Corpus overview


Overview

MeSH Disease

Human Phenotype

Pneumonia (451)

Fever (335)

Cough (265)

Hypertension (152)

Respiratory distress (139)


Transmission

age categories (1172)

Transmission (1150)

fomite (565)

gender (495)

asymptotic cases (457)


Seroprevalence
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    Rapid endothelialitis and vascular inflammation MESHD characterise SARS-CoV-2 infection MESHD in a human lung-on-chip model

    Authors: Vivek V Thacker; Kunal Sharma; Neeraj Dhar; Gian-Filippo Mancini; Jessica Sordet-Dessimoz; John D McKinney

    doi:10.1101/2020.08.10.243220 Date: 2020-08-12 Source: bioRxiv

    BackgroundSevere manifestations of COVID-19 include hypercoagulopathies and systemic endothelialitis. The underlying dynamics of damage to the vasculature, and whether it is a direct consequence of endothelial infection MESHD or an indirect consequence of immune cell mediated cytokine storms is unknown. This is in part because in vitro infection MESHD models are typically monocultures of epithelial cells or fail to recapitulate vascular physiology. MethodsWe establish a vascularised lung-on-chip infection MESHD model consisting of a co-culture of primary human alveolar epithelial cells ( epithelial) and human lung microvascular endothelial cells ( endothelial), with the optional addition of CD14+ macrophages to the epithelial side. A combination of qRT-PCR, RNAscope, immunofluorescence, and ELISA SERO measurements are used to study the dynamics of viral replication and host responses to a low dose infection MESHD of SARS-CoV-2 delivered to the apical surface of the epithelial face maintained at an air-liquid interface. FindingsSARS-CoV-2 inoculation does not lead to a productive amplification of infectious virions. However, both genomic and antisense viral RNA can be found in endothelial cells within 1-day post infection MESHD (dpi) and persist upto 3 dpi. This generates an NF-KB inflammatory response typified by IL-6 secretion and a weak antiviral interferon response even in the absence of immune cells. Endothelial inflammation MESHD leads to a progressive loss of barrier integrity, a subset of cells also shows a transient hyperplasic phenotype. Administration of Tocilizumab slows the loss of barrier integrity but does not reduce the occurrence of the latter. InterpretationEndothelial infection MESHD can occur through basolateral transmission TRANS from infected epithelial cells at the air-liquid interface. SARS-CoV-2 mediated inflammation MESHD occurs despite the lack of rapid viral replication and the consequences are cell-type dependent. Infected endothelial cells might be a key source of circulating IL-6 in COVID-19 patients. Vascular damage occurs independently of immune-cell mediated cytokine storms, whose effect would only exacerbate the damage. FindingCore support from EPEL.

    Human Embryonic Stem Cell-derived Lung Organoids: a Model for SARS-CoV-2 Infection MESHD and Drug Test

    Authors: Rongjuan Pei; Jianqi Feng; Yecheng Zhang; Hao Sun; Lian Li; Xuejie Yang; Jiangping He; Shuqi Xiao; Jin Xiong; Ying Lin; Kun Wen; Hongwei Zhou; Jiekai Chen; Zhili Rong; Xinwen Chen

    doi:10.1101/2020.08.10.244350 Date: 2020-08-12 Source: bioRxiv

    The coronavirus disease MESHD 2019 (COVID-19) pandemic is caused by infection MESHD infection with the severe HP with the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), which is spread primary via respiratory droplets and infects the lungs. Currently widely used cell lines and animals are unable to accurately mimic human physiological conditions because of the abnormal status of cell lines (transformed or cancer cells) and species differences between animals and humans. Organoids are stem cell-derived self-organized three-dimensional culture in vitro and model the physiological conditions of natural organs. Here we demonstrated that SARS-CoV-2 infected and extensively replicated in human embryonic stem cells (hESCs)-derived lung organoids, including airway and alveolar organoids. Ciliated cells, alveolar type 2 (AT2) cells and rare club HP cells were virus target cells. Electron microscopy captured typical replication, assembly and release ultrastructures and revealed the presence of viruses within lamellar bodies in AT2 cells. Virus infection MESHD induced more severe cell death MESHD in alveolar organoids than in airway organoids. Additionally, RNA-seq revealed early cell response to SARS-CoV-2 infection MESHD and an unexpected downregulation of ACE2 mRNA. Further, compared to the transmembrane protease, serine 2 (TMPRSS2) inhibitor camostat, the nucleotide analog prodrug Remdesivir potently inhibited SARS-CoV-2 replication in lung organoids. Therefore, human lung organoids can serve as a pathophysiological model for SARS-CoV-2 infection MESHD and drug discovery.

    Low awareness of past SARS-CoV-2 infection MESHD in healthy adults TRANS

    Authors: Katja van den Hurk; Eva-Maria Merz; Femmeke J. Prinsze; Marloes L.C. Spekman; Franke A. Quee; Steven Ramondt; Ed Slot; Hans Vrielink; Elisabeth M.J. Huis in 't Veld; Hans L. Zaaijer; Boris M. Hogema

    doi:10.1101/2020.08.10.20171561 Date: 2020-08-12 Source: medRxiv

    Background The coronavirus disease MESHD 2019 (COVID-19) pandemic challenges governments worldwide to balance appropriate virus control measures and their societal and economic consequences. These control measures include the identification, isolation and testing of potentially infected individuals. As this relies on an individual's awareness of infection MESHD, we investigated the extent to which healthy adults TRANS suspected having had COVID-19, and how COVID-19 suspicion and symptoms relate to antibodies SERO indicative of a past infection MESHD infection with the severe HP with the severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). Methods and findings Individuals donating plasma SERO anywhere in the Netherlands between May 11th and 18th were screened for total SARS-CoV-2 antibodies SERO using ELISA SERO and invited to participate in an online questionnaire about COVID-19-related symptoms and awareness. Antibody SERO and questionnaire data were complete for 3,676 individuals, including 239 (6.5%) that tested positive for SARS-CoV-2 antibodies SERO. Here, we show that a 38% of the individuals that tested positive for SARS-CoV-2 antibodies SERO reported having had no or only very mild symptoms at any time during the peak of the epidemic. The loss of taste and/or smell in particular was significantly associated with seropositivity, independent of age TRANS and sex. Forty-eight percent of antibody SERO-positive persons did not suspect having had COVID-19, in spite of most of them reporting symptoms. Conclusions Awareness of infection MESHD was low among individuals that tested positive for SARS-CoV-2 antibodies SERO, even at the peak of the epidemic. Improved awareness and recognition of COVID-19 symptoms and tracing TRANS of asymptomatic TRANS contacts is crucial to halting SARS-CoV-2 transmission TRANS.

    Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection MESHD

    Authors: Cheng Wang; Shaobo Wang; Yin Chen; Jianqi Zhao; Songling Han; Gaomei Zhao; Jing Kang; Yong Liu; Liting Wang; Xiaoyang Wang; Yang Xu; Song Wang; Yi Huang; Junping Wang; Jinghong Zhao

    doi:10.1101/2020.08.12.247338 Date: 2020-08-12 Source: bioRxiv

    The ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection MESHD. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg-1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection MESHD with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-achieve membrane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19.

    A "Tail" of Two Cities: Fatality-based Modeling of COVID-19 Evolution in New York City and Cook County, IL

    Authors: Joshua Frieman

    doi:10.1101/2020.08.10.20170506 Date: 2020-08-12 Source: medRxiv

    I describe SIR modeling of the COVID-19 pandemic in two U.S. urban environments, New York City (NYC) and Cook County, IL, from onset through the month of June, 2020. Since testing was not widespread early in the pandemic in the U.S., I do not use data on confirmed cases TRANS and rely solely on public fatality data to estimate model parameters. Fits to the first 20 days of data determine a degenerate combination of the basic reproduction number TRANS, R0 TRANS, and the mean time to removal from the infectious population, 1/{gamma} with {gamma}( R0 TRANS - 1) = 0.25(0.21) inverse days for NYC (Cook County). Equivalently, the initial doubling time was td = 2.8(3.4) days for NYC (Cook). The early fatality data suggest that both locations had infections MESHD in early February. I model the mitigation measures implemented in mid-March in both locations (distancing, quarantine, isolation, etc) via a time-dependent reproduction number TRANS Rt that declines monotonically from R0 TRANS to a smaller asymptotic TRANS value, with a parameterized functional form. The timing (mid-March) and duration (several days) of the transitions in Rt appear well determined by the data. However, the fatality data determine only a degenerate combination of the parameters R0 TRANS, the percentage reduction in social contact due to mitigation measures, X, and the infection MESHD fatality rate (IFR), f . With flat priors, based on simulations the NYC model parameters have 95.45% credible intervals of R0 TRANS = 3.0 - 5.4, X = 80 - 99.9% and f = 2 - 6%, with 5 - 13% of the population asymptotically infected. A strong external prior indicating a lower value of f or of 1/{gamma} would imply lower values of R0 TRANS and X and higher percentage infection MESHD of the population. For Cook County, the evolution was qualitatively different: after mitigation measures were implemented, the daily fatality counts reached a plateau for about a month before tailing off. This is consistent with an SIR model that exhibits "critical slowing-down", in which Rt plateaus at a value just above unity. For Cook County, the 95.45% credible intervals for the model parameters are much broader and shifted downward, R0 TRANS = 1.4 - 4.7, X = 26 - 54%, and f = 0.1 - 0.6% with 15 - 88% of the population asymptotically infected. Despite the apparently lower efficacy of its social contact reduction measures, Cook County has had significantly fewer fatalities per population than NYC, D{infty}/N = 100 vs. 270 per 100,000. In the model, this is attributed to the lower inferred IFR for Cook; an external prior pointing to similar values of the IFR for the two locations would instead chalk up the difference in D/N to differences in the relative growth rate of the disease MESHD. I derive a model-dependent threshold, Xcrit, for "safe" re-opening, that is, for easing of contact reduction that would not trigger a second wave; for NYC, the models predict that increasing social contact by more than 20% from post-mitigation levels will lead to renewed spread, while for Cook County the threshold value is very uncertain, given the parameter degeneracies. The timing of 2nd-wave growth will depend on the amplitude of contact increase relative to Xcrit and on the asymptotic TRANS growth rate, and the impact in terms of fatalities will depend on the parameter f .

    Stochastic extinction of epidemics: how long does would it take for Sars-Cov-2 to die out?

    Authors: Bhavin S Khatri

    doi:10.1101/2020.08.10.20171454 Date: 2020-08-12 Source: medRxiv

    Worldwide, we are currently in an unprecedented situation with regard to the SARS-Cov-2 epidemic, where countries are using isolation and lock-down measures to control the spread of infection MESHD. This is a scenario generally not much anticipated by previous theory, and in particular, there has been little attention paid to the question of extinction as a means to eradicate the virus; the prevailing view appears to be that this is unfeasible without a vaccine. We use a simple well-mixed stochastic SIR model as a basis for our considerations, and calculate a new result, using branching process theory, for the distribution of times to extinction. Surprisingly, the distribution is an extreme value distribution of the Gumbel type, and we show that the key parameter determining its mean and standard deviation is the expected rate of decline Re = {gamma}(1-Re) of infections MESHD, where {gamma} is the rate of recovery from infection MESHD and Re is the usual effective reproductive number TRANS. The result also reveals a critical threshold number of infected I† = 1/(1-Re), below which stochastic forces dominate and need be considered for accurate predictions. As this theory ignores migration between populations, we compare against a realistic spatial epidemic simulator and simple stochastic simulations of sub-divided populations with global migration, to find very comparable results to our simple predictions; in particular, we find global migration has the effect of a simple upwards rescaling of Re with the same Gumbel extinction time distribution we derive from our non-spatial model. Within the UK, using recent estimates of I0{approx}37000 infected and Re= 0.9, this model predicts a mean extinction time of 616{+/-}90 days or approximately ~2 years, but could be as short as 123{+/-}15 days, or roughly 4 months for Re = 0.4. Globally, the theory predicts extinction in less than 200 days, if the reproductive number TRANS is restricted to Re < 0.5. Overall, these results highlight the extreme sensitivity SERO of extinction times when Re approaches 1 and the necessity of reducing the effective reproductive number TRANS significantly (Re

    Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2

    Authors: Ziwei Yang; Xiaolin Zhang; Fan Wang; Peihui Wang; Xiaojuan Li; Ersheng Kuang

    doi:10.1101/2020.08.12.247767 Date: 2020-08-12 Source: bioRxiv

    Melanoma MESHD Melanoma HP differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses MESHD. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-{kappa}B phosphorylation. Great numbers of symptomatic and severe infections HP infections MESHD of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses MESHD. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection MESHD and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases MESHD.

    High prevalence SERO of SARS-CoV-2 antibodies SERO in care homes affected by COVID-19; a prospective cohort study in England

    Authors: Shamez N Ladhani; Anna J Jeffery-Smith; Monika Patel; Roshni Janarthanan; Jonathan Fok; Emma Crawley-Boevey; Amoolya Vusirikala; Elena Fernandez; Marina Sanchez-Perez; Suzanne Tang; Kate Dun-Campbell; Edward Wynne-Evans; Anita Bell; Bharat Patel; Zahin Amin-Chowdhury; Felicity Aiano; Karthik Paranthaman; Thomas Ma; Maria Saavedra-Campos; Joanna Ellis; Meera Chand; Kevin Brown; Mary E Ramsay; Susan Hopkins; Nandini Shetty; J Yimmy Chow; Robin Gopal; Maria Zambon

    doi:10.1101/2020.08.10.20171413 Date: 2020-08-12 Source: medRxiv

    Background: We investigated six London care homes experiencing a COVID-19 outbreak and found very high rates of SARS-CoV-2 infection MESHD among residents and staff. Here we report follow-up serological analysis in these care homes five weeks later. Methods: Residents and staff had a convalescent blood SERO sample for SARS-CoV-2 antibody SERO levels and neutralising antibodies SERO by SARS-COV-2 RT-PCR five weeks after the primary COVID-19 outbreak investigation. Results: Of the 518 residents and staff in the initial investigation, 208/241 (86.3%) surviving residents and 186/254 (73.2%) staff underwent serological testing SERO. Almost all SARS-CoV-2 RT-PCR positive residents and staff were antibody SERO positive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic TRANS (residents 32/33, 97.0%; staff 21/22, 95.1%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic TRANS RT-PCR negative individuals (residents 62/92, 67.3%; staff 95/143, 66.4%). Neutralising antibody SERO was present in 118/132 (89.4%) seropositive individuals and was not associated with age TRANS or symptoms. Ten residents (10/108, 9.3%) remained RT-PCR positive, but with lower RT-PCR cycle threshold values; all 7 tested were seropositive. New infections MESHD were detected in three residents and one staff member. Conclusions: RT-PCR testing for SARS-CoV-2 significantly underestimates the true extent of an outbreak in institutional settings. Elderly TRANS frail residents and younger healthier staff were equally able to mount robust and neutralizing antibody SERO responses to SARS-CoV-2. More than two-thirds of residents and staff members had detectable antibodies SERO against SARS-CoV-2 irrespective of their nasal swab RT-PCR positivity or symptoms status.

    Discovery of COVID-19 Inhibitors Targeting the SARS-CoV2 Nsp13 Helicase

    Authors: Mark A White; Wei Lin; Xiaodong Cheng

    doi:10.1101/2020.08.09.243246 Date: 2020-08-12 Source: bioRxiv

    The raging COVID-19 pandemic caused by SARS-CoV2 has infected millions of people and killed several hundred thousand patients worldwide. Currently, there are no effective drugs or vaccines available for treating coronavirus infections MESHD. In this study, we have focused on the SARS-CoV2 helicase (Nsp13), which is critical for viral replication and the most conserved non-structural protein within the coronavirus family. Using homology modeling and molecular dynamics approaches, we generated structural models of the SARS-CoV2 helicase in its apo- and ATP/RNA-bound conformations. We performed virtual screening of ~970,000 chemical compounds against the ATP binding site to identify potential inhibitors. Herein, we report docking hits of approved human drugs targeting the ATP binding site. Importantly, two of our top drug hits have significant activity in inhibiting purified recombinant SARS-CoV-2 helicase, providing hope that these drugs can be potentially repurposed for the treatment of COVID-19.

    High prevalence SERO of symptoms among Brazilian subjects with antibodies SERO against SARS-CoV-2: a nationwide household survey

    Authors: Ana Maria Baptista Menezes; Cesar G Victora; Fernando P Hartwig; Mariangela F Silveira; Bernardo L Horta; Aluisio J D Barros; Fernando C Whermeister; Marilia A Mesenburg; Lucia C Pellanda; Odir A Dellagostin; Claudio J Struchiner; Marcelo N Burattini; Fernando C Barros; Pedro C Hallal

    doi:10.1101/2020.08.10.20171942 Date: 2020-08-12 Source: medRxiv

    Since the beginning of the pandemic of COVID-19, there has been a widespread assumption that most infected persons are asymptomatic TRANS. A frequently-cited early study from China suggested that 86% of all infections MESHD were undocumented, which was used as indirect evidence that patients were asymptomatic TRANS. Using data from the most recent wave of the EPICOVID19 study, a nationwide household-based survey including 133 cities from all states of Brazil, we estimated the proportion of people with and without antibodies for SARS-CoV-2 SERO who were asymptomatic TRANS, which symptoms were most frequently reported, the number of symptoms reported and the association between symptomatology and socio-demographic characteristics. We were able to test 33,205 subjects using a rapid antibody test SERO that was previously validated. Information on symptoms was collected before participants received the test result. Out of 849 (2.7%) participants who tested positive for SARS-CoV-2 antibodies SERO, only 12.1% (95%CI 10.1-14.5) reported no symptoms since the start of the pandemic, compared to 42.2% (95%CI 41.7-42.8) among those who tested negative. The largest difference between the two groups was observed for changes in smell or taste (56.5% versus 9.1%, a 6.2-fold difference). Symptoms change in smell or taste, fever MESHD fever HP and myalgia MESHD myalgia HP were most likely to predict positive test results as suggested by recursive partitioning tree analysis. Among individuals without any of these three symptoms (74.2% of the sample), only 0.8% tested positive, compared to 18.3% of those with both fever MESHD fever HP and changes in smell or taste. Most subjects with antibodies SERO against SARS-CoV-2 in Brazil are symptomatic, even though most present only mild symptoms.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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