Corpus overview


MeSH Disease

Human Phenotype

Pneumonia (186)

Fever (155)

Cough (128)

Hypertension (89)

Respiratory distress (60)


Transmission (499)

age categories (481)

gender (218)

fomite (217)

asymptotic cases (174)

    displaying 1 - 10 records in total 1851
    records per page

    Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection MESHD

    Authors: Niyati Desai; Azfar Neyaz; Annamaria Szabolcs; Angela R Shih; Jonathan H Chen; Vishal Thapar; Linda T Nieman; Alexander Solovyov; Arnav Mehta; David J Lieb; Anupriya S Kulkarni; Christopher Jaicks; Christopher J Pinto; Dejan Juric; Ivan Chebib; Robert B Colvin; Arthur Y Kim; Robert Monroe; Sarah E Warren; Patrick Danaher; Jason W Reeves; Jingjing Gong; Erroll H Rueckert; Benjamin D Greenbaum; Nir Hacohen; Stephen M Lagana; Miguel N Rivera; Lynette M Sholl; James R Stone; David T Ting; Vikram Deshpande

    doi:10.1101/2020.07.30.20165241 Date: 2020-08-02 Source: medRxiv

    The relationship of SARS-CoV-2 lung infection MESHD and severity of pulmonary disease MESHD is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection MESHD using a combination of different RNA and protein analytical platforms to characterize inter- and intra- patient heterogeneity of pulmonary virus infection MESHD. There was a spectrum of high and low virus cases that was associated with duration of disease MESHD and activation of interferon pathway genes. Using a digital spatial profiling platform, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection MESHD.

    A New Model of SARS-CoV-2 Infection MESHD Based on (Hydroxy)Chloroquine Activity

    Authors: Robert J. Sheaff

    doi:10.1101/2020.08.02.232892 Date: 2020-08-02 Source: bioRxiv

    Chloroquine and hydroxychloroquine [(H)CQ] are well known anti-malarial drugs, while their use against COVID-19 is more controversial. (H)CQ activity was examined in tissue culture cells to determine if their anti-viral benefits or adverse effects might be due to altering host cell pathways. Metabolic analysis revealed (H)CQ inhibit oxidative phosphorylation in mitochondria, likely by sequestering protons needed to drive ATP synthase. This activity could cause cardiotoxicity MESHD because heart muscle relies on beta oxidation of fatty acids. However, it might also explain their therapeutic benefit against COVID-19. A new model of SARS-CoV-2 infection MESHD postulates virus enters host cell mitochondria and uses its protons for genome release. Oxidative phosphorylation is eventually compromised, so glycolysis is upregulated to maintain ATP levels. (H)CQ could prevent viral infection MESHD and/or slow its replication by sequestering these protons. In support of this model other potential COVID-19 therapeutics also targeted mitochondria, as did tobacco smoke, which may underlie smokers protection. The mitochondria of young people are naturally more adaptable and resilient, providing a rationale for their resistance to disease MESHD progression. Conversely, obesity MESHD obesity HP and diabetes could exacerbate disease MESHD severity by providing extra glucose to infected cells dependent on glycolysis. The description of (H)CQ function presented here, together with its implications for understanding SARS-CO-V2 infection MESHD, makes testable predictions about disease progression MESHD and identifies new approaches for treating COVID-19.

    Kinetics of SARS-CoV-2 Antibody SERO Avidity Maturation and Association with Disease MESHD Severity

    Authors: Yiqi Ruben Luo; Indrani Chakraborty; Cassandra Yun; Alan H.B. Wu; Kara Lake Lynch

    doi:10.1101/2020.07.30.20165522 Date: 2020-08-02 Source: medRxiv

    The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD was studied. The IgG avidity assay used a novel label-free immunoassay SERO technology to test IgG against the virus spike protein receptor-binding domain (RBD). The technology, thin-film interferometry (TFI), is able to sense the formation of immune complex on a sensing probe without attaching a reporter (enzyme, fluorophore, etc.). It was found that there was a strong correlation between IgG antibody SERO avidity and days since symptom onset TRANS (p < 0.0001). In addition, peak readings were significantly higher for specimens from ICU than non-ICU patients for the first month after symptom onset TRANS (1-4 weeks) and thereafter (p<0.0001). The findings are consistent for what has been reported for SARS-CoV. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, this suggests that antibody SERO-mediated immune enhancement triggered by suboptimal antibodies SERO may not play a role in COVID-19 disease progression MESHD and severity.

    Unsupervised machine learning reveals key immune cell subsets in COVID-19, rhinovirus infection MESHD, and cancer therapy

    Authors: Sierra M. Barone; Alberta G.A. Paul; Lyndsey M. Muehling; Joanne A. Lannigan; William W. Kwok; Ronald B. Turner; Judith A. Woodfolk; Jonathan M. Irish

    doi:10.1101/2020.07.31.190454 Date: 2020-08-01 Source: bioRxiv

    For an emerging disease MESHD like COVID-19, systems immunology tools may quickly identify and quantitatively characterize cells associated with disease progression MESHD or clinical response. With repeated sampling, immune monitoring creates a real-time portrait of the cells reacting to a novel virus before disease MESHD specific knowledge and tools are established. However, single cell analysis tools can struggle to reveal rare cells that are under 0.1% of the population. Here, the machine learning workflow Tracking Responders Expanding (T-REX) was created to identify changes in both very rare and common cells in diverse human immune monitoring settings. T-REX identified cells that were highly similar in phenotype and localized to hotspots of significant change during rhinovirus and SARS-CoV-2 infections MESHD. MHC tetramers were not used during unsupervised analysis and instead "left out" to serve as a test of whether T-REX identifies biologically significant cells. In the rhinovirus challenge study, T-REX identified virus-specific CD4 + T cells based on these cells being a distinct phenotype that expanded by [≥]95% following infection MESHD. T-REX successfully identified hotspots with virus-specific T cells using pairs of samples comparing Day 7 of infection MESHD to samples taken either after clearing the infection MESHD (Day 28) or samples taken prior to infection MESHD (Day 0). Mapping pairwise comparisons in samples according to both the direction and degree of change provided a framework to compare systems level immune changes during infectious disease MESHD or therapy response. This revealed that the magnitude and direction of systemic immune change in some COVID-19 patients was comparable to that of blast crisis MESHD acute myeloid leukemia MESHD acute myeloid leukemia HP patients undergoing induction chemotherapy and characterized the identity of the immune cells that changed the most. Other COVID-19 patients instead matched an immune trajectory like that of individuals with rhinovirus infection MESHD or melanoma MESHD melanoma HP patients receiving checkpoint inhibitor therapy. T-REX analysis of paired blood SERO samples provides an approach to rapidly identify and characterize mechanistically significant cells and to place emerging diseases MESHD into a systems immunology context.

    Persistence of anti- SARS-CoV-2 antibodies SERO in non-hospitalized COVID-19 convalescent health care workers

    Authors: Margherita Bruni; Valentina Cecatiello; Angelica Diaz-Basabe; Georgia Lattanzi; Erika Mileti; Silvia Monzani; Laura Pirovano; Francesca Rizzelli; Clara Visintin; Giuseppina Bonizzi; Marco Giani; Marialuisa Lavitrano; Silvia Faravelli; Federico Forneris; Flavio Caprioli; Pier Giuseppe Pelicci; Gioacchino Natoli; Sebastiano Pasqualato; Marina Mapelli; Federica Facciotti

    doi:10.1101/2020.07.30.20164368 Date: 2020-08-01 Source: medRxiv

    Background. Coronavirus disease MESHD-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome MESHD CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody SERO response to SARS-CoV-2 can be detected early during the infection MESHD, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody SERO titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum SERO levels of pro-inflammatory mediators. Methods. An ELISA assay SERO has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies SERO as well as soluble pro-inflammatory mediators in the sera. Results. Specificity and sensitivity SERO of the ELISA assays SERO were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA SERO allowed quantification of IgM, IgG and IgA antibody SERO responses against all the viral antigens tested and showed a correlation between magnitude of the antibody SERO response and disease MESHD severity. Non-hospitalized subjects showed lower antibody SERO titers and blood SERO pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested SERO. Noteworthy, in non-severe COVID-19 infections MESHD, antibody SERO titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Conclusions. Rapid decline in antibody SERO titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection MESHD, suggesting that antibody SERO-mediated protection against re- infection MESHD with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing SERO to estimate the prevalence SERO of SARS-CoV-2 infection MESHD in the general population.

    Throat wash as a source of SARS-CoV-2 RNA to monitor community spread of COVID-19.

    Authors: Giselle Ibette Silva Lopez-Lopes; Cintia Mayumi Ahagon; Margarete Aparecida Bonega; Fabiana Pereira dos Santos; Katia Correa de Oliveira Santos; Audrey Cilli; Lincoln Spinazola do Prado; Daniela Bernardes Borges da Silva; Nuria Borges da Luz; Claudia Patara Saraceni; Ana Maria Sardinha Afonso; Maria do Carmo Timenetsky; Luis Fernando de Macedo Brigido

    doi:10.1101/2020.07.29.20163998 Date: 2020-08-01 Source: medRxiv

    Background: SARS-CoV-2 RNA detection with real time PCR is currently the central diagnostic tool to determine ongoing active infection MESHD. Nasopharyngeal and oral swabs are the main collection tool of biological material used as the source of viral RNA outside a hospital setting. However, limitation in swabs availability, trained health professional with proper PPE and potential risk of aerosols may hinder COVID diagnosis. Self-collection with swabs, saliva and throat wash to obtain oropharyngeal wash has been suggested as having comparable performance SERO of regular swab. We performed throat wash (TW) based surveillance with laboratory heath workers and other employees (LHW) at a laboratory research institute. Methods: Consecutive volunteer testing of LWH and external household and close contacts TRANS were included. TW self-collection was performed in 5 mL of sterile saline that was returned to original vial after approximate 5 secs of gargle. RNA extraction and rtPCR were performed as part of routine COVID protocols using Allplex (Seegene, Korea). Results: Four hundred and twenty two volunteers, 387 (93%) LHW and 43 (7%) contacts participated in the survey. One or more positive COVID rtPCR was documented in 63 (14.9% CI95 12%-19%) individuals. No correlation was observed between with direct activities with COVID samples to positivity, with infection MESHD observed in comparable rates among different laboratory areas, administrative or supportive activities. Among 63 with detected SARS-CoV-2 RNA, 59 with clinical information, 58% reported symptoms at a median of 4 days prior to collection, most with mild disease MESHD. Over a third (38%) of asymptomatic TRANS cases developed symptoms 1-3 days after collection. Although overall CT values of TW were higher than that of contemporary swab tests from hospitalized cases, TW from symptomatic cases had comparable CTs. Conclusions: The study suggests that TW may be a valid alternative to the detection of SARS-CoV-2 RNA. The proportion of asymptomatic TRANS and pre-symptomatic cases is elevated and reinforces the need of universal precautions and frequent surveys to limit the spread of the disease TRANS disease MESHD.

    Augmentation of anti-MDA5 antibody SERO implies severe disease MESHD in COVID-19 patients

    Authors: Changzheng Liu; Qian Wang; Yeming Wang; Geng Wang; Linghang Wang; Hong Chen; Tao Jiao; Chaojun Hu; Xiaobo Lei; Li Guo; Lili Ren; Mengtao Li; Xiaofeng Zeng; Dingyu Zhang; Bin Cao; Jianwei Wang

    doi:10.1101/2020.07.29.20164780 Date: 2020-08-01 Source: medRxiv

    Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV2) infection MESHD, which is associated with high mortality of coronavirus disease MESHD 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti- melanoma MESHD melanoma HP differentiation-associated gene 5 (MDA5) antibody SERO (Ab)-related dermatomyositis MESHD (DM), implying a shared autoinflammatory aberrance. However, it is unclear whether anti-MDA5 Ab is present in COVID-19 and correlates with the severity and adverse outcome of COVID-19 patients. Here, we found that the positive rate of anti-MDA5 Ab in patients with COVID-19 was 48.2% and the anti-MDA5 Ab positive patients tended to develop severe disease MESHD (88.6% vs 66.9%, P<0.0001). In particular, the titer of anti-MDA5 Ab was increased in the non-survivals (5.95{+/-}5.16 vs 8.22{+/-}6.64, P=0.030) and the positive rate was also higher than that in the survivals (23.5% vs 12.0%, P=0.012). Regarding to severe COVID-19 patients, we found that high titer of anti-MDA5 Ab ([≥]10.0 U/mL) was more prevalent in the non-survivals (31.2% vs 14.0%, P=0.006). Moreover, early profiling of anti-MDA5 Ab could distinguish severe patients from those with non-severe ones. Overall, our data reveal that anti-MDA5 Ab is prevalent in the COVID-19 patients and high titer of this antibody SERO is correlated with severe disease MESHD and unfavorable outcomes.

    Sustained Cellular Immune Dysregulation HP in Individuals Recovering from SARS-CoV-2 Infection MESHD

    Authors: Jacob K Files; Sushma Boppana; Mildred D Perez; Sanghita Sarkar; Kelsey E Lowman; Kai Qin; Sarah Sterrett; Eric Carlin; Anju Bansal; Steffanie Sabbaj; Dustin M Long; Olaf Kutsch; James Kobie; Paul A Goepfert; Nathan Erdmann

    doi:10.1101/2020.07.30.20165175 Date: 2020-08-01 Source: medRxiv

    SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease MESHD pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, Ox40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (CD25, PD-L1 and TIGIT) remaining elevated in hospitalized and non-hospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation HP following SARS-CoV-2 infection MESHD. Changes in T-cell activation/exhaustion in non-hospitalized patients were found to positively correlate with age TRANS. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation HP following SARS-CoV-2 infection MESHD highlighting the need for additional studies investigating immune dysregulation HP in convalescent individuals.

    Estrogen and COVID-19 symptoms: associations in women from the COVID Symptom Study

    Authors: Ricardo Costeira; Karla A Lee; Benjamin Murray; Colette Christiansen; Juan Castillo-Fernandez; Mary Ni Lochlainn; Joan Capdevila Pujol; Iain Buchan; Louise C Kenny; Jonathan Wolf; Sebastien Ourselin; Claire Steves; Timothy Spector; Louise Newson; Jordana Bell

    doi:10.1101/2020.07.30.20164921 Date: 2020-08-01 Source: medRxiv

    Background: Men and older women have been shown to be at higher risk of adverse COVID-19 outcomes. Animal model studies of SARS-CoV and MERS suggest that the age TRANS and sex difference in COVID-19 symptom severity may be due to a protective effect of the female TRANS sex hormone estrogen. Females TRANS have shown an ability to mount a stronger immune response to a variety of viral infections MESHD because of more robust humoral and cellular immune responses. Objectives: We sought to determine whether COVID-19 positivity increases in women entering menopause. We also aimed to identify whether premenopausal women taking exogenous hormones in the form of the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT) have lower predicted rates of COVID-19, using our published symptom-based model. Design: The COVID Symptom Study developed by Kings College London and Zoe Global Limited was launched in the UK on 24th March 2020. It captured self-reported information related to COVID-19 symptoms. Data used for this study included records collected between 7th May - 15th June 2020. Main outcome measures: We investigated links between COVID-19 rates and 1) menopausal status, 2) COCP use and 3) HRT use, using symptom-based predicted COVID-19, tested COVID-19, and disease MESHD severity based on requirement for hospital attendance or respiratory support. Participants: Female TRANS users of the COVID Symptom Tracker Application in the UK, including 152,637 women for menopause status, 295,689 for COCP use, and 151,193 for HRT use. Analyses were adjusted for age TRANS, smoking and BMI. Results: Post-menopausal women aged TRANS 40-60 years had a higher rate of predicted COVID (P=0.003) and a corresponding range of symptoms, with consistent, but not significant trends observed for tested COVID-19 and disease MESHD severity. Women aged TRANS 18-45 years taking COCP had a significantly lower predicted COVID-19 (P=8.03E-05), with a reduction in hospital attendance (P=0.023). Post-menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P=2.22E-05) for HRT users alone. Conclusions: Our findings support a protective effect of estrogen on COVID-19, based on positive association between predicted COVID-19 and menopausal status, and a negative association with COCP use. HRT use was positively associated with COVID-19 symptoms; however, the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential comorbidities. Trial registration: The App Ethics has been approved by KCL ethics Committee REMAS ID 18210, review reference LRS-19/20-18210

    High rate of major drug-drug interactions of lopinavir-ritonavir for COVID-19 treatment

    Authors: Juan Macias; Ana Pinilla; Francisco A Lao-Dominguez; Anais Corma; Enrique Contreras-Macias; Alejandro Gonzalez-Serna; Antonio Gutierrez-Pizarraya; Marta Fernandez-Fuertes; Ramon Morillo-Verdugo; Marta Trigo; Luis M Real; Juan A Pineda

    doi:10.1101/2020.07.30.20165027 Date: 2020-08-01 Source: medRxiv

    The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease MESHD 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection MESHD treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI: 69%-85%) patients, and in 33 (26%, 95% CI: 19%-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p=0.010). After adjustment, only the Charlson index was independently associated with death MESHD [adjusted OR (95% CI) for Charlson index [≥]5: 85 (10-731), p <0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases MESHD Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p=0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age TRANS and comorbidities. Patients managed by the Infectious Diseases MESHD Unit had lower risk of major DDI.

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MeSH Disease
Human Phenotype

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