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.

Pharmacokinetics of daclatasvir in Egyptian adolescents with genotype-4 HCV infection.

BACKGROUND: Daclatasvir has potent antiviral activity against HCV infection when used in combination with sofosbuvir, however, its pharmacokinetics have not been described in adolescents. The aim is to determine the pharmacokinetic parameters of daclatasvir in adolescents, and to develop a population pharmacokinetic (PopPK) model. METHODS: Seventeen adolescent patients with genotype-4 chronic HCV infection received once daily oral daclatasvir 60 mg in combination with 400 mg sofosbuvir for 12 weeks. Steady state concentrations were determined. Non-compartmental and population PK were determined. RESULTS: The average PK parameters calculated by non-compartmental analysis (NCA): maximum plasma concentration (Cmax), area under the curve (AUC), apparent oral volume of distribution (V/F), apparent oral clearance (CL/F) and half-life (T1/2) were 1,092 ng/ml, 11,178 ng/ml•h, 55 l, 4.5 l/h and 8.5 h, respectively. Daclatasvir was best described by one compartment structural PK model with zero order absorption and first-order elimination. The absorption rate constant (K0), V/F, and CL/F of the final PopPK model of daclatasvir were 1.5/h, 52 l and 4.7 l/h, respectively. Body weight and serum albumin had significant effect on the V/F parameter. CONCLUSIONS: Body weight and serum albumin were the major determinants of daclatasvir V/F in this population. PK parameters were comparable to those reported in adult HCV patients, demonstrating that 60 mg daclatasvir is an appropriate dose for adolescents. ClinicalTrials.gov NCT03540212.