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1.
Viruses ; 12(1)2020 01 20.
Article in English | MEDLINE | ID: covidwho-1969491

ABSTRACT

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.


Subject(s)
Coronavirus Infections/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Line , Coronavirus Infections/prevention & control , Genetic Vectors , Humans , Immunization , Immunoglobulin G/blood , Immunoglobulin G/immunology , Lactococcus lactis/genetics , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus/genetics , Rabies virus/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Viral Vaccines/administration & dosage
2.
Pak J Med Sci ; 36(COVID19-S4): S79-S84, 2020 May.
Article in English | MEDLINE | ID: covidwho-1726822

ABSTRACT

Coronavirus Disease 2019 (CoViD-19) is the third type of coronavirus disease after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) that appears in human population from the past two decades. It is highly contagious and rapidly spread in the human population and compelled global public health institutions on high alert. Due to genetic similarity of this novel coronavirus 2019 with bat virus its emergence from bat to humans is possible. The virus survive in the droplets of coughing and sneezing and spread around the large areas through infected person resulting in its rapid spread among people. Clinical symptoms of CoViD-19 include fever, dry cough, dyspnea, loose stool, nausea and vomiting. The present review discuss the origin of CoViD-19, its rapid spread, mortality rate and recoveries ratio around the world. Since its origin from Wuhan, the CoViD-19 spread very rapidly all across the countries, on April 17, 2020 this disease has affected 210 countries of the globe. The data obtained showed over 2.4 million confirmed cases of CoViD-19. Higher mortality rate was found in Algeria and Belgium as 15% and 13.95%, respectively. Lower mortality rate was found in Qatar 0.17% and Singapore 0.2%. Recovery versus deceased ratio showed that recovery was 68, 59 and 35 times higher than the death in Singapore, Qatar and Thailand respectively. It is concluded that 2019-novel corona virus is a zoonotic pathogen similar to MERS and SARS. Therefore, a barrier should be maintained between and across the human, household and wild animals to avoid such pandemics.

3.
Libyan J Med ; 16(1): 1910195, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1526148

ABSTRACT

The outbreak of corona virus disease (COVID-19) caused by the new severe acute respiratory syndrome corona virus 2 began in Wuhan, China, resulting in respiratory disorders. In January of 2020, the World Health Organization declared the outbreak a pandemic owing to its global spread. Because no studies have investigated COVID-19 in Saudi Arabia, this study investigated similarities and differences between demographic data during the COVID-19 and Middle East respiratory syndrome (MERS) outbreaks in Saudi Arabia. A retrospective trend analysis was performed to assess demographic data of all laboratory-confirmed MERS and COVID-19 cases. Patients' charts were reviewed for data on demographics, mortality, citizenship, sex ratio, and age groups with descriptive and comparative statistics; the data were analyzed using a non-parametric binomial test and chi-square test. Of all COVID-19 patients in Saudi Arabia,78%were male patients and 22% were female patients. This proportion of male COVID-19 patients was similar to that of male MERS patients, which also affected male patients more frequently than female patients. The number of COVID-19-positive Saudi cases was lower than that of non-Saudi cases, which were in contrast to that of MERS; COVID-19 appeared to be remarkably similar to MERS with respect to recovered cases. However, the numbers of critical and dead COVID-19 patients have been much lower than those of MERS patients. The largest proportion of COVID-19 and MERS cases (44.05% and 40.8%, respectively) were recorded in the Western region. MERS and COVID-19 exhibited similar threats to the lives of adults and the elderly, despite lower mortality rates during the COVID-19 epidemic. Targeted prevention of and interventions against MERS should be allocated populations according to the areas where they inhabit. However, much more information regarding the dynamics and epidemiology of COVID-19 in Saudi Arabia is needed.Abbrevation : MERS: Middle East Respiratory syndrome; COVID-19: Corona Virus Disease 2019.


Subject(s)
COVID-19/epidemiology , Coronavirus Infections/epidemiology , Disease Outbreaks , SARS-CoV-2 , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/etiology , Child , Child, Preschool , Coronavirus Infections/etiology , Demography , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Retrospective Studies , Saudi Arabia/epidemiology , Sex Factors , Young Adult
4.
Curr Diabetes Rev ; 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1367728

ABSTRACT

The article has been withdrawn at the request of the authors and editor of the journal Current Diabetes Reviews, due to incoherent content.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submit-ting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

5.
Clin Infect Dis ; 73(3): e550-e558, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338090

ABSTRACT

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Animals , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/drug therapy , Humans , Mice , Republic of Korea , Spike Glycoprotein, Coronavirus
6.
J Biomol Struct Dyn ; 39(10): 3771-3779, 2021 07.
Article in English | MEDLINE | ID: covidwho-1343544

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.


Subject(s)
Antiviral Agents , COVID-19 , RNA-Dependent RNA Polymerase , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning , Humans , RNA-Dependent RNA Polymerase/antagonists & inhibitors , SARS-CoV-2/drug effects
7.
J Taibah Univ Med Sci ; 16(4): 591-595, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1333613

ABSTRACT

OBJECTIVE: As of January 2020, there were 2,519 confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) cases with 866 deaths across 27 countries. Most of these cases (2,121) were reported in Saudi Arabia. Since the initial identification of MERS, few studies have investigated the role of comorbidities that could potentially lead to mortality in cases of the infectious disease. This study aimed to examine the association between comorbidities and MERS mortality in Saudi Arabia. METHODS: This is a retrospective descriptive study. We retrieved the data published by the World Health Organization (WHO) between January 2017 and November 2019, and analysed the association between comorbidities and mortality. RESULTS: We found 572 MERS-CoV cases reported by WHO in Saudi Arabia during the defined period. Of these, 387 (68%) had a history of chronic illness. The overall mortality rate was found to be 25%. Diabetes mellitus was the most prevalent comorbidity-the mortality rate in the diabetics was 32% as opposed to 12% in the non-diabetics (p-value <0.01). Hypertension was second, with a mortality rate of 35%, as opposed to 15% in the non-hypertensive patients (p-value <0.001). The mortality rate in cases with cardiovascular disease was 39% as opposed to 21% in those without cardiovascular disease (p-value <0.05). CONCLUSION: Our study shows that MERS-CoV had a significant case fatality rate in patients with comorbidities. Thus, it will be beneficial if future clinical trials for MERS-CoV examine the impact of improved societal infection control measures such as social distancing and masks, in the context of the coronavirus disease 2019 pandemic, on the prevalence and incidence of MERS and its clinical outcomes.

8.
Clin Microbiol Infect ; 28(2): 292-296, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1312375

ABSTRACT

OBJECTIVES: We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients. METHODS: We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens. RESULTS: The seropositivity rate persisted for up to 4 years (50.7-56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT50, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection. DISCUSSION: The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/epidemiology , Follow-Up Studies , Humans , Spike Glycoprotein, Coronavirus
9.
Methods Mol Biol ; 2099: 89-97, 2020.
Article in English | MEDLINE | ID: covidwho-1292547

ABSTRACT

The Middle East respiratory syndrome (MERS) is the second novel zoonotic disease infecting humans caused by coronavirus (CoV) in this century. To date, more than 2200 laboratory-confirmed human cases have been identified in 27 countries, and more than 800 MERS-CoV associated deaths have been reported since its outbreak in 2012. Rapid laboratory diagnosis of MERS-CoV is the key to successful containment and prevention of the spread of infection. Though the gold standard for diagnosing MERS-CoV infection in humans is still nucleic acid amplification test (NAAT) of the up-E region, an antigen capture enzyme-linked immunosorbent assay (ELISA) could also be of use for early diagnosis in less developed locations. In the present method, a step-by-step guide to perform a MERS-CoV nucleocapsid protein (NP) capture ELISA using two NP-specific monoclonal antibodies is provided for readers to develop their in-house workflow or diagnostic kit for clinical use and for mass-screening project of animals (e.g., dromedaries and bats) to better understand the spread and evolution of the virus.


Subject(s)
Antigens, Viral/immunology , Coronavirus Infections/diagnosis , Enzyme-Linked Immunosorbent Assay/methods , Middle East Respiratory Syndrome Coronavirus/immunology , Nucleocapsid Proteins/immunology , Animals , Camelus/virology , Chiroptera/virology , Coronavirus Infections/virology , Coronavirus Nucleocapsid Proteins , Humans , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Zoonoses
10.
Methods Mol Biol ; 2099: 137-159, 2020.
Article in English | MEDLINE | ID: covidwho-1292550

ABSTRACT

Since 2012, monthly cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to cause severe respiratory disease that is fatal in ~35% of diagnosed individuals. The ongoing threat to global public health and the need for novel therapeutic countermeasures have driven the development of animal models that can reproducibly replicate the pathology associated with MERS-CoV in human infections. The inability of MERS-CoV to replicate in the respiratory tracts of mice, hamsters, and ferrets stymied initial attempts to generate small animal models. Identification of human dipeptidyl peptidase IV (hDPP4) as the receptor for MERS-CoV infection opened the door for genetic engineering of mice. Precise molecular engineering of mouse DPP4 (mDPP4) with clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology maintained inherent expression profiles, and limited MERS-CoV susceptibility to tissues that naturally express mDPP4, notably the lower respiratory tract wherein MERS-CoV elicits severe pulmonary pathology. Here, we describe the generation of the 288-330+/+ MERS-CoV mouse model in which mice were made susceptible to MERS-CoV by modifying two amino acids on mDPP4 (A288 and T330), and the use of adaptive evolution to generate novel MERS-CoV isolates that cause fatal respiratory disease. The 288-330+/+ mice are currently being used to evaluate novel drug, antibody, and vaccine therapeutic countermeasures for MERS-CoV. The chapter starts with a historical perspective on the emergence of MERS-CoV and animal models evaluated for MERS-CoV pathogenesis, and then outlines the development of the 288-330+/+ mouse model, assays for assessing a MERS-CoV pulmonary infection in a mouse model, and describes some of the challenges associated with using genetically engineered mice.


Subject(s)
Coronavirus Infections/virology , Dipeptidyl Peptidase 4/genetics , Disease Models, Animal , Mice/genetics , Middle East Respiratory Syndrome Coronavirus/physiology , Respiratory Distress Syndrome/virology , Animals , CRISPR-Cas Systems , Coronavirus Infections/pathology , Dipeptidyl Peptidase 4/metabolism , Disease Susceptibility , Female , Genetic Engineering , Humans , Lung/virology , Male , Mice, Inbred C57BL , Respiratory Distress Syndrome/pathology
11.
Methods Mol Biol ; 2099: 99-106, 2020.
Article in English | MEDLINE | ID: covidwho-1292548

ABSTRACT

Since the emergence of the Middle East respiratory syndrome-coronavirus (MERS-CoV) in 2012, more than 2280 confirmed human infections and 800 associated deaths had been reported to the World Health Organization. MERS-CoV is a single-stranded RNA virus that belongs to the Coronaviridae family. MERS-CoV infection leads to a variety of clinical outcomes in humans ranging from asymptomatic and mild infection to severe acute lung injury and multi-organ failure and death. To study the pathogenesis of MERS-CoV infection and development of medical countermeasures (MCMs) for MERS, a number of genetically modified mouse models have been developed, including various versions of transgenic mice expressing the human DPP4 viral receptor. Tracking and quantifying viral infection, among others, in permissive hosts is a key endpoint for studying MERS pathogenesis and evaluating the efficacy of selected MCMs developed for MERS. In addition to quantifying infectious progeny virus which requires high-containment biosafety level (BSL)-3 laboratory, here we outlined an established real-time quantitative RT-PCR (RT-qPCR)-based procedure to unequivocally quantify MERS-CoV-specific RNAs within the lungs of infected human DPP4 (hDPP4, transgenic (hDPP4 Tg) mice under a standard BSL-2 laboratory.


Subject(s)
Coronavirus Infections/virology , Middle East Respiratory Syndrome Coronavirus/genetics , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction/methods , Animals , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Disease Models, Animal , Humans , Lung/virology , Mice , Mice, Transgenic , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Real-Time Polymerase Chain Reaction , Receptors, Virus/genetics , Receptors, Virus/metabolism
12.
Clin Infect Dis ; 73(1): e241-e245, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1292193

ABSTRACT

BACKGROUND: A comprehensive understanding of the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of great importance to effectively control the spread of coronavirus disease 2019 (COVID-19). However, the fundamental dose-response relation is missing for evaluation of the infection risk. METHODS: We developed a simple framework to integrate the a priori dose-response relation for SARS-CoV-2 based on mice experiments, the recent data on infection risk from a meta-analysis, and respiratory virus shedding in exhaled breath to shed light on the dose-response relation for humans. The aerosol transmission infection risk was evaluated based on the dose-response model for a typical indoor environment. RESULTS: The developed dose-response relation is an exponential function with a constant k in the range of about 6.4 × 104 to 9.8 × 105 virus copies, which means that the infection risk caused by 1 virus copy in viral shedding is on the order of 10-6 to 10-5. The median infection risk via aerosol transmission with 1-hour exposure (10-6 to 10-4) was significantly lower than the risk caused by close contact (10-1) in a room with an area of 10 to 400 m2 with 1 infected individual in it and with a typical ventilation rate of 1 air change per hour. CONCLUSIONS: The infection risk caused by aerosol transmission was significantly lower than the risk caused by close contact. It is still necessary to be cautious for the potential aerosol transmission risk in small rooms with prolonged exposure duration.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Aerosols , Animals , Humans , Mice , Risk Assessment , SARS-CoV-2
13.
J Allergy Clin Immunol ; 147(6): 2083-2097.e6, 2021 06.
Article in English | MEDLINE | ID: covidwho-1272498

ABSTRACT

BACKGROUND: Excessive inflammation triggered by a hitherto undescribed mechanism is a hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and is associated with enhanced pathogenicity and mortality. OBJECTIVE: Complement hyperactivation promotes lung injury and was observed in patients suffering from Middle East respiratory syndrome-related coronavirus, SARS-CoV-1, and SARS-CoV-2 infections. Therefore, we investigated the very first interactions of primary human airway epithelial cells on exposure to SARS-CoV-2 in terms of complement component 3 (C3)-mediated effects. METHODS: For this, we used highly differentiated primary human 3-dimensional tissue models infected with SARS-CoV-2 patient isolates. On infection, viral load, viral infectivity, intracellular complement activation, inflammatory mechanisms, and tissue destruction were analyzed by real-time RT-PCR, high content screening, plaque assays, luminex analyses, and transepithelial electrical resistance measurements. RESULTS: Here, we show that primary normal human bronchial and small airway epithelial cells respond to SARS-CoV-2 infection by an inflated local C3 mobilization. SARS-CoV-2 infection resulted in exaggerated intracellular complement activation and destruction of the epithelial integrity in monolayer cultures of primary human airway cells and highly differentiated, pseudostratified, mucus-producing, ciliated respiratory tissue models. SARS-CoV-2-infected 3-dimensional cultures secreted significantly higher levels of C3a and the proinflammatory cytokines IL-6, monocyte chemoattractant protein 1, IL-1α, and RANTES. CONCLUSIONS: Crucially, we illustrate here for the first time that targeting the anaphylotoxin receptors C3a receptor and C5a receptor in nonimmune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.


Subject(s)
Bronchi/immunology , COVID-19/immunology , Complement Activation , Epithelial Cells/immunology , Receptor, Anaphylatoxin C5a/immunology , Respiratory Mucosa/immunology , SARS-CoV-2/immunology , Bronchi/pathology , Bronchi/virology , COVID-19/pathology , COVID-19/virology , Cell Line , Complement C3/immunology , Cytokines/immunology , Epithelial Cells/pathology , Epithelial Cells/virology , Humans , Inflammation/immunology , Inflammation/pathology , Respiratory Mucosa/pathology , Respiratory Mucosa/virology
14.
Eur J Pharmacol ; 906: 174248, 2021 Sep 05.
Article in English | MEDLINE | ID: covidwho-1267662

ABSTRACT

Concern regarding coronavirus (CoV) outbreaks has stayed relevant to global health in the last decades. Emerging COVID-19 infection, caused by the novel SARS-CoV2, is now a pandemic, bringing a substantial burden to human health. Interferon (IFN), combined with other antivirals and various treatments, has been used to treat and prevent MERS-CoV, SARS-CoV, and SARS-CoV2 infections. We aimed to assess the clinical efficacy of IFN-based treatments and combinational therapy with antivirals, corticosteroids, traditional medicine, and other treatments. Major healthcare databases and grey literature were investigated. A three-stage screening was utilized, and included studies were checked against the protocol eligibility criteria. Risk of bias assessment and data extraction were performed, followed by narrative data synthesis. Fifty-five distinct studies of SARS-CoV2, MERS-CoV, and SARS-CoV were spotted. Our narrative synthesis showed a possible benefit in the use of IFN. A good quality cohort showed lower CRP levels in Arbidol (ARB) + IFN group vs. IFN only group. Another study reported a significantly shorter chest X-ray (CXR) resolution in IFN-Alfacon-1 + corticosteroid group compared with the corticosteroid only group in SARS-CoV patients. In a COVID-19 trial, total adverse drug events (ADEs) were much lower in the Favipiravir (FPV) + IFN-α group compared with the LPV/RTV arm (P = 0.001). Also, nausea in patients receiving FPV + IFN-α regimen was significantly lower (P = 0.03). Quantitative analysis of mortality did not show a conclusive effect for IFN/RBV treatment in six moderately heterogeneous MERS-CoV studies (log OR = -0.05, 95% CI: (-0.71,0.62), I2 = 44.71%). A meta-analysis of three COVID-19 studies did not show a conclusive nor meaningful relation between receiving IFN and COVID-19 severity (log OR = -0.44, 95% CI: (-1.13,0.25), I2 = 31.42%). A lack of high-quality cohorts and controlled trials was observed. Evidence suggests the potential efficacy of several combination IFN therapies such as lower ADEs, quicker resolution of CXR, or a decrease in inflammatory cytokines; Still, these options must possibly be further explored before being recommended in public guidelines. For all major CoVs, our results may indicate a lack of a definitive effect of IFN treatment on mortality. We recommend such therapeutics be administered with extreme caution until further investigation uncovers high-quality evidence in favor of IFN or combination therapy with IFN.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Coronavirus Infections/drug therapy , Interferons/therapeutic use , Severe Acute Respiratory Syndrome/drug therapy , Antiviral Agents/adverse effects , COVID-19/diagnostic imaging , COVID-19/mortality , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/mortality , Humans , Interferons/adverse effects , Severe Acute Respiratory Syndrome/diagnostic imaging , Severe Acute Respiratory Syndrome/mortality
15.
Cells ; 10(6)2021 05 23.
Article in English | MEDLINE | ID: covidwho-1243956

ABSTRACT

The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.


Subject(s)
Adaptive Immunity/genetics , Camelus/virology , Communicable Diseases, Emerging/immunology , Coronavirus Infections/immunology , Immunity, Innate/genetics , Zoonoses/immunology , Animals , Antibodies, Viral , Bronchi/cytology , Bronchi/physiology , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Camelus/genetics , Camelus/immunology , Cilia/physiology , Communicable Diseases, Emerging/genetics , Communicable Diseases, Emerging/transmission , Communicable Diseases, Emerging/virology , Coronavirus Infections/genetics , Coronavirus Infections/transmission , Coronavirus Infections/virology , Disease Reservoirs/virology , Female , Genetic Predisposition to Disease , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Male , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Respiratory Mucosa/cytology , Respiratory Mucosa/physiology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , United Arab Emirates , Virus Replication/genetics , Virus Replication/immunology , Zoonoses/genetics , Zoonoses/transmission , Zoonoses/virology
16.
PLoS Pathog ; 17(5): e1009229, 2021 05.
Article in English | MEDLINE | ID: covidwho-1239922

ABSTRACT

While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, while interferon stimulated genes (ISGs) were induced along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, seems central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.


Subject(s)
Camelids, New World , Coronavirus Infections/immunology , Interferon Type I/metabolism , Interferons/metabolism , Middle East Respiratory Syndrome Coronavirus/immunology , Animals , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Camelids, New World/immunology , Camelids, New World/metabolism , Camelids, New World/virology , Chlorocebus aethiops , Coronavirus Infections/metabolism , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Disease Reservoirs/veterinary , Disease Resistance/drug effects , Disease Resistance/genetics , Disease Resistance/immunology , Gene Expression Regulation , Immunity, Innate/physiology , Inflammation/immunology , Inflammation/metabolism , Inflammation/veterinary , Inflammation/virology , Interferon Type I/genetics , Interferon Type I/pharmacology , Interferons/genetics , Interferons/pharmacology , Middle East Respiratory Syndrome Coronavirus/drug effects , Middle East Respiratory Syndrome Coronavirus/physiology , Nasal Mucosa/drug effects , Nasal Mucosa/immunology , Nasal Mucosa/metabolism , Nasal Mucosa/virology , Respiratory System/drug effects , Respiratory System/immunology , Respiratory System/metabolism , Respiratory System/virology , Vero Cells , Viral Load/drug effects , Virus Replication/drug effects
17.
Comput Biol Med ; 134: 104451, 2021 07.
Article in English | MEDLINE | ID: covidwho-1237662

ABSTRACT

COVID-19, a global pandemic caused by an RNA virus named SARS-CoV-2 has brought the world to a standstill in terms of infectivity, casualty, and commercial plummet. RNA viruses can encode microRNAs (miRNAs) capable of modulating host gene expression, and with that notion, we aimed to predict viral miRNA like sequences of MERS-CoV, SARS-CoV and SARS-CoV-2, analyze sequence reciprocity and investigate SARS-CoV-2 encoded potential miRNA-human genes interaction using bioinformatics tools. In this study, we retrieved 206 SARS-CoV-2 genomes, executed phylogenetic analysis, and the selected reference genome (MT434792.1) exhibited about 99% similarities among the retrieved genomes. We predicted 402, 137, and 85 putative miRNAs of MERS-CoV (NC_019843.3), SARS-CoV (NC_004718.3), and SARS-CoV-2 (MT434792.1) genome, respectively. Sequence similarity was analyzed among 624 miRNAs which revealed that the predicted miRNAs of SARS-CoV-2 share a cluster with the clad of miRNAs from MERS-CoV and SARS-CoV. Only SARS-CoV-2 derived 85 miRNAs were encountered for target prediction and 29 viral miRNAs seemed to target 119 human genes. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis suggested the involvement of respective genes in various pathways and biological processes. Finally, we focused on eight putative miRNAs influencing 14 genes that are involved in the adaptive hypoxic response, neuroinvasion and hormonal regulation, and tumorigenic progression in patients with COVID-19. SARS-CoV-2 encoded miRNAs may cause misexpression of some critical regulators and facilitate viral neuroinvasion, altered hormonal axis, and tumorigenic events in the human host. However, these propositions need validation from future studies.


Subject(s)
COVID-19 , MicroRNAs , Computer Simulation , Humans , MicroRNAs/genetics , Phylogeny , SARS-CoV-2
18.
Int Rev Immunol ; 40(1-2): 5-53, 2021.
Article in English | MEDLINE | ID: covidwho-1236148

ABSTRACT

Coronavirus infections are responsible for mild, moderate, and severe infections in birds and mammals. These were first isolated in humans as causal microorganisms responsible for common cold. The 2002-2003 SARS epidemic caused by SARS-CoV and 2012 MERS epidemic (64 countries affected) caused by MERS-CoV showed their acute and fatal side. These two CoV infections killed thousands of patients infected worldwide. However, WHO has still reported the MERS case in December 2019 in middle-eastern country (Saudi Arabia), indicating the MERS epidemic has not ended completely yet. Although we have not yet understood completely these two CoV epidemics, a third most dangerous and severe CoV infection has been originated in the Wuhan city, Hubei district of China in December 2019. This CoV infection called COVID-19 or SARS-CoV2 infection has now spread to 210 countries and territories around the world. COVID-19 has now been declared a pandemic by the World Health Organization (WHO). It has infected more than 16.69 million people with more than 663,540 deaths across the world. Thus the current manuscript aims to describe all three (SARS, MERS, and COVID-19) in terms of their causal organisms (SARS-CoV, MERS-CoV, and SARS-CoV2), similarities and differences in their clinical symptoms, outcomes, immunology, and immunopathogenesis, and possible future therapeutic approaches.


Subject(s)
COVID-19/pathology , Coronaviridae/ultrastructure , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/pathology , Animals , COVID-19/diagnosis , COVID-19/mortality , Camelus/virology , Chiroptera/virology , Coronaviridae/classification , Disease Reservoirs/virology , Disease Susceptibility/virology , Humans , Middle East Respiratory Syndrome Coronavirus/pathogenicity , SARS Virus/pathogenicity , SARS-CoV-2/pathogenicity , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Virus Replication/physiology
19.
Ann Clin Microbiol Antimicrob ; 20(1): 35, 2021 May 18.
Article in English | MEDLINE | ID: covidwho-1234561

ABSTRACT

Coronavirus disease 2019 (COVID-19) is the second pandemic of the twenty-first century, with over one-hundred million infections and over two million deaths to date. It is a novel strain from the Coronaviridae family, named Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2); the 7th known member of the coronavirus family to cause disease in humans, notably following the Middle East Respiratory syndrome (MERS), and Severe Acute Respiratory Distress Syndrome (SARS). The most characteristic feature of this single-stranded RNA molecule includes the spike glycoprotein on its surface. Most patients with COVID-19, of which the elderly and immunocompromised are most at risk, complain of flu-like symptoms, including dry cough and headache. The most common complications include pneumonia, acute respiratory distress syndrome, septic shock, and cardiovascular manifestations. Transmission of SARS-CoV-2 is mainly via respiratory droplets, either directly from the air when an infected patient coughs or sneezes, or in the form of fomites on surfaces. Maintaining hand-hygiene, social distancing, and personal protective equipment (i.e., masks) remain the most effective precautions. Patient management includes supportive care and anticoagulative measures, with a focus on maintaining respiratory function. Therapy with dexamethasone, remdesivir, and tocilizumab appear to be most promising to date, with hydroxychloroquine, lopinavir, ritonavir, and interferons falling out of favour. Additionally, accelerated vaccination efforts have taken place internationally, with several promising vaccinations being mass deployed. In response to the COVID-19 pandemic, countries and stakeholders have taken varying precautions to combat and contain the spread of the virus and dampen its collateral economic damage. This review paper aims to synthesize the impact of the virus on a global, micro to macro scale.


Subject(s)
COVID-19/epidemiology , Global Health , SARS-CoV-2 , COVID-19/prevention & control , COVID-19/therapy , COVID-19/transmission , COVID-19 Vaccines/immunology , Humans , Risk Factors , SARS-CoV-2/pathogenicity , Virulence
20.
Adv Exp Med Biol ; 1318: 293-313, 2021.
Article in English | MEDLINE | ID: covidwho-1222720

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) has posed a crucial hazard to global health. The new species share similarities with the two previously emerged entities: severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) that have caused outbreaks in 2002 and 2012, respectively. Interestingly, all of these coronaviruses can cause potentially fatal respiratory syndromes, though behave differently in patients with cancer compared to patients without cancer. Accordingly, the present chapter aims to, through a systematic investigation, estimate the prevalence of cancer among COVID-19, SARS, and MERS confirmed cases. Our analysis based on data from 78 studies with SARS, MERS, and COVID-19 confirmed cases showed that the prevalence of cancer (4.94%) stands at fourth place after hypertension (20.8%), diabetes (11.39%), and cardiovascular diseases (7.46%). According to the findings of the present study, comorbidities are significantly more common in patients with MERS compared to patients with COVID-19 and SARS, and this was the cancer case as well. Further studies need to address whether or not patients with coronaviruses and cancer are different from patients with coronaviruses without cancer in terms of clinical manifestations, laboratory findings, outcomes, and men to women ratio.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Neoplasms , Severe Acute Respiratory Syndrome , Female , Humans , Male , Neoplasms/epidemiology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology
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