MERS-CoV Infection Research Articles

Imperfect storm: is interleukin-33 the Achilles heel of COVID-19?

The unique cytokine signature of COVID-19 might provide clues to disease mechanisms and possible future therapies. Here, we propose a pathogenic model in which the alarmin cytokine, interleukin (IL)-33, is a key player in driving all stages of COVID-19 disease (ie, asymptomatic, mild–moderate, severe–critical, and chronic–fibrotic). In susceptible individuals, IL-33 release by damaged lower respiratory cells might induce dysregulated GATA-binding factor 3-expressing regulatory T cells, thereby breaking immune tolerance and eliciting severe acute respiratory syndrome coronavirus 2-induced autoinflammatory lung disease. Such disease might be initially sustained by IL-33-differentiated type-2 innate lymphoid cells and locally expanded γδ T cells. In severe COVID-19 cases, the IL-33–ST2 axis might act to expand the number of pathogenic granulocyte–macrophage colony-stimulating factor-expressing T cells, dampen antiviral interferon responses, elicit hyperinflammation, and favour thromboses. In patients who survive severe COVID-19, IL-33 might drive pulmonary fibrosis by inducing myofibroblasts and epithelial–mesenchymal transition. We discuss the therapeutic implications of these hypothetical pathways, including use of therapies that target IL-33 (eg, anti-ST2), T helper 17-like γδ T cells, immune cell homing, and cytokine balance.

The second wave of COVID-19 is knocking at the doors: have we learned the lesson?

In light of escalating rates of COVID-19 cases, the world stands stunned. The health, social, and global economic situation continues to deteriorate. The seriousness of the situation became evident to most people, yet no one had a radical solution. Scientifically, there is no sure treatment for viral infections other than strengthening the immune system. Therefore, the idea of ​​a vaccine is the most appropriate to reduce infections. However, vaccines will not be accessible to everyone, considering the genetic changes that the virus may create later. The idea of ​​re-imposing a global quarantine, with international leadership for a limited period, is emerging as a strategic alternative, on the condition that it should be launched simultaneously in all countries of the world. To ensure the quarantine's success, all countries must adhere to the comments of the World Health Organization and the Centers for Disease Control and Prevention.
 
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Urogenital System Damaging Manifestations of 3 Human Infected Coronaviruses.

At present, there are no comparative studies on the damage of the 3 coronaviruses infections to the urinary system. Therefore, we reviewed the correlations and differences between invading mechanisms and resultant urogenital system damage by the 3 kinds of coronaviruses in an effort to help doctors in the prevention and treatment of these damages, which will be of significance in improving prognosis and quality of life after rehabilitation. We searched PubMed® for English language articles published since 2003 with the key words "Coronavirus disease 2019 (COVID-19)," "severe acute respiratory syndrome-2 (SARS-CoV-2)," "severe acute respiratory syndrome (SARS)-CoV" and "Middle East respiratory syndrome (MERS)-CoV "with "semen" and "kidney." We also used relevant data from websites including the World Health Organization and Centers for Disease Control and Prevention. Recent studies have revealed that both SARS-CoV and SARS-CoV-2 invade target cells through a membrane-bound angiotensin-converting enzyme 2, an important component of the renin-angiotensin system, which maintains human homeostasis, whereas MERS utilizes host cells' receptor dipeptidyl peptidase 4 for entry. While pneumonia is the most prominent symptom in patients infected by coronaviruses due to the transmission through respiratory droplets, the urogenital system can also suffer from infection with coronaviruses, resulting in renal failure, testicular atrophy etc. The impairments of the genitourinary system would be different with the 3 coronavirus infections but they still have a strong correlation. The pathogenesis and clinical symptoms of SARS-CoV, MERS-CoV and SARS-CoV-2 coronaviruses in the genitourinary system are comparable. All 3 coronaviruses have been found to affect kidney and testicular function. Therefore, both urologists and nephrologists should pay attention to the damage caused by coronavirus infection to the genitourinary system, especially monitoring renal and semen function.

CURRENT SCENARIO OF COVID19 OUTBREAK IN ANDHRAPRADESH & TELANGANA

The World Health Organization declared the 2019–2020 COVID Emerging coronaviruses are constant global public health threats to society Governments are under increased pressure to stop the outbreak of a global health emergency. In this situation, preparedness, transparency, and sharing of information are crucial. Multiple ongoing clinical trials are conducted for the development of vaccines and antivirals against CoVs. Up to date, there is no specific treatment proven effective against this COVID19. In addition, no vaccine has been licensed by the WHO to prevent MERS-CoV infection thus far. This spillover event is pandemic and a Public Health Emergency of International Concern. Due to its emerging cases day by day there is a need for everyone to act responsibly by taking preventive measures like wearing the masks and avoiding unnecessary outings as possible. There are certain reasons not to get panic regarding a situation like We to know why at it is - we had been identified the virus; We know how to detect-there had many tests to identify; Most cases are mild -about 81% of cases are mild and high recovery rate is seen; Symptoms are mild in young; The virus can be destroyed on the surface; Vaccines are in progress; Many drugs are effective in treating the COVID19. Voluntary reporting of the symptoms helps to prevent the spread of disease. this review details about the origin of the virus, introduction to the anatomical features and pathology, clinical manifestations, its diagnostics, treatment, preventive measures to health workers, and to public.

Friends or foes? The knowns and unknowns of natural killer cell biology in COVID-19 and other coronaviruses in July 2020.

The COVID-19 pandemic has caused more than 575,000 deaths worldwide as of mid-July 2020 and still continues globally unabated. Immune dysfunction and cytokine storm complicate the disease, which in turn leads to the question of whether stimulation or suppression of the immune system would curb the disease. Given the varied antiviral and regulatory functions of natural killer (NK) cells, they could be potent and powerful immune allies in this global fight against COVID-19. Unfortunately, there is somewhat limited knowledge of the role of NK cells in SARS-CoV-2 infections and even in the related SARS-CoV-1 and MERS-CoV infections. Several NK cell therapeutic options already exist in the treatment of tumor and other viral diseases and could be repurposed against COVID-19. In this review, we describe the current understanding and potential roles of NK cells and other Fc receptor (FcR) effector cells in SARS-CoV-2 infection, advantages of using animals to model COVID-19, and NK cell–based therapeutics that are being investigated for COVID-19 therapy.

Identification of 4-anilino-6-aminoquinazoline derivatives as potential MERS-CoV inhibitors

New therapies for treating coronaviruses are urgently needed. A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N4-(3-Chloro-4-fluorophenyl)-N6-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection. Throughout optimization process, compound 20 was found to exhibit high inhibitory effect (IC50 = 0.157 μM, SI = 25) with no cytotoxicity and moderate in vivo PK properties.

A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2.

SummaryEffective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in arhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.

Çocuklarda COVID-19 Hastalığı: Klinik Seyir, Tanı ve Tedaviye Genel Bakış ve Literatür Verilerinin Derlemesi

When compared with SARS-CoV and MERS-CoV, SARS-CoV-2 is a highly contagious infection agent. Although MERS-CoV infection is known to have higher mortality, SARS-CoV-2 has spread to many people all over the world in a very short time. In addition to this, SARS-CoV-2 (like SARS-CoV and MERS) infects less children and results in milder clinic than in adults. Although the reason of it is not known, difference in their immunities or being less likely to be exposed to the source of the infection is thought to be the reason. However, it should not be forgotten that children can contribute to the spread of infection among adults and population, along with being mostly asymptomatic.

Thalidomide combined with low-dose short-term glucocorticoid in the treatment of critical Coronavirus Disease 2019.

Thalidomide combined with low-dose short-term glucocorticoid in the treatment of critical Coronavirus Disease 2019.

COVID-19 in Spain: Transplantation in the midst of the pandemic.

Spain has been one of the most affected countries by the COVID‐19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS‐CoV‐2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.

COVID-19 as a STING disorder with delayed over-secretion of interferon-beta.

COVID-19 as a STING disorder with delayed over-secretion of interferon-beta.

Recommendations and practical management of pregnant women with COVID-19: A scoping review

ObjetivoRecopilar recomendaciones y evidencias en el manejo práctico de las gestantes con infección por COVID-19 para clarificar pautas de atención obstétrica ante esta nueva enfermedad.MétodoScope review a partir de búsqueda bibliográfica en bases de datos nacionales e internacionales en ciencias de la salud (PubMed/Medline, Biblioteca Virtual en Salud, SciELO, Cochrane y CUIDEN) y sitios web y adicionalmente mediante sistema de «bola de nieve». Se utilizaron los términos MeSH: «COVID-19», «Pregnancy», «Delivery, Obstetric», «Pregnant Women» y «Maternal». Como límites en la búsqueda se seleccionaron los idiomas español e inglés. No se establecieron límites en referencia al año de publicación o el tipo de artículo.ResultadosSe detectaron un total de 49 documentos y artículos, de los cuales 27 fueron analizados, utilizándose 18 y desechándose 9 que no contenían recomendaciones prácticas. Las recomendaciones fueron agrupadas en 10 temáticas: prevención de la infección en la embarazada; prevención de la infección en el personal sanitario que atiende a la embarazada; forma de presentación y severidad en la embarazada; transmisión materno-fetal (vertical y perinatal); control materno-fetal de la gestante con COVID-19; control de la gestante grave por COVID-19; tratamiento de la gestante con COVID 19; manejo y vía de finalización del parto; resultados neonatales en mujeres con COVID-19, y lactancia materna.ConclusionesFalta una evidencia sólida que sustente muchas de las recomendaciones para la mujer gestante respecto a la COVID-19, ya que están basadas en la experiencia previa con las infecciones provocadas por los virus SARS-CoV y MERS-CoV. Se necesitan nuevos estudios que confirmen la idoneidad de muchas de las recomendaciones y pautas de actuación en el caso concreto de la mujer gestante y la COVID-19.

Parallel epidemics, or nearly so: Certainties and uncertainties about SARS-CoV-2 in Italy

Parallel epidemics, or nearly so: Certainties and uncertainties about SARS-CoV-2 in Italy

Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection.

A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic approaches is urgently required. Although some progress has been made in understanding the viral structure and invasion mechanism of coronaviruses that may cause severe cases of the syndrome, due to the limited understanding of the immune effects caused by SARS-CoV-2, it is difficult for us to prevent patients from developing acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF), the major complications of coronavirus infection. Therefore, any potential treatments should focus not only on direct killing of coronaviruses and prevention strategies by vaccine development, but also on keeping in check the acute immune/inflammatory responses, resulting in ARDS and PF. In addition, potential treatments currently under clinical trials focusing on killing coronaviruses or on developing vaccines preventing coronavirus infection largely ignore the host immune response. However, taking care of SARS-CoV-2 infected patients with ARDS and PF is considered to be the major difficulty. Therefore, further understanding of the host immune response to SARS-CoV-2 is extremely important for clinical resolution and saving medication cost. In addition to a breif overview of the structure, infection mechanism, and possible therapeutic approaches, we summarized and compared the hematopathologic effect and immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also discussed the indirect immune response caused by SARS and direct infection, replication, and destroying of immune cells by MERS-CoV. The molecular mechanisms of SARS-CoV and MERS-CoV infection-induced lymphopenia or cytokine storm may provide some hint toward fight against SARS-CoV-2, the novel coronavirus. This may provide guidance over using immune therapy as a combined treatment to prevent patients developing severe respiratory syndrome and largely reduce complications.

Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis.

We performed a meta-analysis to determine safety and efficacy of corticosteroids in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. We searched PubMed, Web of Science, Medline, WanFang Chinese database, and ZhiWang Chinese database using Boolean operators and search terms covering SARS-CoV-2, SARS-CoV, OR MERS-CoV AND corticosteroids to find appropriate studies. Review Manager 5.3 was used to analyze results of meta-analysis. Observational studies were analyzed for quality using the modified Newcastle–Ottawa scale and randomized clinical trials, using the Jadad scale. Subjects were divided into those with severe-only and other (severe and not severe) cohorts based on published criteria. Efficacy endpoints studied included mortality, hospitalization duration, rates of intensive care unit (ICU) admission, use of mechanical ventilation, and a composite endpoint (death, ICU admission, or mechanical ventilation). We included 11 reports including 10 cohort studies and 1 randomized clinical trial involving 5249 subjects (2003–2020). Two discussed the association of corticosteroids and virus clearing and 10 explored how corticosteroids impacted mortality, hospitalization duration, use of mechanical ventilation, and a composite endpoint. Corticosteroid use was associated with delayed virus clearing with a mean difference (MD) = 3.78 days (95% confidence Interval [CI] = 1.16, 6.41 days; I2 = 0%). There was no significant reduction in deaths with relative Risk Ratio (RR) = 1.07 (90% CI = 0.81; 1.42; I2 = 80%). Hospitalization duration was prolonged and use of mechanical ventilation increased. In conclusion, corticosteroid use in subjects with SARS-CoV-2, SARS-CoV, and MERS-CoV infections delayed virus clearing and did not convincingly improve survival, reduce hospitalization duration or ICU admission rate and/or use of mechanical ventilation. There were several adverse effects. Because of a preponderance of observational studies in the dataset and selection and publication biases our conclusions, especially regarding SARS-CoV-2, need confirmation in a randomized clinical trial. In the interim we suggest caution using corticosteroids in persons with COVID-19.

Built-in RNA-mediated chaperone (chaperna) for antigen folding tailored to immunized hosts.

High‐quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA‐dependent chaperone, in which the target antigen is genetically fused with an RNA‐interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N‐terminal tRNA‐binding domain of lysyl‐tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the “self” RID tag remained nonimmunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS‐CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc‐mediated effector function was demonstrated, which could be harnessed for the design of next‐generation “universal” influenza vaccines. The nonimmunogenic built‐in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.

Comparison of the COVID-2019 (SARS-CoV-2) Pathogenesis With SARS-CoV and MERS-CoV Infections

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in several patients who traveled to Wuhan or went to a seafood wholesale market in Wuhan. The phylogenetic tree showed that SARS-CoV-2 was 96.2% identical to bat β-coronaviruses from lineage B. Also, several studies reported that SARS-CoV-2 uses the SARS-CoV receptor, angiotensin-converting enzyme 2, for entry to target cells. Lung alveolar and small intestine are potential targets for SARS-CoV-2 due to the high expression of the angiotensin-converting enzyme 2 receptor. In this review, we focused on the zoonotic β-coronaviruses and given there is no specific drug or vaccine for coronavirus disease 2019, we reviewed the literature on the therapy options for SARS and Middle East respiratory syndrome coronavirus infection, in order to discover their possible use in the treatment of SARS-CoV-2 infections.

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 first clusters of Middle East respiratory syndrome coronavirus in Oman: Time to act

IntroductionMiddle East respiratory syndrome coronavirus (MERS-CoV), is an emerging infectious disease of growing global importance. This review describes the latest MERS-CoV clusters and the first cases of nosocomial transmission within health care facilities in Oman. We have highlighted lessons learned and proposed steps to prevent healthcare-associated infections. MethodsA descriptive analysis of MERS-CoV cases was conducted between January 23 and February 16, 2019. The data from officials and other published sources used. ResultsThirteen laboratory-confirmed cases of MERS-CoV were reported from three simultaneous clusters from two governorates without an epidemiological link between the clusters. Two clusters were reported from North Al Batinah Governorate, with nine cases (69%) and 1 cluster from South Ash Sharqiyah Governorate with four cases (31%). In total, four deaths were reported (case fatality rate 31%). Four cases (31%) reported were household contacts from the first cluster, 3 (23%) were nosocomial transmission in health care facilities (two for first and one from the second cluster) and 7 (54%) were community-acquired cases. ConclusionsThe first local clusters of MERS-CoV reported with evidence suggestive of healthcare and household-associated transmission. Early diagnosis and strict implementation of infection control measures remain fundamental in preventing and managing MERS-CoV infection.