scholarly journals Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

2021 ◽  
Author(s):  
Young-Il Kim ◽  
Kwang-Min Yu ◽  
June-Young Koh ◽  
Eun-Ha Kim ◽  
Se-Mi Kim ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Age Groups ◽  
Type I ◽  
Virus Shedding ◽  
Infection Transmission ◽  
Gene Sets ◽  
M1 Macrophage ◽  
Age Dependent ◽  
Activated T Cell ◽  
Severe Lung

Abstract The sero-prevalence of SARS-CoV-2 in healthy people is not significantly different among age groups, but persons age 65 years or older had strikingly higher COVID-19 mortality compared to younger individuals. To understand COVID-19 manifestations in patients of different ages, ferrets in three age groups were infected with SARS-CoV-2. Although SARS-CoV-2 was isolated from all ferrets regardless of age, aged ferrets (≥3 years old) showed higher viral load, longer nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptom compared to ≤6 months juvenile and 1-2 years young adult groups. Transcriptome analysis of aged ferret lungs revealed strong enrichment of gene sets related to type I interferon, activated T cell, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding an age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

scholarly journals Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

2021 ◽  
Author(s):  
Young-Il Kim ◽  
Kwang-Min Yu ◽  
June-Young Koh ◽  
Eun-Ha Kim ◽  
Se-Mi Kim ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Age Groups ◽  
Type I ◽  
Activated T Cells ◽  
Virus Shedding ◽  
Viral Loads ◽  
Gene Sets ◽  
M1 Macrophage ◽  
Age Dependent ◽  
Severe Lung

Abstract While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets were infected with SARS-CoV-2. Although SARS-CoV-2 was isolated from all ferrets regardless of age, aged ferrets (≥ 3 years old) showed higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptoms compared to juvenile (≤ 6 months) and young adult (1–2 years) groups. Transcriptome analysis of aged ferret lungs revealed strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

scholarly journals Age-dependent pathogenic characteristics of SARS-CoV-2 infection in ferrets

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Young-Il Kim ◽  
Kwang-Min Yu ◽  
June-Young Koh ◽  
Eun-Ha Kim ◽  
Se-Mi Kim ◽  
...  
Keyword(s):  
Young Adult ◽  
Direct Contact ◽  
Clinical Symptoms ◽  
Age Groups ◽  
Type I ◽  
Activated T Cells ◽  
Virus Shedding ◽  
Viral Loads ◽  
Gene Sets ◽  
M1 Macrophage

AbstractWhile the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1–2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.

scholarly journals The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies

2022 ◽  
Author(s):  
Jeremy Manry ◽  
Paul Bastard ◽  
Adrian Gervais ◽  
Tom Le Voyer ◽  
Jérémie Rosain ◽  
...  
Keyword(s):  
Relative Risk ◽  
Age Groups ◽  
Type I ◽  
Fatality Rate ◽  
Risk Of Death ◽  
Type I Ifns ◽  
Age Dependent ◽  
Relative Risk Of Death ◽  
Circulating Autoantibodies ◽  
Two Age Groups

Abstract SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

scholarly journals Characteristics of bone metabolism parameters in urban citizens

2017 ◽  
Vol 98 (3) ◽  
pp. 354-358
Author(s):  
M A Kabalyk
Keyword(s):  
Bone Metabolism ◽  
Type I Collagen ◽  
Middle Age ◽  
Age Groups ◽  
Type Ii Collagen ◽  
Type I ◽  
Type Ii ◽  
Age Dependent ◽  
Alkaline Phosphotase ◽  
Second Period

Aim. To reveal the features of age-dependent changes of bone tissue in urban citizens. Methods. The study of bone metabolism parameters was performed on 629 healthy subjects of middle, elderly and senile age living in Vladivostok for longer than 10 years (55 males and 573 females). Concentration of C-terminal telopeptide of type II collagen, osteocalcin, calcitonin, parathyroid hormone, 1,25(OH)2-vitamin D, and bone isoenzyme of alkaline phosphotase were measured by ELISA. Concentration of C-terminal telopeptide of type I collagen was measured in urine. Results. Biochemical markers of bone metabolism in older age groups are different from the parameters of middle age. In the second period of middle age statistically significant decrease of C-terminal telopeptides level (z=2.88, p

COVID - 19 AND THE PROBLEM OF PERSONALITY

2020 ◽  
pp. 31-35
Author(s):  
Mazaeva N.A. ◽  
Golovina A.G.
Keyword(s):  
General Population ◽  
Age Groups ◽  
Personal Transformation ◽  
Personality Changes ◽  
Age Dependent

In order to determine possible trends in the dynamics and characterological structure of personality in the General population caused by the COVID-19 pandemic, which is a long-term strong stressful effect and clinically and psychopathologically comparable to chronic personality changes after experiencing a disaster, the conditions predisposing to personal transformation, including clinical and prognostic patterns, are analyzed. The age-dependent nature of these changes is shown, and a number of features identified for different age groups are discussed.

scholarly journals 1465. Age-Dependent Interactions Among Clinical Characteristics, Viral Loads and Disease Severity in Young Children with Respiratory Syncytial Virus Infection (RSV) Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S734-S735
Author(s):  
Helena Brenes-Chacon ◽  
Cristina Garcia-Maurino ◽  
Melissa Moore-Clingenpeel ◽  
Sara Mertz ◽  
Fang Ye ◽  
...  
Keyword(s):  
Young Children ◽  
Disease Severity ◽  
Age Groups ◽  
Panel Member ◽  
Signs And Symptoms ◽  
Research Support ◽  
Review Panel ◽  
Viral Loads ◽  
Age Dependent ◽  
Rsv Infection

Abstract Background Differences in clinical presentation and viral loads according to age in young children with RSV, and their correlation with disease severity are poorly defined. The aim of this study was to define age-dependent the differences in demographic, clinical factors and viral loads between children &lt; 2 years of age with mild RSV infection evaluated as outpatients versus those hospitalized with severe RSV infection. Figure 1. Sign and Symptoms according to disease severity and age in infants with RSV infection. Most relevant signs and symptoms were stratified in outpatients (orange) vs inpatients (blue) by age in (A) &lt; 3 months, (B) between 3 and 6 months, and (C) &gt; 6 to 24 months of age. The Y axis represents the signs and symptoms in the two disease severity groups and the X axis the frequency of that specific symptom (%). Numbers next to bars represent the exact number of patients with that specific sign/symptom. Comparisons by Fisher exact test. Symbol (*) indicate significant 2-sided p values Figure 2. Viral load differences according to age in infants with RSV infection. The Y axis represents RSV loads in log10 copies/mL and the X axis differences in viral loads in outpatients (orange) and inpatients (blue) in the three age groups. Comparisons by Mann Whitney test. Methods Previously healthy children &lt; 2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and nasopharyngeal swabs were obtained for RSV typing and quantitation by real-time PCR. Patients were stratified by age (0-&lt; 3, 3-6, and &gt;6-24 months) and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. Results From 2014-2018 we enrolled 534 children with RSV infection: 130 outpatients and 404 inpatients. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than inpatient in the three age groups (Fig 1). Wheezing was more frequent in outpatients of older age (&gt;3 months) than in inpatients (p&lt; 0.01), while fever was more common in inpatients that outpatients (p&lt; 0.01) and increased with age (Fig 2). Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants &gt;3 months, and higher RSV loads in children &gt;6-24 months were independently associated with reduced disease severity. Conclusion Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

scholarly journals Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vidya Lakshmi Purushothaman ◽  
Raphael E. Cuomo ◽  
Cedric F. Garland ◽  
Timothy K. Mackey
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Age Groups ◽  
Incidence Rates ◽  
Ultraviolet B ◽  
Inverse Association ◽  
Crude Incidence ◽  
Age Dependent ◽  
Uvb Exposure

Abstract Background Vitamin D has been identified as a potential protective factor in the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally. Methods In this ecological study, a series of linear and polynomial regression tests were performed between country-specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps. Results The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates. Conclusion The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population-wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.

Different ATP-catabolism in reperfused adult and newborn rat hearts

1988 ◽  
Vol 254 (6) ◽  
pp. H1091-H1098
Author(s):  
P. W. Achterberg ◽  
A. S. Nieukoop ◽  
B. Schoutsen ◽  
J. W. de Jong
Keyword(s):  
Oxidase Activity ◽  
Age Groups ◽  
Similar Degree ◽  
Ischemia And Reperfusion ◽  
Xanthine Oxidoreductase ◽  
Newborn Rat ◽  
Age Related ◽  
Rat Hearts ◽  
Age Dependent ◽  
Atp Breakdown

Age-dependent differences in the effects of ischemia and reperfusion on ATP breakdown were studied in perfused adult and newborn (10 days old) rat hearts. No-flow ischemia (15 min at 37, 30, or 23 degrees C) was applied and reperfusion (20 min at 37 degrees C) was studied after ischemia at 23 or 37 degrees C. Hypothermia during ischemia protected both age groups to a similar degree against ATP decline, which was linear with temperature. Reperfusion after normothermic ischemia resulted in higher ATP levels in newborn hearts with less release of ATP catabolites (purines). We found no age-related differences in lactate release but large differences in purine release. During normoxia, adult hearts released mainly urate (80% of total) and inosine (7%), but newborns released hypoxanthine (64%) and inosine (15%). Early during reperfusion adult hearts released inosine (58%) and adenosine (18%), but newborns released inosine (53%) and hypoxanthine (38%). These data suggested a lower activity of the potentially deleterious enzyme xanthine oxidoreductase in newborn hearts, which was confirmed by enzymatic assay. ATP-catabolite release during reperfusion was less in newborn than adult hearts, and this coincided with lower xanthine oxidase activity.

Mechanical loading-induced gene expression and BMD changes are different in two inbred mouse strains

2005 ◽  
Vol 99 (5) ◽  
pp. 1951-1957 ◽  
Author(s):  
Chandrasekhar Kesavan ◽  
Subburaman Mohan ◽  
Susanna Oberholtzer ◽  
Jon E. Wergedal ◽  
David J. Baylink
Keyword(s):  
Gene Expression ◽  
Mechanical Loading ◽  
Quantitative Computed Tomography ◽  
Age Groups ◽  
Marker Genes ◽  
Type I ◽  
Mineral Density ◽  
Anabolic Response ◽  
Bone Response ◽  
C3h Mice

Our goal is to evaluate skeletal anabolic response to mechanical loading in different age groups of C57B1/6J (B6) and C3H/HeJ (C3H) mice with variable loads using bone size, bone mineral density (BMD), and gene expression changes as end points. Loads of 6–9 N were applied at 2 Hz for 36 cycles for 12 days on the tibia of 10-wk-old female B6 and C3H mice. Effects of a 9-N load on 10-, 16-, and 36-wk-old C3H mice were also studied. Changes in bone parameters were measured using peripheral quantitative computed tomography, and gene expression was determined by real-time PCR. Total volumetric BMD was increased by 5 and 15%, respectively, with 8- and 9-N loads in the B6, but not the C3H, mice. Increases of 20 and 12% in periosteal circumference were reflected by dramatic 44 and 26% increases in total area in B6 and C3H mice, respectively. The bone response to bending showed no difference in the three age groups of B6 and C3H mice. At 2 days, mechanical loading resulted in significant downregulation in expression of bone resorption (BR), but not bone formation (BF) marker genes. At 4 and 8 days of loading, expression of BF marker genes (type I collagen, alkaline phosphatase, osteocalcin, and bone sialoprotein) was increased two- to threefold and expression of BR marker genes (matrix metalloproteinase-9 and thrombin receptor-activating peptide) was decreased two- to fivefold. Although expression of BF marker genes was upregulated four- to eightfold at 12 days of training, expression of BR marker genes was upregulated seven- to ninefold. Four-point bending caused significantly greater changes in expression of BF and BR marker genes in bones of the B6 than the C3H mice. We conclude that mechanical loading-induced molecular pathways are activated to a greater extent in the B6 than in the C3H mice, resulting in a higher anabolic response in the B6 mice.

scholarly journals Studies on Spontaneous Platelet Aggregation (PAT III) in Patients with Vascular Disease

1977 ◽  
Author(s):  
H.J. Krzywanek ◽  
K. Breddin
Keyword(s):  
Platelet Aggregation ◽  
Healthy Subjects ◽  
Age Groups ◽  
Arterial Disease ◽  
Peripheral Occlusive Arterial Disease ◽  
Age Dependent ◽  
Patient Groups ◽  
The Difference ◽  
Spontaneous Platelet Aggregation ◽  
Prospective Investigation

Aggregation tests were performed in 345 patients with peripheral occlusive arterial disease (PAD), 274 patients with coronary heart disease (CHD), and 502 diabetics (D). 263 healthy volunteers (N) served as controls. As in previous studies an age dependent increase of strongly enhanced spontaneous platelet aggregation in obviously healthy subjects can be demonstrated, reaching 28% in the 50-59 years’age group. In the various patient groups the incidence of enhanced aggregation is much higher throughout all age groups than in the control s.The overall incidence of missing spontaneous platelet aggregation vs. strongly enhanced aggregation is summarized below. The difference between normals and the various patient groups is significant (X2-test, α<0.0001).A prospective investigation has been started to establish whether enhanced spontaneous platelet aggregation is a risk factor and an early indicator of progressive atherosclerosis.

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