Corpus overview


MeSH Disease

Human Phenotype


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    Genomic epidemiology reveals multiple introductions and spread of SARS-CoV-2 in the Indian state of Karnataka

    Authors: Chitra Pattabiraman; Farhat Habib; Harsha PK; Risha Rasheed; Vijayalakshmi Reddy; Prameela Dinesh; Tina Damodar; Nakka Vijay Kiran Reddy; Kiran Hosallimath; Anson K George; Banerjee John; Amrita Pattanaik; Narendra Kumar; Reeta S Mani; Manjunatha M Venkataswamy; Shafeeq K Shahul Hameed; Prakash Kumar B.G.; Anita Desai; Ravi Vasanthapuram

    doi:10.1101/2020.07.10.20150045 Date: 2020-07-11

    Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome MESHD Coronavirus 2 (SARS-CoV-2) on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing TRANS and genomic epidemiology to trace TRANS the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 47 full genomes of SARS-CoV-2 which clustered into six lineages (Pangolin lineages-A, B, B.1, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel TRANS. Our sequences grouped into 12 contact clusters and 11 cases with no known contacts. We found nine of the 12 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (8/12) were contained within a single district, consistent with local spread. In most of the twelve clusters, the index case (9/12) and spreaders (8/12) were symptomatic. Of the 47 sequences, 31 belonged to the B/B.6 lineage, including seven of eleven cases with no known contact, this is consistent with the ongoing transmission TRANS of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka is consistent with multiple introductions of the virus followed by local transmission TRANS in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.

    Modeling and Preparedness: The Transmission TRANS Dynamics of COVID-19 Outbreak in Provinces of Ecuador

    Authors: Carlos Enrique Bustamante Orellana; Jordy Jose Cevallos Chavez; Cesar Montalvo; Jeff Sullivan; Edwin Michael; Anuj Mubayi

    doi:10.1101/2020.07.09.20150078 Date: 2020-07-11

    Coronavirus disease MESHD 2019 (COVID-19), a novel infectious disease MESHD first identified in December 2019 in the city of Wuhan of China, is caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The disease MESHD has become a pandemic in just a few months and spread globally with more than 2.89 million cases and 203,000 deaths MESHD across 185 countries, as of April 26th, 2020. Ecuador has reported one of the highest rates of COVID-19 in Latin America, with more than 10K cases and 500 deaths MESHD in a country of approximately 17 million people. The dynamics of the outbreak is being observed quite different in different provinces of Ecuador with high reported prevalence SERO in some low population density provinces. In this study, we aim to understand variations in outbreaks between provinces and provide assistance in essential preparedness planning in order to respond effectively to ongoing COVID-19 outbreak. The study estimated the critical level of quarantine rate along with corresponding leakage in order to avoid overwhelming the local health care system. The results suggest that provinces with high population density can avoid a large disease MESHD burden provided they initiate early and stricter quarantine measures even under low isolation rate. To best of our knowledge, this study is first from the region to determine which provinces will need much preparation for current outbreak in fall HP and which might need more help.

    Estimating the Effect of Social Distancing Interventions on COVID-19 in the United States

    Authors: Andrew M. Olney; Jesse Smith; Saunak Sen; Fridtjof Thomas; H. Juliette T. Unwin

    doi:10.1101/2020.07.10.20151001 Date: 2020-07-11

    Since its global emergence in 2020, severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has caused multiple epidemics in the United States. Because medical treatments for the virus are still emerging and a vaccine is not yet available, state and local governments have sought to limit its spread by enacting various social distancing interventions such as school closures and lockdown, but the effectiveness of these interventions is unknown. We applied an established, semi-mechanistic Bayesian hierarchical model of these interventions on SARS-CoV-2 spread in Europe to the United States. We estimated the effect of interventions across all states, contrasted the estimated reproduction number TRANS, Rt , for each state before and after lockdown, and contrasted predicted future fatalities with actual fatalities as a check on the model's validity. Overall, school closures and lockdown are the only interventions modeled that have a reliable impact on Rt , and lockdown appears to have played a key role in reducing Rt below 1.0. We conclude that reversal of lockdown, without implementation of additional, equally effective interventions, will enable continued, sustained transmission TRANS of SARS-CoV-2 in the United States.

    A Highly Immunogenic Measles MESHD Virus-based Th1-biased COVID-19 Vaccine

    Authors: Cindy Hoerner; Christoph Schuermann; Arne Auste; Aileen Ebenig; Samada Muraleedharan; Maike Herrmann; Barbara Schnierle; Michael D Muehlebach

    doi:10.1101/2020.07.11.198291 Date: 2020-07-11

    The COVID-19 pandemic is caused by severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2) and has spread world-wide with millions of cases and hundreds of thousands of deaths MESHD to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles MESHD virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody SERO and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody SERO responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines. Significance: The COVID-19 pandemic has caused hundreds of thousands of deaths MESHD, yet. Therefore, effective vaccine concepts are urgently needed. In search for such a concept, we have analysed a measles MESHD virus-based vaccine candidate targeting SARS-CoV-2. Using this well known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity with the desired immune bias. Therefore, occurrence of immunopathologies such as antibody SERO-dependent enhancement or enhanced respiratory disease MESHD is rather unlikely. Moreover, the candidate still induces immunity against the measles MESHD, recognized as a looming second menace, when countries are entrapped to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles MESHD-based COVID-19 vaccine could be the solution for two significant public health threats.Competing Interest StatementThe authors have declared no competing interest.

    Wastewater SARS-CoV-2 Concentration and Loading Variability from Grab and 24-Hour Composite Samples

    Authors: Kyle Curtis; David Keeling; Kathleen Yetka; Allison Larson; Raul Gonzalez

    doi:10.1101/2020.07.10.20150607 Date: 2020-07-11

    The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) requires a significant, coordinated public health response. Assessing case density and spread of infection MESHD is critical and relies largely on clinical testing data. However, clinical testing suffers from known limitations, including test availability and a bias towards enumerating only symptomatic individuals. Wastewater-based epidemiology (WBE) has gained widespread support as a potential complement to clinical testing for assessing COVID-19 infections MESHD at the community scale. The efficacy of WBE hinges on the ability to accurately characterize SARS-CoV-2 concentrations in wastewater. To date, a variety of sampling schemes have been used without consensus around the appropriateness of grab or composite sampling. Here we address a key WBE knowledge gap by examining the variability of SARS-CoV-2 concentrations in wastewater grab samples collected every 2 hours for 72 hours compared with corresponding 24-hour flow-weighted composite samples. Results show relatively low variability (mean for all assays = 741 copies 100 mL-1, standard deviation = 508 copies 100 mL-1) for grab sample concentrations, and good agreement between most grab samples and their respective composite (mean deviation from composite = 159 copies 100 mL-1). When SARS-CoV-2 concentrations are used to calculate viral load, the discrepancy between grabs (log10 difference = 12.0) or a grab and its associated composite (log10 difference = 11.8) are amplified. A similar effect is seen when estimating carrier TRANS prevalence SERO in a catchment population with median estimates based on grabs ranging 62-1853 carriers TRANS. Findings suggest that grab samples may be sufficient to characterize SARS-CoV-2 concentrations, but additional calculations using these data may be sensitive to grab sample variability and warrant the use of flow-weighted composite sampling. These data inform future WBE work by helping determine the most appropriate sampling scheme and facilitate sharing of datasets between studies via consistent methodology.

    SARS-CoV-2 RNA extraction using magnetic beads for rapid large-scale testing by RT-qPCR and RT-LAMP

    Authors: Steffen Klein; Thorsten G. Mueller; Dina Khalid; Vera Sonntag-Buck; Anke-Mareil Heuser; Baerbel Glass; Matthias Meurer; Ivonne Morales; Angelika Schillak; Andrew Freistaedter; Ina Ambiel; Sophie L. Winter; Liv Zimmermann; Tamara Naumoska; Felix Bubeck; Daniel Kirrmaier; Stephanie Ullrich; Isabel Barreto-Miranda; Simon Anders; Dirk Grimm; Paul Schnitzler; Michael Knop; Hans-Georg Kraeusslich; Viet Loan Dao Thi; Kathleen Boerner; Petr Chlanda

    doi:10.1101/2020.07.08.20147561 Date: 2020-07-11

    Rapid large-scale testing is essential for controlling the ongoing pandemic of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). The standard diagnostic pipeline for testing SARS-CoV-2 presence in patients with an ongoing infection MESHD is predominantly based on pharyngeal swabs, from which the viral RNA is extracted using commercial kits followed by reverse transcription and quantitative PCR detection. As a result of the large demand for testing, commercial RNA extraction kits may be limited and alternative, non-commercial protocols are needed. Here, we provide a magnetic bead RNA extraction protocol that is predominantly based on in-house made reagents and is performed in 96-well plates supporting large-scale testing. Magnetic bead RNA extraction was benchmarked against the commercial QIAcube extraction platform. Comparable viral RNA detection sensitivity SERO and specificity were obtained by fluorescent and colorimetric RT-LAMP using N primers, as well as RT-qPCR using E gene primers showing that the here presented RNA extraction protocol can be combined with a variety of detection methods at high throughput. Importantly, the presented diagnostic workflow can be quickly set up in a laboratory without access to an automated pipetting robot.

    IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals

    Authors: Michal A Stanczak; David E Sanin; Petya Apostolova; Gabriele Nerz; Dimitrios Lampaki; Maike Hofmann; Daniel Steinmann; Robert Thimme; Gerhard Mittler; Cornelius F Waller; Edward J Pearce; Erika L Pearce

    doi:10.1101/2020.07.09.20148056 Date: 2020-07-10

    Our understanding of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence SERO and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members TRANS (155 individuals; ages TRANS 5-79 years). Seropositivity for SARS-CoV-2 spike glycoprotein aligned with PCR results that confirmed previous infection MESHD. Anti-spike IgG titers remained high 60 days post- infection MESHD and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever MESHD fever HP. We found limited household transmission TRANS, with children TRANS of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection MESHD in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults TRANS. TLR7 agonist- activation revealed an increased population of IL-6+TNF-IL-1{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33- producing cells. IL-33 is associated with pulmonary infection MESHD infection and chronic HP and chronic diseases MESHD like asthma MESHD asthma HP and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 revealed a population of IL-33-producing cells that increases with disease MESHD. Together these findings show that IL-33 production is linked to SARS-CoV- 2 infection MESHD and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.

    Robust three-dimensional expansion of human adult TRANS alveolar stem cells and SARS-CoV-2 infection MESHD

    Authors: Jeonghwan Youk; Taewoo Kim; Young-Il Jeong; Yongsuk Hur; Seon Pyo Hong; Je Hyoung Kim; Kijong Yi; Su Yeon Kim; Kwon Joong Na; Thomas Bleazard; Ho Min Kim; Natasha Ivory; Krishnaa T. Mahbubani; Kourosh Saeb-Parsy; Young Tae Kim; Gou Young Koh; Byeong-Sun Choi; Young Seok Ju; Joo-Hyeon Lee

    doi:10.1101/2020.07.10.194498 Date: 2020-07-10

    Severe acute respiratory syndrome MESHD-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection MESHD response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing TRANS of viral mutations acquired during transmission TRANS identifies full infection MESHD of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases MESHD.Competing Interest StatementThe authors have declared no competing interest.View Full Text

    Clinical characteristics and outcomes in diabetes patients admitted with COVID-19 in Dubai: a cross-sectional single centre study.

    Authors: Rahila Bhatti; Amar Omer; Samara Khattib; Seemin Shiraz; Glenn Matfin

    doi:10.1101/2020.07.08.20149096 Date: 2020-07-10

    Aim: To describe the clinical characteristics and outcomes of hospitalised Coronavirus Disease MESHD 2019 (COVID-19) patients with diabetes. Methods: A cross-sectional observational study was conducted in patients with diabetes admitted with COVID-19 to Mediclinic Parkview Hospital in Dubai, United Arab Emirates (UAE) from 30th March to 7th June 2020. They had laboratory and/or radiologically confirmed severe acute respiratory syndrome MESHD-coronavirus-2 (SARS-CoV-2), known as COVID-19. Variation in characteristics, length of stay in hospital, diabetes status, comorbidities and outcomes were examined. Results: A total of 103 patients with confirmed COVID-19 presentations had diabetes. During the same timeframe, 410 patients overall were admitted with COVID-19 infection MESHD. This gives a total proportion of persons admitted with COVID-19 infection MESHD and coexistent diabetes/prediabetes of 25%. 67% (n=69) of the COVID-19 diabetes cohort were male TRANS. Patients admitted with COVID-19 and diabetes represented 17 different ethnicities. Of these, 59.2% (n=61) were Asians and 35% (n=36) were from Arab countries. Mean age TRANS (SD) was 54 (12.5) years. 85.4% (n=88) were known to have diabetes prior to admission, while 14.6% (n=15) were newly diagnosed with either diabetes or prediabetes during admission. Most patients in the study cohort had type 2 diabetes or prediabetes, with only 3% overall having type 1 diabetes (n=3). 46.9% of patients had evidence of good glycaemic control of their diabetes during the preceding 4-12 weeks prior to admission as defined arbitrarily by admission HbA1c <7.5%. 73.8% (n=76) had other comorbidities including hypertension MESHD hypertension HP, ischaemic heart disease MESHD, and dyslipidaemia. Laboratory data Mean(SD) on admission for those who needed ward-based care versus those needing intensive care unit (ICU) care: Fibrinogen 462.75 (125.16) mg/dl vs 660 (187.58) mg/dl ; D-dimer 0.66 (0.55) mcg/ml vs 2.3 (3.48) mcg/ml; Ferritin 358.08 (442.05) mg/dl vs 1762.38 (2586.38) mg/dl; and CRP 33.9 (38.62) mg/L vs 137 (111.72) mg/L were all statistically significantly higher for the ICU cohort (p<0.05). Average length of stay in hospital was 14.55 days. 28.2% of patients needed ICU admission. 4.9% (n=5) overall died during hospitalisation (all in ICU). Conclusions: In this single-centre study in Dubai, 25% of patients admitted with COVID-19 also had diabetes/prediabetes. Most diabetes patients admitted to hospital with COVID-19 disease MESHD were males TRANS of Asian origin. 14.6% had new diagnosis of diabetes/prediabetes on admission. The majority of patients with diabetes/prediabetes and COVID-19 infection MESHD had other important comorbidities (n=76; 73.8%). Only 4 patients had negative COVID-19 RT-PCR but had pathognomonic changes of COVID-19 radiologically. Our comprehensive laboratory analysis revealed distinct abnormal patterns of biomarkers that are associated with poor prognosis: Fibrinogen, D-dimer, Ferritin and CRP levels were all statistically significantly higher (p<0.05) at presentation in patients who subsequently needed ICU care compared with those patients who remained ward-based. 28.2% overall needed ICU admission, out of which 5 patients died. More studies with larger sample sizes are needed to compare data of COVID-19 patients admitted with and without diabetes within the UAE region.

    Which animals are at risk? Predicting species susceptibility to Covid-19

    Authors: Matthew R Alexander; Clara T. Schoeder; Jacquelyn A. Brown; Charles D. Smart; Christopher W. Moth; John P. Wikswo; John Anthony Capra; Jens Meiler; Wenbiao Chen; Meena S. Madhur

    doi:10.1101/2020.07.09.194563 Date: 2020-07-10

    In only a few months, the novel coronavirus severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has caused a global pandemic, leaving physicians, scientists, and public health officials racing to understand, treat, and contain this zoonotic disease MESHD. SARS-CoV-2 has made the leap from animals to humans, but little is known about variations in species susceptibility that could identify potential reservoir species, animal models, and the risk to pets, wildlife, and livestock. While there is evidence that certain species, such as cats, are susceptible, the vast majority of animal species, including those in close contact TRANS with humans, have unknown susceptibility. Hence, methods to predict their infection MESHD infection risk TRANS infection risk TRANS risk are urgently needed. SARS-CoV-2 spike protein binding to angiotensin converting enzyme 2 (ACE2) is critical for viral cell entry and infection MESHD. Here we identified key ACE2 residues that distinguish susceptible from resistant species using in-depth sequence and structural analyses of ACE2 and its binding to SARS-CoV-2. Our findings have important implications for identification of ACE2 and SARS-CoV-2 residues for therapeutic targeting and identification of animal species with increased susceptibility for infection MESHD on which to focus research and protection measures for environmental and public health.Competing Interest StatementThe authors have declared no competing interest.View Full Text

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MeSH Disease
Human Phenotype

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