Occupational Health Hazards Among Veterinarians in Saudi Arabia.

Introduction Veterinarians and other professionals who interact with animals on a daily basis encounter an elevated risk of exposure to both known and as-yet-undiscovered microbial agents. Additionally, they are also exposed to physical, chemical, and environmental hazards. Enhancing occupational health and safety in this context carries significant global significance. Methods This study aimed to comprehensively identify and outline the various biological, physical, chemical, and environmental health threats that were encountered by veterinarians in Saudi Arabia. To achieve this, we designed a self-completed questionnaire for 529 participants. The survey encompassed potential occupational hazards such as microbial diseases, injuries resulting from animal bites and scratches, allergies, and environmental risks like sunstroke and dust storms. Results Among the 529 participating veterinarians, 45.9% (243 individuals) reported instances of zoonotic diseases within the past five years. Notably, potential viral agents included Middle East respiratory syndrome coronavirus, avian influenza, and foot-and-mouth disease virus. Bacterial diseases were also frequently documented, with brucellosis (18.7%) and salmonellosis (7.9%) being notable pathogens. Protozoal infections were led by Leishmaniosis, constituting the most commonly detected protozoa (29 /529, 5.5%). Interestingly, 345 (65.2%) of the individuals reported that they have experienced animal bites and scratches. Needle stick injuries were also a common occupational hazard, with an incidence rate of 19.1%. Additionally, chemical exposure was prevalent, particularly to disinfectants (57.5%) and veterinary drugs (23.4%). The study participants also reported their exposure to various environmental hazards, including sunstroke, dust, sandstorms, and heavy rains. Conclusion The findings of this study draw attention to a concerning trend among veterinarians in Saudi Arabia. Their personal health and safety appear to receive inadequate attention, potentially heightening the risk of occupationally related health hazards. These outcomes highlight the need for a reevaluation of safety protocols and infection control practices within the veterinary profession. The implications of this study can potentially inform the development of policies and initiatives aimed at mitigating occupationally related health hazards among veterinarians in Saudi Arabia.

Enhanced antiviral immunity and dampened inflammation in llama lymph nodes upon MERS-CoV sensing: bridging innate and adaptive cellular immune responses in camelid reservoirs.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection can cause fatal pulmonary inflammatory disease in humans. Contrarily, camelids and bats are the main reservoir hosts, tolerant for MERS-CoV replication without suffering clinical disease. Here, we isolated cervical lymph node (LN) cells from MERS-CoV convalescent llamas and pulsed them with two different viral strains (clades B and C). Viral replication was not supported in LN, but a cellular immune response was mounted. Reminiscent Th1 responses (IFN-γ, IL-2, IL-12) were elicited upon MERS-CoV sensing, accompanied by a marked and transient peak of antiviral responses (type I IFNs, IFN-λ3, ISGs, PRRs and TFs). Importantly, expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-8) or inflammasome components (NLRP3, CASP1, PYCARD) was dampened. The role of IFN-λ3 to counterbalance inflammatory processes and bridge innate and adaptive immune responses in camelid species is discussed. Our findings shed light into key mechanisms on how reservoir species control MERS-CoV in the absence of clinical disease.

Respiratory virus detection in returning travelers and pilgrims from the Middle East.

BACKGROUND: Pilgrims travelling to Saudi Arabia are commonly infected with respiratory viruses. Since the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012, patients with acute respiratory symptoms returning from an endemic area can be suspected to be infected by this virus. METHODS: 98 patients suspected to have MERS-CoV infection from 2014 to 2019 were included in this retrospective cohort study. Upper and lower respiratory tract samples were tested by real-time RT-PCR for the detection of MERS-CoV and other respiratory viruses. Routine microbiological analyses were also performed. Patient data were retrieved from laboratory and hospital databases retrospectively. RESULTS: All patients with suspected MERS-CoV infection travelled before their hospitalization. Most frequent symptoms were cough (94.4%) and fever (69.4%). 98 specimens were tested for MERS-CoV RNA and none of them was positive. Most frequently detected viruses were Enterovirus/Rhinovirus (40/83; 48.2%), Influenzavirus A (34/90; 37.8%) and B (11/90; 12.2%), H-CoV (229E and OC43 10/83; 12% and 7/83; 8.4%, respectively). CONCLUSION: From 2014 to 2019, none of 98 patients returning from endemic areas was MERS-CoV infected. However, infections with other respiratory viruses were frequent, especially with Enterovirus/Rhinoviruses and Influenzaviruses.

Development of virus-like particles-based vaccines against coronaviruses.

Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the most impactful coronaviruses in human history, especially the latter, which brings revolutionary changes to human vaccinology. Due to its high infectivity, the virus spreads rapidly throughout the world and was declared a pandemic in March 2020. A vaccine would normally take more than 10 years to be developed. As such, there is no vaccine available for SARS-CoV and MERS-CoV. Currently, 10 vaccines have been approved for emergency use by World Health Organization (WHO) against SARS-CoV-2. Virus-like particle (VLP)s are nanoparticles resembling the native virus but devoid of the viral genome. Due to their self-adjuvanting properties, VLPs have been explored extensively for vaccine development. However, none of the approved vaccines against SARS-CoV-2 was based on VLP and only 4% of the vaccine candidates in clinical trials were based on VLPs. In the current review, we focused on discussing the major advances in the development of VLP-based vaccine candidates against the SARS-CoV, MERS-CoV, and SARS-CoV-2, including those in clinical and pre-clinical studies, to give a comprehensive overview of the VLP-based vaccines against the coronaviruses.

Review of Thoracic Imaging Manifestations of COVID-19 and Other Pathologic Coronaviruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an easily transmissible coronavirus that emerged in late 2019 and has caused a global pandemic characterized by acute respiratory disease named coronavirus disease 2019 (COVID-19). Diagnostic imaging can be helpful as a complementary tool in supporting the diagnosis of COVID-19 and identifying alternative pathology. This article presents an overview of acute and postacute imaging findings in COVID-19.

Middle East respiratory syndrome coronavirus (MERS-CoV) infection: Analyses of risk factors and literature review of knowledge, attitude and practices.

The study aimed to explore the risk factors for MERS-CoV infection and systematic review of knowledge, attitudes and practices (KAP) with regard to MERS-CoV among the health care workers (HCWs) and the general population. The World Health Organization's MERS-CoV line list (January 2013-January 2020) of the Kingdom of Saudi Arabia (KSA) was analysed. A Poisson regression model was used to calculate the univariate relative risk of outcomes to each potential risk factor, p-values and 95% confidence intervals. An electronic literature search was conducted to assess knowledge, attitudes and practices of the HCWs and general population of the KSA, with regards to transmission of the infection, risk factors and preventative measures. The line list analysis shows that age, gender, comorbidity, exposure to camels and camel milk consumption were associated with an increased risk of fatality; however, year-wise analysis did not show any decline. Over the years, the mean durations between the symptom onset and hospitalization; the hospitalization and laboratory confirmation have reduced. The review of literature shows that the health care workers and the general population had inadequate knowledge about MERS-CoV, lacked motivation and were disconnected from the health authorities. The WHO line list provides information on risk factors for MERS-CoV, KAP analysis helps to know the potential underlying factors. The literature review shows that continuous education for HCWs and increasing public awareness can help effectively manage future MERS-CoV.

Middle East Respiratory Syndrome coronavirus vaccine development: updating clinical studies using platform technologies.

Middle East Respiratory Syndrome coronavirus (MERS-CoV), a contagious zoonotic virus, causes severe respiratory infection with a case fatality rate of approximately 35% in humans. Intermittent sporadic cases in communities and healthcare facility outbreaks have continued to occur since its first identification in 2012. The World Health Organization has declared MERS-CoV a priority pathogen for worldwide research and vaccine development due to its epidemic potential and the insufficient countermeasures available. The Coalition for Epidemic Preparedness Innovations is supporting vaccine development against emerging diseases, including MERS-CoV, based on platform technologies using DNA, mRNA, viral vector, and protein subunit vaccines. In this paper, we review the usefulness and structure of a spike glycoprotein as a MERS-CoV vaccine candidate molecule, and provide an update on the status of MERS-CoV vaccine development. Vaccine candidates based on both DNA and viral vectors coding MERS-CoV spike gene have completed early phase clinical trials. A harmonized approach is required to assess the immunogenicity of various candidate vaccine platforms. Platform technologies accelerated COVID-19 vaccine development and can also be applied to developing vaccines against other emerging viral diseases.

C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?

From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.

Gene signatures and potential therapeutic targets of Middle East respiratory syndrome coronavirus (MERS-CoV)-infected human lung adenocarcinoma epithelial cells.

BACKGROUND: Pathogenic coronaviruses include Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-CoV-2. These viruses have induced outbreaks worldwide, and there are currently no effective medications against them. Therefore, there is an urgent need to develop potential drugs against coronaviruses. METHODS: High-throughput technology is widely used to explore differences in messenger (m)RNA and micro (mi)RNA expression profiles, especially to investigate protein-protein interactions and search for new therapeutic compounds. We integrated miRNA and mRNA expression profiles in MERS-CoV-infected cells and compared them to mock-infected controls from public databases. RESULTS: Through the bioinformatics analysis, there were 251 upregulated genes and eight highly differentiated miRNAs that overlapped in the two datasets. External validation verified that these genes had high expression in MERS-CoV-infected cells, including RC3H1, NF-κB, CD69, TNFAIP3, LEAP-2, DUSP10, CREB5, CXCL2, etc. We revealed that immune, olfactory or sensory system-related, and signal-transduction networks were discovered from upregulated mRNAs in MERS-CoV-infected cells. In total, 115 genes were predicted to be related to miRNAs, with the intersection of upregulated mRNAs and miRNA-targeting prediction genes such as TCF4, NR3C1, and POU2F2. Through the Connectivity Map (CMap) platform, we suggested potential compounds to use against MERS-CoV infection, including diethylcarbamazine, harpagoside, bumetanide, enalapril, and valproic acid. CONCLUSIONS: The present study illustrates the crucial roles of miRNA-mRNA interacting networks in MERS-CoV-infected cells. The genes we identified are potential targets for treating MERS-CoV infection; however, these could possibly be extended to other coronavirus infections.

Detection of Coronaviruses Using RNA Toehold Switch Sensors.

A rapid, sensitive and simple point-of-care (POC) nucleic acid diagnostic test is needed to prevent spread of infectious diseases. Paper-based toehold reaction, a recently emerged colorimetric POC nucleic acid diagnostic test, has been widely used for pathogen detection and microbiome profiling. Here, we introduce an amplification method called reverse transcription loop-mediated amplification (RT-LAMP) prior to the toehold reaction and modify it to enable more sensitive and faster colorimetric detection of RNA viruses. We show that incorporating the modified RT-LAMP to the toehold reaction detects as few as 120 copies of coronavirus RNA in 70 min. Cross-reactivity test against other coronaviruses indicates this toehold reaction with the modified RT-LAMP is highly specific to the target RNA. Overall, the paper-based toehold switch sensors with the modified RT-LAMP allow fast, sensitive, specific and colorimetric coronavirus detection.

Development of A MERS-CoV Replicon Cell Line for Antiviral Screening.

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease with a high mortality of ~ 35%. The lack of approved treatments for MERS-CoV infection underscores the need for a user-friendly system for rapid drug screening. In this study, we constructed a MERS-CoV replicon containing the Renilla luciferase (Rluc) reporter gene and a stable luciferase replicon-carrying cell line. Using this cell line, we showed that MERS-CoV replication was inhibited by combined application of lopinavir and ritonavir, indicating that this cell line can be used to screen inhibitors of MERS-CoV replication. Importantly, the MERS-replicon cell line can be used for high-throughput screening of antiviral drugs without the need for live virus handling, providing an effective and safe tool for the discovery of antiviral drugs against MERS-CoV.

Neuroimaging and neurologic findings in COVID-19 and other coronavirus infections: A systematic review in 116 patients.

Various neurologic syndromes have been described in patients with COVID-19 and other coronavirus infections. In this paper, we systematically reviewed the available imaging findings of patients diagnosed with neurological symptoms associated with coronavirus infections. Diverse radiologic results in the context of different neurologic presentations have been demonstrated using CT and MRI. While many patients have normal imaging evaluations, some patients present with intra-axial and extra-axial abnormalities. Stroke (both ischemic and hemorrhagic), encephalomyelitis, meningitis, demyelinating disorders such as acute disseminated encephalomyelitis (ADEM), and encephalopathy have been reported. Familiarity with these radiologic patterns will guide radiologists and referring clinicians to consider coronavirus infections in patients with worsening or progressive neurologic findings, particularly during the current COVID-19 pandemic. As data on this topic is very limited, further research and investigation are required.

Antibody-dependent enhancement of coronavirus.

Antibody-dependent enhancement (ADE) exists in several kinds of virus. It has a negative influence on antibody therapy for viral infection. This effect was first identified in dengue virus and has since also been described for coronavirus. To date, the rapid spread of the newly emerged coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has affected over 3.8 million people across the globe. The novel coronavirus poses a great challenge and has caused a wave of panic. In this review, antibody-dependent enhancements in dengue virus and two kinds of coronavirus are summarized. Possible solutions for the effects are reported. We also speculate that ADE may exist in SARS-CoV-2.

Does hereditary angioedema make COVID-19 worse?

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2) and depletes ACE2, which is necessary for bradykinin metabolism. The depletion of ACE2 results in the accumulation of des-Arg (9)-bradykinin and possible bradykinin, both of which bind to bradykinin receptors and induce vasodilation, lung injury, and inflammation. It is well known that an overactivated contact system and excessive production of bradykinin comprise the key mechanisms that drive the pathogenesis of hereditary angioedema (HAE). It is reasonable to speculate that COVID-19 may increase disease activity in patients with HAE and vice versa. In this review, we explore the potential interactions between COVID-19 and HAE in terms of the contact system, the complement system, cytokine release, increased T helper 17 cells, and hematologic abnormalities. We conclude with the hypothesis that comorbidity with HAE might favor COVID-19 progression and may worsen its outcomes, while COVID-19 might in turn aggravate pre-existing HAE and prompt the onset of HAE in asymptomatic carriers of HAE-related mutations. Based on the pathophysiologic links, we suggest that long-term prophylaxis should be considered in patients with HAE at risk of SARS-CoV-2 infection, especially the prophylactic use of C1 inhibitor and lanadelumab and that HAE patients must have medications for acute attacks of angioedema. Additionally, therapeutic strategies employed in HAE should be considered for the treatment of COVID-19, and clinical trials should be performed.

Recent apprise on coronavirus and its terrible insinuations.

Epidemically increased evidence reveals that the link between the 2019-nCoV and other similar strain of coronaviruses circulating in bats and specifically the Rhinopodous bat sub-species. These sub-species are ample and widely present in Southern China, Middle East Africa and Europe. Recent studies show that more than 500 CoV have been identified in bats in China. The Center for Diseases Control and Prevention and the World Health Organization maintains a website that is updated frequently with new cases of MERS-CoV infection. As per WHO Situation report 16th, 24,554 number of cases confirmed globally out of which 99.22% cases from china. A new coronavirus (2019-nCoV) is causing respiratory syndrome mostly in Hubei Province, China. Corona Virus spread over 24 countries including Japan, India, Korea, and other countries 2019-CoV infection vary from mild, moderate or severe illness; the later includes severe pneumonia, ARDS, sepsis and septic shock. There are two diagnostic tests for coronavirus infection i.e. molecular test and serology test. In this review article there are the various recent cases of the patients that are suffering from the corona virus, the outcome of these studies is that corona virus infection is an epidemic disease which affects Central Nervous System (CNS).

The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus.

Antiviral drugs for managing infections with human coronaviruses are not yet approved, posing a serious challenge to current global efforts aimed at containing the outbreak of severe acute respiratory syndrome-coronavirus 2 (CoV-2). Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including severe acute respiratory syndrome-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps). Here, we co-expressed the MERS-CoV nonstructural proteins nsp5, nsp7, nsp8, and nsp12 (RdRp) in insect cells as a part a polyprotein to study the mechanism of inhibition of MERS-CoV RdRp by RDV. We initially demonstrated that nsp8 and nsp12 form an active complex. The triphosphate form of the inhibitor (RDV-TP) competes with its natural counterpart ATP. Of note, the selectivity value for RDV-TP obtained here with a steady-state approach suggests that it is more efficiently incorporated than ATP and two other nucleotide analogs. Once incorporated at position i, the inhibitor caused RNA synthesis arrest at position i + 3. Hence, the likely mechanism of action is delayed RNA chain termination. The additional three nucleotides may protect the inhibitor from excision by the viral 3'-5' exonuclease activity. Together, these results help to explain the high potency of RDV against RNA viruses in cell-based assays.

[Coronaviruses as the cause of respiratory infections]. / Coronaviren als Ursache respiratorischer Infektionen.

BACKGROUND: There are six human pathogenic coronaviruses (CoV), which mainly cause infections of the respiratory system. In everyday clinical practice, it is helpful to know the relevance and characteristics of these pathogens. OBJECTIVE: To present the epidemiology, clinical picture and differences of human pathogenic CoV and to provide information on the diagnostics and treatment of patients suspected of having CoV infections. MATERIAL AND METHODS: Selective literature search, presentation of results and discussion of fundamental works and expert recommendations, including publications by the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC) and the Robert Koch Institute. RESULTS: The four endemic human CoVs (HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1) mainly cause mild respiratory tract infections. In addition to these four endemic HCoV, the two epidemic CoV, severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV can cause severe pneumonia. The SARS-CoV has not been detected in humans in the last 15 years and MERS-CoV has been circulating mainly on the Arabian Peninsula since 2012; however, neither a specific treatment nor approved vaccines exist for any of the six human pathogenic CoVs. CONCLUSION: All six human CoVs can be diagnosed using RT-PCR on respiratory specimens but this is rarely necessary for the four endemic strains. In current clinical practice SARS-CoV has no importance as it has not been detected in humans for 15 years; however, a possible MERS-CoV infection should be taken into account in patients with typical symptoms and travel history to endemic regions. In this case, rapid diagnostic and general hygiene practices are important to prevent further transmission.

Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles.

Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target molecules in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye molecules). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compounds at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl2) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral molecules through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV-vis wavelength range. We designed a pair of thiol-modified probes at either the 5' end or 3' end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/µL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, especially in resource-limited settings.

Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling.

The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PLpro), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the IC50 value of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.