MICaFVi: A Novel Magnetic Immuno-Capture Flow Virometry Nano-Based Diagnostic Tool for Detection of Coronaviruses.

COVID-19 has resulted in a pandemic that aggravated the world's healthcare systems, economies, and education, and caused millions of global deaths. Until now, there has been no specific, reliable, and effective treatment to combat the virus and its variants. The current standard tedious PCR-based tests have limitations in terms of sensitivity, specificity, turnaround time, and false negative results. Thus, an alternative, rapid, accurate, and sensitive diagnostic tool that can detect viral particles, without the need for amplification or viral replication, is central to infectious disease surveillance. Here, we report MICaFVi (Magnetic Immuno-Capture Flow Virometry), a novel precise nano-biosensor diagnostic assay for coronavirus detection which combines the MNP-based immuno-capture of viruses for enrichment followed by flow-virometry analysis, enabling the sensitive detection of viral particles and pseudoviruses. As proof of concept, virus-mimicking spike-protein-coated silica particles (VM-SPs) were captured using anti-spike-antibody-conjugated MNPs (AS-MNPs) followed by detection using flow cytometry. Our results showed that MICaFVi can successfully detect viral MERS-CoV/SARS-CoV-2-mimicking particles as well as MERS-CoV pseudoviral particles (MERSpp) with high specificity and sensitivity, where a limit of detection (LOD) of 3.9 µg/mL (20 pmol/mL) was achieved. The proposed method has great potential for designing practical, specific, and point-of-care testing for rapid and sensitive diagnoses of coronavirus and other infectious diseases.

Salivary Antibody Responses to Two COVID-19 Vaccines following Different Vaccination Regimens.

Background: To date, little is known about the salivary mucosal immune response following different COVID-19 vaccine types or after a booster (3rd) dose of the BNT162b2 (BNT) vaccine. Methods: A total of 301 saliva samples were collected from vaccinated individuals and arranged into two cohorts: cohort 1 (n = 145), samples from individuals who had received two doses against SARS-CoV-2; cohort 2 (n = 156), samples from individuals who had received a booster of BNT vaccine. Cohorts 1 and 2 were sub-stratified into three groups based on the types of first and second doses (homologous BNT/BNT, homologous ChAdOx1/ChAdOx1, or heterologous BNT/ChAdOx1vaccinations). Salivary immunoglobulin G (IgG) response to SARS-CoV-2 spike glycoprotein was measured by ELISA, and clinical demographic data were collected from hospital records or questionnaires. Results: Salivary IgG antibody responses against different vaccines, whether homologous or heterogeneous vaccination regimens, showed similar levels in cohorts 1 and 2. Compiling all groups in cohort 1 and 2 showed significant, albeit weak, negative correlations between salivary IgG levels and time (r = -0.2, p = 0.03; r = -0.27, p = 0.003, respectively). In cohort 2, the durability of salivary IgG after a booster dose of BNT162b2 significantly dropped after 3 months compared to the <1 month and 1-3 months groups. Conclusions: Different COVID-19 vaccine types and regimens elicit similar salivary anti-SARS-CoV-2 IgG with modest waning over time. Boosting with BNT162b2 vaccine did not produce an evident increase in mucosal IgG response whereby COVID-19 recovered subjects show higher salivary IgG than naive, post-vaccination subjects. The ChAdOx1/ChAdOx1 regimen showed better correlation between salivary IgG levels and durability. These findings highlight the importance of developing oral or intra-nasal vaccines to induce stronger mucosal immunity.

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.

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).

Risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination.

BACKGROUND: Severe complications from COVID-19 and poor responses to SARS-CoV-2 vaccination were commonly reported in cancer patients compared to those without cancer. Therefore, the identification of predisposing factors to SARS-CoV-2 infection in cancer patients would assist in the prevention of COVID-19 and improve vaccination strategies. The literature lacks reports on this topic from the Kingdom of Saudi Arabia (KSA). Therefore, we studied clinical and laboratory data of 139 cancer patients from King Abdulaziz Medical City, Riyadh, KSA. METHODS: The cancer patients fall into three categories; (i) uninfected with SARS-CoV-2 pre-vaccination and remained uninfected post-vaccination (control group; n = 114; 81%), (ii) pre-vaccination infected group (n = 16; 11%), or (iii) post-vaccination infected group (n = 9; 6%). Next, the clinical and lab data of the three groups of patients were investigated. RESULTS: Comorbidity factors like diabetes and hemodialysis were associated with the risk of infection in cancer patients before the vaccination (p<0.05). In contrast to breast cancer, papillary thyroid cancer was more prevalent in the infected patients pre- and post-vaccination (p<0.05). Pre-vaccination infected group had earlier cancer stages compared with the control group (p = 0.01). On the other hand, combined therapy was less commonly administrated to the infected groups versus the control group (p<0.05). Neutrophil to lymphocyte ratio was lower in the post-vaccination infected group compared to the control group (p = 0.01). CONCLUSION: Collectively, this is the first study from KSA to report potential risk factors of SARS-CoV-2 infection in cancer patients pre- and post-vaccination. Further investigations on these risk factors in a larger cohort are worthwhile to draw a definitive conclusion about their roles in predisposing cancer patients to the infection.

Development and Evaluation of Enzyme-Linked Viral Immune Capture Assay for Detection of SARS-CoV-2

The pandemic of COVID-19 was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 and it has prompted unprecedented research activities for vaccines, therapeutics, and diagnostics. The real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard method of diagnosis;however, immune-based assays offer cost-effective, deployable, easy-to-read solutions for diagnosis and surveillance. Here, we present the development, optimization, and testing of an enzyme-linked viral immune capture assay (ELVICA). It utilizes the spike antigen as the detected target of the virus and antibody-coated beads to capture the virus and enrich the detection. This method can be readout by luminescent and colorimetric equipment. It can also be visualized by the imaging system, offering a variety of detection approaches. ELVICA showed specificity to SARS-CoV-2-pseudotyped viruses as compared to MERS-CoV-pseudotyped viruses. As compared to RT-PCR, ELVICA showed high compatibility in detecting the virus in patient respiratory samples, especially for samples that are below a Ct value of 32 in RT-PCR. This assay is readily adaptable for detecting other pathogens and serves as a quick and affordable diagnostic tool.

Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells.

Lipid rafts in cell plasma membranes play a critical role in the life cycle of many viruses. However, the involvement of membrane cholesterol-rich lipid rafts in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into target cells is not well known. In this study, we investigated whether the presence of cholesterol-rich microdomains is required for the entry of SARS-CoV-2 into host cells. Our results show that depletion of cholesterol in the rafts by methyl-beta-cyclodextrin (MßCD) treatment impaired the expression of the cell surface receptor angiotensin-converting enzyme 2 (ACE2), resulting in a significant increase in SARS-CoV-2 entry into cells. The effects exerted by MßCD could be substantially reversed by exogenous cholesterol replenishment. In contrast, disturbance of intracellular cholesterol homeostasis by statins or siRNA knockdown of key genes involved in the cholesterol biosynthesis and transport pathways reduced SARS-CoV-2 entry into cells. Our study also reveals that SREBP2-mediated cholesterol biosynthesis is involved in the process of SARS-CoV-2 entry in target cells. These results suggest that the host membrane cholesterol-enriched lipid rafts and cellular cholesterol homeostasis are essential for SARS-CoV-2 entry into cells. Pharmacological manipulation of intracellular cholesterol might provide new therapeutic strategies to alleviate SARS-CoV-2 entry into cells.

Immunogenicity of High-Dose MVA-Based MERS Vaccine Candidate in Mice and Camels.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime-boost vaccinations in mice and camels. METHODS: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. RESULTS: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). CONCLUSIONS: MVA-MERS vaccine, administered in a homologous prime-boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans.

Persistence of Anti-SARS-CoV-2 Spike IgG Antibodies Following COVID-19 Vaccines.

Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and Methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.

Comparison of Hospital Readmission and Mortality between COVID-19 and Pneumonia Patients.

Coronavirus disease 2019 (COVID-19) survivors can have lasting signs and symptoms, including various organ damage, indicating that COVID-19 can be a chronic illness. The current study aims to compare the 30-day hospital readmission and death rate of patients admitted to the hospital with COVID-19 and pneumonia due to other causes. A retrospective cohort study was conducted using data from the Saudi National Guard Health Affairs (NGHA). Records of patients admitted with COVID-19 between 1 March 202 and 31 December 2020 (n = 3597) and pneumonia during 2017 and 2019 (n = 6324) were retrieved and analyzed. We compared the likelihood of 30-day hospital readmission, intensive care unit (ICU) admission, and death between the two groups. Compared with the control group, COVID-19 patients had higher odds of 30-day readmission (odds ratio 1.90, 95% confidence interval 1.61-2.24), higher risk of ICU transfer (hazard ratio 1.85, 95% confidence interval 1.65-2.07), more extended hospital stay (7 vs. 4 days), but less risk of death (hazard ratio 0.18, 95% confidence interval 0.14-0.24). The findings that hospital readmission was higher in COVID-19 recovered patients than in other pneumonia patients inform the current discussion about readmission and death in COVID-19 patients.

Assessment of COVID-19 Vaccine Acceptance and Reluctance Among Staff Working in Public Healthcare Settings of Saudi Arabia: A Multicenter Study.

Objective: The study aimed to evaluate the novel coronavirus disease 2019 (COVID-19) vaccination acceptance and reluctance among staff working in Saudi healthcare facilities. Methods: A cross-sectional study was conducted during April - May 2021, among healthcare workers in five public hospitals under the National Guards Health Association located in Alahsa, Dammam, Jeddah, Madinah, and Riyadh. The study used a questionnaire in English language, which was distributed through official email communication among healthcare staff currently working at study venues. The data was analyzed using IBM SPSS v23. An ethical approval was obtained. Results: A total of 1,031 responses were recorded. Most of the staff had both doses of COVID-19 vaccine (89%). The mean score for vaccine acceptance on a scale of 1 (strongly disagree) to 5 (strongly agree) was 3.55 ± 1.6. The mean score for vaccine reluctance on the same scale was 2.71 ± 1.05. Most participants mentioned safety (76.9%) and efficacy (56.3%) as vaccine concerns and believed that COVID-19 vaccine may not be effective because of changes in virus strain (55.5%). The variables of gender and nationality significantly affected vaccine acceptance, while age, gender, nationality, and profession significantly affected vaccine reluctance (p < 0.05). Conclusion: Most healthcare staff were vaccinated, and a high acceptance for COVID-19 vaccination was reported. Several demographic factors affected the vaccine acceptance and reluctance.

COVID-19 reinfection: A multicenter retrospective study in Saudi Arabia.

INTRODUCTION: There are limited direct data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) long-term immune responses and reinfection. This study aimed to evaluate the rate, risk factors, and severity of COVID-19 reinfection. METHODS: This retrospective cohort study included five hospitals across Saudi Arabia. All subjects who were presented or admitted with positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) tests were evaluated between March 2020 and August 2021. Reinfection was defined as a patient who was infected followed by clinical recovery, and later became infected again 90 days post first infection. The infection was confirmed with a positive SARS-CoV-2 (RT-PCR). Four hundred and seventeen recovered cases but with no reinfection were included as a control. RESULTS: A total of 35,288 RT-PCR-confirmed COVID-19 patients were observed between March 2020 and August 2021. Based on the case definition, (0.37%) 132 patients had COVID-19 reinfection. The mean age in the reinfected cases was 40.95 ± 19.48 (range 1-87 years); Females were 50.76%. Body mass index was 27.65 ± 6.65 kg/m2; diabetes and hypertension were the most common comorbidities. The first infection showed mild symptoms in 91 (68.94%) patients; and when compared to the control group, comorbidities, severity of infection, and laboratory investigations were not statistically different. Hospitalization at the first infection was higher, but not statistically different when compared to the control group (P = 0.093). CONCLUSION: COVID-19 reinfection is rare and does not carry a higher risk of severe disease. Further studies are required, especially with the continuously newly emerging variants, with the unpredictable risk of reinfection.

Seroprevalence of COVID-19 in Riyadh city during the early increase of COVID-19 infections in Saudi Arabia, June 2020.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 and caused a global pandemic of the Coronavirus Disease 2019 (COVID-19). More than 170 million cases have been reported worldwide with mortality rate of 1-3%. The detection of SARS-CoV-2 by molecular testing is limited to acute infections, therefore serological studies provide a better estimation of the virus spread in a population. This study aims to evaluate the seroprevalence of SARS-CoV-2 in the major city of Riyadh, Saudi Arabia during the sharp increase of the pandemic, in June 2020. Serum samples from non-COVID patients (n = 432), patients visiting hospitals for other complications and confirmed negative for COVID-19, and healthy blood donors (n = 350) were collected and evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). The overall percentage of positive samples was 7.80% in the combined two populations (n = 782). The seroprevalence was lower in the blood donors (6%) than non-COVID-19 patients (9.25%), p = 0.0004. This seroprevalence rate is higher than the documented cases, indicating asymptomatic or mild unreported COVID-19 infections in these two populations. This warrants further national sero-surveys and highlights the importance of real-time serological surveillance during pandemics.

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.

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.

Immune Responses to MERS-CoV in Humans and Animals.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that circulates in dromedary camels and sporadically transmit into humans, subsequently resulting in community and nosocomial cases. The viral infection in humans has a range of disease severity from asymptomatic to severe pneumonia and death, whereas the infection in camels is usually asymptomatic. There is no approved antiviral therapy or vaccine for MERS-CoV infections although there have been a number of therapeutic and vaccine candidates under development, for both humans and camels. To date, there has been limited research on the immune responses and pathogenesis of MERS-CoV in both humans and camels. Here, this chapter is focused on MERS-CoV specific immunity in different species with some details regarding the various animal models.

Haematological and radiological-based prognostic markers of COVID-19.

BACKGROUND: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged in 2019 and caused a global pandemic in 2020, manifesting in the coronavirus disease 2019 (COVID-19). The majority of patients exhibit a mild form of the disease with no major complications; however, moderate to severe and fatal cases are of public health concerns. Predicting the potential prognosis of COVID-19 could assist healthcare workers in managing cases and controlling the pandemic in an effective way. Therefore, the objectives of the study were to search for biomarkers associated with COVID-19 mortality and predictors of the overall survival (OS). METHODS: Here, clinical data of 6026 adult COVID-19 patients admitted to two large centers in Saudi Arabia (Riyadh and Hafar Al-Batin cities) between April and June 2020 were retrospectively analysed. RESULTS: More than 23% of the study subjects with available data have died, enabling the prediction of mortality in our cohort. Markers that were significantly associated with mortality in this study were older age, increased d-dimer in the blood, higher counts of WBCs, higher percentage of neutrophil, and a higher chest X-ray (CXR) score. The CXR scores were also positively associated with age, d-dimer, WBC count, and percentage of neutrophil. This supports the utility of CXR scores in the absence of blood testing. Predicting mortality based on Ct values of RT-PCR was not successful, necessitating a more quantitative RT-PCR to determine virus quantity in samples. Our work has also identified age, d-dimer concentration, leukocyte parameters and CXR score to be prognostic markers of the OS of COVID-19 patients. CONCLUSION: Overall, this retrospective study on hospitalised cohort of COVID-19 patients presents that age, haematological, and radiological data at the time of diagnosis are of value and could be used to guide better clinical management of COVID-19 patients.