SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, the host cell transcriptome analysis suggests that the mutant N protein produces dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein to modulations of host-virus interactions and underline the potential of the nucleocapsid protein as a drug target during infection.

Clinical Predictors of COVID-19 Mortality Among Patients in Intensive Care Units: A Retrospective Study.

OBJECTIVE: The ongoing pandemic of the coronavirus disease 2019 (COVID-19), which originated from Wuhan, China, has been identified to be caused by the novel beta coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has been spreading rapidly worldwide within just a few months. Our aims were to analyze clinical and laboratory abnormalities in ICU patients with COVID-19, in order to define which predictors can distinguish between those who are at higher risk of developing fatal versus non-fatal forms of the disease. METHODS: A descriptive cross-sectional survey was used; demographics, comorbidities, symptoms, laboratory parameters at ICU admission, and clinical outcomes for the adult patients admitted to ICU were collected from five hospitals in Saudi Arabia. RESULTS: A total of 86 patients with COVID-19 admitted in ICU, 50 patients died, 23 recovered, and 13 were still admitted, with a mortality rate of 58.1%. Septic shock (OR (95% CI): 58.1 (5.97-7812.8), p < 0.001) and acute kidney injury (AKI) (OR (95% CI): 7.279 (1.191-65.43), p = 0.032) had a significant impact on mortality. Cox proportional-hazards regression analysis revealed that septic shock (HR (95% CI): 9.502 (2.958-30.524), p < 0.001) and neutrophil count (HR (95% CI): 1.053 (1.023-1.085), p < 0.001) were significant predictors for mortality. CONCLUSION: Septic shock, AKI, and high neutrophil count were found to be predictive of death in these patients. Further studies are needed to aid efficient recognition and management of severe COVID-19 patients in our population. .

Clinical, epidemiological, and laboratory characteristics of mild-to-moderate COVID-19 patients in Saudi Arabia: an observational cohort study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from China in December 2019 and has presented as a substantial and serious threat to global health. We aimed to describe the clinical, epidemiological, and laboratory findings of patients in Saudi Arabia infected with SARS-CoV-2 to direct us in helping prevent and treat coronavirus disease 2019 (COVID-19) across Saudi Arabia and around the world. MATERIALS AND METHODS: Clinical, epidemiological, laboratory, and radiological characteristics, treatment, and outcomes of pediatric and adult patients in five hospitals in Riyadh, Saudi Arabia, were surveyed in this study. RESULTS: 401 patients (mean age 38.16 ± 13.43 years) were identified to be SARS-CoV-2 positive and 80% of cases were male. 160 patients had moderate severity and 241 were mild in severity. The most common signs and symptoms at presentation were cough, fever, fatigue, and shortness of breath. Neutrophil and lymphocyte counts, aspartate aminotransferase, C-reactive protein, and ferritin were higher in the COVID-19 moderate severity patient group. Mild severity patients spent a shorter duration hospitalized and had slightly higher percentages of abnormal CT scans and X-ray imaging. CONCLUSIONS: This study provides an understanding of the features of non-ICU COVID-19 patients in Saudi Arabia. Further national collaborative studies are needed to streamline screening and treatment procedures for COVID-19.

Clinical characteristics of non-intensive care unit COVID-19 patients in Saudi Arabia: A descriptive cross-sectional study.

INTRODUCTION: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is a global health concern. It has affected more than 5 million patients worldwide and resulted in an alarming number of deaths globally. While clinical characteristics have been reported elsewhere, data from our region is scarce. We investigated the clinical characteristics of mild to moderate cases of COVID-19 in Saudi Arabia. METHODS: This is a descriptive, cross-sectional study. Data of 401 confirmed COVID-19 patients were collected from 22 April 2020 to 21 May 2020 at five tertiary care hospitals in Riyadh, Saudi Arabia. The patients were divided into four groups according to age, Group 1: 0-<18 years, Group 2: 18-<50 years, Group 3: 50-60 years, and Group 4: >60 years; and their clinical symptoms were compared. RESULTS: The median (IQR) age in years was 10.5 (1.5-16) in group I, 34 (29-41) in group II, 53 (51-56) in group III, and 66 (61-76) in group IV. Most patients were male (80%, n = 322) and of Arabian or Asian descent. The median length of stay in the hospital was 10 (8-17) days (range 3-42 days). The most common symptoms were cough (53.6%), fever (36.2%), fatigue (26.4%), dyspnea (21.9%), and sore throat (21.9%). Hypertension was the most common underlying comorbidity (14.7%), followed by obesity (11.5%), and diabetes (10%). Hypertensive patients were less likely to present with shortness of breath, cough, sputum, diarrhea, and fever. CONCLUSION: There was no significant difference in the symptoms among different age groups and comorbidities were mostly seen in the older age group. Interestingly, hypertensive patients were found to have milder symptoms and a shorter length of stay. Further larger collaborative national studies are required to effectively understand clinical characteristics in our part of the world to efficiently manage and control the spread of SARS-CoV-2.

A genetic barcode of SARS-CoV-2 for monitoring global distribution of different clades during the COVID-19 pandemic.

OBJECTIVE: The SARS-CoV-2 pathogen has established endemicity in humans. This necessitates the development of rapid genetic surveillance methodologies to serve as an adjunct with existing comprehensive, albeit though slower, genome sequencing-driven approaches. METHODS: A total of 21,789 complete genomes were downloaded from GISAID on May 28, 2020 for analyses. We have defined the major clades and subclades of circulating SARS-CoV-2 genomes. A rapid sequencing-based genotyping protocol was developed and tested on SARS-CoV-2-positive RNA samples by next-generation sequencing. RESULTS: We describe 11 major mutations which defined five major clades (G614, S84, V251, I378 and D392) of globally circulating viral populations. The clades can specifically identify using an 11-nucleotide genetic barcode. An analysis of amino acid variation in SARS-CoV-2 proteins provided evidence of substitution events in the viral proteins involved in both host entry and genome replication. CONCLUSION: Globally circulating SARS-CoV-2 genomes could be classified into 5 major clades based on mutational profiles defined by an 11-nucleotide barcode. We have successfully developed a multiplexed sequencing-based, rapid genotyping protocol for high-throughput classification of major clade types of SARS-CoV-2 in clinical samples. This barcoding strategy will be required to monitor decreases in genetic diversity as treatment and vaccine approaches become widely available.

The impact of antimicrobial stewardship program implementation at four tertiary private hospitals: results of a five-years pre-post analysis.

BACKGROUND: Antimicrobial stewardship (AMS) programs have shown to reduce the emergence of antimicrobial resistance (AMR) and health-care-associated infections (HAIs), and save health-care costs associated with an inappropriate antimicrobial use. The primary objective of this study was to compare the consumption and cost of antimicrobial agents using defined daily dose (DDD) and direct cost of antibiotics before and after the AMS program implementation. Secondary objective was to determine the rate of HAIs [Clostridium difficile (C. difficile), ventilator-associated pneumonia (VAP), and central line-associated bloodstream infection (CLABSI) before and after the AMS program implementation. METHODS: This is a pre-post quasi-experimental study. Adult inpatients were enrolled in a prospective fashion under the active AMS arm and compared with historical inpatients who were admitted to the same units before the AMS implementation. Study was conducted at four tertiary private hospitals located in two cities in Saudi Arabia. Adult inpatients were enrolled under the pre- AMS arm and post- AMS arm if they were on any of the ten selected restricted broad-spectrum antibiotics (imipenem/cilastatin, piperacillin/tazobactam, colistin, tigecycline, cefepime, meropenem, ciprofloxacin, moxifloxacin, teicoplanin and linezolid). RESULTS: A total of 409,403 subjects were recruited, 79,369 in the pre- AMS control and 330,034 in the post- AMS arm. Average DDDs consumption of all targeted broad-spectrum antimicrobials from January 2016 to June 2019 post- AMS launch was lower than the DDDs use of these agents pre- AMS (233 vs 320 DDDs per 1000 patient-days, p = 0.689). Antimicrobial expenditures decreased by 28.45% in the first year of the program and remained relatively stable in subsequent years, with overall cumulative cost savings estimated at S.R. 6,286,929 and negligible expenses of S.R. 505,115 (p = 0.648). Rates of healthcare associated infections involving C. difficile, VAP, and CLABSI all decreased significantly after AMS implementation (incidence of HAIs in 2015 compared to 2019: for C. difficile, 94 vs 13, p = 0.024; for VAP, 24 vs 6, p = 0.001; for CLABSI, 17 vs 1, p = 0.000; respectively). CONCLUSION: Implementation of AMS program at HMG healthcare facilities resulted in reduced antimicrobials use and cost, and lowered incidence of healthcare associated infections.

Sleep Deprivation Etiologies Among Patients in the Intensive Care Unit: Literature Review.

BACKGROUND: Sleep deprivation among patients is a common problem in the intensive care unit (ICU). Studies have tried to find the etiologies of sleep deprivation. Poor sleep quality in the ICU has effects such as delirium, weakening the wound healing, and anxiety. Researches have concluded that the etiologies for sleep deprivation are multifactorial. OBJECTIVES: The aim of this review is to discuss the etiologies of sleep deprivation among ICU patients. This review also aims to discuss effects of sleep deprivations and provide implications for promoting sleep quality in the ICU. METHODS: For this literature review, ProQuest, MEDLINE, and Up To Date were used to find articles about sleep deprivation among ICU patients. The search was narrowed to articles between 2008 and 2019. A total of 23 articles were included that were found to match the inclusion criteria. RESULTS: Findings indicated that sleep deprivations etiologies among ICU patients can be environmental and nonenvironmental. Sensory overload, sensory deprivation, and patients' care activities are environmental etiologies for sleep deprivation. The nonenvironmental factors include pharmacological, physical, and psychological factors. DISCUSSION: Sleep deprivation etiologies are multifactorial and have several effects on ICU patients. Sleep protocol and staff training should be introduced to reduce unnecessary interventions by ICU staff. Tele-ICU monitoring can also be introduced to reduce unnecessary interventions where clinicians can monitor patients remotely and therefore enhance sleep in the ICU. During their stay in the ICU, patients can be instructed to wear earplugs and also have aromatherapy massage to reduce stress and enhance sleep quality. More research on the physical pain and the psychological factors using objective methods should be conducted in the future.

MERS coronavirus outbreak: Implications for emerging viral infections.

In September 2012, a novel coronavirus was isolated from a patient who died in Saudi Arabia after presenting with acute respiratory distress and acute kidney injury. Analysis revealed the disease to be due to a novel virus which was named Middle East Respiratory Coronavirus (MERS-CoV). There have been several MERS-CoV hospital outbreaks in KSA, continuing to the present day, and the disease has a mortality rate in excess of 35%. Since 2012, the World Health Organization has been informed of 2220 laboratory-confirmed cases resulting in at least 790 deaths. Cases have since arisen in 27 countries, including an outbreak in the Republic of Korea in 2015 in which 36 people died, but more than 80% of cases have occurred in Saudi Arabia.. Human-to-human transmission of MERS-CoV, particularly in healthcare settings, initially caused a 'media panic', however human-to-human transmission appears to require close contact and thus far the virus has not achieved epidemic potential. Zoonotic transmission is of significant importance and evidence is growing implicating the dromedary camel as the major animal host in spread of disease to humans. MERS-CoV is now included on the WHO list of priority blueprint diseases for which there which is an urgent need for accelerated research and development as they have the potential to cause a public health emergency while there is an absence of efficacious drugs and/or vaccines. In this review we highlight epidemiological, clinical, and infection control aspects of MERS-CoV as informed by the Saudi experience. Attention is given to recommended treatments and progress towards vaccine development.

Cytomegalovirus infection in immunocompetent critically ill adults: literature review.

Cytomegalovirus (CMV) infection is increasingly recognized in critically ill immunocompetent patients. Some studies have demonstrated an association between CMV disease and increased mortality rates, prolonged intensive care unit and hospital length of stay, prolonged mechanical ventilation, and nosocomial infections. However, there is a considerable controversy whether such association represents a causal relationship between CMV disease and unfavorable outcomes or just a marker of the severity of the critical illness. Detection of CMV using polymerase chain reaction and CMV antigenemia is the standard diagnostic approach. CMV may have variety of clinical manifestations reflecting the involvement of different organ systems. Treatment of CMV in critical care is challenging due to diagnostic challenge and drug toxicity, and building predictive model for CMV disease in critical care setting would be promising to identify patients at risk and starting prophylactic therapy. Our objective was to broadly review the current literature on the prevalence and incidence, clinical manifestations, potential limitations of different diagnostic modalities, prognosis, and therapeutic options of CMV disease in critically ill patients.