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SARS-CoV-2 proteins

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    TCA-soluble blood serum proteins of COVID-19 MESHD patients as possible predictive markers for the disease severity

    Authors: Andrii Orfin; Tamila Alexanyan; Svitlana Tkachuk Svitlana Tkachuk; Anatoliy Starodub; Taras Luchyshyn; Andriy Sibirny; Serhiy Souchelnytskyi; Yuriy Kit

    doi:10.1101/2021.04.07.21255063 Date: 2021-04-09 Source: medRxiv

    Coronavirus disease MESHD 19 ( COVID-19 MESHD) is a global health crisis on a planetary scale. COVID-19 MESHD in many people has mild or moderate manifestation, although significant number of people, especially the elderly, suffer heavy from this illness, which often resulting in death MESHD. There are reports of similarities in immune response between COVID-19 MESHD and some autoimmune diseases MESHD. Earlier, we have demonstrated that fraction of TCA-soluble blood serum proteins containing a 48 kDA fragment of unconvential Myosin C1 have linked with development of multiple sclerosis MESHD and rheumatoid arthritis MESHD. Here we analyze use of these proteins in determining the severity of disease in COVID-19 MESHD patients. We found that blood serum of COVID-19 MESHD patients in acute disease MESHD manifestation contains, in contrast to healthy individuals, the TCA-soluble proteins with molecular masses 48 kDa and 76 kDA which were identified as a short form of unconventional myosin 1c and a modified form of human serum albumin HGNC.

    Humoral response to Pfizer mRNA vaccine against SARS CoV2, in patients with autoimmune inflammatory rheumatic diseases MESHD and the impact on the rheumatic disease MESHD activity

    Authors: Yolanda Braun-Moscovici; Marielle Kaplan; Doron Markovits; Samy Giryes; Kochava Toledano; Yonit Tavor; Katya Dolnikov; Alexandra Balbir-Gurman

    doi:10.1101/2021.04.02.21254493 Date: 2021-04-06 Source: medRxiv

    Abstract Background: The registration trials of mRNA vaccines against SARS CoV2 did not address patients with autoimmune inflammatory rheumatoid diseases MESHD ( AIRD MESHD). Aims: To assess the humoral response to mRNA vaccine against SARS CoV2, in AIRD MESHD patients treated with immunomodulating drugs and the impact on AIRD MESHD activity. Methods: Consecutive patients treated at the rheumatology institute who received their first SARS-CoV-2 (Pfizer) vaccine were recruited to the study, at their routine visit. The patients were invited for serology test 4-6 weeks after receiving the second dose of vaccine. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay Results: One hundred fifty-six consecutive patients (76% females) treated at a single rheumatology center (mean age (range) 59.1 (21-83) years), mean (range) disease duration 10.8 (1-55) years), were recruited to the study. Thirty-five percents of patients received conventional synthetic (cs)DMARDs only, 64% biological/targeted synthetic (b/ts) DMARDs, 34% received combined treatment with csDMARDs and b/tsDMARDs and 32% corticosteroids (mean dose(range) 5.8mg(2.5-20mg) prednisone). One hundred thirty-seven patients (88%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU MESHD/ml, range 58-29499). Nineteen (12%) patients had negative tests, 11/19 were treated with B cell depleting agents. The reported side effects of the vaccine were minor (muscle sore, headache MESHD, low grade fever MESHD). The rheumatic disease MESHD remained stable in all patients. Conclusions: The vast majority of AIRD MESHD patients developed a significant humoral response following the administration of the second dose of the Pfeizer mRNA vaccine against SARS CoV2 virus. Only minor side effects were reported and no apparent impact on AIRD MESHD activity was noted.

    Oral and Topical Vitamin D, Sunshine, and UVB Phototherapy Safely Control Psoriasis MESHD in Patients with Normal Pretreatment Serum 25-hydroxyvitamin D Concentrations: A Literature Review and Discussion of Health Implications

    Authors: Patrick J McCullough; William McCullough; Douglas Lehrer MD; Jeffrey Travers MD; Steven Repas

    id:10.20944/preprints202103.0061.v1 Date: 2021-03-02 Source: Preprints.org

    Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis MESHD, cure rickets and cure tuberculosis MESHD ( TB MESHD). Vitamin D also controlled asthma MESHD and rheumatoid arthritis MESHD with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis MESHD with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis MESHD—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis MESHD patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis MESHD patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis MESHD and other diseases strongly linked to vitamin D deficiency MESHD, including COVID-19 MESHD infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

    Phosphatases in Toll-Like receptor signaling: the unfairly forgotten

    Authors: Valérie Lannoy; Anthony Côté-Biron; Claude Asselin; Nathalie Rivard

    doi:10.21203/rs.3.rs-276071/v1 Date: 2021-02-25 Source: ResearchSquare

    Toll-like receptors (TLRs) are a highly conserved family of pattern recognition receptors that play a critical role in innate immunity. They evolved before the adaptive immune system, making them an indispensable first line of defense. TLRs are highly studied, and understanding their signaling is critical for developing treatments for autoimmune and chronic inflammatory disorders MESHD. But while kinases and E3 ubiquitin ligases are widely known TLR signaling effectors, another pathway is less well-characterized. Phosphatases are important regulators of TLR signaling through NF-κB, type I interferons, and mitogen-activated protein kinases. TLRs activate several pathways through phosphorylation, and thus an interplay must exist between kinases and phosphatases to tightly regulate TLR signaling. Many phosphatases have roles in TLR signaling, including classical protein tyrosine phosphatases and serine/threonine phosphatases. TLR regulation by phosphatases is implicated in many human diseases, including atherosclerosis MESHD, autoimmune rheumatoid arthritis MESHD, and neuroinflammatory disorders MESHD. Finally, a role may exist for TLR signaling and phosphatases – in particular those associated with TLR4 HGNC and TLR7 HGNC - in patient responses to coronaviruses such as COVID-19 MESHD. While many aspects of the TLR-associated kinase-phosphatase network remain to be uncovered phosphatases could represent novel therapeutic targets to control pathogenic TLR signaling.

    Emerging Trends and Research on Hydroxychloroquine Treatment in Diseases From 1991 to 2020

    Authors: Lingjun Kong; Yanan Wang; Wen Zhang

    doi:10.21203/rs.3.rs-227203/v1 Date: 2021-02-09 Source: ResearchSquare

    Background Recently, hydroxychloroquine (HCQ) has become a controversial point for whether it functioned in the treatment of coronavirus disease 2019 MESHD ( COVID-19 MESHD). The aim of this paper is mainly to explore the international frontiers and trends of HCQ clinical treatment in recent 30 years by bibliometric analysis. Besides, the research prospects and hotspots of HCQ therapy in COVID-19 MESHD have further been investigated quantitatively and qualitatively.         Methods Publications related to HCQ treatment research from 1991 to 2020 and HCQ studies on COVID-19 MESHD from the end of 2019 till now were both obtained from Web of Science Core Collection (WOSCC). Bibliometric analyses were primarily performed via Citespace 5.7.R1 to identify the trends of cooperation between countries and institutions, the research hotspots and frontiers. Results A total of 2642 articles and reviews on HCQ treatment in diseases were included, indicating an increase in number of publications since 2013. The United States was the largest scientific output country, followed by France and China. Trending keywords analysis indicated the hotspot research of HCQ treatment referred to “ rheumatoid arthriti MESHD,” “chloroquine”, “ systemic lupus erythematosus MESHD” and “ COVID-19 MESHD”. Moreover, 568 publications on the study of HCQ in COVID-19 MESHD therapy were also gathered from WOSCC, which showed the USA ranked first again in the world for its most publications. Further, Aix Marseille University, Univ Tehran Med Sci, Univ Paris, Harvard Med Sch and Huazhong Univ Sci & Technol were the five leading institutions in research of HCQ treatment in COVID-19 MESHD.Conclusion Visualization knowledge map analysis regarding HCQ clinical treatment over the past 30 years suggested scientists are mainly focused on the autoimmune diseases MESHD therapy by HCQ. HCQ research have significantly increased since the end of 2019. Obviously, studies on HCQ in COVID-19 MESHD may lead the future direction of this field in recent years. The present study provides valuable information on HCQ research through bibliometric analysis so that researchers may identify new perspective and fields.

    Practices and Behaviors During the COVID-19 Pandemic MESHD in Patients With Rheumatoid Arthritis MESHD Who Attended Previously to An Educational Program. A Cross-Sectional Study

    Authors: Pedro Santos-Moreno; Diana Buitrago-Garcia; Fernando Rodriguez-Florido; Guillermo Sánchez-Vanegas

    doi:10.21203/rs.3.rs-135024/v1 Date: 2020-12-23 Source: ResearchSquare

    Background: To describe the practices and behaviors of patients with rheumatoid arthritis MESHD ( RA MESHD) who attend to a face-to-face education program, during the quarantine of the COVID-19 pandemic MESHD. Methods: Patients who attended previously a face-to-face education program, responded to a telephonic survey in July 2020. The survey included questions about their practices related to the COVID-19 pandemic MESHD, SARS-Cov-2 symptoms, adherence to rheumatoid arthritis MESHD treatment, virtual rheumatology consultancy compliance and, the influence of news on their adherence. Results: A total of 260 patients participated in a survey. In July 2020 88% of patients had accessed a telemedicine-based and 12% a face-to-face rheumatology consultation. 3.5% of patients reported having been less adherent to pharmacological therapy due to information received through media or social networks. In general patients had been compliant with COVID-19 MESHD prevention recommendations.  Only one patient was positive for SARS-CoV-2 and reported only flu symptoms without any complications. Patients highlighted the necessity to have information and education about the relationship between rheumatoid arthritis MESHD, its treatment, and COVID-19 MESHD. Conclusions: An educational program is a helpful tool to maintain high adherence rates to the RA MESHD treatment despite of the new challenges associated to the pandemic; Patient-centered education programs should continue to address the patient's concerns and beliefs about their disease and COVID-19 MESHD.

    Characteristics, outcomes, and mortality amongst 133,589 patients with prevalent autoimmune diseases diagnosed with, and 48,418 hospitalised for COVID-19 MESHD: a multinational distributed network cohort analysis

    Authors: Eng Hooi Tan; Anthony G. Sena; Albert Prats-Uribe; Seng Chan You; Waheed-Ul-Rahman Ahmed; Kristin Kostka; Christian Reich; Scott L. Duvall; Kristine E. Lynch; Michael E. Matheny; Talita Duarte-Salles; Sergio Fernandez Bertolin; George Hripcsak; Karthik Natarajan; Thomas Falconer; Matthew Spotnitz; Anna Ostropolets; Clair Blacketer; Thamir M Alshammari; Heba Alghoul; Osaid Alser; Jennifer C.E. Lane; Dalia M Dawoud; Karishma Shah; Yue Yang; Lin Zhang; Carlos Areia; Asieh Golozar; Martina Recalde; Paula Casajust; Jitendra Jonnagaddala; Vignesh Subbian; David Vizcaya; Lana YH Lai; Fredrik Nyberg; Daniel R. Morales; Jose D. Posada; Nigam H. Shah; Mengchun Gong; Arani Vivekanantham; Aaron Abend; Evan P Minty; Marc A. Suchard; Peter Rijnbeek; Patrick B Ryan; Daniel Prieto-Alhambra

    doi:10.1101/2020.11.24.20236802 Date: 2020-11-27 Source: medRxiv

    Objective: Patients with autoimmune diseases MESHD were advised to shield to avoid COVID-19 MESHD, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 MESHD among patients with prevalent autoimmune diseases MESHD, and compared outcomes after hospital admissions among similar patients with seasonal influenza. Design: Multinational network cohort study Setting: Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment ( HIRA HGNC) (South Korea). Participants: All patients with prevalent autoimmune diseases MESHD, diagnosed and/or hospitalised between January and June 2020 with COVID-19 MESHD, and similar patients hospitalised with influenza in 2017-2018 were included. Main outcome measures: 30-day complications during hospitalisation and death Results: We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 MESHD with prevalent autoimmune diseases MESHD. The majority of participants were female (60.5% to 65.9%) and aged [≥]50 years. The most prevalent autoimmune conditions were psoriasis MESHD (3.5 to 32.5%), rheumatoid arthritis MESHD (3.9 to 18.9%), and vasculitis MESHD (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes MESHD was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis MESHD in HIRA HGNC (18.9%), and psoriasis MESHD in SIDIAP-H (26.4%). Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 MESHD had more respiratory complications including pneumonia MESHD and acute respiratory distress syndrome MESHD, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). Conclusions: Patients with autoimmune diseases MESHD had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19 MESHD. Compared to influenza, COVID-19 MESHD is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 MESHD patients with autoimmune diseases MESHD.

    Detection of anti-SARS-CoV-2 antibodies in patients with rheumatoid arthritis.

    Authors: Shomi Oka; Takashi Higuchi; Hiroshi Furukawa; Kota Shimada; Atsushi Hashimoto; Toshihiro Matsui; Shigeto Tohma

    doi:10.21203/rs.3.rs-112294/v1 Date: 2020-11-20 Source: ResearchSquare

    Objectives: The severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) causes coronavirus disease 2019 MESHD ( COVID-19 MESHD) and the outbreak of COVID-19 MESHD was reported in December 2019 in Wuhan, China. Serological test is conducted to discriminate prior infection of SARS-CoV-2 MESHD. The influence of auto-antibodies on the results of anti-SARS-CoV-2 antibodies was investigated in a few studies. Here, we investigated whether the results of anti-SARS-CoV-2 antibodies would be modified in patients with rheumatoid arthritis MESHD ( RA MESHD). Methods: Patients with RA MESHD were recruited at Sagamihara National Hospital from July 2014 to October 2015 (n=38, 2014 cohort) and at Tokyo National Hospital from June to October 2020 (n=93, 2020 cohort). Anti-SARS-CoV-2 antibodies were measured in collected sera from these RA MESHD patients by electrochemiluminescence immunoassay (ECLIA) or immunochromatographic assay (ICA). Results: Anti-SARS-CoV-2 antibodies were not detected in all the samples form RA MESHD patients in both cohorts by the ECLIA. However, anti-SARS-CoV-2 antibodies were detected in the serum samples from three (7.9%) in 2014 cohort by the ICA and fifteen (16.1%) in 2020 cohort. The IgM rheumatoid MESHD factor levels were increased in RA MESHD patients with IgM anti-SARS-CoV-2 antibodies by ICA compared with RA MESHD without any anti-SARS-CoV-2 antibodies (mean ± standard deviation [IU/ml], 1223.0 ± 1308.7 vs. 503.6 ± 1947.2, P=0.0101). The levels of IgG rheumatoid MESHD factor were also upregulated in RA MESHD patients with IgM anti-SARS-CoV-2 antibodies by ICA (4.0 ± 0.7 vs. 2.4 ± 0.9, P=0.0013). Conclusion: The results of IgM anti-SARS-CoV-2 antibody by the ICA would be modified by IgM or IgG rheumatoid MESHD factors in RA MESHD patients.

    SARS-CoV-2 serological tests can generate false positive results for samples from patients with chronic inflammatory diseases

    Authors: Nastya Kharlamova; Nicky Dunn; Sahl K Bedri; Svante Jerling; Malin Almgren; Francesca Faustini; Iva Gunnarsson; Johan Ronnelid; Rille Pullerits; Inger Gjertsson; Karin Lundberg; Anna Manberg; Elisa Pin; Peter Nilsson; Sophia Hober; Katharina Fink; Anna Fogdell-Hahn

    doi:10.1101/2020.11.13.20231076 Date: 2020-11-13 Source: medRxiv

    Objectives: Patients with chronic inflammatory diseases MESHD are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless the tests give false positive results. The aim of this study was to evaluate the specificity of SARS-Cov-2 serological assays with samples from patients with chronic inflammatory diseases collected before April 2019, thus defined as negative. Methods: Samples from patients with multiple sclerosis MESHD ( MS MESHD, n=10), rheumatoid arthritis MESHD ( RA MESHD, n=47) with or without rheumatoid MESHD factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti- CCP2 HGNC) and RF +/- systemic lupus erythematosus MESHD ( SLE MESHD, n=10), were tested with 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed multiplex bead-based assay. Results: Six LFA and the in-house IgG assay gave the correct negative results for all samples. However, the majority of assays (n=13), gave false positive signal with samples from patients with RA MESHD and SLE MESHD. This was most notable in RF positive RA MESHD samples. MS MESHD samples did not give any false positive in any of the assays. Conclusion: The majority of the verified serological assays were sensitive to interfering antibodies in samples from patients with chronic inflammatory diseases MESHD and therefore may have poor specificity in this context. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.

    CD127 HGNC imprints functional heterogeneity to diversify monocyte responses in human inflammatory diseases

    Authors: Bin Zhang; Yuan Zhang; Lei Xiong; Yuzhe Li; Yunliang Zhang; Jiuliang Zhao; Hui Jiang; Can Li; Yunqi Liu; Xindong Liu; Haofei Liu; Yi-Fang Ping; Qiangfeng Cliff Zhang; Xiu-Wu Bian; Yan Zhao; Xiaoyu Hu; Simone Schuller; Andres Moreira - Soto; Amanda Vicente - Santos; Eugenia Corrales - Aguilar; Nicolas Ruggli; Gergely Tekes; Veronika von Messling; Bevan Sawatsky; Volker Thiel; Ronald Dijkman

    doi:10.1101/2020.11.10.376277 Date: 2020-11-10 Source: bioRxiv

    Studies on human monocytes historically focused on characterization of bulk responses, whereas functional heterogeneity is largely unknown. Here, we identified an inducible population of CD127 HGNC-expressing human monocytes under inflammatory conditions and named the subset M127. M127 is nearly absent in healthy individuals yet abundantly present in patients with infectious and inflammatory conditions such as COVID-19 MESHD and rheumatoid arthritis MESHD. Multiple genomic and functional approaches revealed unique gene signatures of M127 and unified anti-inflammatory properties imposed by the CD127 HGNC-STAT5 axis. M127 expansion correlated with mild COVID-19 MESHD disease outcomes. Thereby, we phenotypically and molecularly characterized a human monocyte subset marked by CD127 HGNC that retained anti-inflammatory properties within the pro-inflammatory environments, uncovering remarkable functional diversity among monocytes and signifying M127 as a potential therapeutic target for human inflammatory disorders MESHD.

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