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    Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases MESHD

    Authors: Claire Deakin; Georgina Cornish; Kevin Ng; Nikhil Faulkner; William Bolland; Veera Panova; Joshua Hope; Annachiara Rosa; Ruth Harvey; Saira Hussain; Chris Earl; Bethany Jebson; Merry Wilkinson; Lucy Marshall; Lizzy Rosser; Ania Radziszewska; Hannah Peckham; Judith Heaney; Hannah Rickman; Stavroula Paraskevopoulou; Catherine Houlihan; Moria Spyer; Steve Gamblin; John Mccauley; Eleni Nastouli; Peter Cherepanov; Coziana Ciurtin; Lucy Wedderburn; George Kassiotis

    doi:10.1101/2021.02.15.431291 Date: 2021-02-16 Source: bioRxiv

    Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction MESHD or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases MESHD, juvenile idiopathic arthritis MESHD ( JIA MESHD), juvenile dermatomyositis MESHD ( JDM MESHD) and juvenile systemic lupus erythematosus MESHD ( JSLE MESHD), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects MESHD this age group. Despite immune dysfunction and immunosuppressive treatment, JIA MESHD, JDM MESHD and JSLE MESHD patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike MESHD, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN. In contrast, responses to HCoV-OC43 and SARS-CoV-2 MESHD nucleoproteins PROTEIN exhibited delayed age-dependent class-switching and were not elevated in JIA MESHD, JDM MESHD and JSLE MESHD patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases MESHD and their treatment were associated with a favourable ratio of spike to nucleoprotein PROTEIN antibodies.

    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.

    Distinct Autoimmune Antibody Signatures Between Hospitalized Acute COVID-19 MESHD Patients, SARS-CoV-2 Convalescent Individuals, and Unexposed Pre-Pandemic Controls

    Authors: Nahid Bhadelia; Anna Belkina; Alex Olson; Thomas Winter; Patricia Urick; Nina Lin; Ian Rifkin; Yachana Kataria; Rachel Yuen; Manish Sagar; Jennifer Cappione

    doi:10.1101/2021.01.21.21249176 Date: 2021-01-25 Source: medRxiv

    Abstract Increasing evidence suggests that autoimmunity may play a role in the pathophysiology of SARS-CoV-2 infection MESHD during both the acute and "long COVID" phases of disease. However, an assessment of autoimmune antibodies in convalescent SARS-CoV-2 patients has not yet been reported. Methodology: We compared the levels of 18 different IgG autoantibodies (AABs) between four groups: (1) unexposed pre-pandemic subjects from the general population (n = 29); (2) individuals hospitalized with acute moderate to severe COVID-19 MESHD (n = 20); (3) convalescent SARS-COV-2-infected subjects with asymptomatic to mild viral symptoms during the acute phase with samples obtained between 1.8 and 7.3 months after infection (n = 9); and (4) unexposed pre-pandemic subjects with systemic lupus erythematous MESHD ( SLE MESHD) (n = 6). Total IgG and IgA levels were also measured from subjects in groups 1-3 to assess non-specific pan-B cell activation. Results: As expected, in multivariate analysis, AABs were detected at much higher odds in SLE MESHD subjects (5 of 6, 83%) compared to non- SLE MESHD pre-pandemic controls (11 of 29, 38%) [odds ratio (OR) 19.4,95% CI, 2.0 - 557.0, p = 0.03]. AAB detection (percentage of subjects with one or more autoantibodies) was higher in SARS-CoV-2 infected MESHD convalescent subjects (7 of 9, 78%) [OR 17.4, 95% CI, 2.0 - 287.4, p = 0.02] and subjects with acute COVID-19 MESHD (12 of 20, 60%) compared with non- SLE MESHD pre-pandemic controls, but was not statistically significant among the latter [OR 1.8,95% CI, 0.6 - 8.1, p = 0.23]. Within the convalescent subject group, AABs were detected in 5/5 with reported persistent symptoms and 2/4 without continued symptoms (p = 0.17). The multivariate computational algorithm Partial Least Squares Determinant Analysis (PLSDA) was used to determine if distinct AAB signatures distinguish subject groups 1-3. Of the 18 autoantibodies measured, anti-Beta 2-Glycoprotein, anti-Proteinase 3-ANCA, anti-Mi-2 and anti-PM/Scl-100 defined the convalescent group; anti- Proteinase 3 HGNC-ANCA, anti-Mi-2, anti-Jo-1 and anti-RNP/SM defined acute COVID-19 MESHD subjects; and anti- Proteinase 3 HGNC-ANCA, anti-Mi-2, anti-Jo-1, anti- Beta 2 HGNC-Glycoprotein distinguished unexposed controls. The AABs defining SARS-COV-2 infected from pre-pandemic subjects are widely associated with myopathies MESHD, vasculitis MESHD, and antiphospholipid syndromes, conditions with some similarities to COVID-19 MESHD. Compared to pre-pandemic non- SLE MESHD controls, subjects with acute COVID-19 MESHD had higher total IgG concentration (p-value=0.006) but convalescent subjects did not (p-value=0.08); no differences in total IgA levels were found between groups. Conclusions: Our findings support existing studies suggesting induction of immune responses to self-epitopes during acute, severe COVID-19 MESHD with evidence of general B cell hyperactivation. Also, the preponderance of AAB positivity among convalescent individuals up to seven months after infection indicates potential initiation or proliferation, and then persistence of self-reactive immunity without severe initial disease MESHD. These results underscore the importance of further investigation of autoimmunity during SARS-CoV-2 infection MESHD and its role in the onset and persistence of post-acute sequelae of COVID-19 MESHD.

    Outcomes of COVID-19 MESHD in a cohort of pediatric patients with rheumatic diseases MESHD

    Authors: Diana Sofia Villacis-Nunez; Christina A. Rostad; Kelly Rouster-Stevens; Arezou Khosroshahi; Shanmuganathan Chandrakasan; Sampath Prahalad

    doi:10.21203/rs.3.rs-145918/v1 Date: 2021-01-12 Source: ResearchSquare

    Background There are few reports of COVID-19 MESHD in pediatric patients with rheumatic diseases MESHD. This study describes the clinical presentation and outcomes of COVID-19 MESHD in this population.Methods We analyzed a single-center case series of pediatric patients with rheumatic diseases MESHD and laboratory-confirmed COVID-19 MESHD. Demographic, baseline and COVID-19 MESHD associated clinical features were compared between ambulatory and hospitalized patients using univariate analysis.Results Forty cases were identified: 32 (80%) in the ambulatory group and 8 (20%) hospitalized. Older age (median age 18 years vs 16 years; p = 0.01) and African American race (OR 8.42; 95% CI [1.20-101.69]; p = 0.01) predominated in hospitalized patients. Systemic lupus erythematosus MESHD (OR 6.77; 95% CI [1.01–56.71]; p = 0.02), medium/high-dose corticosteroid use (OR 10.62; 95% CI [1.46–99.57]; p = 0.008), mycophenolate use (OR 11.91; 95% CI [1.64-149.35]; p = 0.005), and severe immunosuppression (OR 16.83; 95% CI [1.74-861.43]; p = 0.004) were associated with increased odds of hospitalization. Patients with fever MESHD (OR 11.91; 95% CI [1.64-149.35]; p = 0.004), dyspnea MESHD (OR 16.51; CI [1.10-998.37]; p = 0.02), and myalgias MESHD (OR 13.40; 95% CI [1.43-194.56)]; p = 0.009) were more commonly encountered in the hospitalized group. Rheumatic disease MESHD flares were almost exclusive to hospitalized patients (OR 42.13; 95% CI [3.40-2463.87]; p < 0.001).. All patients recovered.Conclusions Medium/high-dose corticosteroid use, mycophenolate use, and severe immunosuppression were risk factors for hospitalization. Fever MESHD, dyspnea MESHD and myalgias MESHD were high-risk symptoms. The type of rheumatic disease MESHD, as well as disease flare could be contributing factors to the need for hospitalization.

    Possible Case of Children Onset Systemic Lupus Erythematosus MESHD Triggered by Covid-19 MESHD

    Authors: Clémence Odile Bettiol; Joseph Ntagerwa; Axel De Greef; David Tuerlinckx; Yves Boutsen

    doi:10.21203/rs.3.rs-133376/v1 Date: 2020-12-21 Source: ResearchSquare

    This case report will present the case of an 11 years old child diagnosed with childhood-onset systemic lupus erythematosus MESHD (cSLE) during the coronavirus Covid-19 pandemic MESHD. Her initial symptoms were compatible with a Covid-19 MESHD infection but repeated PCR on naso-pharyngeal swabs were negative. Two serological assays were carried out but only one showed doubtful IgG results.Considering that viral infection could be responsible for autoimmune disease MESHD outbreaks and with increasing evidences of SARS Cov 2 actions on human inflammatory and immune systems; we discuss here a potential cSLE diagnosis triggered by Covid-19 MESHD infection.

    A novel multi-omics-based identification of symptoms, comorbid conditions, and possible long-term complications in COVID-19 MESHD

    Authors: Debmalya Barh; Sandeep Tiwari; Bruno Silva Andrade; Marianna E. Weener; Aristoteles Goes-Neto; Vasco Azevedo; Preetam Ghosh; Nirmal Kumar Ganguly

    doi:10.1101/2020.12.08.20245753 Date: 2020-12-09 Source: medRxiv

    Till date the comprehensive clinical pictures, comorbid conditions, and long-term complications of COVID-19 MESHD are not known. Recently using a multi-omics-based strategy, we have predicted the drugs for COVID-19 MESHD management with [~]70% accuracy. Here, using a similar multi-omics-based bioinformatics approach and three-ways of analysis, we identified the symptoms, comorbid conditions, and short, mid and possible long-term complications of COVID-19 MESHD with [~]90% precision. In our analysis (i) we identified 27 parent, 170 child, and 403 specific conditions associated with COVID-19 MESHD. (ii) Among the specific conditions, 36 are viral and 53 short-term, 62 short to mid to long-term, 194 mid to long-term, and 57 are congenital conditions. (iii) At a cut off "count of occurrence" of 4, we found [~] 90% of the enriched conditions are associated with COVID-19 MESHD. (iv) Except the dry cough MESHD and loss of taste, all other COVID-19 MESHD associated mild and severe symptoms are enriched. (v) Cardiovascular, pulmonary, metabolic, musculoskeletal MESHD, neuropsychiatric, kidney, liver, and immune system disorders MESHD are found as top comorbid conditions. (vi) Specific diseases such as myocardial infarction MESHD, hypertension MESHD, COPD MESHD, lung injury MESHD, diabetes MESHD, cirrhosis MESHD, mood disorders MESHD, dementia MESHD, macular degeneration MESHD, chronic kidney disease MESHD, lupus MESHD, arthritis MESHD etc. along with several other diseases MESHD are also enriched as top candidates. (vii) Interestingly, many cancers MESHD and congenital disorders MESHD associated with COVID-19 MESHD severity are also identified. (viii) Arthritis MESHD, dermatomyositis MESHD, glioma MESHD, diabetes MESHD, psychiatric disorder MESHD, cardiovascular diseases MESHD having bidirectional relationship with COVID-19 MESHD are also found as top ranked conditions. Based on the accuracy ([~]90%) of this analysis, long presence of SARS-CoV-2 RNA in human, and our previously proposed "genetic remittance" assumption, we hypothesize that all the identified comorbid conditions including the short-long-mid and mid-long non-communicable diseases (NCDs) could also be long-term consequences in COVID-19 MESHD survivors and warrants long-term observational studies.

    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.

    Systemic Lupus Erythematosus triggered by SARS-CoV-2 Infection MESHD: A Systematic Review Based on a Case Report

    Authors: Abraham Edgar Gracia-Ramos; Miguel Angel Saavedra-Salinas

    doi:10.21203/rs.3.rs-105222/v1 Date: 2020-11-09 Source: ResearchSquare

    Systemic lupus erythematosus MESHD ( SLE MESHD) is an autoimmune and multisystemic chronic inflammatory disease MESHD that can affect various organs, including skin, joints, kidneys, lungs and the nervous system. Infectious agents have long been implicated in the pathogenesis of SLE MESHD. The new viral infection MESHD caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has shown that, in genetically predisposed patients, could trigger the presentation or exacerbation of autoimmune disease MESHD. We herein report a case of a 45-year-old man who presented respiratory symptoms MESHD, bilateral pleural effusion MESHD, ascites MESHD, splenomegaly MESHD, severe thrombocytopenia MESHD and renal failure MESHD with proteinuria MESHD and hematuria MESHD. SARS-CoV-2 PCR confirmed the COVID-19 MESHD diagnosis. We diagnosed the patient with SLE MESHD based on the clinical manifestations and positive immunological markers (2019 European League Against Rheumatism MESHD/American College of Rheumatology score of 18). Glucocorticoid pulses were administered to the patient with improvement in renal function. However, thrombocytopenia MESHD was also refractory to IV immunoglobulin and rituximab, so the patient underwent splenectomy. Through a systematic search of the medical literature, we retrieved 2 cases with SLE MESHD new onset and 5 cases with previous SLE MESHD diagnosis that shown activity of disease due SARS-CoV-2 infection MESHD. We herein present a systemic review of these cases and discuss the clinical manifestations that could help to the diagnosis of this clinical condition.

    Association between anti-interferon-alpha autoantibodies and COVID-19 MESHD in systemic lupus erythematosus

    Authors: Sarthak Gupta; Shuichiro Nakabo; Jun Chu; Sarfaraz Hasni; Mariana Kaplan

    doi:10.1101/2020.10.29.20222000 Date: 2020-11-03 Source: medRxiv

    Objectives: Anti- type I interferon (IFN) HGNC autoantibodies have been reported in patients with systemic lupus erythematosus MESHD ( SLE MESHD). Recently, an association of these autoantibodies with severe COVID-19 MESHD was reported in the general population. We assessed whether having pre-existing anti- IFNa HGNC; autoantibodies was associated with COVID-19 MESHD infection in SLE MESHD patients. Methods: Patients with SLE MESHD who developed COVID-19 MESHD between April 1st to October 1st, 2020 were studied. Biobanked pre- COVID-19 MESHD plasma from these SLE MESHD subjects and healthy controls were tested for anti- IFNa HGNC; IgG autoantibodies by ELISA. The ability of plasma anti- IFNa HGNC; autoantibodies to block signal transducer and activator of transcription 1 HGNC ( STAT1 HGNC) phosphorylation by recombinant human IFNa HGNC; in vitro was assessed by flow cytometry. Results: Ten SLE MESHD subjects with COVID-19 MESHD were identified. A 40% of these subjects had stable autoantibodies against IFNa HGNC; for up to three years preceding COVID-19 MESHD diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNa HGNC; induced STAT1 HGNC phosphorylation. None of the other SLE MESHD samples blocked IFNa HGNC; signaling. Conclusions: We noted an increased prevalence of pre-existing anti- IFNa HGNC; autoantibodies in SLE MESHD patients with COVID-19 MESHD compared to the reported prevalence in lupus MESHD patients and the general population with severe COVID-19 MESHD. Autoantibodies against IFNa HGNC; in SLE MESHD patients may be pathogenic and patients with them maybe at-risk of developing COVID-19 MESHD.

    Psychiatric side effects induced by chloroquine and hydroxychloroquine: a systematic review of case reports and population studies

    Authors: Fernanda Talarico; Sucheta Chakravarty; Yang Liu; Angrew Greenshaw; Ives Passos; Bo Cao

    doi:10.1101/2020.10.05.20207423 Date: 2020-10-07 Source: medRxiv

    Chloroquine and hydroxychloroquine are commonly used drugs in the treatment of malaria MESHD as well as chronic diseases, such as rheumatoid arthritis MESHD, and systemic lupus erythematosus MESHD. Although various reports on possible psychiatric MESHD side effects of these drugs exist, the nature and extent of these effects remain poorly understood. Moreover, the relevance of these drugs in the treatment of early stages of COVID-19 MESHD necessitates a careful estimation of their side effects. Here, we provide a systematic review of the psychiatric MESHD side effects associated with chloroquine and hydroxychloroquine. We used PubMed, Scopus, and Web of Science platforms to identify relevant literature published between 1962 and 2020. Search terms included chloroquine, hydroxychloroquine, psychiatry, psychosis MESHD, depression MESHD, anxiety MESHD, bipolar disorder MESHD, delirium MESHD, and psychotic disorders MESHD. Only case reports and clinical trials were included. All studies included records of psychiatric MESHD side effects induced by either chloroquine or hydroxychloroquine or both. Both retrospective and prospective, randomized as well as non-randomized population studies were included. Overall, the psychiatric MESHD side effects are dose- and sex-independent. The most common psychiatric MESHD side effects reported are increased speech output/ excessive talking, increased psychomotor activity, irritable mood MESHD, auditory hallucinations MESHD, delusion of grandiosity, and suicide attempts, likely due to brain intoxicationbe of chloroquine or hydroxychloroquine. The symptoms can develop in a few hours to 11 weeks after drug intake and are normally reversed within a week after the drug withdrawal. We conclude that CQ and HCQ have the potential to induce psychiatric MESHD side effects. This study calls for further investigation of psychiatric symptoms MESHD induced by these drugs in the short and long term.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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