augmentation of anti mda5 antibody implies severe disease in covid 19 patients CORD-Papers-2021-10-25 (Version 1)

Title: Augmentation of anti-MDA5 antibody implies severe disease in COVID-19 patients
Abstract: Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, which is associated with high mortality of coronavirus disease 2019 (COVID-19). Striking similarities has been noted between COVID-19 and anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis (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 (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 is correlated with severe disease and unfavorable outcomes.
Published: 8/1/2020
DOI: 10.1101/2020.07.29.20164780
DOI_URL: http://doi.org/10.1101/2020.07.29.20164780
Author Name: Liu, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_c
Author Name: Wang, Q
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_q
Author Name: Wang, Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_y
Author Name: Wang, G
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_g
Author Name: Wang, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_l
Author Name: Chen, H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/chen_h
Author Name: Jiao, T
Author link: https://covid19-data.nist.gov/pid/rest/local/author/jiao_t
Author Name: Hu, C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hu_c
Author Name: Lei, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lei_x
Author Name: Guo, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/guo_l
Author Name: Ren, L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ren_l
Author Name: Li, M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/li_m
Author Name: Zeng, X
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zeng_x
Author Name: Zhang, D
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhang_d
Author Name: Cao, B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cao_b
Author Name: Wang, J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/wang_j
sha: 61d312c1621266e40efaca9fa27d172c8316176e
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: https://doi.org/10.1101/2020.07.29.20164780 http://medrxiv.org/cgi/content/short/2020.07.29.20164780v1?rss=1
has_full_text: TRUE
Keywords Extracted from Text Content: SARS-CoV2 coronavirus 2 COVID-19 coronavirus disease 2019 patients ≥10.0 MDA5 antimelanoma differentiation-associated gene 5 COVID-19 patients anti-MDA5 Ab 5.95±5.16 mitochondrial MCP1 doi:10.1158 - /0008 LDH SARS-CoV2 cytoplasmic antineutrophil cytoplasmic antibodies medRxiv medRxiv preprint 1 CL lungs serum IFN patients lupus anticoagulant cardiovascular lymphocytes ≥10.0 IP10 muscles anti-MDA5 ferritin Figures 1f and DM plasma samples organ I-like IL-8 type I and III IFNs patient IL-10 D-dimer homotypic-interacting caspase COVID-19 CARD TNFα Figures 4j, 4k anti-Ro antibody MDA5 ≥5.0 corticosteroids MAVS plasma IL-6 COVID-19 patients anti-MDA5 Ab antinuclear antibodies MERS-CoV SARS-CoV https://doi.org/10.1101/2020.07.29.20164780 doi P<0.01 Figure 4a https://doi.org/10.1101 medRxiv preprint coronavirus 2 https://doi.org/10.1101 /2020 4i IFNs Anti-MDA5 WFSO-2 retinoic acid-inducible Figures 4h helicase type I and III interferons IL-2 skin G-CSF Rev 19, blood anti-MDA5 Ab-related CRP lung IL-7
Extracted Text Content in Record: First 5000 Characters:Recent studies have provided insights into the autoinflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, which is associated with high mortality of coronavirus disease 2019 . Striking similarities has been noted between COVID-19 and antimelanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis (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 (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 is correlated with severe disease and unfavorable outcomes. 7 respiratory distress syndrome (ARDS), Innate immunity. . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 1, 2020 . . https://doi.org/10.1101 /2020 Coronavirus Disease 2019 , caused by highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), has become a pandemic involving more than 12 million cases globally by July 2020. 1 The average mortality is estimated to be 1%, 2 but can raise up to 62% in critically ill patients, mostly due to acute respiratory distress syndrome (ARDS). 3 Therefore, reducing mortality of severe COVID-19 patients has become an urgent task in this battle. Unfortunately, few antiviral agents have been proved to be effective enough to treat the disease, and whether to use corticosteroids and other immunomodulatory drugs remains controversial. 4 Accumulating evidence has demonstrated that a bunch of cytokines (e.g. IL-2, IL-6, IL-7, IL-10, G-CSF, IP10, MCP1, TNFα, etc.) are elevated in the blood of patients with severe COVID-19, resembling cytokine storm syndrome. The COVID-19 patients with hypercytokinemia and hyperferritinemia were more likely to exhibit extensive lung damage and ARDS. [5] [6] [7] In addition, high prevalence of antinuclear antibodies (35.6%) and lupus anticoagulant (46.6%), along with antineutrophil cytoplasmic antibodies (6.6%) and anti-Ro antibody (4.4%), were also identified in hospitalized patients with Thus, hypothesis that SARS-CoV2 might trigger autoimmune and/or autoinflammatory aberrance in genetically predisposed subjects has been raised. 9 It is reasonable that all patients with severe COVID-19 should be screened for hyperinflammation to identify the subgroup of patients for whom adjunctive immunosuppression therapy would improve mortality. 4 Striking similarities has been noted between multifaceted features of COVID-19 and a rare autoimmune disease, the . CC-BY-NC 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 1, 2020 . . https://doi.org/10.1101 /2020 anti-melanoma-differentiation-associated gene 5 (MDA5) antibody (Ab)-related dermatomyositis (DM). 10, 11 Both diseases can involve the lungs, skin 12,13 and muscles. 14 Anti-MDA5 Ab-related DM patients often develop rapid progressive interstitial lung disease (RP-ILD), whose prognosis is disappointingly poor with more than half of patients dying within 3 months of disease onset. 15 The initial radiological features of lung in Anti-MDA5 Ab-related DM patients are mainly subpleural ground-glass opacities or mixed with consolidation and signs of ARDS, which resemble severe and critical 16 Besides, similar skin eruptions have been reported in both diseases. 13 Furthermore, serum cytokine profiles are also similar in these two conditions, as serum levels of ferritin, IL-6, IL-8, and IL-10 usually were elevated in patients with RP-ILD secondary to Anti-MDA5 Ab-related DM. 17 The similarity of these two diseases implies a shared underlying autoinflammatory/autoimmune mechanisms. To date, there is no report on whether anti-MDA5 Ab also exists in patients with COVID-19. MDA5 is a well-known cytoplasmic sensor for viral RNA and its expression is induced by RNA viruses. This activates the expression of antiviral type I and III interferons (IFNs) with inflammatory cytokines. Correspondingl
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