Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Effect of Convalescent Plasma SERO on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience

    Authors: Michael J Joyner; Jonathon W Senefeld; Stephen A Klassen; John R Mills; Patrick W Johnson; Elitza S Theel; Chad C Wiggins; Katelyn A Bruno; Allan M Klompas; Elizabeth R Lesser; Katie L Kunze; Matthew A Sexton; Juan C Diaz Soto; Sarah E Baker; John R.A. Shepherd; Noud van Helmond; Camille M van Buskirk; Jeffrey L Winters; James R Stubbs; Robert F Rea; David O Hodge; Vitaly Herasevich; Emily R Whelan; Andrew J Clayburn; Kathryn F Larson; Juan G Ripoll; Kylie J Andersen; Matthew R Buras; Matthew N.P. Vogt; Joshua J Dennis; Riley J Regimbal; Philippe R Bauer; Janis E Blair; Nigel S Paneth; DeLisa Fairweather; R. Scott Wright; Rickey E Carter; Arturo Casadevall

    doi:10.1101/2020.08.12.20169359 Date: 2020-08-12 Source: medRxiv

    Importance: Passive antibody SERO transfer is a longstanding treatment strategy for infectious diseases MESHD that involve the respiratory system. In this context, human convalescent plasma SERO has been used to treat coronavirus disease MESHD 2019 (COVID-19), but the efficacy remains uncertain. Objective: To explore potential signals of efficacy of COVID-19 convalescent plasma SERO. Design: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma SERO. Setting: Multicenter, including 2,807 acute care facilities in the US and territories. Participants: Adult TRANS participants enrolled and transfused under the purview of the US Convalescent Plasma SERO EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome MESHD. Intervention: Transfusion of at least one unit of human COVID-19 convalescent plasma SERO using standard transfusion guidelines at any time during hospitalization. Convalescent plasma SERO was donated by recently-recovered COVID-19 survivors, and the antibody SERO levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. Results: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma SERO transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody SERO levels in the transfused plasma SERO. For patients who received high IgG plasma SERO (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma SERO (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma SERO (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody SERO level plasma SERO units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody SERO level plasma SERO units. Conclusions and Relevance: The relationships between reduced mortality and both earlier time to transfusion and higher antibody SERO levels provide signatures of efficacy for convalescent plasma SERO in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma SERO. Trial Registration: ClinicalTrials.gov Identifier: NCT04338360

    A Large-Scale Clinical Validation Study Using nCapp Cloud Plus Terminal by Frontline Doctors for the Rapid Diagnosis of COVID-19 and COVID-19 pneumonia MESHD pneumonia HP in China

    Authors: Dawei Yang; Tao Xu; Xun Wang; Deng Chen; Ziqiang Zhang; Lichuan Zhang; Jie Liu; Kui Xiao; Li Bai; Yong Zhang; Lin Zhao; Lin Tong; Chaomin Wu; Yaoli Wang; Chunling Dong; Maosong Ye; Yu Xu; Zhenju Song; Hong Chen; Jing Li; Jiwei Wang; Fei Tan; Hai Yu; Jian Zhou; Jinming Yu; Chunhua Du; Hongqing Zhao; Yu Shang; Linian Huang; Jianping Zhao; Yang Jin; Charles A. Powell; Yuanlin Song; Chunxue Bai

    doi:10.1101/2020.08.07.20163402 Date: 2020-08-11 Source: medRxiv

    Background The outbreak of coronavirus disease MESHD 2019 (COVID-19) has become a global pandemic acute infectious disease MESHD, especially with the features of possible asymptomatic TRANS carriers TRANS and high contagiousness. It causes acute respiratory distress HP syndrome MESHD and results in a high mortality rate if pneumonia MESHD pneumonia HP is involved. Currently, it is difficult to quickly identify asymptomatic TRANS cases or COVID-19 patients with pneumonia MESHD pneumonia HP due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans, which facilitates the spread of the disease TRANS disease MESHD at the community level, and contributes to the overwhelming of medical resources in intensive care units. Goal This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist global frontline doctors to efficiently and precisely diagnose asymptomatic TRANS COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan Unversity (approval number B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. These patients had SARS-CoV-2 RT-PCR test results and chest CT scans, both of which were used as the gold standard for the diagnosis of COVID-19 and COVID-19 pneumonia MESHD pneumonia HP. In particular, the dataset included 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, and 122 asymptomatic TRANS cases who had positive RT-PCR test results, amongst whom 31 cases were diagnosed. We also integrated the function of a survey in nCapp to collect user feedback from frontline doctors. Findings We applied the statistical method of a multi-factor regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are fast and accessible: 'Residing or visiting history in epidemic regions', 'Exposure history to COVID-19 patient', 'Dry cough MESHD cough HP', ' Fatigue MESHD Fatigue HP', 'Breathlessness', 'No body temperature decrease after antibiotic treatment', 'Fingertip blood SERO oxygen saturation<=93%', ' Lymphopenia MESHD Lymphopenia HP', and 'C-reactive protein (CRP) increased'. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). To ensure the sensitivity SERO of the model, we used a cutoff value of 0.09. The sensitivity SERO and specificity of the model were 98.0% (95% CI: 96.9%, 99.1%) and 17.3% (95% CI: 15.0%, 19.6%), respectively, in the training dataset, and 96.5% (95% CI: 95.1%, 98.0%) and 18.8% (95% CI: 16.4%, 21.2%), respectively, in the validation dataset. In the subset of the 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, the model predicted 132 cases, accounting for 96.4% (95% CI: 91.7%, 98.8%) of the cases. In the subset of the 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, the model predicted 59 cases, accounting for 95.2% (95% CI: 86.5%, 99.0%) of the cases. Considering the specificity of the model, we used a cutoff value of 0.32. The sensitivity SERO and specificity of the model were 83.5% (95% CI: 80.5%, 86.4%) and 83.2% (95% CI: 80.9%, 85.5%), respectively, in the training dataset, and 79.6% (95% CI: 76.4%, 82.8%) and 81.3% (95% CI: 78.9%, 83.7%), respectively, in the validation dataset, which is very close to the published AI model. The results of the online survey 'Questionnaire Star' showed that 90.9% of nCapp users in WeChat mini programs were 'satisfied' or 'very satisfied' with the tool. The WeChat mini program received a significantly higher satisfaction rate than other platforms, especially for 'availability and sharing convenience of the App' and 'fast speed of log-in and data entry'. Discussion With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic TRANS patients and avoid misdiagnoses of cases with false-negative RT-PCR results. These patients require timely isolation or close medical supervision. By applying the model, medical resources can be allocated more reasonably, and missed diagnoses can be reduced. In addition, further education and interaction among medical professionals can improve the diagnostic efficiency for COVID-19, thus avoiding the transmission TRANS of the disease from asymptomatic MESHD asymptomatic TRANS patients at the community level.

    Telmisartan for treatment of Covid-19 patients: an open randomized clinical trial. Preliminary report.

    Authors: Mariano Duarte; Facundo G Pelorosso; Liliana Nicolosi; M. Victoria Salgado; Hector Vetulli; Analia Aquieri; Francisco Azzato; Mauro Basconcel; Marcela Castro; Javier Coyle; Ignacio Davolos; Eduardo Esparza; Ignacio Fernandez Criado; Rosana Gregori; Pedro Mastrodonato; Maria Rubio; Sergio Sarquis; Fernando Wahlmann; Rodolfo Pedro Rothlin

    doi:10.1101/2020.08.04.20167205 Date: 2020-08-11 Source: medRxiv

    Background. Covid-19, the disease MESHD caused by SARS-CoV-2, is associated with significant respiratory-related morbidity and mortality. Angiotensin receptor blockers (ARBs) have been postulated as tentative pharmacological agents to treat Covid-19-induced lung inflammation MESHD. Trial design. This trial is a parallel group, randomized, two arm, open label, multicenter superiority trial with 1:1 allocation ratio. Methods. Participants included patients who were 18 years of age TRANS or older and who had been hospitalized with confirmed Covid-19 with 4 or fewer days since symptom onset TRANS. Exclusion criteria included intensive care unit admission prior to randomization and use of angiotensin receptor blocker or angiotensin converting enzyme inhibitors at admission. Participants in the treatment arm received telmisartan 80 mg bid during 14 days plus standard care. Participants in the control arm received standard care alone. Primary outcome was to achieve significant reductions in plasma SERO levels of C-reactive protein in telmisartan treated Covid-19 patients at day 5 and 8 after randomization. Key secondary outcomes included time to discharge evaluated at 15 days after randomization and admission to ICU and death MESHD at 15- and 30-days post randomization. We present here a preliminary report. Results. A total of 78 patients were included in the interim analysis, 40 in the telmisartan and 38 in the control groups. CRP levels at day 5 in the control group were 51.1 +/- 44.8 mg/L (mean +/- SD; n=28) and in the telmisartan group were 24.2 +/- 31.4 mg/L (mean +/- SD; n=32, p<0.05). At day 8, CRP levels were 41.6 +/- 47.6 mg/L (mean +/- SD; n=16) and 9.0 +/- 10.0 mg/L (mean +/- SD; n=13, p < 0.05) in the control and telmisartan groups, respectively. Also, analysis of time to discharge by Kaplan-Meier method showed that telmisartan treated patients had statistically significant lower time to discharge (median time to discharge control group=15 days; telmisartan group=9 days). No differences were observed for ICU admission or death MESHD. No significant adverse events related to telmisartan were reported. Conclusions. In the present preliminary report, despite the small number of patients studied, ARB telmisartan, a well-known inexpensive safe antihypertensive drug, administered in high doses, demonstrates anti-inflammatory effects and improved morbidity in hospitalized patients infected with SARS -CoV-2, providing support for its use in this serious pandemia (NCT04355936).

    K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia HP

    Authors: Stanley Perlman; Jian Zheng; LOK YIN ROY WONG; Kun Li; Abhishek K Verma; Miguel E Ortiz Bezara; Christine Wohlford-Lenane; Mariah R. Leidinger; Michael C. Kundson; David K. Meyerholz; Paul B McCray Jr.

    doi:10.1101/2020.08.07.242073 Date: 2020-08-10 Source: bioRxiv

    The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia HP is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease MESHD not easily investigated in human patients. COVID-19 severity ranges from asymptomatic TRANS to lethal. Most experimental infections MESHD provide insights into mild disease MESHD. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection MESHD with SARS-CoV-2 causes severe disease in the lung MESHD, and in some mice, the brain. Evidence of thrombosis MESHD and vasculitis MESHD vasculitis HP was detected in mice with severe pneumonia MESHD pneumonia HP. Further, we show that infusion of convalescent plasma SERO (CP) from a recovered COVID-19 patient provided protection against lethal disease MESHD. Mice developed anosmia HP at early times after infection MESHD. Notably, while treatment with CP prevented significant clinical disease MESHD, it did not prevent anosmia HP. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

    Comparative analyses of SARS-CoV-2 binding (IgG, IgM, IgA) and neutralizing antibodies SERO from human serum samples SERO

    Authors: Livia Mazzini; Donata Martinuzzi; Inesa Hyseni; Giulia Lapini; Linda Benincasa; Pietro Piu; Claudia Maria Trombetta; Serena Marchi; Ilaria Razzano; Alessandro Manenti; Emanuele Montomoli

    doi:10.1101/2020.08.10.243717 Date: 2020-08-10 Source: bioRxiv

    A newly identified coronavirus, named SARS-CoV-2, emerged in December 2019 in Hubei Province, China, and quickly spread throughout the world; so far, it has caused more than 18 million cases of disease MESHD and 700,000 deaths MESHD. The diagnosis of SARS-CoV-2 infection MESHD is currently based on the detection of viral RNA in nasopharyngeal swabs by means of molecular-based assays, such as real-time RT-PCR. Furthermore, serological assays SERO aimed at detecting different classes of antibodies SERO constitute the best surveillance strategy for gathering information on the humoral immune response to infection MESHD and the spread of the virus through the population, in order to evaluate the immunogenicity of novel future vaccines and medicines for the treatment and prevention of COVID-19 disease MESHD. The aim of this study was to determine SARS-CoV-2-specific antibodies SERO in human serum samples SERO by means of different commercial and in-house ELISA SERO kits, in order to evaluate and compare their results first with one another and then with those yielded by functional assays using wild-type virus. It is important to know the level of SARS-CoV-2-specific IgM, IgG and IgA antibodies SERO in order to predict population immunity and possible cross-reactivity with other coronaviruses and to identify potentially infectious subjects. In addition, in a small sub-group of samples, we performed a subtyping Immunoglobulin G ELISA SERO. Our data showed an excellent statistical correlation between the neutralization titer and the IgG, IgM and IgA ELISA SERO response against the receptor-binding domain of the spike protein, confirming that antibodies SERO against this portion of the virus spike protein are highly neutralizing and that the ELISA SERO Receptor-Binding Domain-based assay can be used as a valid surrogate for the neutralization assay in laboratories which do not have Biosecurity level-3 facilities.

    Deciphering the state of immune silence in fatal COVID-19 patients

    Authors: Ido Amit; Pierre Bost; Francesco De Sanctis; Stefania Canè; Ugel Stefano; Katia Donadello; Monica Castellucci; Eyal David; Alessandra Fiore; Cristina Anselmi; Roza Barouni; Rosalinda Trovato; Simone Caligola; Alessia Lamolinara; Manuela Iezzi; Federica Facciotti; Anna Mazzariol; Davide Gibellini; Pasquale De Nardo; Evelina Tacconelli; Leonardo Gottin; Enrico Polati; Benno Schwikowski; Vincenzo Bronte

    doi:10.21203/rs.3.rs-56689/v1 Date: 2020-08-10 Source: ResearchSquare

    Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease MESHD with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocyto-sis, sepsis MESHD sepsis HP or cytokine release syndrome MESHD, their exact nature remains unknown. This is severely imped-ing the ability to treat patients facing severe stages of the disease MESHD. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood SERO samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune sig-nature of disease MESHD severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found mon-ocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex MESHD-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis MESHD paralysis HP that supports secondary bacteria and virus infection MESHD and can progress to “immune silence” in patients facing death MESHD.

    SARS-CoV-2 neutralization and serology testing of COVID-19 convalescent plasma SERO from donors with non-severe disease MESHD

    Authors: Thomas J. Gniadek; Joshua M. Thiede; William E. Matchett; Abigail R. Gress; Kathryn A. Pape; Marc K. Jenkins; Vineet D Menachery; Ryan A. Langlois; Tyler D. Bold

    doi:10.1101/2020.08.07.242271 Date: 2020-08-10 Source: bioRxiv

    We determined the antigen binding activity of convalescent plasma SERO units from 47 individuals with a history of non-severe COVID-19 using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS-CoV-2 targets. We compared these results with functional neutralization activity using a fluorescent reporter strain of SARS-CoV-2 in a microwell assay. This revealed positive correlations of varying strength (Spearman r = 0.37-0.52) between binding and neutralization. Donors age TRANS 48-75 had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75-82%) for those with the highest levels of neutralization.

    Single-cell RNA-seq reveals profound monocyte changes in Paediatric Inflammatory Multisystem Syndrome MESHD Temporally associated with SARS-CoV-2 infection MESHD (PIMS-TS)

    Authors: Eleni Syrimi; Eanna Fennell; Alex Richter; Pavle Vrljicak; Richard Stark; Sascha Ott; Paul G Murray; Eslam Al-abadi; Ashish Chikermane; Pamela Dawson; Scott Hackett; Deepthi Jyothish; Hari Krishnan Kanthimathinathan; Sean Monaghan; Prasad Nagakumar; Barnaby R Scholefield; Steven Welch; Pamela Kearns; Graham Taylor

    doi:10.1101/2020.08.06.20164848 Date: 2020-08-07 Source: medRxiv

    Paediatric inflammatory multisystem inflammatory syndrome MESHD temporally associated with SARS-CoV-2 infection MESHD (PIMS-TS) is a new disease MESHD with overlapping features of Kawasaki disease MESHD (KD) and toxic shock MESHD shock HP syndrome MESHD. Unbiased single cell RNA sequencing analysis of peripheral blood SERO mononuclear cells from PIMS-TS and KD patients shows monocytes are the main source of pro-inflammatory cytokines and large changes in the frequency of classical, intermediate and non-classical monocytes occur in both diseases MESHD.

    Clinical and intestinal histopathological findings in SARS-CoV-2/COVID-19 patients with hematochezia HP

    Authors: Margaret Cho; Weiguo Liu; Sophie Balzora; Yvelisse Suarez; Deepthi Hoskoppal; Neil D Theise; Wenqing Cao; Suparna A Sarkar

    doi:10.1101/2020.07.29.20164558 Date: 2020-08-07 Source: medRxiv

    Gastrointestinal (GI) symptoms of SARS-CoV2/COVID-19 in the form of anorexia MESHD anorexia HP, nausea MESHD nausea, vomiting HP, vomiting MESHD, abdominal pain MESHD abdominal pain HP and diarrhea MESHD diarrhea HP are usually preceeded by respiratory manifestations and are associated with a poor prognosis. Hematochezia HP is an uncommon clinical presentation of COVID-19 disease MESHD and we hypothesize that older patients with significant comorbidites ( obesity MESHD obesity HP and cardiovascular) and prolonged hospitalization are suspectible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute phase reactants, drug/medication history in two elderly TRANS male TRANS patients admitted for COVID-19 respiratory failure HP. Both patients had a complicated clinical course and suffered from hematochezia HP and acute blood SERO loss anemia MESHD anemia HP requiring blood SERO transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopies and changes compatible with ischemia MESHD to nonspecific acute inflammation MESHD, edema MESHD edema HP and increased eosinophils in the lamina propria were noted.Both patients were on anticoagulants, multiple antibiotics and antifungal agents due to respiratory infections MESHD at the time of lower GI bleeding. Hematochezia HP resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly TRANS patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. Hypoxic conditions due to COVID-19 pneumonia MESHD pneumonia HP and respiratory failure HP, compounded by preexisting cardiovascular complications, and/or cytokine storm orchestrated by the viral infection MESHD leading to alteration in coagulation profile and/or drug/medication injury can be difficult to distinguish in these critically ill patients. Presentation of hematochezia HP may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

    SARS-CoV-2 infection MESHD, neuropathogenesis and transmission TRANS among deer mice: Implications for reverse zoonosis MESHD to New World rodents

    Authors: Anna Fagre; Juliette Lewis; Miles Eckley; Shijun Zhan; Savannah M Rocha; Nicole R Sexton; Bradly Burke; Brian J Geiss; Olve Peersen; Rebekah Kading; Joel Rovnak; Gregory D Ebel; Ronald B Tjalkens; Tawfik Aboellail; Tony Schountz

    doi:10.1101/2020.08.07.241810 Date: 2020-08-07 Source: bioRxiv

    Coronavirus disease MESHD-19 (COVID-19) emerged in November, 2019 in China and rapidly became pandemic. As with other coronaviruses, a preponderance of evidence suggests the virus originated in horseshoe bats (Rhinolophus spp.) and likely underwent a recombination event in an intermediate host prior to entry into human populations. A significant concern is that SARS-CoV-2 could become established in secondary reservoir hosts outside of Asia. To assess this potential, we challenged deer mice (Peromyscus maniculatus) with SARS-CoV-2 and found robust virus replication in the upper respiratory tract, lungs and intestines, with detectable viral RNA for up to 21 days in oral swabs and 14 days in lungs. Virus entry into the brain also occurred, likely via gustatory-olfactory-trigeminal pathway with eventual compromise to the blood SERO brain barrier. Despite this, no conspicuous signs of disease MESHD were observed and no deer mice succumbed to infection MESHD. Expression of several innate immune response genes were elevated in the lungs, notably IFN, Cxcl10, Oas2, Tbk1 and Pycard. Elevated CD4 and CD8{beta} expression in the lungs was concomitant with Tbx21, IFN{gamma} and IL-21 expression, suggesting a type I inflammatory immune response. Contact transmission TRANS occurred from infected to naive deer mice through two passages, showing sustained natural transmission TRANS. In the second deer mouse passage, an insertion of 4 amino acids occurred to fixation in the N-terminal domain of the spike protein that is predicted to form a solvent-accessible loop. Subsequent examination of the source virus from BEI Resources indicated the mutation was present at very low levels, demonstrating potent purifying selection for the insert during in vivo passage. Collectively, this work has determined that deer mice are a suitable animal model for the study of SARS-CoV-2 pathogenesis, and that they have the potential to serve as secondary reservoir hosts that could lead to periodic outbreaks of COVID-19 in North America.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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