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MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Disruption of Adaptive Immunity Enhances Disease MESHD in SARS-CoV-2 Infected Syrian Hamsters

    Authors: Rebecca Brocato; Lucia Principe; Robert Kimi; Xiankun Zeng; Janice Williams; Yanan Liu; Rong Li; Jeffrey Smith; Joseph Golden; Dave Gangemi; Sawsan Youssef; Zhongde Wang; Jacob Glanville; Jay W Hooper

    doi:10.21203/rs.3.rs-43931/v1 Date: 2020-07-15 Source: ResearchSquare

    Animal models recapitulating human COVID-19 disease MESHD, especially with severe disease MESHD, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models MESHD for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease MESHD that were more severe than in immunocompetent hamsters, notably weight loss MESHD weight loss HP, viral loads, and fatality (RAG2 KO only). Disease MESHD was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody SERO and found that pretreatment, even in immunosuppressed animals, limited infection MESHD. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease MESHD.

    Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease MESHD

    Authors: Joseph Golden; Curtis Cline; Xiankun Zeng; Aura Garrison; Brian Carey; Eric Mucker; Lauren White; Joshua Shamblin; Rebecca Brocato; Jun Liu; April Babka; Hypaitia Rauch; Jeffrey M Smith; Bradley Hollidge; Collin Fitzpatrick; Catherine Badger; Jay Hooper

    doi:10.1101/2020.07.09.195230 Date: 2020-07-09 Source: bioRxiv

    ABSTRACTThe emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease MESHD are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection MESHD due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male TRANS and female TRANS mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease MESHD including weight loss MESHD weight loss HP, lung injury MESHD, brain infection MESHD and lethality. Vasculitis MESHD Vasculitis HP was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury MESHD and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female TRANS mice with 60% surviving infection MESHD whereas all male TRANS mice succumbed to disease MESHD. Male TRANS mice that succumbed to disease MESHD had higher levels of inflammatory transcripts compared to female TRANS mice. This is the first highly lethal murine infection MESHD model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Favipiravir and severe acute respiratory syndrome MESHD coronavirus 2 in hamster model

    Authors: Jean-Sélim Driouich; Maxime Cochin; Guillaume Lingas; Grégory Moureau; Franck Touret; Paul-Rémi Petit; Géraldine Piorkowski; Karine Barthélémy; Bruno Coutard; Jérémie Guedj; Xavier de Lamballerie; Caroline Solas; Antoine Nougairède

    doi:10.1101/2020.07.07.191775 Date: 2020-07-07 Source: bioRxiv

    Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we used a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment was initiated before or simultaneously to infection MESHD, favipiravir had a strong dose effect, leading to dramatic reduction of infectious titers in lungs and clinical alleviation of the disease MESHD. Antiviral effect of favipiravir correlated with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. The antiviral efficacy observed in this study was achieved with plasma SERO drug exposure comparable with those previously found during human clinical trials and was associated with weight losses MESHD weight losses HP in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.

    Evaluation of K18-hACE2 mice as a model of SARS-CoV-2 infection MESHD

    Authors: G. Brett Moreau; Stacey L Burgess; Jeffrey M Sturek; Alexandra N Donlan; William A Petri Jr.; Barbara J Mann

    doi:10.1101/2020.06.26.171033 Date: 2020-06-26 Source: bioRxiv

    Abstract/SummaryMurine models of SARS-CoV-2 infection MESHD are critical for elucidating the biological pathways underlying COVID-19 disease MESHD. Because human ACE2 is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. Mice were followed twice daily for five days and scored for weight loss MESHD weight loss HP and clinical symptoms. Infected mice did not exhibit any signs of infection MESHD until day four, when weight loss MESHD weight loss HP, but no other obvious clinical symptoms were observed. By day five all infected mice had lost around 10% of their original body weight MESHD, but exhibited variable clinical symptoms. All infected mice showed high viral titers in the lungs as well as altered lung histology associated with proteinaceous debris in the alveolar space, interstitial inflammatory cell infiltration and alveolar septal thickening. Overall, these results show that symptomatic SARS-CoV-2 infection MESHD can be established in the K18-hACE2 transgenic background and should be a useful mouse model for COVID-19 disease MESHD.

    A single dose of recombinant VSV-{triangleup}G-spike vaccine provides protection against SARS-CoV-2 challenge

    Authors: Yfat Yahalom-Ronen; Hadas Tamir; Sharon Melamed; Boaz Politi; Ohad Shifman; Hagit Achdout; Einat B. Vitner; Ofir Israeli; Elad Milrot; Dana Stein; Inbar Cohen-Gihon; Shlomi Lazar; Hila Gutman; Itai Glinert; Lilach Cherry; Yaron Vagima; Shirley Lazar; Shay Weiss; Amir Ben-Shmuel; Roy Avraham; Reut Puni; Edith Lupu; Elad Bar David; Assa Sittner; Noam Erez; Ran Zichel; Emanuelle Mamroud; Ohad Mazor; Haim Levy; Orly Laskar; Shmuel Yitzhaki; Shmuel C. Shapira; Anat Zvi; Adi Beth-Din; Nir Paran; Tomer Israely

    doi:10.1101/2020.06.18.160655 Date: 2020-06-19 Source: bioRxiv

    The COVID-19 pandemic caused by SARS-CoV-2 that emerged in December 2019 in China resulted in over 7.8 million infections MESHD and over 430,000 deaths MESHD worldwide, imposing an urgent need for rapid development of an efficient and cost-effective vaccine, suitable for mass immunization. Here, we generated a replication competent recombinant VSV-{Delta}G-spike vaccine, in which the glycoprotein of VSV was replaced by the spike protein of the SARS-CoV-2. In vitro characterization of the recombinant VSV-{Delta}G-spike indicated expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2. A golden Syrian hamster in vivo model for COVID-19 was implemented. We show that vaccination of hamsters with recombinant VSV-{Delta}G-spike results in rapid and potent induction of neutralizing antibodies SERO against SARS-CoV-2. Importantly, single-dose vaccination was able to protect hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight MESHD weight loss HP of the immunized hamsters compared to unvaccinated hamsters. Furthermore, whereas lungs of infected hamsters displayed extensive tissue damage and high viral titers, immunized hamsters lungs showed only minor lung pathology, and no viral load. Taken together, we suggest recombinant VSV-{Delta}G-spike as a safe, efficacious and protective vaccine against SARS-CoV-2 infection MESHD.

    Disruption of Adaptive Immunity Enhances Disease MESHD in SARS-CoV-2 Infected Syrian Hamsters

    Authors: Rebecca Brocato; Lucia Principe; Robert Kim; Xiankun Zeng; Janice Williams; Yanan Liu; Rong Li; Jeffrey Smith; Joseph Golden; Dave Gangemi; Sawsan Youssef; Zhongde Wang; Jacob Glanville; Jay Hooper

    doi:10.1101/2020.06.19.161612 Date: 2020-06-19 Source: bioRxiv

    Animal models recapitulating human COVID-19 disease MESHD, especially with severe disease MESHD, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models MESHD for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease MESHD that were more severe than in immunocompetent hamsters, notably weight loss MESHD weight loss HP, viral loads, and fatality (RAG2 KO only). Disease MESHD was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody SERO and found that pretreatment, even in immunosuppressed animals, limited infection MESHD. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease MESHD. One Sentence SummaryAn antibody SERO targeting the spike protein of SARS-CoV-2 limits infection MESHD in immunosuppressed Syrian hamster models.

    Lung Function Decline and Other Physiological Changes in Health Workers after Working in COVID-19 Isolation Wards: An Observational Study

    Authors: Kailei Chen; Peipei Zhu; Liyuan Wang; Siting Zuo; CuiPing Wu; Ying Hu; YiSi Wang; Feng Wu; Xin Tang

    doi:10.21203/rs.3.rs-36291/v1 Date: 2020-06-17 Source: ResearchSquare

    Background:Global healthcare systems have been under huge pressure since Coronavirus Disease MESHD 2019 (COVID-19) was declared a pandemic. It is critical to prevent further spread of COVID-19 and to protect health workers from infection MESHD. This study aims to figure out short-term physiological impact on health workers induced by working in isolation wards for hours with personal protective equipment (PPE), so as to provide insights on reducing physiological impact and infection MESHD infection risk TRANS infection risk TRANS risk of health workers.Methods:Health workers who had worked in COVID-19 isolation wards for at least five weeks in Wuhan, China were recruited. Parameters including lung function, heart rate, oxygen saturation and weight were respectively measured before and after they worked in isolation wards. Comparison and regression analyses were conducted. Correlations between changing levels of measured parameters (lung function and heart rate) and baseline characteristics (body mass index, age TRANS, and working duration) were also analyzed. Results: After working in isolation wards for four to nine hours, the forced vital capacity (FVC) of health workers (74.32±17.59 versus 81.28±16.35, P<0.001) as well as weight (54.79 (48.50, 61.00) versus 55.50 (48.90, 61.00) P<0.01) showed significant decrease, while HR showed significant increase (110.31±14.65 versus 103.94±16.38, P=0.04). Correlation between BMI and the decline levels of FEV1/FVC (β=2.87, P=0.02) and correlation between BMI and the decline levels of FEF25-75 % predicted (β=1.80, P<0.05) were reported.Conclusions:After working in COVID-19 isolation wards with PPE for four to nine hours, the lung function of health workers declined. The decline levels were associated with BMI. HR increase and weight loss MESHD weight loss HP were reported. In order to reduce the potential infection MESHD infection risk TRANS infection risk TRANS risk of health workers, the balance between working duration and physiological changes should be considered when making shifting schedule. 

    Self-reported food choices before and during COVID-19 lockdown

    Authors: Ellen Siobhan Mitchell; Qiuchen Yang; Heather Behr; Laura Deluca; Paul Schaffer

    doi:10.1101/2020.06.15.20131888 Date: 2020-06-17 Source: medRxiv

    Stressful situations can cause changes in individual food choices, most notably, choices of highly rewarding foods that are high in fat or sugar. Few studies have examined how a population's food choices change during a country-wide stress-inducing event such as the beginning of the COVID-19 stay-at-home orders in the United States. Food data from a digital behavior change weight loss MESHD weight loss HP program, which includes an interface for logging meals, were analyzed to assess self-reported food choices from March 5-March 11 ("pre-COVID") and during the first week of the COVID-19 lockdown (March 12-March 18; "during-COVID"). The final sample consisted of 381,564 participants: 318,076 (83.4%) females TRANS, the majority who were aged TRANS 45-65 years (45.2%). Results indicate that self-reported servings of fresh fruit and vegetable intake decreased from pre- to during-COVID, while intake of red meat and starchy vegetables increased. More men than women increased their intake of red meat and processed meat. There was less overall change in fruit and vegetable consumption in participants aged TRANS 66 and older, compared to younger participants ( aged TRANS 18-35). The percentage of older participants who reported lean meat and starchy vegetable intake increased, but these groups had a negligible change in younger subjects. More subjects aged TRANS 18-35 years reduced their intake of caffeine, desserts, lean meat and salads compared to older participants. No changes were observed in terms of snack or alcoholic beverage intake logged. In conclusion, this study of 381,564 US participants revealed that intake of particular food groups were altered during the first weeks of COVID lockdown.

    Age TRANS-dependent progression of SARS-CoV-2 infection MESHD in Syrian hamsters

    Authors: Nikolaus Osterrieder; Luca D. Bertzbach; Kristina Dietert; Azza Abdelgawad; Daria Vladimirova; Dusan Kunec; Donata Hoffmann; Martin Beer; Achim D. Gruber; Jakob Trimpert

    doi:10.1101/2020.06.10.144188 Date: 2020-06-10 Source: bioRxiv

    In late 2019, an outbreak of a severe respiratory disease MESHD caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans1. Complete understanding of COVID-19, the multi-faceted disease MESHD caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals2. Because age TRANS-dependent differences of COVID-19 were identified in humans3, we compared the course of SARS-CoV-2 infection MESHD in young and aged TRANS Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age TRANS of the animals. However, older hamsters exhibited more pronounced and consistent weight loss MESHD weight loss HP. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age TRANS-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged TRANS hamsters. The latter developed conspicuous alveolar and perivascular edema MESHD edema HP, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection MESHD only in young hamsters. We propose that comparative assessment in young versus aged TRANS hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information as this small-animal model appears to mirror age TRANS-dependent differences in human patients.

    Diet and physical activity during the COVID-19 lockdown period (March-May 2020): results from the French NutriNet-Sante cohort study

    Authors: Melanie Deschasaux-Tanguy; Nathalie Druesne-Pecollo; Younes Esseddik; Fabien Szabo de Edelenyi; Benjamin Alles; Valentina A Andreeva; Julia Baudry; Helene Charreire; Valerie Deschamps; Manon Egnell; Leopold K Fezeu; Pilar Galan; Chantal Julia; Emmanuelle Kesse-Guyot; Paule Latino-Martel; Jean-Michel Oppert; Sandrine Peneau; Charlotte Verdot; Serge Hercberg; Mathilde Touvier

    doi:10.1101/2020.06.04.20121855 Date: 2020-06-05 Source: medRxiv

    Background: Since December 2019, the coronavirus disease MESHD (COVID-19) has massively spread, with overwhelming of health care systems and numerous deaths MESHD worldwide. To remedy this, several countries, including France, have taken strict lockdown measures, requiring the closure of all but essential places. This unprecedented disruption of daily routines has a strong potential for disrupting nutritional behaviours. Nutrition being one of the main modifiable risk factors for chronic disease MESHD risk, this may have further consequences for public health. Our objective was therefore to describe nutritional behaviours during the lockdown period and to put them in light of individual characteristics. Methods: 37,252 French adults TRANS from the web-based NutriNet-Sante cohort filled lockdown-specific questionnaires in April-May 2020 (nutritional behaviours, body weight MESHD, physical activity, 24h-dietary records). Nutritional behaviours were compared before and during lockdown using Student paired t-tests and associated to individual characteristics using multivariable logistic or linear regression models. Clusters of nutritional behaviours were derived from multiple correspondence analysis and ascending hierarchical classification. Results: During the lockdown, trends for unfavourable nutritional behaviours were observed: weight gain MESHD (for 35%; +1.8kg on average), decreased physical activity (53%), increased sedentary time (63%), increased snacking, decreased consumption of fresh food products (especially fruit and fish), increased consumption of sweets, biscuits and cakes. Yet, opposite trends were also observed: weight loss MESHD weight loss HP (for 23%, -2kg on average), increased home-made cooking (40%), increased physical activity (19%). These behavioural trends related to sociodemographic and economic position, professional situation during the lockdown (teleworking or not), initial weight status, having children TRANS at home, anxiety HP and depressive symptoms, as well as diet quality before the lockdown. Modifications of nutritional practices mainly related to routine change, food supply, emotional reasons but also to voluntary changes to adjust to the current situation. Conclusion: These results suggest that the lockdown led, in a substantial part of the population, to unhealthy nutritional behaviours that, if maintained in the long term, may increase the nutrition-related burden of disease MESHD and also impact immunity. Yet, the lockdown situation also created an opportunity for some people to improve their nutritional behaviours, with high stakes to understand the leverages to put these on a long-term footing.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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