Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinN (1)


SARS-CoV-2 Proteins
    displaying 1 - 10 records in total 18
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    Suboptimal response to COVID-19 MESHD mRNA vaccines in hematologic malignancies MESHD patients

    Authors: Mounzer Agha; Maggie Blake; Charles Chilleo; Alan Wells; Ghady Haidar

    doi:10.1101/2021.04.06.21254949 Date: 2021-04-07 Source: medRxiv

    Studies describing SARS-CoV-2 immune responses following mRNA vaccination in hematology malignancy MESHD ( HM MESHD) patients are virtually non-existent. We measured SARS-CoV-2 IgG production in 67 HM MESHD patients who received 2 mRNA vaccine doses. We found that 46% of HM MESHD patients did not produce antibodies and were therefore vaccine non-responders. Patients with B-cell CLL were at a particularly high risk, as only 23% had detectable antibodies despite the fact that nearly 70% of these patients were not undergoing cancer MESHD therapy. HM MESHD patients should be counseled about the ongoing risk of COVID-19 MESHD despite vaccination. Routine measurement of post-vaccine antibodies in HM MESHD patients should be considered. Novel strategies are needed to prevent COVID-19 MESHD in these individuals.

    Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Dynamics Tracking

    Authors: Hui Chen; Zhao Li; Sheng Feng; Anni Wang; Melissa Richard-Greenblatt; Emily Hutson; Stefen Andrianus; Laurel Glaser; Kyle G Rodino; Jianing Qian; Dinesh Jayaraman; Ronald Collman; Abigail L Glascock; Frederic Bushman; Jae Seung Lee; Sara Cherry; Alejandra Fausto; Susan R Weiss; Hyun Koo; Patricia M Corby; Una ODoherty; Alfred L Garfall; Dan T Vogl; Edward A Stadtmauer; Ping Wang

    doi:10.1101/2021.03.17.21253847 Date: 2021-03-26 Source: medRxiv

    Background: Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples. Methods: We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients. Results: The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/mL (10.6 fM) recombinant nucleocapsid (N PROTEIN) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs, comparable to many rRT-PCR methods. The assay had high analytical specificity towards SARS-CoV-2. Compared to EUA-approved rRT-PCR methods, the Microbubbling Antigen Assay demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) in symptomatic individuals within 7 days of symptom onset and positive SARS-CoV-2 nucleic acid results, and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in symptomatic and asymptomatic individuals with negative nucleic acid results. Antigen positivity rate in NP swabs gradually decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity of the same samples. The computer vision and machine learning-based automatic microbubble image classifier could accurately identify positives and negatives, based on microbubble counts and sizes. Total microbubble volume, a potential marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Antigen was detected for longer periods of time in immunocompromised patients with hematologic malignancies MESHD, compared to immunocompetent individuals. Simultaneous detectable antigens and nucleic acids may indicate the presence of replicating viruses in patients with persistent infections. Conclusions: The Microbubbling SARS-CoV-2 Antigen Assay enables sensitive and specific detection of acute infections MESHD, and quantitation and tracking of antigen dynamics in different patient populations at various stages of infection. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.

    Interim results of the safety and immune-efficacy of 1 versus 2 doses of COVID-19 MESHD vaccine BNT162b2 for cancer MESHD patients in the context of the UK vaccine priority guidelines

    Authors: Leticia Monin-Aldama; Adam G. Laing; Miguel Munoz-Ruiz; Duncan R. McKenzie; Irene del Molino del Barrio; Thanussuyah Alaguthurai; Clara Domingo Vila; Thomas S. Hayday; Carl Graham; Jeffrey Seow; Sultan Abdul-Jawad; Shraddha Kamdar; Elizabeth Harvey-Jones; Rosalind Graham; Jack Cooper; Muhammad Khan; Jennifer Vidler; Helen Kakkassery; Shubhankar Sinha; Richard Davis; Liane Dupont; Isaac Francos Quijorna; Puay Lee; Josephine Eum; Maria Conde Poole; Magdalene Joseph; Daniel Davies; Yin Wu; Ana Montes; Mark Harries; Anne Rigg; James Spicer; Michael H. Malim; Paul Fields; Piers Patten; Francesca Di Rosa; Sophie Papa; Tim Tree; Katie Doores; Adrian C. Hayday; Sheeba Irshad

    doi:10.1101/2021.03.17.21253131 Date: 2021-03-17 Source: medRxiv

    BackgroundThe efficacy and safety profile of vaccines against severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) have not been definitively established in immunocompromised patient populations. Patients with a known cancer MESHD diagnosis were hitherto excluded from trials of the vaccines currently in clinical use. MethodsThis study presents data on the safety and immune efficacy of the BNT162b2 (Pfizer-BioNTech) vaccine in 54 healthy controls and 151 mostly elderly patients with solid and haematological malignancies MESHD, respectively, and compares results for patients who were boosted with BNT162b2 at 3 weeks versus those who were not. Immune efficacy was measured as antibody seroconversion, T cell responses, and neutralisation of SARS-CoV-2 Wuhan MESHD strain and of a variant of concern (VOC) (B.1.1.7). We also collected safety data for the BNT162b2 vaccine up to 5 weeks following first dose. FindingsThe vaccine was largely well tolerated. However, in contrast to its very high performance in healthy controls (>90% efficacious), immune efficacy of a single inoculum in solid cancer MESHD patients was strikingly low (below 40%) and very low in haematological cancer MESHD patients (below 15%). Of note, efficacy in solid cancer MESHD patients was greatly and rapidly increased by boosting at 21-days (95% within 2 weeks of boost). Too few haematological cancer MESHD patients were boosted for clear conclusions to be drawn. ConclusionsDelayed boosting potentially leaves most solid and haematological cancer MESHD patients wholly or partially unprotected, with implications for their own health; their environment and the evolution of VOC strains. Prompt boosting of solid cancer MESHD patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer MESHD patients. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSSome cancer MESHD patients have been shown to exhibit sustained immune dysregulation MESHD, inefficient seroconversion and prolonged viral shedding as a consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD. Consequently, their exclusion and, in particular, the exclusion of patients receiving systemic anti-cancer therapies, from the registry trials of the 5 approved COVID-19 MESHD vaccines raises questions about the efficacy and safety of SARS-CoV-2 vaccination in this patient population. In addition, whilst the change in the UKs dosing interval to 12-weeks aimed to maximise population coverage, it is unclear whether this strategy is appropriate for cancer MESHD patients and those on systemic anti- cancer MESHD therapies. Added value of this studyWe report that the RNA-based SARS-CoV-2 BNT162b2 vaccine administered in cancer MESHD patients was well tolerated, and we provide first insights into both antibody and T cell responses to the vaccine in an immunocompromised patient population. Implications of all the available evidenceIn cancer MESHD patients, one dose of 30ug of BNT162b2 yields poor vaccine efficacy, as measured by seroconversion rates, viral neutralisation capacity and T cell responses, at 3- and 5-weeks following the first inoculum. Patients with solid cancers MESHD exhibited a significantly greater response following a booster at 21-days. These data support prioritisation of cancer MESHD patients for an early (21-day) second dose of the BNT162b2 vaccine. Given the globally poor responses to vaccination in patients with haematological cancers MESHD, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of ring vaccination, and careful follow-up should be prioritised.

    Pre-existing and post- COVID-19 MESHD immune responses to SARS-CoV-2 in cancer MESHD patients

    Authors: Tatjana Bilich; Malte Roerden; Yacine Maringer; Annika Nelde; Jonas S. Heitmann; Marissa L. Dubbelaar; Andreas Peter; Sebastian Hörber; Jens Bauer; Jonas Rieth; Marcel Wacker; Fiamma Berner; Lukas Flatz; Stefanie Held; Peter Brossart; Melanie Märklin; Hans-Georg Rammensee; Helmut R. Salih; Juliane S. Walz

    doi:10.21203/ Date: 2021-02-12 Source: ResearchSquare

    Cancer MESHD patients, in particular patients with hematological malignancies MESHD, are at increased risk for critical illness upon COVID-19 MESHD. We here assessed antibody as well as CD4+ and CD8+ T cell responses in unexposed and SARS-CoV-2-infected cancer MESHD patients to characterize SARS-CoV MESHD‑2 immunity and to identify immunological parameters contributing to COVID-19 MESHD outcome. Unexposed patients with hematological malignancies MESHD presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses and signs of T cell exhaustion when compared to solid tumor MESHD patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 MESHD cancer MESHD patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer MESHD patients, and the latter associated with a severe course of COVID-19 MESHD. This identifies impaired SARS-CoV-2 MESHD T cell immunity as determinant for dismal outcome of COVID-19 MESHD in cancer MESHD patients.

    COVID-19 MESHD increases age- and sex-controlled 21-day fatality rates for patients with melanoma MESHD, hematologic malignancies MESHD, uterine cancer MESHD, or kidney cancer MESHD

    Authors: Haiquan Li; Edwin Alexander Baldwin; Xiang Zhang; Colleen Kenost; Wenting Luo; Elizabeth A Calhoun; Lingling An; Charles L Bennett; Yves A Lussier

    doi:10.1101/2021.02.06.21251099 Date: 2021-02-08 Source: medRxiv

    Introduction: Prior research has reported an increased risk of fatality for cancer MESHD patients, but most studies investigated the risk by comparing cancer MESHD patients to non-cancer MESHD patients among COVID-19 MESHD infections. Only a few studies have compared the impact of a COVID-19 MESHD infection to non-infection with matched cancer MESHD patients and types. Methods & Materials: We conducted survival analyses of 4,606 cancer MESHD patients with COVID-19 MESHD test results from March 16 to October 11, 2020 in UK Biobank and estimated the overall hazard ratio of fatality with and without COVID-19 MESHD infection. We also examined the hazard ratios of thirteen specific cancer MESHD types with at least 100 patients. Results: COVID-19 MESHD resulted in an overall hazard ratio of 7.76 (95% CI: [5.78, 10.40], p<10-10) by studying the survival rate of 4,606 cancer MESHD patients for 21-days after the tests. The hazard ratio was shown to vary among cancer MESHD type, with over a 10-fold increase in fatality rate (false discovery rate[≤]0.02) for melanoma MESHD, hematologic malignancies MESHD, uterine cancer MESHD, and kidney cancer MESHD using a stratified analysis on each of the cancer MESHD types. Although COVID-19 MESHD imposed a higher risk for localized cancers MESHD compared to distant metastasis ones, those of distant metastasis yielded higher fatality rates due to their multiplicative effects. Conclusion: The results highlight the importance of timely care for localized and hematological cancer MESHD patients and the necessity to vaccinate uninfected patients as soon as possible, particularly for the cancer MESHD types influenced most by COVID-19 MESHD.

    Convalescent Plasma and Improved Survival in Patients with Hematologic Malignancies MESHD and COVID-19 MESHD

    Authors: Michael A Thompson; Jeffrey P Henderson; Pankil K Shah; Samuel M Rubinstein; Michael J Joyner; Toni K Choueiri; Daniel B Flora; Elizabeth A Griffiths; Anthony P Gulati; Clara Hwang; Vadim S Koshkin; Esperanza B Papadopoulos; Elizabeth V Robilotti; Christopher T Su; Elizabeth M Wulff-Burchfield; Zoey Xie; Peter Paul Yu; Sanjay Mishra; Jonathon W Senefeld; Dimpy P Shah; Jeremy L Warner; - COVID-19 and Cancer Consortium

    doi:10.1101/2021.02.05.21250953 Date: 2021-02-05 Source: medRxiv

    Convalescent plasma may benefit immunocompromised individuals with COVID-19 MESHD, including those with hematologic malignancy MESHD. We evaluated the association of convalescent plasma treatment with 30-day mortality in hospitalized adults with hematologic malignancy MESHD and COVID-19 MESHD from a multi-institutional cohort. 143 treated patients were compared to 823 untreated controls. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (hazard ratio, 0.60; 95% CI, 0.37-0.97). This association remained significant after propensity-score matching (hazard ratio, 0.52; 95% CI, 0.29-0.92). These findings suggest a potential survival benefit in the administration of convalescent plasma to patients with hematologic malignancy MESHD and COVID-19 MESHD.

    Characteristics and outcomes of 118,155 COVID-19 MESHD individuals with a history of cancer MESHD in the United States and Spain

    Authors: Elena Roel Mrs; Andrea Pistillo Mr; Martina Recalde Mrs; Anthony G Sena Mr; Sergio Fernandez-Bertolin Mr; Maria Aragon Mrs; Diana Puente Dr; Waheed-Ul-Rahman Ahmed Mr; Heba Alghoul Mr; Osaid Alser Mr; Thamir M Alshammari Dr; Carlos Areia Mr; Clair Blacketer Mrs; William Carter Mr; Paula Casajust Mrs; Aedin C Culhane Dr; Dalia Dawoud Dr; Frank DeFalco Mr; Scott L Duvall Dr; Thomas Falconer Mr; Asieh Golozar Dr; Mengchun Gong Mr; Laura Hester Dr; George Hripcsak Mr; Eng Hooi Tan Dr; Hokyun Jeon Mr; Jitendra Jonnagaddala Dr; Lana YH Lai Dr; Kristine E Lynch Dr; Michael E Matheny Mr; Daniel R Morales Dr; Karthik Natarajan Dr; Fredrik Nyberg Dr; Anna Ostropolets Mrs; Jose D Posada Dr; Albert Prats-Uribe Mr; Christian G Reich Dr; Donna Rivera Mrs; Lisa M Schilling Mrs; Isabelle Soerjomataram Dr; Karishma Shah Mrs; Nigam Shah Dr; Yang Shen Mr; Matthew Spotnitz Mr; Vignesh Subbian Dr; Marc A Suchard Dr; Annalisa Trama Dr; Lin Zhang Dr; Ying Zhang Dr; Patrick Ryan Dr; Daniel Prieto-Alhambra Dr; Kristin Kostka Mrs; Talita Duarte-Salles Dr

    doi:10.1101/2021.01.12.21249672 Date: 2021-01-15 Source: medRxiv

    PurposeWe aimed to describe the demographics, cancer MESHD subtypes, comorbidities and outcomes of patients with a history of cancer MESHD with COVID-19 MESHD from March to June 2020. Secondly, we compared patients hospitalized with COVID-19 MESHD to patients diagnosed with COVID-19 MESHD and patients hospitalized with influenza. MethodsWe conducted a cohort study using eight routinely-collected healthcare databases from Spain and the US, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer MESHD were included: i) diagnosed with COVID-19 MESHD, ii) hospitalized with COVID-19 MESHD, and iii) hospitalized with influenza in 2017-2018. Patients were followed from index date to 30 days or death MESHD. We reported demographics, cancer MESHD subtypes, comorbidities, and 30-day outcomes. ResultsWe included 118,155 patients with a cancer MESHD history in the COVID-19 MESHD diagnosed and 41,939 in the COVID-19 MESHD hospitalized cohorts. The most frequent cancer MESHD subtypes were prostate and breast cancer MESHD (range: 5-19% and 1-14% in the diagnosed cohort, respectively). Hematological malignancies MESHD were also frequent, with non-Hodgkins lymphoma MESHD being among the 5 most common cancer MESHD subtypes in the diagnosed cohort. Overall, patients were more frequently aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 8% to 14% and from 18% to 26% in the diagnosed and hospitalized COVID-19 MESHD cohorts, respectively. Patients hospitalized with influenza (n=242,960) had a similar distribution of cancer MESHD subtypes, sex, age and comorbidities but lower occurrence of adverse events. ConclusionPatients with a history of cancer MESHD and COVID-19 MESHD have advanced age, multiple comorbidities, and a high occurence of COVID-19 MESHD-related events. Additionaly, hematological malignancies MESHD were frequent in these patients.This observational study provides epidemiologic characteristics that can inform clinical care and future etiological studies.

    Adaptive immunity to SARS-CoV-2 in cancer patients: The CAPTURE study

    Authors: Annika Fendler; Lewis Au; Laura Amanda Boos; Fiona Byrne; Scott Thomas Colville Shepherd; Ben Shum; Camille L Gerard; Barry Ward; Wenyi Xie; Maddalena Cerrone; Georgina H Cornish; Martin Pule; Leila Mekkaoui; Kevin Ng; Richard Stone; Camilla Gomes; Helen R Flynn; Ana Agua-Doce; Phillip Hobson; Simon Caidan; Mike Howell; Robert Goldstone; Mike Gavrielides; Emma Nye; Bram Snijders; James Macrae; Jerome Nicod; Adrian Hayday; Firza Gronthoud; Christina Messiou; David Cunningham; Ian Chau; Naureen Starling; Nicholas Turner; Jennifer Rusby; Liam Welsh; Nicholas van As; Robin Jones; Joanne Droney; Susana Banerjee; Kate Tatham; Shaman Jhanji; Olivia Curtis; Kevin Harrington; Shreerang Bhide; Tim Slattery; Yasir Khan; Zayd Tippu; Isla Leslie; Spyridon Gennatas; Alicia Okines; Alison Reid; Kate Young; Andrew Furness; Lisa Pickering; Sonia Ghandi; Steve Gamblin; Charles Swanton; Emma Nicholson; Sacheen Kumar; Nadia Yousaf; Katalin Andrea Wilkinson; Anthony Swerdlow; Ruth Harvey; George Kassiotis; Robert Wilkinson; James Larkin; Samra Turajlic

    doi:10.1101/2020.12.21.20248608 Date: 2020-12-23 Source: medRxiv

    There is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer MESHD patients and inform risk-reduction strategies and preserve cancer MESHD outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer MESHD patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer MESHD patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers MESHD and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. SARS-CoV-2-specific T-cell responses were detected, and CD4+ T-cell responses correlated with S1 antibody levels. Patients with haematological malignancies MESHD had impaired but partially compensated immune responses. Overall, cancer MESHD stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in the cancer MESHD population.

    Patterns of seroconversion for SARS-CoV2-IgG in patients with malignant disease MESHD and association with anti- cancer MESHD therapy

    Authors: Astha Thakkar; Kith Pradhan; Shawn Jindal; Zhu Cui; Bradley Rockwell; Akash Shah; Stuart Packer; R.Alejandro Sica; Joseph Sparano; D.Yitzhak Goldstein; Amit Verma; Sanjay Goel; Balazs Halmos

    doi:10.21203/ Date: 2020-12-12 Source: ResearchSquare

    Patients with cancer MESHD have been identified in several studies to be at high risk of developing severe COVID-19 MESHD; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer MESHD types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer MESHD that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one cancer MESHD patients underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies MESHD (82%), patients that received anti-CD-20 antibody therapy (59%), CAR-T/cellular therapy (33%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/ PD-L1 HGNC monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic MESHD

    Preclinical evaluation of Imatinib does not support its use as an antiviral drug against SARS-CoV-2

    Authors: Franck Touret; Jean-Selim Driouich; Maxime Cochin; Paul Remy Petit; Magali Gilles; Karine Barthelemy; Gregory Moureau; Denis Malvy; Caroline Solas; Xavier de Lamballerie; Antoine Nougairede; Katia Koelle; Thomas Friedrich; Klaus Hansen; Bo Jespersen; Marie Norsker Folke; Per Meden; Anne-Mette Hejl; Christian Warmberg; Michael Benros; Daniel Kondziella

    doi:10.1101/2020.11.17.386904 Date: 2020-11-17 Source: bioRxiv

    Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies MESHD. In this context, Imatinib was rapidly evaluated in clinical trials against Covid-19 MESHD. Here, we present the pre-clinical evaluation of Imatinib in multiple models. Our results indicated that Imatinib and another TKI, the Masitinib, exhibit an antiviral activity in VeroE6 cells. However, Imatinib was inactive in a reconstructed bronchial human airway epithelium model. In vivo, Imatinib therapy failed to impair SARS-CoV-2 replication in a golden Syrian hamster model despite high concentrations in plasma and in the lung. Overall, these results do not support the use of Imatinib and similar TKIs as antivirals in the treatment of Covid-19 MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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