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 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 Pathogenicity of novel goose-origin astrovirus causing gout in goslings

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Dan Yin ◽  
Jiajun Tian ◽  
Jing Yang ◽  
Yi Tang ◽  
Youxiang Diao
Keyword(s):  
Biochemical Parameters ◽  
Clinical Symptoms ◽  
Future Research ◽  
Tissue Tropism ◽  
Virus Shedding ◽  
Viral Loads ◽  
Blood Biochemical ◽  
Copy Numbers ◽  
Viral Copy ◽  
Kidney Liver

Abstract Background A novel goose-origin astrovirus (GoAstV) has broken out across China in recent years, causing gout in goslings with a mortality rate of around 50%. However, our understanding of the dynamic distribution, tissue tropism and pathogenesis of GoAstV is incomplete. In order to assess its pathogenicity, one-day-old goslings were inoculated separately with GoAstV via oral and subcutaneous injection routes. Results Clinical symptoms, gross and microscopic lesions, blood biochemical parameters and viral loads were detected and recorded for 20 days after infection. Typical gout was observed in experimental goslings. GoAstV can be replicated in tissues and cause pathological damage, especially in the kidney, liver, heart and spleen. Virus-specific genomic RNA was detected in blood, cloacal swabs and all representative tissues, and virus shedding was detected up to 20 days after inoculation, suggesting that GoAstV has a wide tissue tropism and spread systematically after inoculation. The viral copy numbers examined in kidney were the highest, followed by spleen and liver. Conclusion This experiment determined the accurate value of viral loads and biochemical indicators of GoAstV-induced goslings. These findings increase our understanding of the pathogenicity of GoAstV in goslings and provide more reference for future research.

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 < 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) < 3 months, (B) between 3 and 6 months, and (C) > 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 < 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-< 3, 3-6, and >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 (>3 months) than in inpatients (p< 0.01), while fever was more common in inpatients that outpatients (p< 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 >3 months, and higher RSV loads in children >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 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 UBXN3B Restricts Viral Pathogenesis by Maintaining Hematopoietic Homeostasis

2021 ◽  
Author(s):  
Tingting Geng ◽  
Duomeng Yang ◽  
Tao Lin ◽  
Andrew Harrison ◽  
Binsheng Wang ◽  
...  
Keyword(s):  
Viral Infection ◽  
Type I ◽  
Lung Pathology ◽  
Viral Loads ◽  
Type I Ifns ◽  
Multipotent Progenitors ◽  
Specific Immunoglobulin ◽  
The Right ◽  
Severe Lung

ABSTRACTHematopoiesis is finely regulated to enable timely production of the right number and type of mature immune cells to maintain tissue homeostasis. Dysregulated hematopoiesis may compromise antiviral immunity and/or exacerbate immunopathogenesis. Herein, we report an essential and new role of ubiquitin X domain containing gene 3B (UBXN3B) in balancing myelopoiesis and lymphopoiesis. Ubxn3b deficiency (Ubxn3b-/-) results in a remarkable increase in myeloid cells and neutrophil-to-lymphocyte ratio, along with a reduction in lymphocytes in steady-state mice. This dysregulation is exacerbated during viral infection and renders mice highly vulnerable to severe lung pathology induced by severe acute respiratory syndrome coronavirus 2 and arthritis by arthritogenic alphaviruses. Ubxn3b-/- mice present normal type I IFNs, higher viral loads and inflammatory mediators, lower virus-specific immunoglobulin G and slower resolution of disease, when compared to Ubxn3b+/+ littermates. Mechanistically, Ubxn3b-/- mice have fewer multipotent progenitors and common lymphoid progenitors, but more common myeloid progenitors. In particular, the precursor and immature B cell numbers are dramatically decreased in the bone marrow of Ubxn3b-/- mice. These data demonstrate that UBXN3B signaling is essential for restricting viral infection and immunopathogenesis by maintaining hematopoietic homeostasis.

scholarly journals Fibromodulin Ablation Exacerbates the Severity of Acute DSS Colitis

2022 ◽  
Author(s):  
Marianna Halasi ◽  
Mor Grinstein ◽  
Avner Adini ◽  
Irit Adini
Keyword(s):  
Clinical Symptoms ◽  
Inflammatory Diseases ◽  
Epidemiological Studies ◽  
Age Related Macular Degeneration ◽  
Type I ◽  
Acute Colitis ◽  
Activated T Cells ◽  
Dss Colitis ◽  
Age Related ◽  
Potential Biomarker

Epidemiological studies have linked pigment production to protection against certain human diseases. In contrast to African Americans, European descendants are more likely to suffer from angiogenesis-dependent diseases, and inflammatory diseases such as wet age-related macular degeneration (ARMD) and ulcerative colitis (UC), respectively. Here, we found that albino mice producing high levels of fibromodulin (FMOD) developed less severe acute colitis than mice lacking FMOD as assessed by the clinical symptoms and the histopathological changes. In a dextran sodium sulfate (DSS)-induced acute colitis mouse model, depletion of FMOD affected the expression and localization of tight junction proteins contributing to destruction of the epithelial barrier. Furthermore, this study demonstrates the development of a stronger inflammatory response after DSS treatment in the absence of FMOD. FMOD depletion led to an increase in activated T cells, plasmacytoid dendritic cells (pDCs), and type I IFN production. These findings strongly suggest that FMOD may serve as a potential biomarker in determining disease severity of UC in the population of light-skinned individuals with European descent.

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

scholarly journals Age-dependent association between SARS-CoV-2 cases reported by passive surveillance and viral load in wastewater

2021 ◽  
Author(s):  
Ryosuke Omori ◽  
Fuminari Miura ◽  
Masaaki Kitajima
Keyword(s):  
Time Series ◽  
Viral Load ◽  
Time Lag ◽  
Age Groups ◽  
Age Group ◽  
Passive Surveillance ◽  
Northern Area ◽  
Viral Loads ◽  
Southern Area ◽  
Age Dependent

The true number of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is difficult to estimate using a case-reporting system (i.e., passive surveillance) alone because of asymptomatic infection. While wastewater-based epidemiology has been implemented as an alternative/additional monitoring tool to reduce reporting bias, the relationship between passive and wastewater surveillance data has yet to be explicitly examined. Since there is strong age dependency in the symptomatic ratio of SARS-CoV-2 infections, this study aimed to estimate i) an age-dependent association between the number of reported cases and the viral load in wastewater and ii) the time lag between those time series. The viral load in wastewater was modeled as a combination of contributions from different age groups' virus shedding, incorporating the delay, and fitted with daily case count data collected from the Massachusetts Department of Public Health and SARS-CoV-2 RNA concentrations in wastewater collected by the Massachusetts Water Resources Authority. The estimated lag between the time series of viral loads in wastewater and of reported cases was 10.8 days (95% confidence interval =[10.2, 11.6]) for wastewater treatment plant's northern area and 8.8 days [8.4, 9.1] for southern area. The estimated contribution rate of a reported case to the viral load in wastewater in the 0-19 yr age group was 0.38 [0.35, 0.41] for northern area and 0.40 [0.37, 0.43] for southern area, that in the 80+ yr age group was 0.67 [0.65, 0.69] for northern area and 0.51 [0.49, 0.52] for southern area. The estimated lag between those time series suggested the predictability of reported cases ten days later using viral loads in wastewater. The contribution of a reported case in passive surveillance to the viral load in wastewater differed by age, suggesting a large variation in viral shedding kinetics among age groups.

scholarly journals Saliva Quantification of SARS-CoV-2 in Real-Time PCR From Asymptomatic or Mild COVID-19 Adults

2022 ◽  
Vol 12 ◽  
Author(s):  
Florence Carrouel ◽  
Emilie Gadea ◽  
Aurélie Esparcieux ◽  
Jérome Dimet ◽  
Marie Elodie Langlois ◽  
...  
Keyword(s):  
Viral Load ◽  
Real Time ◽  
Real Time Pcr ◽  
Clinical Symptoms ◽  
Age Groups ◽  
Nasal Discharge ◽  
Viral Loads ◽  
Co Morbidity ◽  
Significant Difference ◽  
The Relationship

The fast spread of COVID-19 is related to the highly infectious nature of SARS-CoV-2. The disease is suggested to be transmitted through saliva droplets and nasal discharge. The saliva quantification of SARS-CoV-2 in real-time PCR from asymptomatic or mild COVID-19 adults has not been fully documented. This study analyzed the relationship between salivary viral load on demographics and clinical characteristics including symptoms, co-morbidities in 160 adults diagnosed as COVID-19 positive patients recruited between September and December 2020 in four French centers. Median initial viral load was 4.12 log10 copies/mL (IQR 2.95–5.16; range 0–10.19 log10 copies/mL). 68.6% of adults had no viral load detected. A median load reduction of 23% was observed between 0–2 days and 3–5 days, and of 11% between 3–5 days and 6–9 days for the delay from onset of symptoms to saliva sampling. No significant median difference between no-symptoms vs. symptoms patients was observed. Charge was consistently similar for the majority of the clinical symptoms excepted for headache with a median load value of 3.78 log10 copies/mL [1.95–4.58] (P &lt; 0.003). SARS-CoV-2 RNA viral load was associated with headache and gastro-intestinal symptoms. The study found no statistically significant difference in viral loads between age groups, sex, or presence de co-morbidity. Our data suggest that oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

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