Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (465)

Fever (273)

Cough (217)

Hypertension (192)

Respiratory distress (119)


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    Pre-diagnostic circulating concentrations of insulin-like growth factor-1 and risk of COVID-19 mortality: results from UK Biobank

    Authors: Xikang Fan; Cheng Yin; Jiayu Wang; Mingjia Yang; Hongxia Ma; Guangfu Jin; Mingyang Song; Zhibin Hu; Hongbing Shen; Dong Hang

    doi:10.1101/2020.07.09.20149369 Date: 2020-07-11

    Background: Coronavirus disease MESHD 2019 (COVID-19) deteriorates suddenly primarily due to excessive inflammatory injury, and insulin-like growth factor-1 (IGF-1) is implicated in endocrine control of the immune system. However, the effect of IGF-1 levels on COVID-19 prognosis remains unknown. Objective: To investigate the association between circulating IGF-1 concentrations and mortality risk among COVID-19 patients. Design: Prospective analysis. Setting: UK Biobank. Participants: 1425 COVID-19 patients who had pre-diagnostic serum SERO IGF-1 measurements at baseline (2006-2010). Main outcome measures: COVID-19 mortality (available death MESHD data updated to 22 May 2020). Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of mortality across the IGF-1 quartiles. Results: Among 1425 COVID-19 patients, 365 deaths MESHD occurred due to COVID-19. Compared to the lowest quartile of IGF-1 concentrations, the highest quartile was associated with a 37% lower risk of mortality (OR: 0.63, 95% CI: 0.43-0.93, P-trend=0.03). The association was stronger in women and nonsmokers (both P-interaction=0.01). Conclusions: Higher IGF-1 concentrations are associated with a lower risk of COVID-19 mortality. Further studies are required to determine whether and how targeting IGF-1 pathway might improve COVID-19 prognosis.

    Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy

    Authors: Sara Conti; Pietro Ferrara; Giampiero Mazzaglia; Marco I D'Orso; Roberta Ciampichini; Carla Fornari; Fabiana Madotto; Michele Magoni; Giuseppe Sampietro; Andrea Silenzi; Claudio V Sileo; Andrea Zucchi; Giancarlo Cesana; Lamberto Manzoli; Lorenzo G Mantovani

    doi:10.1101/2020.07.10.20150565 Date: 2020-07-11

    Background: The real impact of SARS-CoV-2 on overall mortality remains uncertain and surveillance reports attributed to COVID-19 a limited amount of deaths MESHD during the outbreak. Aim of this study is to assess the excess mortality (EM) during COVID-19 outbreak in highly impacted areas of northern Italy. Methods: We analyzed data on deaths MESHD occurred in the first four months of 2020 in health protection agencies (HPA) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths MESHD and predicting the daily standardized mortality ratio (SMR) and cumulative number of excess deaths MESHD (ED) through a Poisson generalized additive model of the observed counts in 2020, using 2019 data as a reference. Results: We estimated 5740 (95% Credible Set (CS): 5552-5936) ED in the HPA of Bergamo and 3703 (95% CS: 3535 - 3877) in Brescia, corresponding to 2.55 (95% CS: 2.50-2.61) and 1.93 (95% CS: 1.89-1.98) folds increase in the number of deaths MESHD. The ED wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly two weeks after the introduction of lock-down measures, with significantly higher estimates in Bergamo (9.4, 95% CI: 9.1-9.7). Conclusion: EM was significantly larger than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower EM in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.

    Societal heterogeneity contributes to complex dynamic patterns of the COVID-19 pandemics: insights from a novel Stochastic Heterogeneous Epidemic Model (SHEM)

    Authors: Alexander V Maltsev; Michael Stern

    doi:10.1101/2020.07.10.20150813 Date: 2020-07-11

    After months of COVID-19 quarantine, businesses are reopening their doors and people are reentering society. Within the current COVID-19 data, after a slow-down of infection MESHD, a new peak in active cases is already forming. Here we developed a new Stochastic Heterogeneous Epidemic Model (SHEM) to investigate genesis of complex pandemic patterns with the focus on the role of heterogenous societal structure. Using this model with R0 TRANS of COVID-19, we simulated viral infection MESHD in different scenarios where isolated, communities surround the main cluster of the population. Depending on the parameters of heterogeneity and isolation period, our simulations generated a multimodal growth periods with multiple peaks, an extended plateau, a prolonged tail, or a delayed second wave of infection MESHD. We show that timing and magnitude of infection MESHD for previously unaffected isolated clusters of people, such as suburban neighborhoods, are critical aspects of these patterns. Our model can be applied to communities at any given scale of population described as a fractal-like structure, i.e. from the entire human population, to a country, down to a province or city levels with relevant societal heterogeneity structure. The current COVID-19 pandemic development worldwide and in the US follows a bimodal rise pattern, qualitatively similar to that in our simulations. We interpret our data to indicate that the secondary peak in the pattern is contributed by the states and counties in the US with late infection MESHD surges that are analogous to isolated suburbs in our model. Furthermore, the on-going early reopening, i.e. premature partial reopening in our model, is further accelerating the peak rise. This peak now reaches new heights, forcing many states in the US to reverse their policies and reestablish their quarantine measures. Our results support these timely and effective measures: we show that longer quarantine periods can reduce the number of deaths MESHD and transform the current trend into a substantially delayed (>1 year) second wave. If this scenario becomes a reality, it is important (i) to develop the vaccine and/or effective treatment before the second wave; (ii) to warn people living in suburbs that it is these isolated areas that may hold a false sense of security, but they should continue to take extra care for their public health.

    The diagnostic accuracy of nucleic acid point-of-care tests for human coronavirus: A systematic review and meta-analysis

    Authors: Pakpoom Subsoontorn; Manupat Lohitnavy; Chuenjid Kongkaew

    doi:10.1101/2020.07.09.20150235 Date: 2020-07-11

    Many recent studies reported coronavirus point of care tests (POCTs) based on isothermal amplification. However, the performances SERO of these tests have not been systematically evaluated. We searched databases for studies that provide data to calculate sensitivity SERO, specificity and diagnostic odds ratio (DOR). We included 43 studies on 5204 specimens. Most studies had high risk of patient selection and index test bias but low risk in other domains. Most studies (n = 21) used reverse-transcribed loop-mediated isothermal amplification (RT-LAMP) to diagnose Coronavirus disease MESHD 2019 (COVID-19). Summary estimated ln(DOR) for RT-LAMP of RNA purified COVID-19 samples is 6.50 (95%CI 5.25-7.76), similar to the previously reported value for RT-LAMP of other RNA virus. RT-LAMP from crude samples has significantly lower ln(DOR) at 4.46 (95%CI 3.53-5.38). SAMBA-II has the highest ln(DOR) at 8.00 (95%CI 6.14-9.87). Abbott ID Now performance SERO is similar to RT-LAMP of crude sample. The performances SERO of CRISPR diagnosis and RT-LAMP are not significantly different. Types of coronaviruses and publication status have no significant effect on diagnosis performance SERO. Existing nucleic acid POCTs, particularly RT-LAMP, CRISPR diagnosis and SAMBA-II, have good diagnostic performance SERO. Future work should focus on improving a study design to minimize the risk of biases.

    ACE2-expressing endothelial cells in aging mouse brain

    Authors: SU Bin Lim; Valina L. Dawson; Ted M. Dawson; Sung-Ung Kang

    doi:10.1101/2020.07.11.198770 Date: 2020-07-11

    Angiotensin-converting enzyme 2 (ACE2) is a key receptor mediating the entry of SARS-CoV-2 into the host cell. Through a systematic analysis of publicly available mouse brain sc/snRNA-seq data, we found that ACE2 is specifically expressed in small sub-populations of endothelial cells and mural cells, namely pericytes and vascular smooth muscle cells. Further, functional changes in viral mRNA transcription and replication, and impaired blood SERO-brain barrier regulation were most prominently implicated in the aged TRANS, ACE2-expressing endothelial cells, when compared to the young adult TRANS mouse brains. Concordant EC transcriptomic changes were further found in normal aged TRANS human brains. Overall, this work reveals an outline of ACE2 distribution in the mouse brain and identify putative brain host cells that may underlie the selective susceptibility of the aging brain to viral infection MESHD.Competing Interest StatementThe authors have declared no competing interest.

    Psychological state and family functioning of University of Ibadan students during the COVID-19 lockdown

    Authors: Lucia Yetunde Ojewale

    doi:10.1101/2020.07.09.20149997 Date: 2020-07-11

    Background: The curtailment of social gatherings as well as lack of online academic engagement, due to the COVID-19 lockdown, could have potentially damaging effects on the psychological state of university students in Nigeria. This study examined the prevalence SERO of anxiety HP and depression, including associated factors and coping methods among undergraduate students in a Nigerian university. It also examined the association between psychological state and family functioning. Methods: The study design was cross-sectional and involved 386 undergraduate students across the main faculties. The university's ethical review board approved the study with approval number UI/EC/20/0242. An online questionnaire, using Google form, was circulated among the students through their faculty representatives. The Hospital Anxiety HP and Depression scale (HADs) was used in assessing anxiety HP and depression, while family functioning was assessed using the McMaster Family Assessment Device, (FAD). Data was entered into Statistical Package for Social Sciences (SPSS), and analysis carried out using descriptive statistics, chi-square, independent t-test, Analysis of Variance (ANOVA), Post-Hoc analysis and linear logistics regression, at 0.05. Results: The mean age TRANS was 21 {+/-} 2.9 years, with a female TRANS population of 60.1%. Prevalence SERO of anxiety HP and depression were 41.5% and 31.9% respectively. Students in health-related faculties were significantly less anxious than those in other faculties. Inability to afford three square meals, negative family functioning, having a chronic illness and living in a State/Region with a high incidence of COVID-19, was significantly associated with depression. These factors jointly accounted for 14% of depression seen in undergraduate students. Most of the students coped by engaging themselves in social media, watching television/movies and participating in other online skill development programmes. Conclusion: There was a high prevalence SERO of anxiety HP and depression among university students with poor family functioning, inability to afford three meals/day, living in a state with a high incidence of COVID-19 and having a chronic illness, contributing to depression. Measures need to be taken to support undergraduate students and their families to prevent the negative consequences of poor mental health. Keywords: COVID-19; lockdown; undergraduate students; anxiety HP; depression; psychological state; family-functioning, coping.

    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.

    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.

    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.

    Community prevalence SERO of SARS-CoV-2 virus in England during May 2020: REACT study

    Authors: Steven Riley; Kylie E. C. Ainslie; Oliver Eales; Benjamin Jeffrey; Caroline E. Walters; Christina J Atchison; Peter J. Diggle; Deborah Ashby; Christl A. Donnelly; Graham Cooke; Wendy Barclay; Helen Ward; Graham Taylor; Ara Darzi; Paul Elliott

    doi:10.1101/2020.07.10.20150524 Date: 2020-07-11

    Background England has experienced one of the highest rates of confirmed COVID-19 mortality in the world. SARS-CoV-2 virus has circulated in hospitals, care homes and the community since January 2020. Our current epidemiological knowledge is largely informed by clinical cases with far less understanding of community transmission TRANS. Methods The REal-time Assessment of Community Transmission TRANS (REACT) study is a nationally representative prevalence SERO survey of SARS-CoV-2 virus swab-positivity in the community in England. We recruited participants regardless of symptom status. Results We found 159 positives from 120,610 swabs giving an average prevalence SERO of 0.13% (95% CI: 0.11%,0.15%) from 1st May to 1st June 2020. We showed decreasing prevalence SERO with a halving time of 8.6 (6.2, 13.6) days, implying an overall reproduction number TRANS R of 0.57 (0.45, 0.72). Adults TRANS aged TRANS 18 to 24 yrs had the highest swab-positivity rates, while those >64 yrs had the lowest. Of the 126 participants who tested positive with known symptom status in the week prior to their swab, 39 reported symptoms while 87 did not, giving an estimate that 69% (61%,76%) of people were symptom-free for the 7 days prior testing positive in our community sample. Symptoms strongly associated with swab-positivity were: nausea MESHD nausea and/or vomiting HP and/or vomiting MESHD, diarrhoea, blocked nose, loss of smell, loss of taste, headache MESHD headache HP, chills MESHD chills HP and severe fatigue MESHD fatigue HP. Recent contact with a known COVID-19 case was associated with odds of 24 (16, 38) for swab-positivity. Compared with non-key workers, odds of swab-positivity were 7.7 (2.4, 25) among care home (long-term care facilities) workers and 5.2 (2.9, 9.3) among health care workers. However, some of the excess risk associated with key worker status was explained by recent contact with COVID-19 cases. We found no strong evidence for geographical variability in positive swab results. Conclusion Our results provide a reliable baseline against which the impact of subsequent relaxation of lockdown can be assessed to inform future public health efforts to control transmission TRANS.

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MeSH Disease
Human Phenotype

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