Characterization of recurrent cytomegalovirus reactivations post allogenic stem cell transplantation in a population with high seropositivity.

OBJECTIVES: This study aimed to characterize incidences of CMV reactivations within one year post-allo-SCT and identify risk factors for CMV second reactivation episode in population with high seropositivity where first CMV reactivation episode deemed to be high. METHODS: This retrospective cohort study analyzed data from 359 allo-SCT patients aged 14 and older admitted to a tertiary academic hospital. Data on demographic and clinical factors, CMV serostatus, conditioning regimens, graft-versus-host disease prophylaxis, engraftment time, and CMV reactivations were collected. RESULTS: First and second CMV reactivations occurred in 88.9% and 18.4% of post-allo-SCT patients respectively. Patients were stratified into two groups based on primary disease necessitating allo-SCT, patients with malignant (Group 1) and non-malignant (Group 2) hematological disease. Factors associated with the second reactivation included cord blood as a stem cell source, human leukocyte antigen mismatch, acute graft-versus-host disease, and hematological malignancies. Patients with non-malignant hematological disease displayed better outcomes, including a higher rate of spontaneous clearance of first CMV reactivation (70% versus 49.4%) and lower rates of second CMV reactivation (9.6% versus 31%) than those with malignant hematological disease. The one-year overall survival rate was 87.7% (95.5% in non-malignant hematological disease and 78.13% in malignant hematological disease). CONCLUSION: Our findings are concordant with previous local study in regard to high rate of first CMV reactivation post-allo-SCT. It appears that patients with nonmalignant hematological disease had better outcomes, such as lower second CMV reactivation and higher survival rates compared to patients with malignant hematological disease. Further investigation is needed to identify other factors affecting recurrent CMV reactivations in allo-SCT in patients with malignant hematological disease.

Clinical Characteristics and Outcome of Candidemia: Experience from a Tertiary Referral Center in Saudi Arabia.

Background: Candida bloodstream infections cause significant excess morbidity and mortality in the health-care setting. There is limited evidence regarding Candida species causing invasive infections in Saudi Arabia. Objective: To identify Candida species causing bloodstream infection and determine the clinical outcome and factors associated with mortality in a tertiary center in Saudi Arabia. Materials and Methods: This retrospective study included all cases of positive blood culture for Candida in patients admitted to King Abdulaziz Medical City, a tertiary care center in Riyadh, Saudi Arabia, between January 1, 2013 and June 30, 2019. Results: A total of 532 patients with candidemia were identified (male: 55.4%; mean age: 54 ± 26.2 years). The most common Candida species isolated was Candida albicans (26.7%), followed by Candida glabrata (22.7%), Candida parapsilosis (22.2%), and Candida tropicalis (18.4%). Non-albicans candidemia was more common in patients with diabetes (76.7%; P = 0.0560), neutropenia (89.8%; P = 0.0062), recent exposure to fluconazole (85.7%; P = 0.0394), and active chemotherapy (83.1%; P = 0.0128). In non-albicans, susceptibility to fluconazole varied from 95.9% with C. tropicalis to 41.5% with C. parapsilosis; nonetheless, all species were highly susceptible to echinocandins. The overall 30- and 90-day mortality rates were 39.9% and 56.4%, respectively. The mortality rate was nonsignificantly higher with non-albicans species at 30 days (41.2% vs. 35.9%; P = 0.2634) and 90 days (58.2% vs. 51.4%; P = 0.1620). Conclusion: This study found a changing pattern in the Candida species causing bloodstream infections and an epidemiological shift toward more non-albicans Candida species in Saudi Arabia.

Safety and immunogenicity of ChAdOx1 MERS vaccine candidate in healthy Middle Eastern adults (MERS002): an open-label, non-randomised, dose-escalation, phase 1b trial.

BACKGROUND: ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. METHOD: MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18-50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. FINDINGS: Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. INTERPRETATION: The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.

Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia.

BACKGROUND: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients. METHODS: A total of 11,703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates. RESULTS: Overall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the reported COVID-19 infection rate. Among HCWs, 7.5% (4.95-10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population. INTERPRETATION: Our study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions. This indicates the prevalence of asymptomatic or mild unreported COVID-19 cases.

Infections and patterns of antibiotic utilization in support and comfort care patients: A tertiary care center experience.

PURPOSE: Little is known regarding the burden of infections and clinical practice towards hospitalized patients with limits on life-sustaining measures. We aim to describe the infectious syndromes, clinical care, the emergence of multi-drug resistant organisms and outcomes in this population. PATIENTS AND METHODS: Retrospective cohort of patients labeled as support or comfort care in a tertiary care center between 2016-2019. RESULTS: A total of 347 patients were included with a mean age of 68.5 years, who were predominantly males (59.94%), bedbound (69.74%), on tube feeding (66.86%), and required indwelling urinary catheters (61.96%). The total number of admissions during the first year was 498, with the mean length of stay being 30 days. The number of infectious syndromes identified during that period was 821episodes, with a mean of 2 infectious syndromes per admission. The most common infection identified was pneumonia (41.66%) followed by urinary tract infections (27.16%). A total of 3891 microbiological cultures were taken with a mean of 5 cultures per infectious syndrome. The most commonly identified pathogens were Gram-negative bacteria (61.03%), with a high rate of multidrug-resistant organisms (MDROs) (48.53%). The one-year mortality was 86.4%. Using carbapenem antibiotic and pneumonia were the independent predictors used for the MDROs. CONCLUSION: Our study reflects the high burden of infections, antimicrobial resistance, and hospital admissions among a population with limited life expectancy. A consensus regarding investigating and managing of infectious syndromes, and antimicrobial prescription is needed to reduce the harms associated with overuse of antimicrobials.