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State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans
... During the 1918 Spanish flu pandemic, convalescent plasma was used to treat those with pneumonia [3,4]. More recently, convalescent plasma was utilized with reported success in the management of MERS [5], Ebola [6], H5N1 [7], H1N1 [8], and SARS infections [9]. COVID-19 convalescent plasma (CP) is procured by plasmapheresis from donors who have recently recovered from COVID-19. ...
... This led to wordof-mouth spread to external donors, increasing the interest of many. Volunteer donors were screened at UHB based on the following criteria: (1) self-reported recovery from a documented COVID-19 infection, (2) asymptomatic for at least 14 days, (3) negative SARS-CoV-2 RNA RT PCR assay (only for those asymptomatic for 28 days), (4) positive lateral flow test (POS++ or greater), (5) high ELISA IgG titer (titer of at least 1:1024) and (6) no detectable anti-HLA antibody (Immucor, Delux Screen, Atlanta, GA). While the donation program was ramping up, the UHB blood bank reached out to New York Blood Center (NYBC) for COVID-19 CP. ...
Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.
... Although corticosteroids interfere with a wide array of inflammatory pathways, they were initially actively discouraged by WHO for COVID-19, based on small-sized studies on SARS-CoV-1 and MERS coronavirus infections [13]. In such diseases, either safety concerns or no clinical efficacy were reported [14,15], with possibly increase in viral load and prolonged viral shedding [16]. In China, however, corticosteroids were used in up to 50% of severe COVID-19 patients [17][18][19]. ...
... COVID-19-related cytokine storm is reminiscent of immune-mediated diseases, such as hemophagocytic lymphohistiocytosis, cytokine release in leukemia patients receiving engineered T-cell therapy [29,30], and undesirable side effects of immune checkpoint inhibitors [31]. Owing to their mitigated outcome in the MERS-CoV [13,14], SARS--CoV-1 infections [16], and ARDS [32], the WHO did not recommend corticosteroid use. Given that corticosteroids are cheap and widely available, we felt they should be tested in COVID-19-related hyper-inflammation. ...
Background
The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated.
Material and methods
A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3–5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects.
Results
Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80–1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%).
Conclusion
In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.
... While coronaviruses that infect humans usually present mild symptoms (e.g. 15% of cases involving the common cold are caused by a coronavirus), several previous outbreaks, such as SARS and Middle East respiratory syndrome (MERS) [2], have caused significant fatalities in infected populations [3]. ...
... After an epidemic episode (e.g. SARS) there is little financial incentive for private companies to develop vaccines against a specific strain of virus [10,2,8]. To address these incentive issues, governments might provide greater funding support to create vaccines against past and future outbreaks. ...
As of early March, 2019-nCoV has infected more than one hundred thousand people and claimed thousands of lives. 2019-nCoV is a novel form of coronavirus that causes COVID-19 and has high similarity with SARS-CoV. No approved vaccine yet exists for any form of coronavirus. Here we use computational tools from structural biology and machine learning to identify 2019-nCoV T-cell and B-cell epitopes based on viral protein antigen presentation and antibody binding properties. These epitopes can be used to develop more effective vaccines and identify neutralizing antibodies. We identified 405 viral peptides with good antigen presentation scores for both human MHC-I and MHC-II alleles, and two potential neutralizing B-cell epitopes near the 2019-nCoV spike protein receptor binding domain (440-460 and 494-506). Analyzing mutation profiles of 68 viral genomes from four continents, we identified 96 coding-change mutations. These mutations are more likely to occur in regions with good MHC-I presentation scores (p=0.02). No mutations are present near the spike protein receptor binding domain. Based on these findings, the spike protein is likely immunogenic and a potential vaccine candidate. We validated our computational pipeline with SARS-CoV experimental data.
Significance Statement
The novel coronavirus 2019-nCoV has affected more than 100 countries and continues to spread. There is an immediate need for effective vaccines that contain antigens which trigger responses from human T-cells and B-cells (known as epitopes). Here we identify potential T-cell epitopes through an analysis of human antigen presentation, as well as B-cell epitopes through an analysis of protein structure. We identify a list of top candidates, including an epitope located on 2019-nCoV spike protein that potentially triggers both T-cell and B-cell responses. Analyzing 68 samples, we observe that viral mutations are more likely to happen in regions with strong antigen presentation, a potential form of immune evasion. Our computational pipeline is validated with experimental data from SARS-CoV.
... Severe MERS is characterized predominantly by ARDS, acute kidney failure, and in the most severe cases, by multiple organ failure that can be fatal [49,50]. One third of patients develop pneumonia and 20% develop ARDS [51]. ...
... Finally, co-infection with other respiratory viruses, in particular influenza, has been described although the impact of such combined infections have not been evaluated [44,55]. Co-infections with bacteria have also been reported in the patients developing the most severe disease [49,51]. ...
Since the first case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of confirmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.
... The WHO noted that more than 8000 individuals were harmed, and 774 were killed in 2002-2003 due to the coronavirus known as SARS [7]. More than 2494 people were affected by the MERS-CoV outbreak in 2012, and more than 858 people died worldwide [8]. ...
Background
The first hit of the COVID-19 pandemic was reported in December 2019 in Wuhan, Hubei province, China, and wholesale seafood markets were reported to be the source of infection. The development of effective and safe vaccines against SARS-CoV-2 has been extremely fast. The development of the COVID-19 mRNA vaccine started in early January 2020, after the release of the SARS-CoV-2 genetic sequence by the Chinese Center for Disease Control and Prevention and its global dissemination by the Global Initiative on Sharing All Influenza Data (GISAID).
Aim
The current study aims to evaluate the taste detection threshold after the second shot of Pfizer COVID-19 vaccination at different intervals and after the booster shot.
Materials and methods
A multistage sampling technique was used to select all Iraqi healthcare workers (HCWs) to whom the inclusion criteria were applied, from Baghdad Medical City and Al-Yarmouk Teaching Hospital participated in this study. The total number of selected subjects was 85. The ages of HCWs ranged from 24 to 60 years. The first study group (G1) comprised 30 HCWs who received the COVID-19 vaccination from Pfizer in two doses. The subjects were recruited into this group two weeks to three months after being vaccinated and had no history of COVID-19 symptoms. The second group (G2) comprised 30 HCWs who received the COVID-19 vaccination from Pfizer in two doses. They were recruited three to six months after they were vaccinated and had no prior history of the virus’ symptoms. The third group (G3) was of 25 HCWs who received a third booster dose of COVID-19 vaccination from Pfizer two weeks after the booster dose. The taste detection threshold was performed for four basic tastes: sweet, sour, salt, and bitter.
Results
The taste detection threshold for (sweets) showed a significant difference between the first and second groups and the second and third groups. The taste detection threshold of sweets was significantly higher in the second group.
Conclusions
After three to six months from getting the second dose, the taste detection threshold for sweets was assessed as high. This means that the flavor will be harder to perceive. Pfizer COVID-19 immunization may be assumed to be one of the causes of defected taste sensation to sweet flavor.
... Coronaviruses (CoV) are enveloped positive-stranded RNA-viruses [2] belonging to a family of zoonotic viruses [3] which infect a variety of mammals including bats and humans [4]. They are implicated in previous outbreaks such as, Middle East Respiratory Syndrome (MERS-CoV) [5], Severe Acute Respiratory Syndrome (SARS-CoV) [4] and most recently SARS-CoV-2 [6], which has created an urgent need to develop diagnostics, therapeutics and vaccines against SARS-CoV-2. Although a few vaccines have been rolled-out in some major developed and developing countries, a number of vaccine candidates are still under clinical trials at various laboratories across the world in non-profit, public, academic, multinational pharmaceutical companies and other industries [7]. ...
The current global pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken a substantial number of lives across the world. Although few vaccines have been rolled-out, a number of vaccine candidates are still under clinical trials at various pharmaceutical companies and laboratories around the world. Considering the intrinsic nature of viruses in mutating and evolving over time, persistent efforts are needed to develop better vaccine candidates. In this study, various immuno-informatics tools and bioinformatics databases were deployed to derive consensus B-cell and T-cell epitope sequences of SARS-CoV-2 spike glycoprotein. This approach has identified four potential epitopes which have the capability to initiate both antibody and cell-mediated immune responses, are non-allergenic and do not trigger autoimmunity. These peptide sequences were also evaluated to show 99.82% of global population coverage based on the genotypic frequencies of HLA binding alleles for both MHC class-I and class-II and are unique for SARS-CoV-2 isolated from human as a host species. Epitope number 2 alone had a global population coverage of 98.2%. Therefore, we further validated binding and interaction of its constituent T-cell epitopes with their corresponding HLA proteins using molecular docking and molecular dynamics simulation experiments, followed by binding free energy calculations with molecular mechanics Poisson-Boltzmann surface area, essential dynamics analysis and free energy landscape analysis. The immuno-informatics pipeline described and the candidate epitopes discovered herein could have significant impact upon efforts to develop globally effective SARS-CoV-2 vaccines.
... Coronaviruses (CoVs) are positive-sense, single-stranded, enveloped RNA viruses, many of which commonly infect humans and cause mild symptoms. However, over the past two decades, emerging pathogenic CoVs that can cause lifethreatening disease in humans and animals have been identified, namely severe acute respiratory syndrome coronavirus (SARS-CoV) (1, 2), Middle Eastern respiratory syndrome coronavirus (MERS-CoV) (3)(4)(5), and SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19) (6). The global pandemic caused by SARS-CoV-2 has resulted in severe respiratory illness throughout the world. ...
Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients with coronavirus disease 2019 (COVID-19). In October 2020, the U.S. FDA approved intravenous RDV as the first treatment for hospitalized COVID-19 patients. Furthermore, RDV has been approved or authorized for emergency use in more than 50 countries. To make RDV more convenient for nonhospitalized patients earlier in disease, alternative routes of administration are being evaluated. Here, we investigated the pharmacokinetics and efficacy of RDV administered by head dome inhalation in African green monkeys (AGM). Relative to an intravenous administration of RDV at 10 mg/kg, an about 20-fold lower dose administered by inhalation produced comparable concentrations of the pharmacologically active triphosphate in lower respiratory tract tissues. Distribution of the active triphosphate into the upper respiratory tract was also observed after inhaled RDV exposure. Inhalation RDV dosing resulted in lower systemic exposures to RDV and its metabolites as compared with intravenous RDV dosing. An efficacy study with repeated dosing of inhaled RDV in an AGM model of SARS-CoV-2 infection demonstrated reductions in viral replication in bronchoalveolar lavage fluid and respiratory tract tissues compared with placebo. Efficacy was observed with inhaled RDV administered once daily at a pulmonary deposited dose of 0.35 mg/kg beginning about 8 hours after infection. Moreover, the efficacy of inhaled RDV was similar to that of intravenous RDV administered once at 10 mg/kg followed by 5 mg/kg daily in the same study. Together, these findings support further clinical development of inhalation RDV.
... The case fatality rate is 35-40% [134,[199][200][201][202] Novel coronavirus COVID-19 [203][204][205] C.-X. Li et al. According to taxonomic classification, SARS-CoV-2 is categorized as a strain of the species SARS-CoV-1 [71]. ...
Coronavirus is a family of viruses that can cause diseases such as the common cold, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). The universal outbreak of coronavirus disease 2019 (COVID-19) caused by SARS coronaviruses 2 (SARS-CoV-2) has become a global pandemic. The β-Coronaviruses, which caused SARS-CoV-2 (COVID-19), have spread in more than 213 countries, infected over 81 million people, and caused more than 1.79 million deaths. COVID-19 symptoms vary from mild fever, flu to severe pneumonia in severely ill patients. Difficult breathing, acute respiratory distress syndrome (ARDS), acute kidney disease, liver damage, and multi-organ failure ultimately lead to death. Researchers are working on different pre-clinical and clinical trials to prevent this deadly pandemic by developing new vaccines. Along with vaccines, therapeutic intervention is an integral part of healthcare response to address the ongoing threat posed by COVID-19. Despite the global efforts to understand and fight against COVID-19, many challenges need to be addressed. This article summarizes the current pandemic, different strains of SARS-CoV-2, etiology, complexities, surviving medications of COVID-19, and so far, vaccination for the treatment of COVID-19.
... Although MERS-CoV rapidly spread globally [53], it is generally regarded less human-to-human transmissible than SARS-CoV or SARS-CoV-2, with an early estimate of an R 0 below 1 in the general community and in households [54 ]. In healthcare settings human-to-human transmission has led to large outbreaks with higher R 0 , providing a warning sign for pandemic potential [55][56][57]. Continuous zoonotic events are being reported. The current consensus is that close and prolonged contact with an index case seems to be required for MERS-CoV transmission and adaptation would be required for efficient human-to-human transmission. ...
SARS-CoV-2 emerged in China as a zoonotic virus in December 2019. The virus proved to be human-to-human transmissible and its global spread resulted in the ongoing COVID-19 pandemic, associated with high morbidity and mortality. Vaccines were developed at an unprecedented speed and proved to be efficacious in preventing disease, but it remains to be determined if vaccines are able to interrupt transmission. Moreover, virus variants of concern continue to emerge that appear more transmissible and/or less sensitive to virus-specific immune responses. Here, we briefly review the role of animal models in assessing prophylactic and therapeutic options to interrupt SARS-CoV-2 transmission.
... It was more common for males (73%) with a median age of 49 years to have COVID-19 (13). The situation was the same for MERS-CoV (14). The WHO has reported that 75.5% of patients infected with MERS-CoV were male, and the median age was 54 years (interquartile range 40-65.5, range 10-93 years) (15). ...
Purpose
Coronavirus disease 2019 (COVID-19) has become a topic of concern worldwide; however, the impacts of type 2 diabetes mellitus (T2DM) on disease severity, therapeutic effect, and mortality of patients with COVID-19 are unclear.
Methods
All consecutive patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020, were included in this study.
Results
A total of 663 patients with COVID-19 were included, while 67 patients with T2DM accounted for 10.1% of the total. Compared with patients with COVID-19 without T2DM, those with T2DM were older (aged 66 years vs 57 years; P < 0.001) and had a male predominance (62.7% vs 37.3%; P = 0.019) and higher prevalence of cardiovascular diseases (61.2% vs 20.6%; P < 0.001) and urinary diseases (9% vs 2.5%; P = 0.014). Patients with T2DM were prone to developing severe (58.2% vs 46.3%; P = 0.002) and critical COVID-19 (20.9% vs 13.4%; P = 0.002) and having poor therapeutic effect (76.1% vs 60.4%; P = 0.017). But there was no obvious difference in the mortality between patients with COVID-19 with and without T2DM (4.5% vs 3.7%; P = 0.732). Multivariate logistic regression analysis identified that T2DM was associated with poor therapeutic effect in patients with COVID-19 (odd ratio [OR] 2.99; 95% confidence interval [CI], 1.07-8.66; P = 0.04). Moreover, having a severe and critical COVID-19 condition (OR 3.27; 95% CI, 1.02-9.00; P = 0.029) and decreased lymphocytes (OR 1.59; 95% CI, 1.10-2.34; P = 0.016) were independent risk factors associated with poor therapeutic effect in patients with COVID-19 with T2DM.
Conclusions
T2DM influenced the disease severity and therapeutic effect and was one of the independent risk factors for poor therapeutic effect in patients with COVID-19.
... Although less frequent, Haemophilus influenzae and Pseudomonas aeruginosa may also cause secondary bacterial pneumonia (26). Klebsiella pneumoniae, Staphylococcus aureus, and Acinetobacter species have also been reported to cause secondary bacterial pneumonia in patients with the Middle East respiratory syndrome (MERS), which is also caused by a coronavirus (27)(28)(29). In this study, Staphylococcus aureus was detected in 2 of 7 patients, and Klebsiella pneumoniae and Haemophilus influenzae were detected in 1 patient each. ...
Objective To describe the clinical features and clinical course of individuals diagnosed with asymptomatic SARS-CoV-2 infection or mild COVID-19.
Patients The study participants consisted of 7 crewmembers of the passenger cruise-liner, Diamond Princess, who were admitted to our hospital after becoming infected with SARS-CoV-2 aboard the ship.
Methods The data on patient background and biochemical test results were obtained from the patients' medical records. All patients had a chest X-ray, and a throat swab and sputum samples were sent for culture on admission.
Results The median age of the 7 patients, of whom 4 were male and 3 were female, was 39 years (range: 23-47 years). On admission, none of them had fever, but 4 (57%) had a cough. None of them showed any signs of organ damage on laboratory testing. Chest X-ray showed pneumonia in one individual, which resolved spontaneously, while the other 6 had normal chest X-ray findings. Culture of throat swabs and sputum samples revealed that 4 patients (57%) had bacterial upper respiratory infections (Haemophilus influenzae, Klebsiella pneumoniae, and Staphylococcus aureus). The period from a positive PCR test to negative conversion ranged from 5 to 13 days, with a median of 8 days.
Conclusion Healthy young adults without risk factors who acquire SARS-CoV-2 infection may have an asymptomatic infection or may experience mild COVID-19. In addition to obesity, an older age, underlying illness, and being overweight can lead to a risk of exacerbation; thus, hospital management for such individuals may be desirable. Culturing respiratory samples may be useful for diagnosing secondary bacterial pneumonia.
... The positive response of CP with reference to the recently, avian H1N1, H5N1 and other organism related acute respiratory infections (SARI) was evaluated based on clinical applications on patients, in the coming decades. In addition, animal models of influenza pneumonia have also shown satisfactory response of convalescent serum [20][21][22][23][24][25][26][27][28][29][30]. Other viral infections [31][32][33] such as Influenza [34], mumps [35], Herpes zoster [36], Poliomyelitis [37], and measles were also treated effectively [29,38]. ...
Background: The COVID-19 virus, in terms of pathogenesis and disease spectrum, resembles its predecessor viral strains which caused outbreaks of SARS and MERs. Due to unavailability of approved treatment protocols, healthcare workers initiated treatment of COVID-19 patients with convalescent plasma therapy. Objective: To appraise similarities between the three Coronaviruses and deduce the effectiveness of CP therapy based on exploration of its efficacy in the SARS and MERS outbreaks. Analysis: A narrative review of case reports, randomised controlled trials and meta-analysis studies, on use of CP therapy in SARs and MERS, was conducted. Studies evaluated for the purpose of this review were added through search engines of PubMed Central and Google Scholar. Results: We concluded that CP therapy had been able to play pivotal roles in treating critically-ill SARS and MERS patients. The risks of unintended immunological responses among other factors, hindering CP Therapy’s approval from drug administration authorities, were weighed against favourable chanisms, such as hypercoagulability, that support its use in COVID-19 patients. Conclusion: Findings collected from these studies steered our path to theorize the possibility of reducing mortality with convalescent plasma therapy and support our rallying efforts for enlisting this in the official treatment protocol of COVID-19.
Doi: 10.28991/SciMedJ-2020-0204-6
Full Text: PDF
... Convalescent blood products obtained by collecting whole blood or plasma from patients who has survived in previous infection and produce humoral immune against the disease [65]. Convalescent plasma is widely used after large-scale epidemics of various viruses, such as MERS and Ebola virus (EBOV) [66,67]. The results of a phase I clinical trial showed that 10 patients with severe COVID-19 pneumonia had all symptoms, especially fever, cough, shortness of breath, and chest pain, improved within 3 days after infusion of plasma from recovered patients, and laboratory tests, Imaging performance and viral load have improved significantly [68]. ...
The rapid growth of 2019 novel coronavirus (COVID-19) outbreak in Wuhan, China, at the early December 2019. COVID-19 spread all over the word just a few months. The outbreak of COVID-19 infection poses major threat to international health and economy. World Health Organization (WHO) announced that the new coronavirus was an international public health emergency on January 30, 2020. However, with the spread of COVID-19, the routine medical care of lung cancer patients was affected. Because lung cancer patients have low immunity after anti-tumor treatment, they should become the main targets for epidemic prevention. Lung cancer patients are increasingly concerned about the prevention of COVID-19. It is necessary to provide individualized medical treatment and management for lung cancer patients based on patients' conditions and regional epidemic patterns.
... In effect, prognosis likely depends Cerebrovascular events in COVID-19 may be related to a coagulopathic, pro-inflammatory state that results in a cytokine release storm and thrombogenic, vascular endothelial dysfunction, as well as vasculitis, 5,[9][10][11][12] similar to phenomena observed in previous coronavirus outbreaks including Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome. 4,[13][14][15] It is possible that vascular endothelial injury, angiotensin-converting enzyme 2 (ACE2) receptor downreg-NEUROSURGERY OPEN VOLUME 1 | NUMBER 3 | 2020 | 5 Downloaded from https://academic.oup.com/neurosurgeryopen/article-abstract/1/3/okaa008/5872917 by guest on 18 July 2020 ulation, 16 and a systemic coagulopathic state may lead to a spectrum of neurovascular complications of COVID-19, including hemorrhage, ischemia, venous thrombosis, and arterial dissection ( Figure 5). This may explain not only the observation of strokes (in otherwise healthy patients without risk factors for stroke), but also the high rate of hemorrhagic conversion, as well as hemorrhage from otherwise stable lesions (eg, aneurysm and pituitary adenoma). ...
BACKGROUND
Preliminary data suggest that Coronavirus Disease-2019 (COVID-19) is associated with hypercoagulability and neurovascular events, but data on outcomes is limited.
OBJECTIVE
To report the clinical course and outcomes of a case series of COVID-19 patients with a variety of cerebrovascular events.
METHODS
We performed a multicentric, retrospective chart review at our three academic tertiary care hospitals, and identified all COVID-19 patients with cerebrovascular events requiring neuro-intensive care and/or neurosurgical consultation.
RESULTS
We identified 26 patients between March 1 and May 24, 2020, of whom 12 (46%) died. The most common event was a large-vessel occlusion (LVO) in 15 patients (58%), among whom 8 died (8/15, 53%). A total of 9 LVO patients underwent mechanical thrombectomy, of whom 5 died (5/9, 56%). A total of 7 patients (27%) presented with intracranial hemorrhage. Of the remaining patients, 2 had small-vessel occlusions, 1 had cerebral venous sinus thrombosis, and another had a vertebral artery dissection. Acute Respiratory Distress Syndrome occurred in 8 patients, of whom 7 died. Mortalities had a higher D-dimer on admission (mean 20 963 ng/mL) than survivors (mean 3172 ng/mL). Admission Glasgow Coma Scale (GCS) score was poor among mortalities (median 7), whereas survivors had a favorable GCS at presentation (median 14) and at discharge (median 14).
CONCLUSION
COVID-19 may be associated with hemorrhage as well as ischemia, and prognosis appears poorer than expected—particularly among LVO cases, where outcome remained poor despite mechanical thrombectomy. However, a favorable neurological condition on admission and lower D-dimer may indicate a better outcome.
... Patients with MERS-CoV infection usually present with pneumonia-related symptoms, such as fever, myalgia, cough, and dyspnea. Severe cases can lead to acute respiratory distress syndrome (ARDS), septic shock, multiple organ failure, and death (WHO MERS-Cov Research, 2013). MERS-CoV is known to be potentially neuroinvasive, and that a retrospective study found that 25.7% of patients with MERS can develop insanity and 8.6% of patients have seizures (Saad et al., 2014). ...
Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.
... T he point-of-care testing (POCT) market of infectious disease represents promising and significant growth in the global in vitro diagnostics (IVD) industry. 1 There are several factors that are stimulating the demand for infectious disease POCT, including the increasing spread of human immunodeficiency virus (HIV), tuberculosis (TB), and malaria in developing countries, and the threat of emerging and reemerging infectious diseases such as the Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), ZIKA, a variety of influenza strains, and the West Nile virus. 2 Infectious diseases pose a significant risk to human health and has led to more than half of the deaths worldwide. 3 Additionally, widespread infectious diseases have caused a continuous increase in fatality rates in developing countries. ...
... The Coalition for Epidemic Preparedness Innovations has committed 1 billion dollars to vaccine development efforts, starting with 3 of these pathogens: Middle East respiratory syndrome coronavirus, Lassa virus, and Nipah virus (2). These 3 pathogens, as well as others on the World Health Organization's list, such as Zika virus, have high proportions of asymptomatic or mild infection (2)(3)(4)(5)(6)(7). Vaccine efficacy (VE) against susceptibility to infection (VE S ) (8), regardless of symptom level, is an important endpoint of vaccine trials for these pathogens, because infection may contribute to onward transmission and to outcomes such as congenital Zika syndrome, even without primary symptoms (9)(10)(11)(12)(13)(14). ...
Vaccine efficacy against susceptibility to infection (VES), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, as such infections may contribute to onward transmission and long-term sequelae such as Congenital Zika Syndrome. However, estimating VES is resource-intensive. We aim to identify approaches to accurately estimate VES when limited information is available and resources are constrained. We model an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history follows a Susceptible, Exposed, Infectious/Symptomatic or Infectious/Asymptomatic, Recovered model. We then use seven approaches to estimate VES, and we also estimate vaccine efficacy against progression to symptoms (VEP). A corrected relative risk and an interval censored Cox model accurately estimate VES and only require serologic testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VES estimates across values of R0 and accurate estimates of VEP for higher R0 values. Identifying resource-preserving methods for accurately estimating VES and VEP is important in designing trials for diseases with a high proportion of asymptomatic infection.
... Several studies show that, in the Middle East, humans are infected with MERS-CoV through direct or indirect contact with dromedary camels, indicating that dromedary camels are implicated as amplifying host of MERS-CoV and a strong potential source of zoonotic infection (Al Hammadi et al., 2015;Who Mers-Cov Research, 2013). Furthermore, MERS-CoV appears to be circulating outside the Middle East since the virus has been detected in dromedary camels in East, West, http://dx.doi.org/10.1016/j.jviromet.2017.10.008 ...
Since discovering the Middle East respiratory syndrome coronavirus (MERS-CoV) as a causative agent of severe respiratory illness in the Middle East in 2012, serological testing has been conducted to assess antibody responses in patients and to investigate the zoonotic reservoir of the virus. Although the virus neutralization test is the gold standard assay for MERS diagnosis and for investigating the zoonotic reservoir, it uses live virus and so must be performed in high containment laboratories. Competitive ELISA (cELISA), in which a labeled monoclonal antibody (MAb) competes with test serum antibodies for target epitopes, may be a suitable alternative because it detects antibodies in a species-independent manner. In this study, novel MAbs against the spike protein of MERS-CoV were produced and characterized. One of these MAbs was used to develop a cELISA. The cELISA detected MERS-CoV-specific antibodies in sera from MERS-CoV-infected rats and rabbits immunized with the spike protein of MERS-CoV. The MAb-based cELISA was validated using sera from Ethiopian dromedary camels. Relative to the neutralization test, the cELISA detected MERS-CoV-specific antibodies in 66 Ethiopian dromedary camels with a sensitivity and specificity of 98% and 100%, respectively. The cELISA and neutralization test results correlated well (Pearson's correlation coefficients=0.71-0.76, depending on the cELISA serum dilution). This cELISA may be useful for MERS epidemiological investigations on MERS-CoV infection.
... A typical MERS symptom represents fever, shortness of breath, and cough commonly, but not always accompanied by pneumonia [17]. In addition, gastrointestinal symptoms, including diarrhea, nausea, and vomiting, have also been observed [21]. The global mortality rate was about 35.7% as of July 29, 2015, while it was 19.4% in Korea as of Aug 1, 2015 [3,4]. ...
From May to July 2015, there was a nation-wide outbreak of Middle East respiratory syndrome (MERS) in Korea. MERS is caused by MERS-CoV, an enveloped, positive-sense, single stranded RNA virus belonging to the family Coronaviridae. Despite expert opinions that the danger of MERS might be exaggerated, there was an overreaction by the public according to the Korean mass media, which led to a noticeable reduction in social and economic activities during the outbreak. To explain this phenomenon, we presumed that machine learning-based analysis of media outlets would be helpful and collected a number of Korean mass media articles and short-text comments produced during the 10-week outbreak. To process and analyze the collected data (over 86 million words in total) effectively, we created a methodology composed of machine-learning and information-theoretic approaches. Our proposal included techniques for extracting emotions from emoticons and Internet slang, which allowed us to significantly (approximately 73%) increase the number of emotion-bearing texts needed for robust sentiment analysis of social media. As a result, we discovered a plausible explanation for the public overreaction to MERS in terms of the interplay between the disease, mass media, and public emotions.
BACKGROUND
The efficacy of SARS-CoV2 single donor convalescent plasma (CP) varied according to the application time and the amount of antibody that is administered. Single donor CP has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the safety and efficacy of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled CP product was investigated.
METHODS
A total of sixteen patients were treated with either single donor CP (n=9) or pathogen-free, concentrated, pooled CP (ACB-IP 1.0) (n=7).
RESULTS
Five out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor CP. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor CP (0.9642) in 1:256 dilution (ρ<0.01)
The mortality rates of the patients treated with ACB-IP 1.0 plasma were statistically lower (p< 0.05) than the patients treated with single donor CP. The administration of either single donor CP or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization (ρ< 0.05).
CONCLUSION
The present study established ACB-IP 1.0 plasma product as a safe and potentially effective treatment for COVID-19, allowing rapid access to patients in need.
TRIAL REGISTRATION
Trial Registration Number: NCT04769245
Trial Registration Date: 17.03.2021
BACKGROUND
The efficacy of SARS-CoV2 single donor convalescent plasma (CP) varied according to the application time and the amount of antibody that is administered. Single donor CP has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the safety and efficacy of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled CP product was investigated.
METHODS
A total of sixteen patients were treated with either single donor CP (n=9) or pathogen-free, concentrated, pooled CP (ACB-IP 1.0) (n=7).
RESULTS
Five out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor CP. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor CP (0.9642) in 1:256 dilution (ρ<0.01)
The mortality rates of the patients treated with ACB-IP 1.0 plasma were statistically lower (p< 0.05) than the patients treated with single donor CP. The administration of either single donor CP or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization (ρ< 0.05).
CONCLUSION
The present study established ACB-IP 1.0 plasma product as a safe and potentially effective treatment for COVID-19, allowing rapid access to patients in need.
TRIAL REGISTRATION
Trial Registration Number: NCT04769245
Trial Registration Date: 17.03.2021
The fight against infectious diseases calls for the development of safe and effective vaccines that generate long-lasting protective immunity. In a few situations, vaccine-mediated immune responses may have led to exacerbated pathology upon subsequent infection with the pathogen targeted by the vaccine. Such vaccine-associated enhanced disease (VAED) has been reported, or at least suspected, in animal models, and in a few instances in humans, for vaccine candidates against the respiratory syncytial virus (RSV), measles virus (MV), dengue virus (DENV), HIV-1, simian immunodeficiency virus (SIV), feline immunodeficiency virus (FIV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), and the Middle East respiratory syndrome coronavirus (MERS-CoV). Although alleviated by clinical and epidemiological evidence, a number of concerns were also initially raised concerning the short- and long-term safety of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is causing the ongoing COVID-19 pandemic. Although the mechanisms leading to this phenomenon are not yet completely understood, the individual and/or collective role of antibody-dependent enhancement (ADE), complement-dependent enhancement, and cell-dependent enhancement have been highlighted. Here, we review mechanisms that may be associated with the risk of VAED, which are important to take into consideration, both in the assessment of vaccine safety and in finding ways to define models and immunization strategies that can alleviate such concerns.
This study aimed to investigate the prevalence of COVID-19 in domestic cats, focusing on the disease in the north-west of Iran and then showing the natural transmission of SARS-COV-2 circulating between domestic cats and humans.
After receiving ethic codes from Tehran University of Medical Sciences (IR.TUMS.VCR.REC.1399.303) and confirmed by the Center of Communicable Diseases Control (CDC) of Iran, 124 domestic cats were collected from the homes and only one hospital of Meshkin -Shahr district from northwestern Iran where SARS-CoV-2 patients were hospitalized and quarantined during 2020. Samples were prepared from fluid materials of oropharynx and nasopharynx. All samples were tested by real-time PCR (RT-PCR) using specific genes N and ORF1ab in Pasteur Institute of Iran, and then partial sequence analyses of S gene were performed. All collected cats were kept in separated cages until SARS-COV-2 infection was confirmed with the RT-PCR.
RT- PCR Ct values of 123 collected cats were ≥40; thus, all of them showed negative results, but one of the collected cats with close contact with its owner, whom confirmed SARS-CoV-2 showed positive results with gene N(Ct=30) and gene ORF1ab (Ct=32). Furthermore, the positive pet cat showed respiratory and gastro-intestinal clinical manifestations, and its owner was infected with SARS-CoV-2 two weeks ago.
Cats are susceptible animals to SARS-CoV-2 infection. Epidemiological evidence showed that SARS-COV-2 is able to transmit to healthy cats due to having close contact with its owner as a reverse zoonosis.
The past two decades have witnessed the emergence of three zoonotic coronaviruses which have jumped species to cause lethal disease in humans: severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. MERS-CoV emerged in Saudi Arabia in 2012 and the origins of MERS-CoV are not fully understood. Genomic analysis indicates it originated in bats and transmitted to camels. Human-to-human transmission occurs in varying frequency, being highest in healthcare environment and to a lesser degree in the community and among family members. Several nosocomial outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by World Health Organization as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. MERS-CoV has been identified in dromedaries in several countries in the Middle East, Africa, and South Asia. MERS-CoV-2 causes a wide range of clinical presentations, although the respiratory system is predominantly affected. There are no specific antiviral treatments, although recent trials indicate that combination antivirals may be useful in severely ill patients. Diagnosing MERS-CoV early and implementation infection control measures are critical to preventing hospital-associated outbreaks. Preventing MERS relies on avoiding unpasteurized or uncooked animal products, practicing safe hygiene habits in health care settings and around dromedaries, community education and awareness training for health workers, as well as implementing effective control measures. Effective vaccines for MERS-COV are urgently needed but still under development.
Fluorescent probes have long been valuable tools in the study of biological systems. With the ever-expanding range of known enzymatic biomarkers for disease, it has never been more important to develop synthetically facile, sensitive, selective, and robust methods for the detection of these analytes. The 1,8-naphthalimide fluorophore presents an ideal scaffold on which to design a range of fluorescent probes for an unknowable diversity of biomarkers. With tuneable photophysical properties, synthetic versatility, photostability and a large Stokes shift, the 1,8-naphthalimide has, and continues to be, exploited for the detection of a wide range of enzymatic conversions. This review will outline the recent progress towards the design and synthesis of 1,8-naphthalimide fluorophores for the detection of selected enzymatic conversions.
Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.
Background
Until now, no antiviral treatment has been proven to be effective for the coronavirus disease 2019 (COVID-19). The timing of oxygen therapy was considered to have a great influence on the symptomatic relief of hypoxemia and seeking medical intervention, especially in situations with insufficient medical resources, but the evidence on the timing of oxygen therapy is limited.
Methods and findings
Medical charts review was carried out to collect the data of hospitalized patients with COVID-19 infection confirmed in Tongji hospital, Wuhan from 30th December 2019 to 8th March 2020. In this study, the appropriate timing of oxygen therapy and risk factors associated with severe and fatal illness were identified and the effectiveness of antivirus on disease progression was assessed. Among 1362 patients, the prevalence of hypoxia symptoms was significantly higher in those patients with severe and fatal illness than in those with less severe disease. The onset of hypoxia symptoms was most common in the second to third week after symptom onset, and patients with critical and fatal illness experienced these symptoms earlier than those with mild and severe illness. In multivariable analyses, the risk of death increased significantly when oxygen therapy was started more than 2 days after hypoxia symptoms onset among critical patients (OR, 1.92; 95%CI, 1.20 to 3.10). Compared to the critically ill patients without IFN-a, the patients who were treated with IFN-a had a lower mortality (OR, 0.60; 95%CI, 0.39 to 0.91).
Conclusions
Early initiation of oxygen therapy was associated with lower mortality among critical patients. This study highlighted the importance of early oxygen therapy after the onset of hypoxia symptoms. Our results also lend support to potentially beneficial effects of IFNα on critical illness.
During the past decades, many studies have significantly broadened our understanding of complex virus-host interactions to control chromatin structure and dynamics.1, 2 However, the role and impact of such modifications during viral infections is not fully revealed. Indeed, this type of regulation is bidirectional between the virus and the host. While viral replication and gene expression are significantly impacted by histone modifications on the viral chromatin,³ studies have shown that some viral pathogens dynamically manipulate cellular epigenetic factors to enhance their own survival and pathogenesis, as well as escape the immune system defense lines.⁴ In this dynamic, histone posttranslational modifications (PTMs) appear to play fundamental roles in the regulation of chromatin structure and recruitment of other factors.⁵ Genuinely, those PTMs play a vital role in lytic infection, latency reinforcement, or, conversely, viral reactivation.⁶ In this chapter, we will examine and review the involvement of histone modifications as well as their potential manipulation to control infections during various viral life cycle stages, highlighting their prospective implications in the clinical management of human immunodeficiency virus (HIV), herpes simplex virus (HSV), human cytomegalovirus (HCMV), hepatitis B and C viruses (HBV and HCV, respectively), Epstein–Barr virus (EBV), and other viral diseases. Targeting histone modifications is critical in setting the treatment of chronic viral infections with both lytic and latent stages (HIV, HCMV, HSV, RSV), virus-induced cancers (HBV, HCV, EBV, KSHV, HPV), and epidemic/emerging viruses (e.g. influenza virus, arboviruses).
Started in late 2019, coronavirus disease 2019 (COVID-19) has rapidly turned into a global pandemic. Considering there is no proven therapy for COVID-19 infection, there is a need to propose potential treatment options. The use of convalescent plasma is one such option as convalescent plasma has previously been used for treating outbreaks of Ebola, influenza, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and severe acute respiratory (SAR) viruses. Therefore, we carried out an early systematic review to evaluate the efficacy of convalescent plasma (CP) therapy and its effects on COVID-19 patient outcomes. A structured and rigorous systematic review was carried out that included all studies conducted on this topic between December 2019 and June 2020. A total of 10 studies containing a mix of case reports, case series, observational studies, and randomized control trials were identified. Most of the studies lacked randomization and included only small groups of patients. Considering the limitations in the design of current studies, it is difficult to draw a definitive conclusion. However, our results showed that plasma therapy produces notable improvements in patients' clinical symptoms and radiological and biochemical parameters associated with COVID-19 infection. Based on the available information, it is difficult to draw a tangible conclusion about whether plasma therapy improves patient mortality. Until we have concrete evidence to prove otherwise, convalescent plasma therapy may be used as adjuvant therapy for treating COVID-19 infection in critically ill patients.
It is urgent to find an effective antiviral drug against SARS-CoV-2. In this study, 96 virus-drug associations (VDAs) from 12 viruses including SARS-CoV-2 and similar viruses and 78 small molecules are selected. Complete genomic sequence similarity of viruses and chemical structure similarity of drugs are then computed. A KATZ-based VDA prediction method (VDA-KATZ) is developed to infer possible drugs associated with SARS-CoV-2. VDA-KATZ obtained the best AUCs of 0.8803 when the walking length is 2. The predicted top 3 antiviral drugs against SARS-CoV-2 are remdesivir, oseltamivir, and zanamivir. Molecular docking is conducted between the predicted top 10 drugs and the virus spike protein/human ACE2. The results showed that the above 3 chemical agents have higher molecular binding energies with ACE2. For the first time, we found that zidovudine may be effective clues of treatment of COVID-19. We hope that our predicted drugs could help to prevent the spreading of COVID.
During previous coronavirus epidemic infections, numerous clinical studies reported the efficacy of glucocorticoids in the treatment of pneumonia, but to date, no consensus has been reached on their effectiveness. Glucocorticoids are nowadays preferred by physicians to treat and relief COVID-19 symptoms because of their ability to stop the cytokine storm and to prevent lung fibrosis. However, it is essential to validate the clinical use of drugs based on evidence derived by good-quality trials, and not only based on physiopathological findings or previous experiences. This narrative review aims to resemble the evidence about the clinical efficacy of the use of glucocorticoid for the treatment of patients with SARS-CoV-2 infection.
Similar to other epidemics, the novel coronavirus (COVID-19) spread very fast and infected almost two hundreds countries around the globe since December 2019. The unique characteristics of the COVID-19 include its ability of faster expansion through freely existed viruses or air molecules in the atmosphere. Assuming that the spread of virus follows a random process instead of deterministic. The continuous time Markov Chain (CTMC) through stochastic model approach has been utilized for predicting the impending states with the use of random variables. The proposed study is devoted to investigate a model consist of three exclusive compartments. The first class includes white nose based transmission rate (termed as susceptible individuals), the second one pertains to the infected population having the same perturbation occurrence and the last one isolated (quarantined) individuals. We discuss the model’s extinction as well as the stationary distribution in order to derive the the sufficient criterion for the persistence and disease’ extinction. Lastly, the numerical simulation is executed for supporting the theoretical findings.
An ongoing outbreak of pneumonia associated with a novel coronavirus has been reported worldwide and become a global health problem; hence, the diagnosis and differentiation of this virus from other types of coronavirus is essential to control of the disease. To this end, the analysis of genomics data plays a vital role in introducing a stronger target and consequently provides better results in laboratory examinations. The modified comparative genomics approach helps us to find novel specific targets by comparing two or more sequences on the nucleotide collection database. We, for the first time, detected ORF8 gene as a potential target for the detection of the novel coronavirus. Unlike previous reported genes (RdRP, E and N genes), ORF8 is entirely specific to the novel coro-navirus (COVID-19) and has no cross-reactivity with other kinds of coronavirus. Accordingly, ORF8 gene can be used as an additional confirmatory assay.
Since December 2019, the global pandemic caused by the highly infectious novel coronavirus 2019-nCoV (COVID-19) has been rapidly spreading. As of April 2020, the outbreak has spread to over 210 countries, with over 2,400,000 confirmed cases and over 170,000 deaths [1]. COVID-19 causes a severe pneumonia characterized by fever, cough, and shortness of breath. Similar coronavirus outbreaks have occurred in the past causing severe pneumonia like COVID-19, most recently, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). However, over time, SARS-CoV and MERS-CoV were shown to cause extra-pulmonary signs and symptoms including hepatitis, acute renal failure, encephalitis, myositis, and gastroenteritis. Similarly, sporadic reports of COVID-19 related extrapulmonary manifestations emerge. Unfortunately, there is no comprehensive summary of the multi-organ manifestations of COVID-19, making it difficult for clinicians to quickly educate themselves about this highly contagious and deadly pathogen. What's more, is that SARS-CoV and MERS-CoV are the closest humanity has come to combating something similar to COVID-19, however, there exists no comparison between the manifestations of any of these novel coronaviruses. In this review, we summarize the current knowledge of the manifestations of the novel coronaviruses SARS-CoV, MERS-CoV, and COVID-19, with a particular focus on the latter, and highlight their differences and similarities.
Background:
At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.
Methods:
The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.
Discussion:
The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.
Trial registration:
ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.
Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. These biologically diverse viruses enter and replicate within host cells triggering viral- and host-mediated damage that results in pneumonia and multiorgan failure in severe cases. Early case identification and strict infection control limit healthcare transmission. Vaccination allowed smallpox eradication and limits global measles and seasonal influenza mortality. While SARS-coronavirus (CoV) is no longer circulating, MERS-CoV and zoonotic influenza viruses, with pandemic potential, remain persistent threats. Supportive critical care is the mainstay of treatment for severe disease due to these viral infections.
To investigate a cluster of Middle East respiratory syndrome (MERS) cases in a women-only dormitory in Riyadh, Saudi Arabia, in October 2015, we collected epidemiologic information, nasopharyngeal/oropharyngeal swab samples, and blood samples from 828 residents during November 2015 and December 2015-January 2016. We found confirmed infection for 19 (8 by reverse transcription PCR and 11 by serologic testing). Infection attack rates varied (2.7%-32.3%) by dormitory building. No deaths occurred. Independent risk factors for infection were direct contact with a confirmed case-patient and sharing a room with a confirmed case-patient; a protective factor was having an air conditioner in the bedroom. For 9 women from whom a second serum sample was collected, antibodies remained detectable at titers >1:20 by pseudoparticle neutralization tests (n = 8) and 90% plaque-reduction neutralization tests (n = 2). In closed high-contact settings, MERS coronavirus was highly infectious and pathogenicity was relatively low.
Background:
The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) emerged in 2012 and attracted an international attention as the virus caused multiple healthcare associated outbreaks. There are reports of the role of asymptomatic individuals in the transmission of MERS-CoV, however, the exact role is not known.
Method:
The MEDLINE/PubMed and Scopus databases were searched for relevant papers published till August 2018 describing asymptomatic MERS-CoV infection.
Results:
A total of 10 papers were retrieved and included in the final analysis and review. The extent of asymptomatic MERS infection had increased with change in the policy of testing asymptomatic contacts. In early cases in April 2012-October 2013, 12.5% were asymptomatic among 144 PCR laboratory-confirmed MERS-CoV cases while in 2014 the proportion rose to 25.1% among 255 confirmed cases. The proportion of asymptomatic cases reported among pediatric confirmed MERS-CoV cases were higher (41.9%-81.8%). Overall, the detection rate of MERS infection among asymptomatic contacts was 1-3.9% in studies included in this review. Asymptomatic individuals were less likely to have underlying condition compared to fatal cases. Of particular interest is that most of the identified pediatric cases were asymptomatic with no clear explanation.
Conclusions:
The proportion of asymptomatic MERS cases were detected with increasing frequency as the disease progressed overtime. Those patients were less likely to have comorbid disease and may contribute to the transmission of the virus.
Introduction
The frequent outbreaks of novel or emerging infectious diseases are alarming. There is a need for urgent and appropriate intervention that can be adapted quickly for such diseases. Middle East respiratory syndrome coronavirus (MERS-CoV) previously known as novel CoV is a viral infection that causes severe acute respiratory illness. MERS-CoV is a respiratory pathogen and contagious that is contracted via close contact with infected subject. It appears to have been transmitted from camels to humans, recent studies have revealed an association among the virus found in humans and that found in camels (Drosten, et al., 2014). The epidemic that started in 2012 in the Kingdom of Saudi Arabia has spread to many countries, mostly in the Middle East and North Africa, and more recently South Korea. The new epidemic started when the virus crossed from an infected individual who had recently traveled to the Middle East and subsequently began spreading between people via direct contact while in some cases the infection crossed from animal to human. This has exposed the general populace and especially the healthcare workers to greater risk. Similar to the reaction during other infection outbreaks, such as SARS and Ebola virus, many countries have issued travel restrictions and advisories to the affected countries because of fear of international spread of the disease. The rate at which the outbreak is evolving cannot be overemphasized and the geographical extension of its spread is widening. Neighborhoods constitute a key determinant of socioeconomic disparities and health habits, and therefore there is a high risk that people at geographical proximity to the infection are particularly vulnerable. Additionally, people with preexisting chronic medical conditions are more prone to being infected by the illness or developing a severe case resulting in fatality (Assiri, et al., 2013). Strong links between healthcare facilities and the outbreak of the disease has been found in Jeddah, where the majority of patients were in contact with other patients or health care facilities (Oboho, et al., 2015). Elsewhere, the transmission of MERS-CoV in household contacts revealed that an outcome of approximately 5% as the rate of secondary transmission occurred at home (Assiri, et al., 2013). In spite of the many research conducted on MERS-CoV, very few have investigated the effect of ecological factors on the transmission of the disease. Moreover, very little is known on the possibility of airborne transmission of the virus and discussion is still on going on this issue. Airborne transmission of the pathogen may also occur through dust and movement of people, equipment and animals within infected countries which may contribute to the spread of the virus. Additionally, the effect of alternating temperature highs and lows may imply seasonality that could alter the transmission and survivability of the virus. Objectives During infectious disease outbreaks, transmission of disease may form networks of infected individuals because of the way virus crossed from infected individual to susceptible individual. See figure 1a for a subset of the infection network for MERS disease used in this study. The infected individuals may form network of individuals connected by source of infection (contact) as direct or indirection connection. The study intends to (1) explore and investigate the relationship between the intensity of the disease in a given region and environmental variables, (2) We sought to evaluate the risk factors of and trends in mortality as a result of MERS-CoV infection in a large cohort of patients between June 6, 2012 and May 19, 2015. Use covariate adjustment to correctly assess the disease-risk factor associated with the survival outcome, (3) It also aims to understand the dynamic pattern of the disease over different temporal and spatial scales. A functional spatial time series method of estimating the death rate in the outbreaks will be formulated. Spatial time series analysis of disease outbreaks are versatile tools for studying and understanding transmission and spread of a disease and may be useful in the different frontiers of its upsurge and in the possibility of its containment or eradication. And lastly, (3) a flexible dependence model that reflect the relationship among infected individuals in the same network.
Figure 1: (Top) Network for subset of the MERS data. The numbers represent the identification number of the patient while the arrow represents the infection direction. (Bottom) Showing the patients that were infected by patient 27.
Figure 2: Number of patients infected by each main contact (patient ID). Preliminary Exploratory Analysis This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in the Arabian Peninsula between June 6, 2012 and May 19, 2015.
Table 1 presents the summary of data used in this study. Of the 958 cases recorded during the study period more than 90% (866) of the disease incidence occurred in the Kingdom of Saudi Arabia while Kuwait has the least incidence of 3. Seventeen percent of those infected with MERS disease were heath care worker. The fatality for the disease is about 0.35 among the total population. The mean age of the infected persons was 50.22 ± 18.37 years, with large percentage (55%) reported that they had some kind of comorbidity. Spatial analyses of disease outbreaks are versatile tools for studying and understanding transmission and spread of a disease.
Figure 3 shows the spread of MERS disease across the Arabian Peninsula within the study period. Majority of the disease incidence occurred in KSA and closed countries.
Table 1. Summary of the MERS data Country No. of Patients No. of Male/female No. with comorbidity Age at incidence % of HCW % fatal Mean/median mean SD KSA 866 565/284 469 49.66/50 49.66 ± 18.54 153 302 UAE 70 50/18 49 54/56 54 ± 15.33 9 30 Qatar 12 9/3 5 59.1/58 59.1 ± 15.99 1 3 Kuwait 3 1/2 3 54/43 54 ± 27.22 0 1 Oman 7 7/0 2 56.28/60 56.28 ± 17.54 1 3 Total 958 632/307 528 50.22/50.5 50.22 ± 18.37 164 339
Emerging infectious diseases (EIDs), including West Nile virus, severe acute respiratory syndrome (SARS) and Lyme disease, have had a direct effect within Canada, while many more EIDs such as Zika, chikungunya and Ebola are a threat to Canadians while travelling. Over 75% of EIDs affecting humans are, or were originally, zoonoses (infectious diseases transmitted from animals to humans). There are two main ways by which infectious diseases can emerge: by changes in their geographical ranges and by adaptive emergence, a genetic change in a microorganism that results in it becoming capable of invading a new niche, often by jumping to a new host species such as humans. Diseases can appear to emerge simply because we become capable of detecting and diagnosing them. Management of EID events is a key role of public health globally and a considerable challenge for clinical care. Increasingly, emphasis is being placed on predicting EID occurrence to "get ahead of the curve" - that is, allowing health systems to be poised to respond to them, and public health to be ready to prevent them. Predictive models estimate where and when EIDs may occur and the levels of risk they pose. Evaluation of the internal and external drivers that trigger emergence events is increasingly considered in predicting EID events. Currently, global changes are driving increasing occurrence of EIDs, but our capacity to prevent and deal with them is also increasing. Web-based scanning and analysis methods are increasingly allowing us to detect EID outbreaks, modern genomics and bioinformatics are increasing our ability to identify their genetic and geographical origins, while developments in geomatics and earth observation will enable more real-time tracking of outbreaks. EIDs will, however, remain a key, global public health challenge in a globalized world where demographic, climatic, and other environmental changes are altering the interactions between hosts and pathogen in ways that increase spillover from animals to humans and global spread.
Objective
When faced with an emergent epidemic with high mortality and morbidity potential, policy makers must decide what public health interventions to deploy at different stages of the outbreak. However, almost nothing is known about how the public view these interventions or how they trade off risks (of disease) with inconvenience (of interventions). In this paper, we aim to understand public perceptions on pandemic interventions, as well as to identify if there are any distinct respondent preference classes.
Design
A discrete choice experiment.
Setting
This study was fielded in Singapore between November 2012 and February 2013.
Participants
A random sample of 500 Singapore residents aged 21 and over, including 271 women and 229 men, was analysed.
Outcome measures
Demographic information was collected from each participant. Participants were also shown a series of pairs of alternatives, each combining interventions and morbidity, mortality and cost outcomes and declared a preference for one combination. A random utility model was developed to determine the individual’s preference for interventions and a hierarchical cluster analysis was performed to identify distinct respondent preference classes.
Results
On average, participants preferred more intense interventions, and preferred scenarios with fewer deaths and lower tax. The number of infections did not significantly influence respondents’ responses. We identified two broad classes of respondents: those who were mortality averse and those who were expenditure averse. Education was found to be a predictor of group membership.
Conclusion
Overall, there was considerable support for government interventions to prevent or mitigate outbreaks of emerging infectious diseases, including those that greatly restricted individual liberties, as long as the restrictions showed a reasonable chance of reducing the adverse health effects of the outbreak.
Introduction
Every year around 150,000 pilgrims from Bangladesh perform Umrah and Hajj. Emergence and continuous reporting of MERS-CoV infection in Saudi Arabia emphasize the need for surveillance of MERS-CoV in returning pilgrims or travelers from the Middle East and capacity building of health care providers for disease containment. The Institute of Epidemiology, Disease Control & Research (IEDCR) under the Bangladesh Ministry of Health and Family welfare (MoHFW), is responsible for MERS-CoV screening of pilgrims/ travelers returning from the Middle East with respiratory illness as part of its outbreak investigation and surveillance activities.
Methods
Bangladeshi travelers/pilgrims who returned from the Middle East and presented with fever and respiratory symptoms were studied over the period from October 2013 to June 2016. Patients with respiratory symptoms that fulfilled the WHO MERS-CoV case algorithm were tested for MERS-CoV and other respiratory tract viruses. Beside surveillance, case recognition training was conducted at multiple levels of health care facilities across the country in support of early detection and containment of the disease.
Results
Eighty one suspected cases tested by real time PCR resulted in zero detection of MERS-CoV infection. Viral etiology detected in 29.6% of the cases was predominantly influenza A (H1N1 and H3N2), and influenza B infection (22%). Peak testing occurred mostly following the annual Hajj season.
Conclusions
Respiratory tract infections in travelers/pilgrims returning to Bangladesh from the Middle East are mainly due to influenza A and influenza B. Though MERS-CoV was not detected in the 81 patients tested, continuous screening and surveillance are essential for early detection of MERS-CoV infection and other respiratory pathogens to prevent transmissions in hospital settings and within communities. Awareness building among healthcare providers will help identify suspected cases.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is well known to cause severe respiratory infection and was first reported in the Kingdom of Saudi Arabia in 2012. We report here the first confirmed MERS-CoV infection in the Kingdom of Bahrain in a Saudi gentleman who was admitted electively for coronary bypass surgery, postoperatively developed an acute respiratory illness, and tested positive for MERS-CoV. 40 close contacts, all healthcare workers, were traced and followed with no documented secondary cases.
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for asymptomatic infection with MERS-CoV. In order to discover more about non-lethal infections and to learn whether a single infection with MERS-CoV would protect against reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response. Following intranasal infection, rabbits developed a transient dose-dependent pulmonary infection with moderately high levels of viral RNA, viral antigen, and perivascular inflammation in multiple lung lobes that was not associated with clinical signs. The rabbits developed antibodies against viral proteins that lacked neutralizing activity and the animals were not protected from reinfection. In fact, reinfection resulted in enhanced pulmonary inflammation, without an associated increase in viral RNA titers. Interestingly, passive transfer of serum from previously infected rabbits to naïve rabbits was associated with enhanced inflammation upon infection. We further found this inflammation was accompanied by increased recruitment of complement proteins compared to primary infection. However, reinfection elicited neutralizing antibodies that protected rabbits from subsequent viral challenge. Our data from the rabbit model suggests that people exposed to MERS-CoV who fail to develop a neutralizing antibody response, or persons whose neutralizing antibody titers have waned, may be at risk for severe lung disease on re-exposure to MERS-CoV.
Background
Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities.
Data and methods
This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach.
Results
Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities.
Conclusion
Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.
The existence of pathogenic viruses was inferred by experiments at the turn of the twentieth century. Key developments in detection of viruses, including electron microscopy and monolayer cell culture, were made in the middle of that century. However, in terms of patient care, the results from the virology laboratory often arrived the patient was ‘better or dead’. The advent of molecular techniques, particularly polymerase chain reaction and more recently whole genome sequencing made timely and accurate diagnosis of viral infections feasible. A range of approaches have been taken to identify and characterise new viruses. Vaccines against viruses have made it possible to eliminate two pathogenic mammalian viruses altogether, with several others close to eradication. The role of biomedical scientists working in diagnostic virology is more relevant to patient care than ever.
Middle East respiratory syndrome coronavirus (MERS-CoV) still causes outbreaks despite public awareness and implementation of health care measures, such as rapid viral diagnosis and patient quarantine. Here we describe the current epidemiological picture of MERS-CoV, focusing on humans and animals affected by this virus and propose specific intervention strategies that would be appropriate to control MERS-CoV. One-third of MERS-CoV patients develop severe lower respiratory tract infection and succumb to a fatal outcome; these patients would require effective therapeutic antiviral therapy. Because of the lack of such intervention strategies, supportive care is the best that can be offered at the moment. Limiting viral spread from symptomatic human cases to health care workers and family members, on the other hand, could be achieved through prophylactic administration of MERS-CoV neutralizing antibodies and vaccines. To ultimately prevent spread of the virus into the human population, however, vaccination of dromedary camels – currently the only confirmed animal host for MERS-CoV – may be the best option to achieve a sustained drop in human MERS cases in time. In the end, a One Health approach combining all these different efforts is needed to tackle this zoonotic outbreak.
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