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

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.

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

10.21203/rs.3.rs-131380/v2 ◽

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.

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

10.21203/rs.3.rs-131380/v1 ◽

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.

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Pathogenicity of novel goose-origin astrovirus causing gout in goslings

BMC Veterinary Research ◽

10.1186/s12917-020-02739-z ◽

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.

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Differential effects of mild therapeutic exercise during a period of inactivity on power generation in soleus type I single fibers with age

Journal of Applied Physiology ◽

10.1152/japplphysiol.01077.2011 ◽

2012 ◽

Vol 112 (10) ◽

pp. 1752-1761 ◽

Cited By ~ 4

Author(s):

Jong-Hee Kim ◽

LaDora V. Thompson

Keyword(s):

Young Adult ◽

Peak Power ◽

Fiber Diameter ◽

Weight Bearing ◽

Age Groups ◽

Exercise Program ◽

Type I ◽

Therapeutic Exercise ◽

Middle Aged ◽

Single Fibers

The purpose of this study was to investigate the effects of mild therapeutic exercise (treadmill) in preventing the inactivity-induced alterations in contractile properties (e.g., power, force, and velocity) of type I soleus single fibers in three different age groups. Young adult (5- to 12-mo-old), middle-aged (24- to 31-mo-old), and old (32- to 40-mo-old) F344BNF1 rats were randomly assigned to three experimental groups: weight-bearing control (CON), non-weight bearing (NWB), and NWB with exercise (NWBX). NWB rats were hindlimb suspended for 2 wk, representing inactivity. The NWBX rats were hindlimb suspended for 2 wk and received therapeutic exercise on a treadmill four times a day for 15 min each. Peak power and isometric maximal force were reduced following hindlimb suspension (HS) in all three age groups. HS decreased fiber diameter in young adult and old rats (−21 and −12%, respectively). Specific tension (isometric maximal force/cross-sectional area) was significantly reduced in both the middle-aged (−36%) and old (−23%) rats. The effects of the mild therapeutic exercise program on fiber diameter and contractile properties were age specific. Mild treadmill therapeutic exercise attenuated the HS-induced reduction in fiber diameter (+17%, 93% level of CON group) and peak power (μN·fiber length·s−1) (+46%, 63% level of CON group) in young adult rats. In the middle-aged animals, this exercise protocol improved peak power (+60%, 100% level of CON group) and normalized power (kN·m−2·fiber length·s−1) (+45%, 108% level of CON group). Interestingly, treadmill exercise resulted in a further reduction in shortening velocity (−42%, 67% level of CON group) and specific tension (−29%, 55% level of CON group) in the old animals. These results suggest that mild treadmill exercise is beneficial in attenuating and preventing inactivity-induced decline in peak power of type I soleus single fibers in young adult and middle-aged animals, respectively. However, this exercise program does not prevent the HS-induced decline in muscle function in the old animals.

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Fibromodulin Ablation Exacerbates the Severity of Acute DSS Colitis

10.1101/2022.01.12.475640 ◽

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.

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

Frontiers in Microbiology ◽

10.3389/fmicb.2021.786042 ◽

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 < 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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Rare Presentation of the Type I Choledochal Cyst in a Young Adult

HPB ◽

10.1016/j.hpb.2020.11.897 ◽

2021 ◽

Vol 23 ◽

pp. S352

Author(s):

N.Y. Muppalla ◽

S. Sankar

Keyword(s):

Young Adult ◽

Choledochal Cyst ◽

Type I ◽

Rare Presentation

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Zika RNA and Flavivirus-Like Antigens in the Sperm Cells of Symptomatic and Asymptomatic Subjects

Viruses ◽

10.3390/v13020152 ◽

2021 ◽

Vol 13 (2) ◽

pp. 152

Author(s):

Hernan Vanegas ◽

Fredman González ◽

Yaoska Reyes ◽

Edwing Centeno ◽

Jayrintzina Palacios ◽

...

Keyword(s):

Clinical Symptoms ◽

Time Frame ◽

Sperm Cells ◽

Human Semen ◽

Zikv Infection ◽

Virus Shedding ◽

One Year ◽

Asymptomatic Subjects ◽

A Prospective Study ◽

Male Subjects

Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in León to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (≥18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 × 106/mL vs. 63.5 × 106/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1646 ◽

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)

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