams University Hospitals (April 2020-February 2021) were included in this retrospective cohort study (n = 3663). Data were retrieved from patients' records. Kaplan-Meier survival and Cox proportional hazard regression were used. Binary logistic regression was used for creating mortality prediction models. RESULTS: Patients were 53.6% males, 4.6% current smokers, and their median age was 58 (IQR 41-68) years. Admission to intensive care units was 41.1% and mortality was 26.5% (972/3663, 95% CI 25.1-28.0%). Independent mortality predictors-with rapid mortality onset-were age ≥ 75 years, patients' admission in critical condition, and being symptomatic. Current smoking and presence of comorbidities particularly, obesity, malignancy, and chronic haematological disorders predicted mortality too. Some biomarkers were also recognized. Two prediction models exhibited the best performance: a basic model including age, presence/absence of comorbidities, and the severity level of the condition on admission (Area Under Receiver Operating Characteristic Curve (AUC) = 0.832, 95% CI 0.816-0.847) and another model with added International Normalized Ratio (INR) value (AUC = 0.842, 95% CI 0.812-0.873). CONCLUSION: Patients with the identified mortality risk factors are to be prioritized for preventive and rapid treatment measures. With the provided prediction models, clinicians can calculate mortality probability for their patients. Presenting multiple and very generic models can enable clinicians to choose the one containing the parameters available in their specific clinical setting, and also to test the applicability of such models in a non-COVID-19 respiratory infection.

Emotional distress symptoms and their determinants: screening of non-clinical hospital staff in an Egyptian University hospital.

BACKGROUND: Non-clinical hospital staff were rarely studied despite their potential exposure to workplace stressors. We aimed to measure the prevalence of depression, anxiety, and stress (emotional distress symptoms) and determine their association with perceived job stress level and socioeconomic factors among non-clinical hospital staff. METHODS: This cross-sectional study was conducted in Ain-Shams University Hospitals from March to May 2019. Tools were the Arabic Depression, Anxiety, and Stress Scale-21, Workplace Stress Scale, and Socioeconomic status scale. Independent correlates were determined using multivariable ordinal regression. RESULTS: Out of 462 participants, 72.5% reported receiving insufficient income and 54.8% showed Effort-reward imbalance. Job stress was scored as severe/potentially dangerous by 30.1%. The prevalence of depression, anxiety, and stress were 67.5, 69.0, and 51.7%; and the severe/extremely severe levels were 20.8, 34.6, and 17.6% respectively. Across all the severity levels, the likelihood of depression, anxiety, and stress were progressively higher with more serious levels of income insufficiency [in debt versus able to save, OR:5.82 (95%CI:2.35-14.43), OR:3.84 (95%CI:1.66-8.91), and OR:3.01 (95%CI:1.20-7.55) respectively] and with higher job stress levels. Specifically, the likelihood of depression, anxiety, and stress increased by 74, 56, and 53% respectively with feelings of unpleasant/unsafe work conditions and by 64, 38, and 62% respectively with the presence of work-life conflict; while the likelihood of depression and stress increased by 32 and 33% respectively when there was difficult communication with superiors; and only the likelihood of depression increased by 23% with underutilization of skills. CONCLUSION: Non-clinical hospital staff were commonly affected by emotional distress symptoms with high rates of severe/very severe levels, and they often considered their workplace stress as severe/potentially dangerous. Workplace stress and income insufficiency were strong correlates with emotional distress symptoms. Decreasing work-life conflict, enhancing leadership skills, and mitigation of the economic hardship are needed.

Synthesis, biological evaluation and X-ray analysis of bicalutamide sulfoxide analogues for the potential treatment of prostate cancer.

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of sulfoxide derivatives were prepared and their antiproliferative activity evaluated in vitro against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP and VCap). Bicalutamide and enzalutamide were used as positive controls. Compound 28 displayed significant enhancement in anticancer activity across the four PC cell lines with IC50 = 9.09 - 31.11 µM compared to the positive controls: bicalutamide (IC50 = 45.20 -51.61 µM) and enzalutamide (IC50 = 11.47 - 53.04 µM). Sulfoxide derivatives of bicalutamide were prepared efficiently from the corresponding sulfides using only one equivalent of mCPBA, limiting the reaction time to 15-30 min and maintaining the temperature at 0 °C. Interestingly, three pairs of sulfoxide diastereomers were separated and NMR comparison of their diastereotopic methylene (CH2) group is presented. X-ray diffraction crystal structure analysis provided relative configuration assignment at the chiral sulfur and carbon centres. Molecular modelling study of the four diastereoisomers of compound 28 is described.

SARS-Co-V2 infection in never, former, and current tobacco/nicotine users: a cohort study of 4040 Egyptian healthcare workers.

BACKGROUND: Smoking negatively impacts COVID-19 severity and adverse outcomes. Evidence on whether smoking is associated with SARS-Co-V2 infection and having a positive test is scarce, particularly from low-and middle-income countries, where most of the world's billion smokers live. The inconsistency in relevant findings calls for study designs and analyses to account for possible confounders including background characteristics and pre-existing co-morbidities, to disentangle the specific effect of smoking. In healthcare workers (HCWs) the frequency of exposure to COVID-19 cases adds another layer of risk that was not factored in previous studies. We examined the association of HCWs' tobacco/nicotine use (never, former, and current use) with having a positive SARS-Co-V2 test result and symptoms suggestive of infection, accounting for demographics, exposures, and co-morbidities. METHODS: A prospective cohort study of 4040 healthcare workers with baseline and follow-up screening took place during April-June 2020 in 12 healthcare facilities in Cairo, Egypt. Data on demographics, tobacco/nicotine use (manufactured or roll-your-own cigarettes, waterpipe tobacco, and electronic devices), co-morbidities, symptoms, exposures, and SARS-Co-V2 investigations were analyzed. Multinomial and multivariable logistic regression analyses were performed. RESULTS: Overall, 270/4040 (6.7, 95%CI: 5.9-7.5) had positive SARS-CoV-2 tests, 479 (11.9%) were current and 79 (2.0%) were former tobacco/nicotine users. The proportion of positive tests was 7.0% (243/3482, 95%CI: 6.1-7.8) among never, 5.1% (4/79, 95%CI: 0.1-10.0) among former, and 4.8% (23/479, 95%CI: 2.9-6.7) among current users. HCWs' SARS-CoV-2 test results did not vary significantly by single/multiple or daily/non-daily tobacco/nicotine use. Compared to never users, former users were more likely to self-report a pre-existing medical condition (ORadjusted1.87, 95%CI: 1.05-3.33, p = 0.033), and to experience symptoms suggestive of COVID-19 (ORadjusted1.76, 95%CI: 1.07-2.90, p = 0.027). After adjustment, former (ORadjusted0.45, 95%CI: 0.11-1.89, p = 0.273) and current (ORadjusted0.65, 95%CI: 0.38-1.09, p = 0.101) tobacco/nicotine use was not associated with HCWs' SARS-CoV-2 positive test results. CONCLUSIONS: This is the first report on this association from low- and middle-income countries with high tobacco/nicotine use prevalence. In this HCW cohort, having a positive SARS-CoV-2 test was not associated with tobacco/nicotine use after accounting for demographics, exposures, and co-morbidities. Additional population-based studies could use such preliminary evidence to investigate this controversial association.

Epidemiology of Severe Acute Respiratory Infection (SARI) Cases at a sentinel site in Egypt, 2013-15.

BACKGROUND: Sentinel surveillance for severe acute respiratory infection (SARI) in Egypt began in 2006 and occurs at eight sites. Avian influenza is endemic, and human cases of influenza A (H5N1) have been reported annually since 2006. This study aimed to describe the epidemiology of SARI at a major sentinel site in the country. METHODS: Data included in the study were collected from a major SARI sentinel site in Egypt during three consecutive years (2013-15). RESULTS: A total of 1254 SARI patients conforming to the WHO case definition were admitted to the sentinel site, representing 5.6% of admitted patients for all causes and 36.6% of acute respiratory infection patients. A total of 99.7% of the patients were tested, and 21.04% tested positive; 48.7% of cases involved influenza A viruses, while 25% involved influenza B. The predominant age group was under 5 years of age, accounting for 443 cases. The seasonality of the influenza data conformed to the Northern Hemisphere pattern. CONCLUSIONS: The present study's results show that SARI leads to substantial morbidity in Egypt. There is a great need for high-quality data from the SARI surveillance system in Egypt, especially with endemic respiratory threats such as influenza A (H5N1) in Egypt.

Synthesis and Biological Evaluation of Bicalutamide Analogues for the Potential Treatment of Prostate Cancer.

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of 15 bicalutamide analogues (sulfide, deshydroxy, sulfone, and O-acetylated) were prepared and their antiproliferative activity evaluated against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP, and VCap). Bicalutamide and enzalutamide were used as positive controls. Seven of these compounds displayed remarkable enhancement in anticancer activity across the four PC cell lines. The deshydroxy analogue (16) was the most active compound with IC50 = 6.59-10.86 µM. Molecular modeling offers a plausible explanation of the higher activity of the sulfide analogues compared to their sulfone counterparts.

Structure-Based Virtual Screening, Synthesis and Biological Evaluation of Potential FAK-FAT Domain Inhibitors for Treatment of Metastatic Cancer.

Focal adhesion kinase (FAK) is a tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. In cancer cells, FAK promotes the progression and metastasis of tumours. In this study, we used structure-based virtual screening to filter a library of more than 210K compounds against the focal adhesion targeting FAK-focal adhesion targeting (FAT) domain to identify 25 virtual hit compounds which were screened in the invasive breast cancer line (MDA-MB-231). Most notably, compound I showed low micromolar antiproliferative activity, as well as antimigratory activity. Moreover, examination in a model of triple negative breast cancer (TNBC), revealed that, despite not effecting FAK phosphorylation, compound I significantly impairs proliferation whilst impairing focal adhesion growth and turnover leading to reduced migration. Further optimisation and synthesis of analogues of the lead compound I using a four-step synthetic procedure was performed, and analogues were assessed for their antiproliferative activity against three breast cancer (MDA-MB-231, T47D, BT474) cell lines and one pancreatic cancer (MIAPaCa2) cell line. Compound 5f was identified as a promising lead compound with IC50 values in the range of 4.59-5.28 µM in MDA-MB-231, T47D, BT474, and MIAPaCa2. Molecular modelling and pharmacokinetic studies provided more insight into the therapeutic features of this new series.

Polyfluoroaromatic stavudine (d4T) ProTides exhibit enhanced anti-HIV activity.

Human Immunodeficiency Virus (HIV) damages the immune system and leads to the life-threatening acquired immunodeficiency syndrome (AIDS). Despite the advances in the field of antiretroviral treatment, HIV remains a major public health challenge. Nucleosides represent a prominent chemotherapeutic class for treating viruses, however their cellular uptake, kinase-mediated activation and catabolism are limiting factors. Herein, we report the synthesis and in vitro evaluation of stavudine (d4T) ProTides containing polyfluorinated aryl groups against two strains; HIV-1 (IIIB) and HIV-2 (ROD). ProTide 5d containing a meta-substituted pentafluorosulfanyl (3-SF5) aryl group showed superior antiviral activity over the parent d4T and the nonfluorinated analogue 5a. ProTide 5d has low nanomolar antiviral activity; (IC50 = 30 nM, HIV-1) and (IC50 = 36 nM, HIV-2) which is over tenfold more potent than d4T. Interestingly, ProTide 5d showed a significantly high selectivity indices with SI = 1753 (HIV-1) and 1461 (HIV-2) which is more than twice that of the d4T. All ProTides were screened in wild type as well as thymidine kinase deficient (TK-) cells. Enzymatic activation of ProTide 5d using carboxypeptidase Y enzyme and monitored using both 31P and 19F NMR is presented.

Association between hepatitis C infection and cerebro-cardiovascular disease: analysis of a national population-based survey in Egypt.

OBJECTIVES: To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro-cardiovascular (CCV) disease. METHODS: The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25-59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. RESULTS: 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV-RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27-2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23-1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62-4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. CONCLUSION: The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV-positive reactors for preventive and curative programmes addressing extrahepatic complications.

Hypertension and associated cardiovascular risk factors among urban slum dwellers in Egypt: a population-based survey.

BACKGROUND: The economic deprivation of most slum inhabitants, and the lack of services and facilities may increase their vulnerability to unhealthy lifestyles and cardiovascular diseases. AIMS: This study aimed to determine the prevalence of modifiable risk factors for cardiovascular diseases in slum residents in Cairo, Egypt and evaluate their association with hypertension. METHODS: A household cluster survey was conducted in Mansheiet Nasser, a large slum area in Cairo. The study included 984 adult participants. The World Health Organization STEPS instrument for noncommunicable disease risk factor surveillance was used to determine the prevalence of smoking, fruit/vegetable consumption, overweight/obesity, physical activity, diabetes and hypertension. RESULTS: Smoking, insufficient fruit/vegetable consumption, low physical activity and diabetes were reported by 43.4%, 92.2%, 98.4% and 8.7% of the sample respectively. The prevalence of hypertension and overweight/obesity were 31.2% and 73.0% respectively. Most of the participants (83.8%) had ≥ 3 cardiovascular risk factors. A significantly higher proportion of men smoked, engaged in less physical activity, had diabetes and had multiple risk factors. Hypertension was significantly associated with age 30-< 50 years (OR = 3.04, 95% CI: 1.66-5.58), age ≥ 50 years (OR = 12.5, 95% CI: 6.71-23.26), overweight (OR = 1.58, 95% CI: 1.0-62.35), obesity (OR = 2.23, 95% CI: 1.49-3.35), low fruit/vegetable consumption (OR = 1.88, 95% CI: 1.02-3.48), and diabetes (OR = 1.77, 95% CI: 1.08-2.92). CONCLUSIONS: Urban slum dwellers in Mansheiet Nasser have an increased vulnerability to cardiovascular diseases compared with the Egyptian population. Measures are needed to improve their lifestyles and reduce their risk of cardiovascular diseases.

7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer.

The clinically used androgen receptor (AR) antagonists (bicalutamide, flutamide and nilutamide) bind with low affinity to AR and can induce escape mechanisms. Furthermore, under AR gene amplification or mutation conditions they demonstrate agonist activity and fail to inhibit AR, causing relapse into castration resistant prostate cancer (CRPC). Discovery of new scaffolds distinct from the 4-cyano/nitro-3-(trifluoromethyl)phenyl group common to currently used antiandrogens is urgently needed to avoid cross-resistance with these compounds. In this study, a series of twenty-nine 7-substituted umbelliferone derivatives was prepared and their antiproliferative activities were evaluated. The most active compound 7a demonstrated submicromolar inhibitory activity in the human prostate cancer cell line (22Rv1); IC50=0.93 µM which represents a 50 fold improvement over the clinical antiandrogen bicalutamide (IC50=46 µM) and a more than 30 fold improvement over enzalutamide (IC50=32 µM). Interestingly, this compound showed even better activity against the human breast cancer cell line (MCF-7); IC50=0.47 µM. Molecular modelling studies provided a plausible theoretical explanation for our findings.

ProTides of BVdU as potential anticancer agents upon efficient intracellular delivery of their activated metabolites.

Nucleosides represent a major chemotherapeutic class for treating cancer, however their limitations in terms of cellular uptake, nucleoside kinase-mediated activation and catabolism are well-documented. The monophosphate pro-nucleotides known as ProTides represents a powerful strategy for bypassing the dependence on active transport and nucleoside kinase-mediated activation. Herein, we report the structural tuning of BVdU ProTides. Forty six phosphoramidates were prepared and biologically evaluated against three different cancer cell lines; murine leukemia (L1210), human CD4+ T-lymphocyte (CEM) and human cervical carcinoma (HeLa). Twenty-fold potency enhancement compared to BVdU was achieved against L1210 cells. Interestingly, a number of ProTides showed low micromolar activity against CEM and HeLa cells compared to the inactive parent BVdU. The ProTides showed poor, if any measurable toxicity to non-tumourigenic human lung fibroblast cell cultures. Separation of four pairs of the diastereoisomeric mixtures and comparison of their spectral properties, biological activities and enzymatic activation rate is reported.

Rational design and synthesis of novel anti-prostate cancer agents bearing a 3,5-bis-trifluoromethylphenyl moiety.

Prostate cancer is a major cause of male death worldwide and the identification of new and improved treatments is constantly required. Among the available options, different non-steroidal androgen receptor (AR) antagonists are approved also to treat castration-resistant forms. Most of these drugs show limited application due to the development of resistant mutants of their biological target. Following docking-based studies on a homology model for the AR open antagonist conformation, a series of novel 3,5-bis-trifluoromethylphenyl compounds was designed with the aim to improve the antiproliferative activity of anti-androgen drugs bicalutamide and enzalutamide. The new structural modifications might impede the receptor to adopt its closed agonist conformation also in the presence of adaptive mutations. Among the novel compounds synthesised, several displayed significantly improved in vitro activity in comparison with the parent structures, with IC50 values in the low micromolar range against four different prostate cancer cell lines (LNCaP, VCaP, DU-145, 22Rv1). Selected hits demonstrated full AR antagonistic behaviour and promising candidates for further development were identified.

Prognostic factors of treatment among patients with multidrug-resistant tuberculosis in Egypt.

BACKGROUND/PURPOSE: Multidrug-resistant tuberculosis (MDR-TB) represents 5% of TB cases globally. In Egypt, it represents 11.4% of TB cases (2.2% of new and 38.2% of previously treated). Our objectives were to evaluate the treatment outcomes and determine the associated prognostic factors among the first national treatment cohort of MDR-TB from 2006 to 2010. METHODS: All patients diagnosed with MDR-TB from July 2006 to December 2010 who were admitted to Abbassia Chest Hospital, the first Egyptian national center established for MDR-TB treatment, were included. They were followed up clinically, radiologically, and bacteriologically by sputum smear, culture, and drug-susceptibility testing at regular intervals. Individualized treatment regimens were prescribed according to each patient's drug-susceptibility testing and the drug treatment history. Patients received at least five effective drugs. Outcome rates, and crude and adjusted odds ratios of unsuccessful outcomes were calculated. RESULTS: The number of bacteriologically proven MDR-TB patients was 228, of which 225 were pulmonary cases. Half of the cases showed moderate or extensive lung lesions, and 15.8% were diabetics. A total of 158 (119 cured and 39 completed treatment) patients achieved successful outcome (69.3%), 16 (7.1%) failed treatment, 27 (11.8%) were lost to follow up, and 27 (11.8%) died. Predictors of unsuccessful outcome were delay in sputum culture conversion to 2 months or more, moderate or extensive lung lesions, and a history of diabetes. CONCLUSION: A treatment success rate of approximately 69% was achieved with the first national treatment cohort of MDR-TB under the Egyptian program. Predictors of unsuccessful treatment were delayed culture conversion, moderate or extensive lung affection, and diabetes.

ProTides of N-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents.

The flavin-dependent thymidylate synthase X (ThyX), rare in eukaryotes and completely absent in humans, is crucial in the metabolism of thymidine (a DNA precursor) in many microorganisms including several human pathogens. Conserved in mycobacteria, including Mycobacterium leprae, and Mycobacterium tuberculosis, it represents a prospective anti-mycobacterial therapeutic target. In a M. tuberculosis ThyX-enzyme inhibition assay, N-(3-(5-(2'-deoxyuridine-5'-phosphate))prop-2-ynyl)octanamide was reported to be the most potent and selective 5-substituted 2'-deoxyuridine monophosphate analogue. In this study, we masked the two charges at the phosphate moiety of this compound using our ProTide technology in order to increase its lipophilicity and then allow permeation through the complex mycobacterial cell wall. A series of N-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide phosphoroamidates were chemically synthesized and their biological activity as potential anti-tuberculars was evaluated. In addition to mycobacteria, several DNA viruses depend on ThyX for their DNA biosynthesis, thus these prodrugs were also screened for their antiviral properties.

Impact of COVID-19 pandemic on cancer care: A cross-sectional study of Egyptian patients' perspectives and concerns.

BACKGROUND: Worldwide, COVID-19 greatly reduced healthcare accessibility and utilization by non-COVID patients including cancer. This study aimed to quantify and characterize cancer care adjustments experienced by cancer patients/survivors; and to explore their concerns, beliefs, and knowledge regarding COVID-19. METHODS: A cross-sectional study was conducted using a questionnaire distributed through social media patients' groups (June-December 2020). Questionnaire included basic information, care adjustments (in "care provision" and in "treatment plan"), and patients' concerns, beliefs, and knowledge. Data description and analysis were done. RESULTS: Out of 300 participants, there were 68.0% on-treatment and 32.0% in follow-up stage. Care adjustments were reported by 29.7%; mostly in care provision (27.3%) rather than treatment plan (4.9%). Adjustments were less likely to occur when healthcare facility was in governorate other than that of residence (OR:0.53, 95%CI:0.30-0.96, P = 0.037) and more likely with long-standing diagnosis (≥12 months) compared with recent (<3 months) (adjusted-OR:4.13, 95%CI:1.19-14.34, P = 0.026). Lower proportion of on-treatment patients used remote consultation than patients in follow-up [4.4% versus 17.7%, P < 0.001]. Patients were concerned about fulfilling their care visits more than the probable COVID-19 infection (72.3%). It was uncommon to feel that the risk of COVID-19 infection is higher in care places than in the community (27.3%) or to feel safe with remote consultations (34.3%). However, patients increased their infection control practice (64.0%) and the majority were aware of their increased susceptibility to complications (86.0%). Somewhat, they were also concerned about the care quality (57.3%). Many had adequate access to COVID-19 information (69.0%) and their main sources were the Ministry of Health webpage and ordinary media (radio/TV). CONCLUSION: Cancer patients were primarily concerned about fulfilling their planned care and COVID-19 infection was less appreciated. POLICY SUMMARY: Launching of a policy for enhancement of telemedicine experience through more patients' engagement-as essential stakeholders-may be required. To heighten pandemic resilience for cancer care in Egypt, more investment in establishing specialized end-to-end cancer care facilities that ensure continuity of care may be justified.

SARS-CoV-2 seroconversion among 4040 Egyptian healthcare workers in 12 resource-limited healthcare facilities: A prospective cohort study.

BACKGROUND: We examined Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) seroconversion incidence and risk factors 21 days after baseline screening among healthcare workers (HCWs) in a resource-limited setting. METHODS: A prospective cohort study of 4040 HCWs took place at 12 university healthcare facilities in Cairo, Egypt; April-June 2020. Follow-up exposure and clinical data were collected through online survey. SARS-CoV-2 testing was done using rapid IgM and IgG serological tests and reverse transcriptase-polymerase chain reaction (RT-PCR) for those with positive serology. Cox proportional hazards modelling was used to estimate adjusted hazard ratios (HR) of seroconversion. RESULTS: 3870/4040 (95.8%) HCWs tested negative for IgM, IgG and PCR at baseline; 2282 (59.0%) returned for 21-day follow-up. Seroconversion incidence (positive IgM and/or IgG) was 100/2282 (4.4%, 95% CI:3.6-5.3), majority asymptomatic (64.0%); daily hazard of 0.21% (95% CI:0.17-0.25)/48 746 person-days of follow-up. Seroconversion was: 4.0% (64/1596; 95% CI:3.1-5.1) among asymptomatic; 5.3% (36/686; 95% CI:3.7-7.2) among symptomatic HCWs. Seroconversion was independently associated with older age; lower education; contact with a confirmed case >15 min; chronic kidney disease; pregnancy; change/loss of smell; and negatively associated with workplace contact. CONCLUSIONS: Most seroconversions were asymptomatic, emphasizing need for regular universal testing. Seropositivity was three-fold that observed at baseline. Cumulative infections increased nationally by a similar rate, suggesting HCW infections reflect community not nosocomial transmission.

Universal COVID-19 screening of 4040 health care workers in a resource-limited setting: an Egyptian pilot model in a university with 12 public hospitals and medical centers.

BACKGROUND: The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care workers (HCWs), particularly in resource-limited settings, remains unclear. To address this concern, universal (non-symptom-based) screening of HCWs was piloted to determine the proportion of SARS-CoV-2 infection and the associated epidemiological and clinical risk factors at a large public health care facility in Egypt. METHODS: Baseline voluntary screening of 4040 HCWs took place between 22 April and 14 May 2020 at 12 hospitals and medical centres in Cairo. Epidemiological and clinical data were collected using an online survey. All participants were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) and rapid IgM and IgG serological tests. RESULTS: Of the 4040 HCWs screened, 170 [4.2%; 95% confidence interval (CI): 3.6-4.9] tested positive for SARS-CoV-2 by either of the three tests (i.e. infected); 125/170 (73.5%) tested PCR-positive. Most infected HCWs were nurses (97/170, 57.5%). Median age of infected HCWs was 31.5 [interquartile range (IQR): 27.0-41.3] years. Of infected HCWs, 78 (45.9%) reported contact with a suspected case and 47 (27.6%) reported face-to-face contact within 2 m with a confirmed case. The proportion of infection among symptomatic HCWs (n = 54/616) was 8.8% (95% CI: 6.7-11.3); 6/54 (11.1%) had fever ≥38°C and 7/54 (13.0%) reported severe symptoms. Most infected HCWs were asymptomatic (116/170, 68.2%). The proportion of infection among asymptomatic HCWs (n = 116/3424) was 3.4% (95% CI: 2.8-4.0). CONCLUSIONS: The high rate of asymptomatic infections among HCWs reinforces the need for expanding universal regular testing. The infection rate among symptomatic HCWs in this study is comparable with the national rate detected through symptom-based testing. This suggests that infections among HCWs may reflect community rather than nosocomial transmission during the early phase of the COVID-19 epidemic in Egypt.

Discovery of a novel HCV helicase inhibitor by a de novo drug design approach.

Herein we report a successful application of a computer-aided design approach to identify a novel HCV helicase inhibitor. A de novo drug design methodology was used to generate an initial set of structures that could potentially bind to a putative binding site. Further structure refinement was carried out through docking a series of focused virtual libraries. The most promising compound was synthesised and it exhibited a submicromolar inhibition of the HCV helicase.

Discovery of deshydroxy bicalutamide derivatives as androgen receptor antagonists.

Deshydroxy propioanilides were synthesised by Michael addition reaction between substituted thiophenols onto four different phenylacrylamide derivatives to give twenty-three novel deshydroxy bicalutamide derivatives lacking the central hydroxyl group. The antiproliferative activities of these compounds were evaluated against human prostate cancer cell lines and thirteen compounds showed better inhibitory activities (IC50 = 2.67-13.19 µM) compared to bicalutamide (IC50 = 20.44 µM) in LNCaP. Remarkably, novel double branched bicalutamide analogues (27 and 28) were isolated as major by-products and found to have the best activity across three human prostate cancer cell lines (LNCaP, VCaP and PC3). The most active compound 28 shows sub-micromolar activity (IC50 = 0.43 µM in LNCaP), which represents more than 40-fold improvement over the clinical anti-androgen bicalutamide (IC50 = 20.44 µM) and a more than 3 fold improvement over enzalutamide (IC50 = 1.36 µM). Moreover, strong reduction of PSA expression in LNCaP cells upon treatment with compounds 27, 28 and 33 was observed during qPCR analysis, confirming their AR antagonist activity. Molecular modelling studies revealed a novel binding mode of these structurally distinct double branched analogues within the ligand binding domain (LBD) of the androgen receptor.