scholarly journals The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera

2021 ◽  
Author(s):  
Raveen Rathnasinghe ◽  
Sonia Jangra ◽  
Anastasija Cupic ◽  
Carles Martínez-Romero ◽  
Lubbertus C.F. Mulder ◽  
...  
Keyword(s):  
Viral Infections ◽  
Small Animal ◽  
The Elderly ◽  
Post Vaccination ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Sera ◽  
Development And Validation ◽  
Diabetes And Obesity ◽  
Entry Receptor

AbstractThe current COVID-19 (coronavirus disease 19) pandemic, caused by SARS-CoV-2, disproportionally affects the elderly and people with comorbidities like obesity and associated type 2 diabetes mellitus. Small animal models are crucial for the successful development and validation of antiviral vaccines, therapies and to study the role that comorbidities have on the outcome of viral infections. The initially available SARS-CoV-2 isolates require adaptation in order to use the mouse angiotensin converting enzyme 2 (mACE-2) entry receptor and to productively infect the cells of the murine respiratory tract. We have “mouse-adapted” SARS-CoV-2 by serial passaging a clinical virus isolate in the lungs of mice. We then used low doses of this virus in mouse models for advanced age, diabetes and obesity. Similar to SARS-CoV-2 infection in humans, the outcome of infection with mouse-adapted SARS-CoV-2 resulted in enhanced morbidity in aged and diabetic obese mice. Mutations associated with mouse adaptation occurred in the S, M, N and ORF8 genes. Interestingly, one mutation in the receptor binding domain of the S protein results in the change of an asparagine to tyrosine residue at position 501 (N501Y). This mutation is also present in the newly emerging SARS-CoV-2 variant viruses reported in the U.K. (20B/501Y.V1, B1.1.7 lineage) that is epidemiologically associated with high human to human transmission. We show that human convalescent and post vaccination sera can neutralize the newly emerging N501Y virus variant with similar efficiency as that of the reference USA-WA1/2020 virus, suggesting that current SARS-CoV-2 vaccines will protect against the 20B/501Y.V1 strain.

scholarly journals Human metapneumovirus - what we know now

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 135 ◽  
Author(s):  
Nazly Shafagati ◽  
John Williams
Keyword(s):  
Viral Infections ◽  
Clinical Manifestations ◽  
Adult Life ◽  
Small Animal ◽  
The Elderly ◽  
Human Metapneumovirus ◽  
Subtype C ◽  
Polymerase Chain ◽  
Human Primate ◽  
Made In

Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response.

scholarly journals Coronavirus Infections and Type 2 Diabetes—Shared Pathways with Therapeutic Implications

2020 ◽  
Vol 41 (3) ◽  
pp. 457-470 ◽  
Author(s):  
Daniel J Drucker
Keyword(s):  
Type 2 Diabetes ◽  
Viral Infections ◽  
Biological Activities ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Therapeutic Implications ◽  
Increased Risk ◽  
Coronavirus Infection ◽  
Coronavirus Infections

Abstract Abstract Individuals with diabetes are at increased risk for bacterial, mycotic, parasitic, and viral infections. The severe acute respiratory syndrome (SARS)-CoV-2 (also referred to as COVID-19) coronavirus pandemic highlights the importance of understanding shared disease pathophysiology potentially informing therapeutic choices in individuals with type 2 diabetes (T2D). Two coronavirus receptor proteins, angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. Here, we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.

scholarly journals Mast Cell Tryptase and Implications for SARS-CoV-2 Pathogenesis

BioMed ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 136-149
Author(s):  
Negar Karimi ◽  
Solmaz Morovati ◽  
Lily Chan ◽  
Christina Napoleoni ◽  
Yeganeh Mehrani ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Severe Acute Respiratory Syndrome ◽  
Serine Proteases ◽  
Respiratory Diseases ◽  
Viral Infections ◽  
Converting Enzyme ◽  
Mast Cell Tryptase ◽  
Angiotensin Converting Enzyme 2 ◽  
Entry Receptor

Mast cells (MCs) are heterogenous innate leukocytes producing many inflammatory mediators during viral infections that can be protective or damaging to the host, as is seen in the infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the coronavirus disease that was first identified in 2019 (COVID-19). MCs can sense viruses by diverse mechanisms. They express angiotensin-converting enzyme 2 (ACE2), known as the principal entry receptor for SARS-CoV-2, and tryptase that can promote SARS-CoV-2 infection. Tryptase is one of the most abundant serine proteases released by MCs during degranulation and is reported to have both beneficial and detrimental roles in respiratory diseases. Reviewed here are the potential roles of MC-derived tryptase during COVID-19, the implications it has in the pathogenesis of SARS-CoV-2, and the possibility of treating COVID-19 by targeting tryptase.

Highlighting the Correlation Between Telomere Shortening and the Susceptibility to the Novel SARS-CoV-2 Virus (COVID-19)

2020 ◽  
Author(s):  
Aml Ghanem
Keyword(s):  
Telomere Length ◽  
Stress Responses ◽  
Viral Infections ◽  
Deep Understanding ◽  
The Elderly ◽  
The Novel ◽  
Telomere Shortening ◽  
Infection Pathways ◽  
And Gender ◽  
Demographic Distribution

COVID-19 is a global crisis that requires a deep understanding of infection pathways to facilitate the development of effective treatments and vaccines. Telomere, which is regarded as a biomarker for other respiratory viral infections, might influence the demographic distribution of COVID-19 infection and fatality rates. Viral infection can induce many cellular remodeling events and stress responses, including telomere specific alterations, just as telomere shortening. In brief, this letter aims to highlight the connection between telomere shortening and susceptibility to COVID-19 infection, in addition to changes in telomeric length according to the variation of age and gender of confirmed cases with COVID-19 infection. To sum up, the correlation is revealed from the available data that connect telomere length and COVID-19 infection, demonstrated in the fact that the elderly patients and males are more susceptible to COVID-19 due to shortening in their telomere length.

Polymyalgia Rheumatica - a Disease of the Elderly

2018 ◽  
Vol 69 (1) ◽  
pp. 152-154
Author(s):  
Vasilica Cristescu ◽  
Aurelia Romila ◽  
Luana Andreea Macovei
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Polymyalgia Rheumatica ◽  
Temporal Arteritis ◽  
Viral Infections ◽  
Clinical Manifestations ◽  
The Elderly ◽  
Clinical Aspects ◽  
Immune Disorder ◽  
Markers Of Inflammation

Polymyalgia rheumatica is a disease that occurs mostly in the elderly and is rarely seen in patients less than 50 years of age. Polymyalgia rheumatica is a vasculitis, which manifests itself as an inflammatory disease of the vascular wall that can affect any type of blood vessel, regardless of its size. It has been considered a form of giant cell arteritis, involving primarily large and medium arteries and to a lesser extent the arterioles. Clinical manifestations are caused by the generic pathogenic process and depend on the characteristics of the damaged organ. PMR is a senescence-related immune disorder. It has been defined as a stand-alone condition and a syndrome referred to as rheumatic polyarteritis with manifestations of giant cell arteritis (especially in cases of Horton�s disease and temporal arteritis) which are commonly associated with polymyalgia. The clinical presentation is clearly dominated by the painful girdle syndrome, with a feeling of general discomfort. Polymyalgia and temporal arteritis may coexist or be consecutive to each other in the same patient, as in most of our patients. The present study describes 3 cases of polymyalgia rheumatica, admitted to the Clinic of Rheumatology of Sf. Apostol Andrei Hospital, Galati. The cases were compared with the literature. Two clinical aspects (polymyalgia rheumatica and/or Horton�s disease) and the relationship between them were also considered. Polymyalgia rheumatica is currently thought to have a multifactorial etiology, in which the following factors play a role: genetic factors or hereditary predisposition (some individuals are more prone to this disease), immune factors and viral infections (triggers of the disease). Other risk factors of polymyalgia rheumatica include age over 50 years and the association with giant cell arteritis. The characteristic feature of the disease is girdle pain, with intense stiffness of at least one hour�s duration. Markers of inflammation, erythrocyte sedimentation rate and C-reactive protein are almost always increased at the onset of the disease. Diseases that can mimic the clinical picture of polymyalgia rheumatica are neoplasia, infections, metabolic disorders of the bone and endocrine diseases.

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