Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (184)

Fever (129)

Hypertension (106)

Cough (100)

Respiratory distress (51)


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    COVID-19 severity is predicted by earlier evidence of accelerated aging

    Authors: Chia-Ling Kuo; Luke C Pilling; Janice C Atkins; Jane Masoli; Joao Delgado; Christopher Tignanelli; George Kuchel; David Melzer; Kenneth B Beckman; Morgan Levine

    doi:10.1101/2020.07.10.20147777 Date: 2020-07-11

    With no known treatments or vaccine, COVID-19 presents a major threat, particularly to older adults TRANS, who account for the majority of severe illness and deaths MESHD. The age TRANS-related susceptibility is partly explained by increased comorbidities including dementia MESHD dementia HP and type II diabetes. While it is unclear why these diseases MESHD predispose risk, we hypothesize that increased biological age TRANS, rather than chronological age TRANS, may be driving disease MESHD-related trends in COVID-19 severity with age TRANS. To test this hypothesis, we applied our previously validated biological age TRANS measure (PhenoAge) composed of chronological age TRANS and nine clinical chemistry biomarkers to data of 347,751 participants from a large community cohort in the United Kingdom (UK Biobank), recruited between 2006 and 2010. Other data included disease MESHD diagnoses (to 2017), mortality data (to 2020), and the UK national COVID-19 test results (to May 31, 2020). Accelerated aging 10-14 years prior to the start of the COVID-19 pandemic was associated with test positivity (OR=1.15 per 5-year acceleration, 95% CI: 1.08 to 1.21, p=3.2x10-6) and all-cause mortality with test-confirmed COVID-19 (OR=1.25, per 5-year acceleration, 95% CI: 1.09 to 1.44, p=0.002) after adjustment for demographics including current chronological age TRANS and pre-existing diseases MESHD or conditions. The corresponding areas under the curves were 0.669 and 0.803, respectively. Biological aging, as captured by PhenoAge, is a better predictor of COVID-19 severity than chronological age TRANS, and may inform risk stratification initiatives, while also elucidating possible underlying mechanisms, particularly those related to inflammaging.

    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.

    Using simulation to assess the potential effectiveness of implementing screening at national borders during international outbreaks of influenza, SARS, Ebola virus disease MESHD and COVID-19

    Authors: Declan Bays; Emma Bennett; Thomas Finnie

    doi:10.1101/2020.07.10.20150664 Date: 2020-07-11

    The effectiveness of screening travellers for signs of infection MESHD during times of international disease MESHD outbreak is contentious, especially as the reduction of the risk of disease MESHD importation can be very small. Border screening typically consists of arriving individuals being thermally scanned for signs of fever MESHD fever HP and/or completing a survey to declare any possible symptoms, and while more thorough testing typically exists, these would generally prove more disruptive to deploy. In this paper, we utilise epidemiological data and Monte Carlo simulation to calculate the potential success rate of deploying border screening for a range of diseases MESHD (including the current COVID-19 pandemic) in varying outbreak scenarios. We negate the issue of testing precision by assuming a perfect test is used; our outputs then represent the best-case scenario. We then use these outputs to briefly explore the types of scenarios where the implementation of border screening could prove most effective. Our models only considers screening implemented at airports, due to air travel TRANS being the predominant method of international travel TRANS. Primary results showed that in the best-case scenario, screening has the potential to detect 46.4%, 12.9% and 4.0% of travellers infected with influenza, SARS and ebola respectively, while screening for COVID-19 could potentially detect 12.0% of infected travellers. We compare our results to those already in the published literature.

    In-house modification and improvement of the CDC real-time PCR diagnostic assay for SARS-CoV-2 detection.

    Authors: Srirupa Das; Candice Dowell-Martino; Lisa Arrigo; Paul N. Fiedler; Sandra Lobo

    doi:10.1101/2020.07.10.20150771 Date: 2020-07-11

    The world is currently facing an unprecedented pandemic caused by the novel coronavirus SARS-CoV-2 (COVID-19) which was first reported in late 2019 by China to the World Health Organization (WHO). The containment strategy for COVID-19, which has non-specific flu-like symptoms and where upwards of 80% of the affected has either mild or no symptoms, is critically centered upon diagnostic testing, tracking and isolation. Thus, the development of specific and sensitive diagnostic tests for COVID-19 is key towards the first successful step of disease MESHD management. Public health organizations like the WHO and the US-based Centers for Disease MESHD Control and Prevention (CDC) have developed real-time PCR (RT-PCR) based diagnostic tests to aid in the detection of acute infection MESHD. In this study we sought to modify the CDC RT-PCR diagnostic assay protocol to increase its sensitivity SERO and to make the assay directly portable to health care providers in a community-based hospital setting. A number of modifications to the original protocol were tested. Increasing the RT-PCR annealing temperature by 7{degrees}C to 62{degrees}C was associated with the most significant improvement in sensitivity SERO, wherein the cycle-threshold (Ct) value for the N2 assay was reduced by ~3 units, in effect both reducing the overall number of inconclusive results and yielding N1/N2 assays to have similar Ct values. The limit of detection of the modified assay was also improved (0.86 RNA copies/l for both nCoV 2019_N1/N2 assays) compared to the CDC RT-PCR diagnostic assay (1 and 3.16 RNA copies/l for nCoV 2019_N1 and N2 assay, respectively). Using this modification, there was no significant effect on SARS-CoV-2 detection rate when viral RNA extraction was performed either manually or through an automated extraction method. We believe this modified protocol allows for more sensitive detection of the virus which in turn will be useful for pandemic management.

    No Excess Mortality of COVID-19 in Japan until April, 2020

    Authors: Junko Kurita; Tamie Sugawara; Yoshiyuki Sugishita; Yasushi Ohkusa

    doi:10.1101/2020.07.09.20143164 Date: 2020-07-11

    Background: As of the end of June, 2020, the COVID-19 outbreak exhibited its highest peak on April 3. Nevertheless, no remarkable excess mortality attributable to COVID-19 has been observed. Object: We sought to quantify excess mortality in April using the National Institute of Infectious Diseases MESHD (NIID) model. Method: We applied the NIID model to deaths MESHD of all causes from 1987 up through April, 2020. Results: Results show no significant excess mortality in March or April, 2020, when the COVID-19 outbreak affected Japan most. Discussion and Conclusion: Because changes in application rule of the International Classification of Diseases MESHD in 2017 affected the number of pneumonia MESHD pneumonia HP deaths MESHD drastically, we were unable to use pneumonia MESHD pneumonia HP deaths MESHD to estimate excess mortality. it might be important to continue to monitor excess mortality of COVID-19 carefully after May 2020.

    Decreased serum SERO levels of inflammaging marker miR-146a are associated with clinical response to tocilizumab in COVID-19 patients

    Authors: Jacopo Sabbatinelli; Angelica Giuliani; Giulia Matacchione; Silvia Latini; Noemi Laprovitera; Giovanni Pomponio; Alessia Ferrarini; Silvia Svegliati Baroni; Marianna Pavani; Marco Moretti; Armando Gabrielli; Antonio Domenico Procopio; Manuela Ferracin; Massimiliano Bonafè; Fabiola Olivieri

    doi:10.1101/2020.07.11.20151365 Date: 2020-07-11

    Background. Current COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. At least in western countries, the most amount of the death MESHD toll is accounted by old people affected by age TRANS-related diseases MESHD. In this regard, we proposed that COVID-19 severity may be tightly related to inflammaging, i.e. the age TRANS-related onset of inflammation MESHD, which is responsible for age TRANS-related diseases MESHD. It has been reported that systemic hyper- inflammation MESHD may turn to be detrimental in COVID-19 patients. Objective. Here, we exploited a recently closed clinical trial (NCT04315480) on the anti-IL-6 drug tocilizumab to assess whether microRNAs regulating inflammaging can be assessed as biomarkers of drug response and outcome. Methods. Serum SERO levels of miR-146a-5p, -21-5p, and -126-3p were quantified by RT-PCR and Droplet Digital PCR by two independent laboratories on 30 patients with virologically confirmed COVID-19, characterized by multifocal interstitial pneumonia MESHD pneumonia HP confirmed by CT-scan and requiring oxygen therapy, and 29 age TRANS- and gender TRANS-matched healthy control subjects. COVID-19 patients were treated with a single-dose intravenous infusion of 8 mg/kg tocilizumab and categorized into responders and non-responders. Results. We showed that COVID-19 patients who did not respond to tocilizumab have lower serum SERO levels of miR-146a-5p after the treatment (p=0.007). Moreover, among non-responders, those with the lowest serum SERO levels of miR-146a-5p experienced the most adverse outcome (p=0.008). Conclusion. Our data show that blood SERO-based biomarkers, such as miR-146a-5p, can provide a molecular link between inflammaging and COVID-19 clinical course, thus allowing to enlarge the drug armory against this worldwide health threat.

    Undocumented infectives in the Covid-19 pandemic

    Authors: Maurizio Melis; Roberto Littera

    doi:10.1101/2020.07.09.20149682 Date: 2020-07-11

    Background. A crucial role in epidemics is played by the number of undetected infective individuals who continue to circulate and spread the disease TRANS disease MESHD. Epidemiological investigations and mathematical models have revealed that the rapid diffusion of Covid-19 can mostly be attributed to the large percentage of undocumented infective individuals who escape testing. Methods. The dynamics of an infection MESHD can be described by the SIR model, which divides the population into susceptible (S), infective (I) and removed (R) subjects. In particular, we exploited the Kermack and McKendrick epidemic model which can be applied when the population is much larger than the fraction of infected subjects. Results. We proved that the fraction of undocumented infectives, in comparison to the total number of infected subjects, is given by 1-1/ R0 TRANS , where R0 TRANS is the basic reproduction number TRANS. Its mean value R0=2.10 (2.09-2.11) in three Italian regions for the Covid-19 epidemic yielded a percentage of undetected infectives of 52.4% (52.2% - 52.6%) compared to the total number of infectives. Conclusions. Our results, straightforwardly obtained from the SIR model, highlight the role played by undetected carriers TRANS in the transmission TRANS and spread of the SARS-CoV-2 infection MESHD. Such evidence strongly recommends careful monitoring of the infective population and ongoing adjustment of preventive measures for disease MESHD control until a vaccine becomes available.

    Longitudinal evaluation and decline of antibody SERO responses in SARS-CoV-2 infection MESHD

    Authors: Jeffrey Seow; Carl Graham; Blair Merrick; Sam Acors; Kathryn J.A. Steel; Oliver Hemmings; Aoife O'Bryne; Neophytos Kouphou; Suzanne Pickering; Rui Galao; Gilberto Betancor; Harry D Wilson; Adrian W Signell; Helena Winstone; Claire Kerridge; Nigel Temperton; Luke Snell; Karen Bisnauthsing; Amelia Moore; Adrian Green; Lauren Martinez; Brielle Stokes; Johanna Honey; Alba Izquierdo-Barras; Gill Arbane; Amita Patel; Lorcan OConnell; Geraldine O Hara; Eithne MacMahon; Sam Douthwaite; Gaia Nebbia; Rahul Batra; Rocio Martinez-Nunez; Jonathan D. Edgeworth; Stuart J.D. Neil; Michael H. Malim; Katie Doores

    doi:10.1101/2020.07.09.20148429 Date: 2020-07-11

    Antibody SERO (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re- infection MESHD. Using sequential serum samples SERO collected up to 94 days post onset of symptoms TRANS (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody SERO (nAb) responses when sampled beyond 8 days POS. We demonstrate that the magnitude of the nAb response is dependent upon the disease MESHD severity, but this does not affect the kinetics of the nAb response. Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy's and St Thomas' Hospitals. We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection MESHD that causes low disease MESHD severity and the circulating seasonal coronaviruses that are associated with common colds MESHD. This study has important implications when considering widespread serological testing SERO, Ab protection against re- infection MESHD with SARS-CoV-2 and the durability of vaccine protection.

    In vivo demonstration of microvascular thrombosis MESHD in severe Covid-19

    Authors: Douglas Alexandre Espirito Santo; Anna Cristina Bertoldi Lemos; Carlos Henrique Miranda

    doi:10.1101/2020.07.09.20149971 Date: 2020-07-11

    Several autopsies studies showed the presence of microthrombi in the pulmonary circulation of the severe COVID-19. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation MESHD disseminated intravascular coagulation HP (DIC) observed as the final common pathway of the multisystem organ failure exhibited in the critical patient. We report the preliminary results of an in vivo evaluation of the sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation at the beginning of the hospitalization. They did not have any laboratorial DIC evidence. We observed multiple filling defects moving within the sublingual microvessels indicative of microthrombi in 11 (85%) patients. This is the first imaging documentation of microvascular thrombosis MESHD in living patients with severe COVID-19. The clinical relevance of microvascular thrombosis MESHD in this disease MESHD requires further research.

    Commercial Serology Assays Predict Neutralization Activity Against SARS-CoV-2

    Authors: Raymond T Suhandynata; Melissa A Hoffman; Deli Huang; Jenny T Tran; Michael J Kelner; Sharon L Reed; Ronald W McLawhon; James E Voss; David Nemazee; Robert Fitzgerald

    doi:10.1101/2020.07.10.20150946 Date: 2020-07-11

    Background. Currently it is unknown whether a positive serology results correlates with protective immunity against SARS-CoV-2. There are also concerns regarding the low positive predictive value SERO of SARS-CoV-2 serology tests, especially when testing populations with low disease MESHD prevalence SERO. Methods. A neutralization assay was validated in a set of PCR confirmed positive specimens and in a negative cohort. 9,530 specimens were screened using the Diazyme SARS-CoV-2 IgG serology assay and all positive results (N=164) were reanalyzed using the neutralization assay, the Roche total immunoglobin assay, and the Abbott IgG assay. The relationship between the magnitude of a positive SARS-CoV-2 serology result and the levels of neutralizing antibodies SERO detected was correlated. Neutralizing antibody SERO titers (ID50) were also longitudinally monitored in SARS-CoV-2 PCR confirmed patients. Results. The SARS-CoV-2 neutralization assay had a PPA of 96.6% with a SARS-CoV-2 PCR test and a NPA of 98.0% across 100 negative controls. ID50 neutralization titers positively correlated with all three clinical serology platforms. Longitudinal monitoring of hospitalized PCR confirmed COVID-19 patients demonstrates they made high neutralization titers against SARS-CoV-2. PPA between the Diazyme IgG assay alone and the neutralization assay was 50.6%, while combining the Diazyme IgG assay with either the Roche or Abbott platforms increased the PPA to 79.2% and 78.4%, respectively. Conclusions. For the first time, we demonstrate that three widely available clinical serology assays positively correlate with SARS-CoV-2 neutralization activity observed in COVID-19 patients. When a two-platform screen and confirm approach was used for SARS-CoV-2 serology, nearly 80% of two-platform positive specimens had neutralization titers (ID50 >50).

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MeSH Disease
Human Phenotype

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