scholarly journals SARS-CoV-2 Delta variant pathogenesis and host response in Syrian hamsters

2021 ◽  
Author(s):  
Sreelekshmy Mohandas ◽  
Pragya Dhruv Yadav ◽  
Anita Aich Shete ◽  
Dimpal Nyayanit ◽  
Gajanan N Sapkal ◽  
...  
Keyword(s):  
Lung Disease ◽  
Host Response ◽  
Virus Isolate ◽  
Genomic Rna ◽  
Hamster Model ◽  
Moderate Severity ◽  
Virus Shedding ◽  
Transmission Potential ◽  
Significant Difference ◽  
Study Support

B.1.617 lineage is becoming a dominant SARS-CoV-2 lineage worldwide and was the dominant lineage reported in second COVID-19 wave in India, which necessitated studying the properties of the variant. We evaluated the pathogenicity and virus shedding of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 and compared with that of B.1, an early virus isolate with D614G mutation in Syrian hamster model. Viral load, antibody response and lung disease were studied. No significant difference in the virus shedding pattern was observed among these variants studied. A significantly high SARS-CoV-2 sub genomic RNA could be detected in the respiratory tract of hamsters infected with Delta variant for 14 days. Delta variant induced lung disease of moderate severity in 40% of infected animals. The neutralizing capability of the B.1, Delta and B.1.617.3 variant infected animals were found significantly lower with the B.1.351 (Beta variant). The findings of the study support the attributed disease severity and the increased transmission potential of the Delta variant.

scholarly journals SARS-CoV-2 Delta Variant Pathogenesis and Host Response in Syrian Hamsters

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1773
Author(s):  
Sreelekshmy Mohandas ◽  
Pragya Dhruv Yadav ◽  
Anita Shete ◽  
Dimpal Nyayanit ◽  
Gajanan Sapkal ◽  
...  
Keyword(s):  
Lung Disease ◽  
Neutralizing Antibodies ◽  
Host Response ◽  
Virus Isolate ◽  
Hamster Model ◽  
Moderate Severity ◽  
Virus Shedding ◽  
Neutralizing Capacity ◽  
Significant Difference ◽  
Transmission Studies

B.1.617 is becoming a dominant Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) lineage worldwide with many sublineages, of which B.1.617.2 is designated as a variant of concern. The pathogenicity of B.1.617.2 (Delta) and B.1.617.3 lineage of SARS-CoV-2 was evaluated and compared with that of B.1, an early virus isolate with D614G mutation in a Syrian hamster model. Viral load, antibody response, and lung disease were studied. There was no significant difference in the virus shedding pattern among these variants. High levels of SARS-CoV-2 sub genomic RNA were detected in the respiratory tract of hamsters infected with the Delta variant for 14 days, which warrants further transmission studies. The Delta variant induced lung disease of moderate severity in about 40% of infected animals, which supports the attributed disease severity of the variant. Cross neutralizing antibodies were detected in animals infected with B.1, Delta, and B.1.617.3 variant, but neutralizing capacity was significantly lower with B.1.351 (Beta variant).

Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases

Rheumatology ◽  
2020 ◽  
Author(s):  
Shan Li ◽  
Yuxin Sun ◽  
Chi Shao ◽  
Hui Huang ◽  
Qian Wang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Retrospective Study ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Mortality Rates ◽  
Trna Synthetase ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Objectives Few studies have investigated the prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) across different clinical/serological phenotypes. Methods We conducted a retrospective analysis of patients diagnosed with IIM between January 2012 and December 2017. Results Of the 760 IIM cases registered, 679 adult cases were included in this study. ILD was present in 508 cases, and the presence of ILD in the clinically amyopathic DM, DM and PM groups was 92.7, 73.6 and 55.1%, respectively (P < 0.01). The prevalence of ILD in the anti-synthetase antibody (ASA)+-IIM group was higher than that in ASA–-IIM group (95.2 vs 72.4%, P < 0.01); no such difference was found between the anti-histidyl-tRNA synthetase (Jo-1)+-IIM and Jo-1–ASA+-IIM groups (93.0 vs 98.5%, P > 0.05). The prevalence of ILD in the melanoma differentiation-associated protein-5 (MDA-5)+-IIM group was higher than that in MDA-5–-IIM group (97.8 vs 72.1%, P < 0.01). Among adults with IIM, men with concurrent ILD, who were older than 50 years, were most likely to die. No significant difference was found in the all-cause mortality rates between DM-ILD and clinically amyopathic DM-ILD groups (33.3 vs 23%, P > 0.05), although both were higher than that in PM group (13.2%, P = 0.01 and P < 0.05, respectively). No difference was found in the all-cause mortality rates between MDA5–ASA–-IM-ILD and MDA5–ASA+-IM-ILD groups (17.2 vs 12.8%, P > 0.05), and both were lower than that in MDA5+ASA–-IM-ILD group (33.7%, P < 0.05). Conclusion The prevalence of ILD in IIM and the prognosis of IIM-ILD patients may vary depending on the statuses of the ASA and MDA-5 antibodies.

scholarly journals Defining genetic risk factors for scleroderma-associated interstitial lung disease

2020 ◽  
Vol 39 (4) ◽  
pp. 1173-1179 ◽  
Author(s):  
Carmel J. W. Stock ◽  
Angelo De Lauretis ◽  
Dina Visca ◽  
Cecile Daccord ◽  
Maria Kokosi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Allele Frequency ◽  
Lung Fibrosis ◽  
Genetic Basis ◽  
Genetic Associations ◽  
European Descent ◽  
Key Points ◽  
Significant Difference

AbstractAlthough several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10–1.54), pcorr = 0.015) and rs10488631 (OR 1.48 (1.14–1.92), pcorr = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18–1.73), pcorr = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24–2.39), pcorr = 0.0098), and rs2004640 (OR 1.39 (1.11–1.75), pcorr = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45–2.38), pcorr = 6.6 × 10−6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51–0.85), pcorr = 0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD.Key points• We confirm the associations of the IRF5 SNPs rs2004640 and rs10488631, and the STAT4 SNP rs7574865, with SSc as a whole.• None of the tested SNPs were risk factors for SSc-ILD specifically.• The STAT4 rs7574865 T allele was protective against the development of lung fibrosis in SSc patients.• Further work is required to understand the genetic basis of lung fibrosis in association with scleroderma.

scholarly journals Neutrophil Oxidized-Modified Proteins and Neutrophil Extracellular Traps in Patients with Community-Acquired Pneumonia

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Vilen Molotov-Luchanskiy ◽  
Altynbek Nukhuly ◽  
Larissa Muravlyova ◽  
Ryszhan Bakirova ◽  
Aruna Kossybayeva ◽  
...  
Keyword(s):  
Severe Pneumonia ◽  
Neutrophil Extracellular Traps ◽  
Community Acquired Pneumonia ◽  
Control Group ◽  
Moderate Severity ◽  
Extracellular Traps ◽  
Detection Frequency ◽  
Group I ◽  
Significant Difference ◽  
Modified Proteins

Background and Objectives. Community-acquired pneumonia (CAP) has a high mortality rate among adult patients throughout the world. The highest mortality is registered in the older age group with a steady increase in the number of cases of morbidity among persons of working age. Neutrophils are one of the most urgent areas of research, since their condition largely determines the development and outcome of acute pneumonia. We study the indices of oxidative stress and oxidized-modified proteins of neutrophils in CAP patients, depending on the degree of severity, and also compare the detection frequency of neutrophil extracellular traps in the progression of pneumonia. Materials and Methods. 51 patients with CAP were divided into 2 groups depending on the severity of the pathological process. The first group (I) consisted of 32 patients with moderate severity of pneumonia. The second group (II) consisted of 19 patients with severe pneumonia. The third group (III), the comparison group, consisted of 14 CAP patients with chronic obstructive pulmonary disease (COPD). The control group consisted of 19 volunteers. Results. Statistically significant increase in the level of carbonyl derivatives (CD) in patients of all study groups relative to the control group was revealed. In the group of patients with moderate severity and severe pneumonia, also in CAP patients with COPD, the level of CD exceeded the control group. There was no statistically significant difference in the level of advanced oxidation protein products (AOPP) and myeloperoxidase (MPO) in blood neutrophils between the studied groups. Conclusion. Results indicate an oxidative imbalance in neutrophils and contribute to the worsening of the course of the disease.

scholarly journals The Correlation of Francisella tularensis on Size and Supercooling of Dermacentor variabilis

2018 ◽  
Vol 10 (2) ◽  
pp. 15
Author(s):  
Amal El Nabbout ◽  
Brittany J. Taylor ◽  
James Kho ◽  
Mandy Mitton ◽  
Tatiana Rossolimo
Keyword(s):  
Francisella Tularensis ◽  
Cold Hardiness ◽  
Dermacentor Variabilis ◽  
Physical Size ◽  
Significant Difference ◽  
Bacterium Species ◽  
Tick Survival ◽  
Study Support ◽  
Polymerase Chain ◽  
The Relationship

Overwintering tick survival is essential for the continuation of a tick’s lifecycle. Recent studies have found that infections with particular microorganisms can alter the physiology of ticks and, in some cases, increase their cold hardiness. To date, the influence of Francisella tularensis on Dermacentor variabilis (Say) has not been studied and thus the symbiosis between the two has been unknown. This study determined the infection rate of F. tularensis as well as examined the relationship between F. tularensis and the supercooling point (SCP) and size of D. variabilis of ticks from Nova Scotia, Canada. Local veterinarians provided adult ticks. The SCP of each tick was recorded using Logger Pro and infection status was found using Polymerase Chain Reaction. Of the 203 ticks tested, 9.8% were infected with F. tularensis. When the sexes were considered separately, 4% of males, 11.7% engorged females and 17.3% of non-engorged females were infected. Upon further analysis, a statistically significant difference was found between infected ticks and changes in thier SCPs, but there was no statistically significant difference between infected ticks and changes in size. This suggests that F. tularensis benefits D. variabilis by decreasing their SCPs, and thereby enhancing their overwintering capabilities. While other physiological influences of F. tularensis on D. variabilis remain unknown, the results from this study support previous research that bacterium species such as F. tularensis is able to influence the survivability of its tick host in the form of altering their freezing tolerance but does not affect the physical size of D. variabilis.

Effect of hosiery on skin temperature in spastic quadriplegia. A preliminary study

1994 ◽  
Vol 84 (3) ◽  
pp. 120-123 ◽  
Author(s):  
C Ufer ◽  
A Cryer ◽  
M Stevenson
Keyword(s):  
Skin Temperature ◽  
Hollow Core ◽  
Significant Difference ◽  
Spastic Quadriplegia ◽  
Before And After ◽  
Study Support ◽  
Preliminary Study ◽  
Core Fiber ◽  
Skin Temperatures

The effect of hosiery on 21 patients with spastic quadriplegia was studied by examining skin temperatures before and after wearing control socks (cotton or cotton/acrylic), compared with the test socks (21% stretch nylon and 80% synthetic hollow-core fiber). The latter are claimed by the manufacturers to provide superior warmth. Other investigations suggest that no material for a given thickness has superior insulation properties. The results of this preliminary study support these investigations, in that no significant difference in skin temperatures was found between the control and test socks when worn by this population.

Pre-existing interstitial lung abnormalities are risk factors for immune checkpoint inhibitor-induced interstitial lung disease in non-NSCLC cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15171-e15171
Author(s):  
Kiyofumi Shimoji ◽  
Takeshi Masuda ◽  
Yu Nakanishi ◽  
Kakuhiro Yamaguchi ◽  
Shinjiro Sakamoto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Risk Factor ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Logistic Regression Analysis ◽  
Independent Risk Factor ◽  
Patient Characteristics ◽  
Significant Difference

e15171 Background: Immune check point inhibitor (ICI) induced interstitial lung disease (ICI-ILD) is a clinically serious and life-threatening toxicity. Pre-existing ILD has been reported to be a risk factor for ICI-ILD in patients with non-small cell lung cancer (NSCLC). In addition, we have previously reported that interstitial lung abnormality (ILA) is also a risk factor for the ICI-ILD. Therefore, we investigated whether any patient characteristics, including ILA, were risk factors for ICI-ILD in patients with non-NSCLC cancers. Methods: Head and neck cancer, malignant melanoma, oral cavity cancer, renal cell carcinoma or gastric cancer patients who received anti PD-1 antibody (Nivolumab or Pembrolizumab) at Hiroshima University Hospital from December 2015 to May 2019 were enrolled. Information on patient characteristics before anti-PD-1 antibody administration, including chest CT findings and laboratory data, were obtained. Results: Two hundred patients were enrolled, and 20 (10%) developed ICI-ILD. Grade1 was observed in 15 patients, grade2 in 3, and grade3 and 5 in 1. There was no significant difference in the background factors between patients with and without ICI-ILD. On the other hand, the proportion of patients with ILA was significantly higher in the patients with ICI-ILD than those without (P < 0.01). Furthermore, univariate logistic regression analysis revealed ILA was the risk factor for ICI-ILD (p < 0.01), and multivariate logistic regression analysis showed that GGA or reticulation in ILA was an independent risk factor for ICI-ILD (p = 0.016, 0.011). Conclusions: Pre-existing ILA is a risk factor for ICI-ILD, and GGA or reticulation in ILA is an independent risk factor for ICI-ILD in patients with non-NSCLC cancers. Therefore, we should pay more attention to the development of ICI-ILD in patients with ILA, especially GGA or reticulation.

scholarly journals Pulmonary Collectins Modulate Strain-Specific Influenza A Virus Infection and Host Responses

2004 ◽  
Vol 78 (16) ◽  
pp. 8565-8572 ◽  
Author(s):  
Samuel Hawgood ◽  
Cynthia Brown ◽  
Jess Edmondson ◽  
Amber Stumbaugh ◽  
Lennell Allen ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Host Response ◽  
Influenza A ◽  
Small Difference ◽  
Alveolar Epithelium ◽  
Host Responses ◽  
Cytokine Release ◽  
Significant Difference

ABSTRACT Collectins are secreted collagen-like lectins that bind, agglutinate, and neutralize influenza A virus (IAV) in vitro. Surfactant proteins A and D (SP-A and SP-D) are collectins expressed in the airway and alveolar epithelium and could have a role in the regulation of IAV infection in vivo. Previous studies have shown that binding of SP-D to IAV is dependent on the glycosylation of specific sites on the HA1 domain of hemagglutinin on the surface of IAV, while the binding of SP-A to the HA1 domain is dependent on the glycosylation of the carbohydrate recognition domain of SP-A. Here, using SP-A and SP-D gene-targeted mice on a common C57BL6 background, we report that viral replication and the host response as measured by weight loss, neutrophil influx into the lung, and local cytokine release are regulated by SP-D but not SP-A when the IAV is glycosylated at a specific site (N165) on the HA1 domain. SP-D does not protect against IAV infection with a strain lacking glycosylation at N165. With the exception of a small difference on day 2 after infection with X-79, we did not find any significant difference in viral load in SP-A−/− mice with either IAV strain, although small differences in the cytokine responses to IAV were detected in SP-A−/− mice. Mice deficient in both SP-A and SP-D responded to IAV similarly to mice deficient in SP-D alone. Since most strains of IAV currently circulating are glycosylated at N165, SP-D may play a role in protection from IAV infection.

scholarly journals The Impact of Diabetes and African American Race in COVID-19 Severity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A350-A351
Author(s):  
Marilyn A Arosemena ◽  
Athalia Pyzer ◽  
Jovian Yu ◽  
Blake Flood ◽  
Sherin Rouhani ◽  
...  
Keyword(s):  
African American ◽  
Pearson Correlation ◽  
Severity Index ◽  
Older Age ◽  
Moderate Severity ◽  
High Severity ◽  
Significant Difference ◽  
The Impact ◽  
The Relationship ◽  
African American Race

Abstract Introduction: COVID-19, an illness caused by the novel coronavirus usually presents as a mild to moderate flu like illness, but can lead to pneumonia, acute respiratory distress syndrome and death in some patients. Since the onset of the COVID-19 pandemic there has been special attention towards patients with diabetes. Not only is diabetes highly prevalent in patients with COVID-19, but diabetes has been reported as a significant predictor of morbidity and mortality. Furthermore, race seems to be a predictor of severity with black people dying at 2.3 times the rate of white people. Methods: Here we performed a retrospective study of 524 cases of COVID-19 at an academic center in Chicago between March 2020 until August 2020. Data were obtained from patients that consented to the study to examine the relationship between diabetes, BMI, age, and race with degree of COVID-19 severity. Not all patients had all clinical and demographic data available. COVID-19 severity was determined using a severity index obtained from the measured SpO2 divided by the FiO2/fraction of inspired oxygen times 100. Numbers ≥ 315 mmHg were defined as low severity with patients generally requiring outpatient care, while 235–314 mm Hg were classified as moderate severity generally requiring inpatient care and≤ 234 mm Hg indicated high severity generally requiring intubation/ICU care. The Pearson correlation coefficient was used for linear correlation analyses. Proportion for categorical values were compared using the Chi squared test, the means for continuous variables were compared using two-tailed t tests or one way ANOVA (with Tukey post-test) for comparisons involving more than two conditions. A multiple linear regression model was used to assess the contribution of different variables. Differences were considered statistically significant at p&lt;0.05 Results: Among 120 patients with an A1c, 55 (46%) patients had diabetes and 65 (54%) did not have diabetes. More patients with a high severity index were seen in the cohort with diabetes compared to those without diabetes (72% compared to 28% p=0.004). Univariate analyses revealed statistically significant positive correlations with higher COVID-19 severity and older age, BMI, and African American race. ANOVA analysis revealed a statistically significant difference between increasing BMI and worse severity category with a BMI mean of 29.3 kg/m2 in the low severity category compared to 34.9 kg/m2 in the moderate severity category (p=0.006). A multi-variate analysis adjusting for all variables revealed that A1c, older age and race were positively associated with higher COVID-19 severity. Conclusion: Increased A1c, older age and race are positively and independently associated with a higher COVID-19 severity index. Further research regarding the relationship between COVID-19 and these associations is urgently needed.

scholarly journals Dissecting genetic and sex-specific sources of host heterogeneity in pathogen shedding and spread

2021 ◽  
Vol 17 (1) ◽  
pp. e1009196
Author(s):  
Jonathon A. Siva-Jothy ◽  
Pedro F. Vale
Keyword(s):  
Viral Load ◽  
Individual Variation ◽  
Disease Transmission ◽  
Genetic Background ◽  
Pathogen Transmission ◽  
Published Data ◽  
Virus Shedding ◽  
Transmission Potential ◽  
Sources Of Variation ◽  
Host Heterogeneity

Host heterogeneity in disease transmission is widespread but precisely how different host traits drive this heterogeneity remains poorly understood. Part of the difficulty in linking individual variation to population-scale outcomes is that individual hosts can differ on multiple behavioral, physiological and immunological axes, which will together impact their transmission potential. Moreover, we lack well-characterized, empirical systems that enable the quantification of individual variation in key host traits, while also characterizing genetic or sex-based sources of such variation. Here we used Drosophila melanogaster and Drosophila C Virus as a host-pathogen model system to dissect the genetic and sex-specific sources of variation in multiple host traits that are central to pathogen transmission. Our findings show complex interactions between genetic background, sex, and female mating status accounting for a substantial proportion of variance in lifespan following infection, viral load, virus shedding, and viral load at death. Two notable findings include the interaction between genetic background and sex accounting for nearly 20% of the variance in viral load, and genetic background alone accounting for ~10% of the variance in viral shedding and in lifespan following infection. To understand how variation in these traits could generate heterogeneity in individual pathogen transmission potential, we combined measures of lifespan following infection, virus shedding, and previously published data on fly social aggregation. We found that the interaction between genetic background and sex explained ~12% of the variance in individual transmission potential. Our results highlight the importance of characterising the sources of variation in multiple host traits to understand the drivers of heterogeneity in disease transmission.

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