Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-ß1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-ß1b and lopinavir-ritonavir did not significantly differ between the two groups. Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

Heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir in patients with Middle East respiratory syndrome by cytokine levels.

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir-Ritonavir and Interferon ß-1b), we evaluated the heterogeneity of treatment effect of interferon-ß1b and lopinavir-ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-ß1b and lopinavir-ritonavir and 38 received placebo. Interferon-ß1b and lopinavir-ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-ß1b and lopinavir-ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).

Hajj 2021: Role of mitigation measures for health security.

PURPOSE: After the impressive results of the 2020 Hajj management, Saudi authorities decided to expand the quota to 60,000 pilgrims in 2021, which resulted in a convenient and successful experience. PATIENTS AND METHODS: This was a retrospective pre and post-study study conducted on all pilgrims attending the 2021 Hajj using the polymerase chain reaction (PCR) test surveillance with paired-swab samples (pre-Hajj and post-Hajj) to evaluate the risk potential of COVID-19 among Hajj pilgrims, the effectiveness of preventive measures and the potential effect of the Hajj ritual as a huge mass gathering on the epidemiological situation of the Saudi Arabian population. RESULT: Forty-one cases had positive COVID-19 infections out of a total of 58,428 pilgrims who attended the 2021 Hajj season, as detected by nonmandatory pre- and post-Hajj PCR. Notably, the 2021 Hajj season achieved a decreasing leg of the COVID-19 pandemic curve. The adjusted incidence rate in KSA from July 11th to August 7th ranged from 19 to 24 cases per 100,000 population. In contrast, the incidence rate for the same duration in Hajj ranged from 3 to 7 cases per 100,000 pilgrims. CONCLUSION: The Saudi mitigation plan ensured the safety of pilgrims and healthcare workers for Hajj, successfully limited the risk of COVID-19 transmission inside and contributed to global health security. The success story of Hajj in 2020 and 2021 during the pandemic represents a successful model for planning, achieving and managing future mass gatherings by integrating technology with global and national health policies and public health measures.

A combined model for COVID-19 pandemic control: The application of Haddon's matrix and community risk reduction tools combined.

INTRODUCTION: To mitigate morbidity, mortality, and impacts of COVID-19 on health, it was essential to implement a comprehensive framework for COVID-19 control and prevention. A well-recognized tool from the field of injury prevention known as the Haddon matrix was utilized. The matrix states that any accident is affected by the host, agent, and environment. Another well-recognized tool used by the national fire protection association known as the Community risk reduction tool (CRR). The (CRR) tool utilizes the Five E's of Community Risk Reduction. AIM OF THE STUDY: To describe the risk factors that increase the susceptibility and the severity of COVID-19 infection based on the Haddon matrix and the proposed prevention strategies by the CRR tool by using the combined model. METHODOLOGY: We reviewed the literature to assess known factors contributing to COVID-19 susceptibility, infection, and severity of infection. We then used the Haddon matrix to structure, separating human factors from technical and environmental details and timing. We then used the community risk reduction (CRR) model to set all responses and control measures for each element obtained from the Haddon matrix tool. Subsequently, we incorporated both tools to develop the combined model. CONCLUSION: we proposed and implemented a combined model that utilizes the CRR model as the systematic strategy for the more theoretical framework of Haddon's matrix. Combining both models was practical and helpful in planning the preparedness and control of the COVID-19 pandemic in Saudi Arabia that can be generalized to national and international levels.

Potential Cross-Reactive Immunity to COVID-19 Infection in Individuals With Laboratory-Confirmed MERS-CoV Infection: A National Retrospective Cohort Study From Saudi Arabia.

BACKGROUND: A growing number of experiments have suggested potential cross-reactive immunity between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and previous human coronaviruses. We conducted the present retrospective cohort study to investigate the relationship between previous Middle East respiratory syndrome-coronavirus (MERS-CoV) infection and the risk of SARS-CoV-2 infection as well as the relationship between previous MERS-CoV and COVID-19-related hospitalization and mortality. METHODS: Starting in March 2020, we prospectively followed two groups of individuals who tested negative for COVID-19 infection. The first group had a previously confirmed MERS-CoV infection, which was compared to a control group of MERS-negative individuals. The studied cohort was then followed until November 2020 to track evidence of contracting COVID-19 infection. FINDINGS: A total of 82 (24%) MERS-positive and 260 (31%) MERS-negative individuals had COVID-19 infection. Patients in the MERS-positive group had a lower risk of COVID-19 infection than those in the MERS-negative group (Risk ratio [RR] 0.696, 95% confidence interval [CI] 0.522-0.929; p =0.014). The risk of COVID-19-related hospitalization in the MERS-positive group was significantly higher (RR 4.036, 95% CI 1.705-9.555; p =0.002). The case fatality rate (CFR) from COVID-19 was 4.9% in the MERS-positive group and 1.2% in the MERS-negative group (p =0.038). The MERS-positive group had a higher risk of death than the MERS-negative group (RR 6.222, 95% CI 1.342-28.839; p =0.019). However, the risk of mortality was similar between the two groups when death was adjusted for age (p =0.068) and age and sex (p =0.057). After controlling for all the independent variables, only healthcare worker occupation and >1 comorbidity were independent predictors of SARS-CoV-2 infection. INTERPRETATION: Individuals with previous MERS-CoV infection can exhibit a cross-reactive immune response to SARS-CoV-2 infection. Our study demonstrated that patients with MERS-CoV infection had higher risks of COVID-19-related hospitalization and death than MERS-negative individuals.

The Role of Digital Technology in Responding to COVID-19 Pandemic: Saudi Arabia's Experience.

INTRODUCTION: The novel coronavirus (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-chain ribonucleic acid (RNA) virus. As of March 25, 2021, the total number of positive cases and fatalities in the Kingdom of Saudi Arabia (KSA) had reached 386,300 and 6624, respectively, with a case fatality rate of 1.71%. The KSA was among the leading nations to heed the advice of WHO officials and put strict precautionary and preventive measures in place to curb the early spread of COVID-19 before it was declared a global pandemic. METHODOLOGY: This was an uncontrolled before-after study following a mixed-method approach for data collection. National and regional data were extracted from the Health Electronic Surveillance Network (HESN), a centralized public health collection system for quantitative and statistical data. Quantitative and qualitative methods have been utilized in studying data derived from tech media. RESULTS: The Saudi authorities utilized different technological tools to aid in managing and combating the COVID-19 pandemic. In the case of Al Madinah Al Mounawarah, after the implementation of several technologies, the most important being Tawakkalna, the number of active daily cases decreased by 61%. CONCLUSION: The use of the Tawakkalna application was proven to be a successful method in fighting the COVID-19 pandemic in the KSA. This vital and essential experience warrants the use of different digital technology that offers a personalized profile displaying the person's status (affected, vaccinated, or no history of infection). This application played and will continue to play a crucial and effective role in pandemic containment in Saudi Arabia.

Risk Communication Effectiveness During COVID-19 Pandemic Among General Population in Saudi Arabia.

PURPOSE: The novel coronavirus (COVID-19), declared a pandemic by WHO in March 2020, is an unprecedented occurrence in our recent history. Effective risk communication by health authorities, through relaying reliable and authoritative information, is imperative in combating the spread of the outbreak. We aimed to measure the effectiveness of risk communication campaign and overall awareness during COVID-19 pandemic among the general population in Saudi Arabia. PATIENTS AND METHODS: A cross-sectional survey of 5472 individuals in Saudi Arabia was conducted to assess several factors regarding the risk communication messages during the COVID-19 pandemic, including the knowledge and response of the general population toward COVID-19 and MoH efforts. The questionnaire was divided into five main sections: general knowledge of COVID-19, channels and social media platforms used perceived risk and stress or panic toward COVID-19, satisfaction and community perception, most trusted source of information, and type of information received. RESULTS: A total of 5472 individuals participated in the study residing in Saudi Arabia. Overall knowledge of COVID-19 was determined to be above average (0.58 + 0.159). Of the general population, 57.1% perceived that the risk of getting sick with COVID-19 is low, while nearly half of the respondents (45.7%) have a high level of stress and panic toward COVID-19. The majority of responders to the questionnaire reinforced that MoH was their most trusted source of information for the COVID-19 pandemic (91.7%). CONCLUSION: This study showed that the risk communication campaign by healthcare authorities during the COVID-19 pandemic has improved the awareness among the general population in Saudi Arabia, where the overwhelming majority placed high trust in the MoH as its main reference for COVID-19 information.

Controlling COVID-19 Pandemic: A Mass Screening Experience in Saudi Arabia.

A highly accelerating number of people around the world have been infected with novel Coronavirus disease 2019 (COVID-19). Mass screening programs were suggested by the World Health Organization (WHO) as an effective precautionary measure to contain the spread of the virus. On 16 April 2020, a COVID-19 mass screening program was initiated in Saudi Arabia in multiple phases. This study aims to analyze the number of detected COVID-19 cases, their demographic data, and regions most affected in the initial two phases of these mass screening programs. A retrospective cross-sectional study was conducted among the high-risk population as part of the COVID-19 mass screening program across all regions in Saudi Arabia during April and May 2020. A Chi-square-test was used to determine the associations between positive cases and various demographic variables. Out of 71,854 screened individuals, 13.50% (n = 9701) were COVID-19 positive, of which 83.27% (n = 59,835) were males. Among positive cases, in the 30-39 years age group, 6.36% were in the active phase, and 2.19% were in the community phase. Based on our experience, launching mass screening programs is crucial for early case detection, isolation, and pattern recognition for immediate public interventions.

Epidemiological and clinical features of COVID-19 patients in Saudi Arabia.

BACKGROUND: The aim of this study is to describe the clinical and demographic characteristics of COVID-19 patients, and the risk factors associated with death in Saudi Arabia to serve as a reference to further understand this pandemic and to help in the future decisions and control of this global crisis. METHODS: This multicenter, retrospective, observational, cross-sectional study was conducted on 240,474 patients with confirmed COVID-19 in Saudi Arabia. Data was collected retrospectively through the Health Electronic Surveillance Network at the Ministry of Health. Patients were classified based on their outcome as recovered, dead, or active with no definite outcome. We must specify the date period. RESULTS: As of 20th of June 2020, 79.7% of COVID-19 cases were young and middle-aged, ranging between 20-59 years. There was evidently a difference in the sex ratio, where males constituted 71.7% of cases. The majority were non-Saudi nationals, representing 54.7% of cases. Furthermore, the contraction of COVID-19 was travel-related in 45.1% of cases. Signs and symptoms were reported in 63% of cases, the most common of which were fever; 85.2%, and cough; 85%. Deaths occurred more frequently in patients 40-49 years, 50-59 years, and 60-69 years, representing 19.2%, 27.9%, and 21.3% of deaths, respectively. Additionally, the case fatality rate (CFR) was higher in older age-groups, reaching 10.1% in those ≥80 years. Moreover, the CFR of males was higher than that of females, with 0.95% and 0.62%, respectively. As for nationality, Saudis had a CFR of 0.46% versus 1.19% in non-Saudis. CONCLUSION: The total number of positive COVID-19 cases detected constitute 0.7% of the Saudi population to date. Older age, non-Saudi nationalities, being male, travelling outside Saudi Arabia, and the presence of symptoms, as opposed to being asymptomatic were considered risk factors and found to be significantly more associated with death in patients with COVID-19.

Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).