Non-SARS Non-MERS Human Coronaviruses: Clinical Characteristics and Outcome.

Human coronaviruses (HCoVs) have become evident sources of human respiratory infections with new emerging HCoVs as a significant cause of morbidity and mortality. The common four coronaviruses (229E, HKU1, NL63, and OC43) are known to cause respiratory illness in humans, but their clinical impact is poorly described in the literature. We analyzed the data of all patients who tested positive for at least one of the four HCoVs from October 2015 to January 2020 in a tertiary care center. HCoVs were detected in 1062 specimens, with an incidence rate of 1.01%, out of all documented respiratory illnesses. Detection of these viruses was reported sporadically throughout the years, with a peak of occurrence during winter seasons. OC43 had the highest incidence (53.7%), followed by NL63 (21.9%), HKU1 (12.6%), and 229E (11.8%). Most of these infections were community-acquired, with symptoms of both upper and lower respiratory tract. Co-detection with other viruses were observed, mostly with rhinovirus. 229E was the most frequent (26.4%) HCoV in patients requiring intensive care, while NL63 and 229E were the most common in patients requiring invasive ventilation. The highest 30-day mortality rate was observed in patients infected with 229E (6.4%). HCoVs are common circulating pathogens that have been present for decades, with 229E being the most virulent in this study cohort.

Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.

BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose. METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test). RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups. CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.

Detection of erythroid progenitors and erythrocytopathies in patients with severe COVID-19 disease.

OBJECTIVES: To assess the effect of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on erythropoiesis and red blood cells (RBC) surface markers by evaluating erythroid progenitor cells (CD [cluster of differentiation]71+/CD235a+) and RBC surface markers (CD235a and CD36), together with various hematological parameters. METHODS: This case-control study includes 47 participants recruited in the study: 30 patients with coronavirus disease 2019 (COVID-19) and 17 healthy individuals. The COVID-19 patients were recruited from the intensive care unit (ICU) of various hospitals in Makkah, Saudi Arabia. Blood samples were collected during July and September 2021. Red blood cells indices were measured using a CBC analyzer. The expression of CD235a, CD71, and CD36 was obtained using flow cytometry technique. The unpaired t-test was conducted to evaluate the differences in these markers in COVID-19 patients and healthy individuals. RESULTS: The data showed that more than half of the COVID-19 patients were anemic (64%). Expansion of erythroid progenitors (CD71+/CD235a+) was detected in the COVID-19 patients. Analysis of the expression of RBC surface markers, such as CD235a and CD36, showed that SARS-CoV-2 was associated with significantly higher expression of these markers in COVID-19 patients. CONCLUSION: Severe acute respiratory syndrome coronavirus-2 promoted the expansion of erythroid progenitors in the peripheral blood of COVID-19 patients. In addition, the expression of RBC surface markers was higher in COVID-19 patients. The expansion of erythroid progenitors and alteration of RBC surface markers can contribute to erythrocytopathies observed in severe COVID-19 patients and can therefore be used as prognostic factors.

Outcomes of single dose COVID-19 vaccines: Eight month follow-up of a large cohort in Saudi Arabia.

BACKGROUND: Two vaccines for COVID-19 have been approved and administered in the Kingdom of Saudi Arabia (KSA); Pfizer-BioNtech BNT162b2 and AstraZeneca-Oxford AZD1222 vaccines. The purpose of this study was to describe the real-world data on the outcome of single dose of these COVID-19 vaccines in a large cohort in KSA and to analyse demographics and co-morbidities as risk factors for infection post one-dose vaccination. METHODS: In this prospective cohort study, a total of 18,543 subjects received one dose of either of the vaccines at a vaccination centre in KSA, and were followed up for three to eight months. Data were collected from three sources; clinical data from medical records, adverse events (AEs) from a self-reporting system, and COVID-19 infection data from the national databases. The study was conducted during the pandemic restrictions on travel, mobility, and social interactions. RESULTS: The median age of participants was 33 years with an average body mass index of 27.3. The majority were males (60.1%). Results showed that 92.17% of the subjects had no COVID-19 infection post-vaccination as infection post-vaccination was documented for 1452 (7.83%). Diabetes mellitus 03), organ transplantation (p = 0.02), and obesity (p < 0.01) were associated with infection post-vaccination. Unlike vaccine type, being Saudi, male, or obese was associated with the occurrence breakthrough infections more than other parameters. AEs included injection site pain, fatigue, fever, myalgia, headache and was reported by 5.8% of the subjects. CONCLUSION: Single dose COVID-19 vaccines showed a protection rate of 92.17% up to eight months follow-up in this cohort. This rate in AZD1222 was higher than what have been previously reported in effectiveness studies and clinical trials. Obese, male, and Saudi were at higher risk of contracting the infection post-vaccination, Saudi and male might have more social interaction with the public when mobility and social interactions were limited during the pandemic. Side effects and AEs were within what has been reported in clinical trials.

Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial.

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo. METHODS: In this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality. RESULTS: Two hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32-44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6-12 days) in the favipiravir group and 8 days (IQR: 6-12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571-1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4-11 days) in the favipiravir group and 7 days (IQR: 5-10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events. CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

Crowd Models for Last Mile Delivery in an Emerging Economy

The dramatic rise in online shopping means that the last mile delivery (LMD) task is becoming extremely important. However, last mile delivery faces many economic, social, and environmental challenges. A fast-growing innovative solution is Crowd Logistics Delivery (CLD). This study investigates how CLD is meeting these challenges in a rapidly emerging economy (Saudi Arabia). It uses semi-structured interviews to analyse CLD from the perspectives of multiple stakeholders, focusing on its implementation, benefits to different stakeholders, and its limitations. While the findings of this study broadly support the work of other studies in this area, it provides several new insights. It observed three different business models being used for CLD: B2B, B2C, and C2C. It identified the internal success factors of each business model, including registration, assigning orders, compensation, and the payment model. It revealed the motivations for stakeholders to use CLD as a last mile delivery solution, such as LMD-related benefits and the social impact on society. In addition, the study highlighted the four main challenges these CLD implementations face that impede their success: legislation, availability of supply/drivers, trust, and culture. These results add to the rapidly expanding field of CLD.

Outcomes associated with tocilizumab with or without corticosteroid versus dexamethasone for treatment of patients with severe to critical COVID-19 pneumonia.

INTRODUCTION: Immunomodulators, including dexamethasone (DEX), have been recommended by the Infectious Disease Society of America (IDSA) to treat moderate, severe, and critical COVID-19. Tocilizumab (TCZ) was added to the treatment recommendations based on recent data from two large randomized controlled trials and its potential synergistic effect with DEX. METHOD: We included adult patients admitted from June until October 2020 with a PCR confirmed SARS-CoV-2 infection. 135 patients with severe to critical COVID-19 and received TCZ and/or corticosteroid or DEX were retrospectively evaluated and followed until hospital discharge or death. RESULTS: The cohort was divided into two different groups of patients; TCZ group received TCZ ± corticosteroid, N = 100 and DEX group received DEX, N = 35. Groups were analyzed for hospital mortality. The rate of hospital mortality was 36% in TCZ and 37% in the DEX group, p = 0.91. Age of 60 years and above was associated with higher mortality rate with OR = 1.030 and 95% CI = (1.004, 1.057). More than 50% of patients required MV in both groups. Development of bacterial or fungal infection post immunomodulator were similar in TCZ and DEX groups, 29% vs. 31.4%. CONCLUSION: Our study revealed that age of 60 years and above is the only factor associated with higher mortality rate regardless of the type of immunomodulator therapy. Findings of this study also revealed the lack of synergistic effect between TCZ and DEX on the hospital mortality.

Neurological Symptoms and Complications of COVID-19 Among Patients in a Tertiary Hospital in Saudi Arabia.

Objectives In this study, we aimed to determine the frequency of neurological signs, symptoms, and complications in coronavirus disease 2019 (COVID-19) patients. We also sought to explore the general characteristics of stroke patients in particular. Methods A retrospective cohort study was conducted among COVID-19 patients who were hospitalized between April-September 2020 at the Al-Noor Specialist Hospital in Makkah city, Saudi Arabia. The study included patients who were aged ≥18 years and presented with or were reported to have any neurological manifestations and/or complications secondary to COVID-19 infection. Results A total of 79 patients were included. The mean age of the cohort was 63.6 years, with a significant male predominance (67.1%). The most commonly reported neurological signs and symptoms were altered level of consciousness (45.9%), dizziness (11.5%), and focal neurological deficit (10.4%). Acute ischemic stroke was seen in 18 patients. Most of them were males (66.7%). Most strokes were in the right middle cerebral artery territory (MCA) (50.0%). Diabetic patients were four times more at risk to develop stroke [odds ratio (OR)=3.76; 95% confidence interval (CI): 1.1-29.9]. Patients with respiratory failure were 21 times more likely to have a stroke (OR=21.3; 95% CI: 2.2-54.6). Patients with acute respiratory distress syndrome recorded a three-fold increased risk for developing stroke (OR=2.96; 95% CI: 1.25-37.3). Critically ill patients had double the risk of stroke (OR=1.8; 95% CI: 1.1-6.9). Other neurological complications were hemorrhagic stroke (3.3%), subacute/chronic infarction (23.3%), meningitis (10%), and brain mass lesion (3.3%). Conclusions Neurological symptoms and complications are not uncommon among COVID-19 patients. Most of these patients had poor outcomes. Acute ischemic stroke was the most common finding on neuroimaging.

Variations in length of stay of inpatients with COVID-19: A nationwide test of the new model of care under vision 2030 in Saudi Arabia.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has impacted the Kingdom of Saudi Arabia (KSA) as it has other nations. However, length of stay (LOS), as a healthcare quality indicator, has not been examined across the healthcare regions in the KSA. Therefore, this study aimed to examine factors associated with LOS to better understand the Saudi Health System's performance in response to the COVID-19 pandemic in the newly suggested five Saudi regional business units (BUs). METHODS: A retrospective study was conducted using Ministry of Health (MOH) data on hospital LOS during the period from March to mid-July 2020. Participants were adult inpatients (18 years or older) with confirmed COVID-19 (n = 1743 patients). The 13 regions of the KSA were united into the defined five regional BUs during the reorganization of the health system. Covariates included demographics such as age and sex, comorbidities, and complications of COVID-19. A multiple linear regression with stepwise forward selection was used to model LOS for other explanatory variables associated with LOS, including demographic, comorbidities, and complications. RESULTS: The mean LOS was 11.85 days which differed significantly across the BUs, ranging from 9.3 days to 13.3 days (p value < 0.001). BUs differed significantly in LOS for transferred patients but not for patients in the intensive care unit (ICU) or those who died in-hospital. The multiple regression analysis revealed that the LOS for inpatients admitted in the Eastern and Southern BUs was significantly shorter than for those in the Central BU. (p value < 0.001). Admission to the ICU was associated with lengthier stays (p value < 0.0001). Factors significantly associated with shorter stays (compared to the reference), were being Saudi, death during admission, and patients referred to another hospital (p value < 0.05). CONCLUSION: The LOS for patients with COVID-19 differed across the proposed regional healthcare BUs, suggesting regional differences in quality of care under the reorganization of the national health system. Since patient and disease characteristics did not explain these findings, differences in staffing and other resources need to be examined to develop interventions.

Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial.

INTRODUCTION: Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. METHODS: An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. RESULTS: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617-1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. CONCLUSION: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04392973).

Level of Adherence to COVID-19 Preventive Measures Among Health Care Workers in Saudi Arabia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Health-care workers (HCWs) are at a high risk of contracting SARS-CoV-2 infection. Thus, different infection control strategies have been used to reduce SARS-CoV-2 transmission. Our study aims to assess the level of adherence of HCWs to the preventive measures against COVID-19 in Saudi Arabia. METHODS: An observational study was carried out using data collected by a self-administrated dual-language (Arabic and English) online questionnaire directed to HCWs in Saudi Arabia to measure the level of adherence to COVID-19 preventive measures. All HCWs involved in patient care in Saudi Arabia were included in this study. RESULTS: A total of 214 HCWs were included in the study (median age = 30 years; 62% male). Among all the participants, 65% of HCWs were in direct contact with COVID-19 patients, and 18% were diagnosed with COVID-19. The level of overall adherence to mask use was 82%. HCWs were committed to wearing gloves, gowns, and goggles with a percent of 95%, 85%, and 68%, respectively. CONCLUSION: Our findings demonstrated that HCWs in Saudi Arabia have an acceptable level of adherence to COVID-19 preventive measures during the pandemic. Larger studies are required to evaluate the effectiveness of these preventive measures in reducing the transmission of respiratory microbes between HCWs and patients.

Regional differences in COVID-19 ICU admission rates in the Kingdom of Saudi Arabia: A simulation of the new model of care under vision 2030.

OBJECTIVE: Saudi Arabia has succeeded in having one of the lowest rates of COVID-19 worldwide due to the government's initiatives in taking swift action to control both the spread and severity of the virus. However, Covid-19 can serve as a test case of the expected response of the new healthcare system under Vision 2030. This study used data from the thirteen present administrative regions of KSA to simulate the variations in ICU admission as a quality indicator in the five business units proposed by a new Model of Care. METHODS: We determined the rates of ICU admission for patients with confirmed SARS-CoV-2 (COVID-19) from March to mid-July 2020. The final sample included 1743 inpatients with moderate to severe COVID-19. Patient characteristics, including demographics, pre-existing chronic conditions, and COVID-19 complications, were collected. Business units (BUs) were compared with respect to the relative odds of ICU admission by using multiple logistic regression. RESULTS: After keeping patient and clinical characteristics constant, clear BU differences were observed in the relative odds of ICU admission of COVID-19 patients. Inpatient admission to ICU in our total sample was almost 50%. Compared to the Central BU, the Northern and Western BUs showed significantly higher odds of ICU admission while the Eastern & Southern BUs had significantly lower odds. CONCLUSION: ICU use for COVID-19 patients differed significantly in KSA healthcare BUs, consistent with variations in care for other non-COVID-19-related conditions. These differences cannot be explained by patient or clinical characteristics, suggesting quality-of-care differences. We believe that privatization and the shift to fewer administrative BUs will help lessen or eliminate altogether the present variations in healthcare service provision.

Multicentre randomised double-blinded placebo-controlled trial of favipiravir in adults with mild COVID-19.

INTRODUCTION: A novel coronavirus, designated SARS-CoV-2, caused an international outbreak of a respiratory illness, termed COVID-19 in December 2019. There is a lack of specific therapeutic agents based on evidence for this novel coronavirus infection; however, several medications have been evaluated as a potential therapy. Therapy is required to treat symptomatic patients and decrease the virus carriage duration to limit the communitytransmission. METHODS AND ANALYSIS: We hypothesise that patients with mild COVID-19 treated with favipiravir will have a shorter duration of time to virus clearance than the control group. The primary outcome is to evaluate the effect of favipiravir on the timing of the PCR test conversion from positive to negative within 15 days after starting the medicine.Adults (>18 years, men or nonpregnant women, diagnosed with mild COVID-19 within 5 days of disease onset) are being recruited by physicians participating from the Ministry of National Guard Health Affairs and the Ministry of Health ethics committee approved primary healthcare centres. This double-blind, randomised trial comprises three significant parts: screening, treatment and a follow-up period. The treating physician and patients are blinded. Eligible participants are randomised in a 1:1 ratio to either the therapy group (favipiravir) or a control group (placebo) with 1800 mg by mouth two times per day for the first day, followed by 800 mg two times per day for 4-7 days. Serial nasopharyngeal/oropharyngeal swab samples are obtained on day 1 (5 days before therapy). On day5±1 day, 10±1 day, 15±2 days, extra nasopharyngeal/oropharyngeal PCR COVID-19 samples are requested.The primary analysis population for evaluating both the efficacy and safety outcomes will be a modified intention to treat population. Anticipating a 10% dropout rate, we expect to recruit 288 subjects per arm. The results assume that the hazard ratio is constant throughout the study and that the Cox proportional hazard regression is used to analyse the data. ETHICS AND DISSEMINATION: The study was approved by the King Abdullah International Medical Research Centre Institutional Review Board (28 April 2020) and the Ministry of Health Institutional Review Board (1 July 2020). Protocol details and any amendments will be reported to https://clinicaltrials.gov/ct2/show/NCT04464408. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: National Clinical Trial Registry (NCT04464408).

A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. TRIAL DESIGN: This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. PARTICIPANTS: All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. INTERVENTION AND COMPARATOR: The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . MAIN OUTCOMES: The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). RANDOMISATION: Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. BLINDING (MASKING): This is an Open label study and only the analyst will be blinded during the study conduct. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). TRIAL STATUS: Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04392973 , 19 May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

COVID-19 and endoscopy services in intermediately affected countries: a position statement from the saudi gastroenterology association.

With the global pandemic due to coronavirus disease 2019 (COVID-19), there has been a significant strain on healthcare facilities. The infectivity rate, as well as the rate of healthcare workers who have fallen ill to the disease, has raised concerns globally on the proper management of patients as well as the role of safe healthcare provision utilizing personal protective equipment (PPE). Furthermore, the limited supply of PPEs has mandated rationing their use to achieve maximum utility and preservation. Multiple gastroenterology associations have issued guidance and statements that would help healthcare providers in navigating these unprecedented and difficult times, and the Saudi Gastroenterology Association has provided this statement in an effort to bring the most up to date information for the management of endoscopy units in terms of resources, manpower planning, scheduling, as well as infection control policies and leadership.