Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 and other diseases MESHD with tissue inflammation MESHD

    Authors: Lorien Shakib; Sara Shanaj; Aparna Nathan; - Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus; Laura T. Donlin

    doi:10.1101/2020.08.05.238360 Date: 2020-08-05 Source: bioRxiv

    Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases MESHD with established therapies may help nominate immunomodulatory therapies. Using an integrative strategy, we built a reference by meta-analyzing > 300,000 immune cells from COVID-19 and 5 inflammatory diseases MESHD including rheumatoid arthritis MESHD rheumatoid arthritis HP (RA), Crohns disease MESHD (CD), ulcerative colitis MESHD ulcerative colitis HP (UC), lupus, and interstitial lung disease MESHD. Our cross- disease MESHD analysis revealed that an FCN1+ inflammatory macrophage state is common to COVID-19 bronchoalveolar lavage samples, RA synovium, CD ileum, and UC colon. We also observed that a CXCL10+ CCL2+ inflammatory macrophage state is abundant in severe COVID-19, inflamed CD and RA, and expresses inflammatory genes such as GBP1, STAT1, and IL1B. We found that the CXCL10+ CCL2+ macrophages are transcriptionally similar to blood SERO-derived macrophages stimulated with TNF- and IFN-{gamma} ex vivo. Our findings suggest that IFN-{gamma}, alongside TNF-, might be a key driver of this abundant inflammatory macrophage phenotype in severe COVID-19 and other inflammatory diseases MESHD, which may be targeted by existing immunomodulatory therapies.

    Frequency and severity of Covid-19 in patients treated with biological Disease MESHD Modifying Anti-Rheumatic Drugs (bDMARDs) for inflammatory rheumatic disease MESHD. A case-control study

    Authors: Dr. Anne LOHSE; Dr. Marie BOSSERT; Dr. Ana-Maria BOZGAN; Charlotte BOURGOIN; Dr. Aline CHARPENTIER; Dr. Cerise GUILLOCHON; Dr. Julie KESSLER; Dr. Jean-Charles BALBLANC; Dr. Thierry CONROZIER

    doi:10.21203/rs.3.rs-50490/v1 Date: 2020-07-29 Source: ResearchSquare

    The aim of the study was to assess the impact (frequency and severity) of Covid-19 on patients treated with biological Disease MESHD Modifying Anti-Rheumatic Drugs (bDMARDs) for inflammatory rheumatic disease MESHD and to compare it to a control group consisting of patients with musculoskeletal conditions not treated with bDMARDs.Patients and methods:A case control study in 200 outpatients with musculoskeletal conditions. 100 consecutive patients who have been treated with bDMARDs and 100 other consecutive patients who did not take bDMARDs were asked to complete a 15-item standardized questionnaire regarding demographic data. The following information was recorded: gender TRANS, age TRANS, weight, height, body mass index, professional activity, family status, total number of children TRANS and number of children TRANS under 18, rheumatic disease MESHD diagnosis, current treatment for rheumatism, type of containment, close contact TRANS with Covid-19 patients, Covid-19 symptoms, Covid-19 test result and hospitalization for Covid-19.Results:bDMARD patients mostly suffered from rheumatoid arthritis MESHD rheumatoid arthritis HP, or RA, (47%) and ankylosing spondylitis MESHD (42%). The most prescribed bDMARDs were TNFα inhibitors (57%), IL-6 blockers (12%) and JAK inhibitors (11%). The mean duration of the current biological treatment was 38.6 months. Patients from the control group were suffering chiefly from osteoarthritis MESHD osteoarthritis HP (45%) and RA (21%). Compared to the control group, patients treated with bDMARDs were 10 years younger (p<0.001), fewer were retired (56% versus 31%) and more were on sick or incapacity leave (6% versus 18%). During lockdown, they were more likely to be working from home or working short term (27% versus 9%). 18 patients from the bDMARDs group stopped biological treatment: one because of Covid-19 evidenced by PCR, 11 because of symptoms suggesting Covid- 19 and only six from fear of contracting the disease MESHD. 12 patients, including the one Sars-CoV-2 +, resumed their treatment after a few weeks of interruption. There was no severe Covid-19 infection MESHD in the bDMARDs group. Among the three patients from the control group who had contracted Covid-19, one developed a very severe disease MESHD.Conclusion :This case-control study did not show an increase in the frequency or severity of Covid-19 in subjects suffering from chronic inflammatory rheumatism treated with biotherapies. Larger-scale studies are necessary before affirming that biologics do not expose patients to an increased risk of disease MESHD and complications.

    C-C chemokine receptor type 5 links COVID-19, Rheumatoid arthritis MESHD Rheumatoid arthritis HP, and Hydroxychloroquine

    Authors: Mahmood Yaseen Hachim; Ibrahim Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi

    doi:10.21203/rs.3.rs-48001/v1 Date: 2020-07-23 Source: ResearchSquare

    Background: Patients with rheumatoid arthritis MESHD rheumatoid arthritis HP (RA) represent one of the fragile patient groups that might be susceptible to coronavirus disease MESHD -19 (COVID-19) and its severe form. On the other side, RA patients have been found not to have an increased risk of COVID19 infection MESHD. Moreover, some of the Disease MESHD-Modifying Anti-Rheumatic Drugs (DMARDS)  commonly used to treat rheumatic diseases MESHD like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases MESHD at the molecular side Methods: We used the in silico approach to investigate the transcriptomic profile of RA synovium compared to osteoarthritis MESHD osteoarthritis HP and healthy controls to identify RA specific molecular pathways shared with that of severe acute respiratory syndrome MESHD-corona virus-2 (SARS-COV-2) infected lung tissue. Results: Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases MESHD; RA and COVID-19. Moreover, our results also highlighted that HCQ might interfere with the COVID-19 infection MESHD through its ability to upregulate specific immune cell populations like activated natural killer (NK) cells, besides blocking CCR5 rich immune cell recruitment to the SARS-COV-2 infected lungs Conclusion: Our results might explain some of the reports that showed beneficial effects and indicate the need for proper patients stratification on their immune profile before selecting the therapeutic protocol or clinical trial enrollment. Keyword COVID-19, SARS-COV-2, Hydroxychloroquine, rheumatoid arthritis MESHD rheumatoid arthritis HP

    The effect of hydroxychloroquine against SARS-CoV-2 infection MESHD in rheumatoid arthritis MESHD rheumatoid arthritis HP patients

    Authors: Okan Küçükakkaş; Teoman Aydın

    doi:10.21203/rs.3.rs-43812/v1 Date: 2020-07-15 Source: ResearchSquare

    INTRODUCTION: The effectiveness of hydroxychloroquine in SARS-CoV-2 prophylaxis and treatment is still controversial. In this study, our aim is to investigate the potential effects of hydroxychloroquine therapy on patients with diagnosed with rheumatoid arthritis MESHD rheumatoid arthritis HP and a confirmed SARS-CoV-2 infection MESHD.METHOD: We included patients who were followed up with a diagnosis of rheumatoid arthritis MESHD rheumatoid arthritis HP and whose SARS-CoV-2 infection MESHD infection was confirmed TRANS was confirmed. The patients were divided into two groups as those who previously used hydroxychloroquine and those who did not, and were compared in terms of clinical and laboratory data.RESULTS: Our study included 17 patients with adequate data (2 males TRANS, 15 females TRANS). The mean age TRANS of the patients was 57.2 ± 11.6 years. 7 (41.2%) patients were receiving hydroxychloroquine regularly for the last 6 months. When the effect of hydroxychloroquine on clinical and laboratory parameters of patients was examined, there was no significant difference between the groups of patients using and not using hydroxychloroquine. The patients using and not using hydroxychloroquine were compared for the presence of typical SARS-CoV-2 infection MESHD findings on computed tomography images, admission to the hospital and intensive care. No significant differences were observed between these two groups.CONCLUSIONS: Many studies on the effectiveness of hydroxychloroquine use in SARS-CoV-2 infection MESHD are still ongoing. Due to its importance in rheumatology practice, it is very important to clarify the position of hydroxychloroquine in SARS-CoV-2 therapy. Our findings suggest that having previously used hydroxychloroquine does not have any negative or positive effect on the infection MESHD.

    Successful management of a case of SARS‐CoV‐2 infection MESHD in an advanced Rheumatoid Arthritis MESHD Rheumatoid Arthritis HP patient by dose reduction of immunosuppressive medication

    Authors: Ahmadreza Bazmjoo; Mohammad Aref Bagherzadeh; Farida Farahmandpoor; Rahim Raoofi; Amir Abdoli

    doi:10.21203/rs.3.rs-40731/v1 Date: 2020-07-08 Source: ResearchSquare

    Rheumatoid Arthritis MESHD Rheumatoid Arthritis HP (RA) patients usually managed with immunosuppressive agents and they are at a higher risk of infections TRANS risk of infections TRANS infections MESHD. There are limited data regarding RA patients with COVID-19. This article reports a RA patient with an acute SARS‐CoV‐2 infection MESHD that successfully managed by dose reduction of immunosuppressive medication.

    C-C Chemokine Receptor Type 5 Links COVID-19, Rheumatoid Arthritis MESHD Rheumatoid Arthritis HP, and Hydroxychloroquine

    Authors: Mahmood Yaseen HACHIM; Ibrahim Y. Hachim; Kashif Naeem; Haifa Hannawi; Issa Al Salmi; Suad Hannawi

    doi:10.21203/rs.3.rs-37404/v1 Date: 2020-06-22 Source: ResearchSquare

    Background: Patients with rheumatoid arthritis MESHD rheumatoid arthritis HP (RA) represent one of the fragile patient groups that might be susceptible to coronavirus disease MESHD -19 (COVID-19) and its severe form. On the other side, RA patients have been found not to have an increased risk of COVID19 infection MESHD. Moreover, some of the Disease MESHD-Modifying Anti-Rheumatic Drugs (DMARDS)  commonly used to treat rheumatic diseases MESHD like Hydroxychloroquine (HCQ) were proposed as a potential therapy for COVID19 with a lack of full understanding of their molecular mechanisms. This highlights the need for the discovery of common pathways that may link both diseases MESHD at the molecular side Methods: We used the in silico approach to investigate the transcriptomic profile of RA synovium compared to osteoarthritis MESHD osteoarthritis HP and healthy controls to identify RA specific molecular pathways shared with that of severe acute respiratory syndrome MESHD-corona virus-2 (SARS-COV-2) infected lung tissue. Results: Our results showed upregulation of chemotactic factors, including CCL4, CCL8, and CCL11, that all shared CCR5 as their receptor, as a common derangement observed in both diseases MESHD; RA and COVID-19. Moreover, our results also highlighted that HCQ might interfere with the COVID-19 infection MESHD through its ability to upregulate specific immune cell populations like activated natural killer (NK) cells, besides blocking CCR5 rich immune cell recruitment to the SARS-COV-2 infected lungs Conclusion: Our results might explain some of the reports that showed beneficial effects and indicate the need for proper patients stratification on their immune profile before selecting the therapeutic protocol or clinical trial enrollment. Keyword COVID-19, SARS-COV-2, Hydroxychloroquine, rheumatoid arthritis MESHD rheumatoid arthritis HP

    An Anti-CD6 Monoclonal Antibody SERO (Itolizumab) Reduces Circulating IL-6 in Severe Covid-19 Elderly TRANS Patients

    Authors: Danay Saavedra; Ana Laura Añé-Kourí; Naivy Sánchez; Lázaro Manuel Filgueira; Julio Betancourt; Carlos Herrera; Leniel Manso; Elibet Chavez; Armando Caballero; Carlos Hidalgo; Geydi Lorenzo; Meylan Cepeda; Carmen Valenzuela; Mayra Ramos; Kalet León; Zaima Mazorra; Tania Crombet

    doi:10.21203/rs.3.rs-32335/v1 Date: 2020-05-29 Source: ResearchSquare

    Background: Since the COVID-19 outbreak an unprecedented challenge for healthcare systems around the world has been placed. In Cuba, the first case of COVID-19 was reported on March 11. Elderly TRANS with multiple comorbidities have been the most risky population. Although most patients present a mild to moderate disease MESHD, some have developed severe symptoms. One of the possible mechanisms underlying rapid disease progression MESHD is a cytokine storm, in which interleukin (IL) -6 seems to be a major mediator. Itolizumabis a humanized recombinant anti-CD6 monoclonal antibody SERO(MAb), with the ability of reducingserum interferon gamma(INF-γ), tumournecrosis factor alpha(TNFα) and IL-6. Based on these previous results in patients with psoriasis MESHD and rheumatoid arthritis MESHD rheumatoid arthritis HP, an expanded access clinical trial was approved by the Cuban regulatory agency for COVID-19 critically, severely and moderately ill patients. Results: We show here a short kinetic of IL-6 serum SERO concentration in the first 24 COVID-19 patients treated with itolizumab. Most of patients were elderly TRANS with multiple comorbidities.We found that with one itolizumabdose, the circulating IL-6 decreased in critically and severely ill patients, whereas in moderately ill patients the values didn’trise as compared to theirlow baseline levels.Conclusion: These findings suggest that itolizumabcould be an attractive therapeutic option to decrease the negative outcome of the cytokine storm in COVID-19 patients.Trial registration: CECMED IIC RD-EC 179, RPCEC00000311. Registered 4May 2020 - Retrospectively registered, http://rpcec.sld.cu/ensayos/RPCEC00000311-Sp or http://rpcec.sld.cu/trials/RPCEC00000311-En

    Blocking of the CD80/86 axis as a therapeutic approach to prevent progression to more severe forms of COVID-19

    Authors: Antonio Julià; Irene Bonafonte; Antonio Gómez; María López-Lasanta; Mireia López-Corbeto; Sergio H. Martínez-Mateu; Jordi Lladós; Iván Rodríguez-Nunez; Richard M. Myers; Sara Marsal

    id:2005.10055v1 Date: 2020-05-20 Source: arXiv

    In its more severe forms, COVID-19 progresses towards an excessive immune response, leading to the systemic overexpression of proinflammatory cytokines like IL6, mostly from the infected lungs. This cytokine storm can cause multiple organ damage and death MESHD. Consequently, there is a pressing need to identify therapies to treat and prevent severe symptoms during COVID-19. Based on previous clinical evidence, we hypothesized that inhibiting T cell co-stimulation by blocking CD80/86 could be an effective therapeutic strategy against progression to severe proinflammatory states. To support this hypothesis, we performed an analysis integrating blood SERO transcriptional data we generated from rheumatoid arthritis MESHD rheumatoid arthritis HP patients treated with abatacept -- a CD80/86 co-stimulation inhibitor -- with the pathological features associated with COVID-19, particularly in its more severe forms. We have found that many of the biological processes that have been consistently associated with COVID-19 pathology are reversed by CD80/86 co-stimulation inhibition, including the downregulation of IL6 production. Also, analysis of previous transcriptional data from blood SERO of SARS-CoV-infected patients showed that the response to abatacept has a very high level of antagonism to that elicited by COVID-19. Finally, analyzing a recent single cell RNA-seq dataset from bronchoalveolar lavage fluid cells from COVID-19 patients, we found a significant correlation along the main elements of the C80/86 axis: CD86+/80+ antigen presenting cells, activated CD4+ T cells and IL6 production. Our in-silico study provides additional support to the hypothesis that blocking of the CD80/CD86 signaling axis may be protective of the excessive proinflammatory state associated with COVID-19 in the lungs.

    Network theoretic analysis of JAK/STAT pathway and extrapolation to drugs and viruses including COVID-19

    Authors: Arindam Banerjee; Rudra Prosad Goswami; Moumita Chatterjee

    doi:10.21203/rs.3.rs-25845/v1 Date: 2020-04-28 Source: ResearchSquare

    Whenever some phenomenon can be represented as a graph or a network it seems pertinent to explore how much the mathematical properties of that network impact the phenomenon. In this study we explore the same philosophy in the context of immunology. Our objective was to assess the correlation of “size” (number of edges and minimum vertex cover) of the JAK/STAT network with treatment effect in rheumatoid arthritis MESHD rheumatoid arthritis HP (RA), phenotype of viral infection MESHD and effect of immunosuppressive agents on a system infected with the coronavirus. We extracted the JAK/STAT pathway from Kyoto Encyclopedia of Genes and Genomes (KEGG, hsa04630). The effects of the following drugs, and their combinations, commonly used in RA were tested: methotrexate, prednisolone, rituximab, tocilizumab, tofacitinib and baricitinib. Following viral systems were also tested for their ability to evade the JAK/STAT pathway: Measles MESHD, Influenza A, West Nile virus, Japanese B virus, Yellow Fever MESHD Fever HP virus, respiratory syncytial virus, Kaposi’s sarcoma MESHD sarcoma HP virus, Hepatitis B MESHD Hepatitis HP and C virus, cytomegalovirus, Hendra and Nipah virus and Coronavirus. Good correlation of edges and minimum vertex cover with clinical efficacy were observed (for edge, rho= -0.815, R2= 0.676, p=0.007, for vertex cover rho= -0.793, R2= 0.635, p=0.011). In the viral systems both edges and vertex cover were associated with acuteness of viral infections MESHD. In the JAK/STAT system already infected with coronavirus, maximum reduction in size was achieved with baricitinib. To conclude, algebraic and combinatorial invariant of a network may explain its biological behaviour. At least theoretically, baricitinib may be an attractive target for treatment of coronavirus infection MESHD.

    Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients

    Authors: Justin Stebbing; Venkatesh Krishnan; Stephanie de Bono; Silvia Ottaviani; Giacomo Casalini; Peter J. Richardson; Vanessa Monteil; Volker M. Lauschke; Ali Mirazimi; Jorge A. Ross Terres; Brian J. Nickoloff; Richard E. Higgs; Guilherme Rocha; Nicole L. Byers; Douglas E. Schlichting; Anabela Cardoso; Mario Corbellino

    doi:10.21203/rs.3.rs-23195/v1 Date: 2020-04-15 Source: ResearchSquare

    Baricitinib, is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis MESHD rheumatoid arthritis HP (RA) that was independently hypothesized, using artificial intelligence (AI)-algorithms, to be useful for the treatment of COVID-19 infection MESHD via a proposed anti-cytokine effects and as an inhibitor of host cell viral propagation1,2. We validated the AI-predicted biochemical inhibitory effects of baricitinib on human numb-associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids, which express hAAK1 and hGAK. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID-19 infection MESHD. In a case series of patients with bilateral COVID-19 pneumonia MESHD pneumonia HP, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS-CoV-2 viral load, inflammatory markers, and IL-6 levels. This represents an important example of an AI-predicted treatment showing scientific and clinical promise during a global health crisis. Collectively, these data support further evaluation of the AI-derived hypothesis on anti-cytokine and anti-viral activity and supports its assessment in randomized trials in hospitalized COVID-19 patients.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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