predominance of distinct autoantibodies in response to sars cov 2 infection CORD-Papers-2021-10-25 (Version 1)

Title: Predominance of Distinct Autoantibodies in Response to SARS-CoV-2 Infection
Abstract: BackgroundImproved knowledge regarding the prevalence and clinical significance of the broad spectrum of autoantibodies triggered by SARS-CoV2 infection can clarify the underlying pathobiology, enhance approaches to evaluating heterogeneity of COVID-19 clinical manifestations, and potentially guide options for targeting immunosuppressive therapy as the need for more effective interventions continues to evolve. In this study, we sought to determine the prevalence of autoimmune antibodies in diverse cohort of SARS-CoV-2 positive healthcare workers and measure the extent to which factors associated with triggered autoimmunity are activated even following mild and asymptomatic infection. MethodsAntigen microarrays were used to profile reactivity of IgG autoantibodies against 91 proteins and cytokines based on autoantibody profiling studies in autoimmune diseases. ResultsIn this discovery screening study, we found that 90% of the IgG positive individuals demonstrated reactivity to at least one autoantibody. When compared to results of the same assays conducted on samples from pre-COVID-19 controls, our primary cohort of individuals with SARS-CoV-2 IgG antibody positivity had significantly elevated IgG against twelve additional proteins including CHD3, CTLA4, HARS, IFNA4, INS, MIF, MX1, RNF41, S100A9, SRP19, TROVE2, and VEGFA. These findings confirmed that all severity levels of SARS-CoV-2 infection, even asymptomatic infections, trigger a robust and diverse autoimmune response; our results also highlight the utility of multiparametric autoantibody detection in this setting. InterpretationTaken together, our findings underscore the serological diversity underlying the clinical heterogeneity of COVID-19 infection and its sequelae, including the long-Covid phenotypes. FundingThis work was supported in part by Cedars-Sinai Medical Center (JEE; SC), the Erika J Glazer Family Foundation (JEE; JEVE; SC), CSMC Precision Health Grant (JFB), the F. Widjaja Family Foundation (JGB, GYM, DM), the Helmsley Charitable Trust (JGB, GYM, DM), and NIH grants K23-HL153888 (JEE) and DK062413 (DPBM). RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSCurrently, several studies have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID-19). In contrast to cytokine storms, which tend to cause systemic, short-duration problems, autoantibodies (AABs) are thought to result in targeted, longer-term damage and development of autoimmune diseases. Added value of this studyAccording to our knowledge, we evaluated the largest number of protein antigens to characterize the prevalence and heterogeneity of the AABs signature in SARS-CoV-2 convalescent individuals. We examined autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease to acknowledge the existence of AABs even among those who had mild-to-moderate or no symptoms during their illness, as a hallmark of ongoing long-COVID syndrome. Through our analysis we suggest that VEGFA, MIF, IFNA4, SPP1 and APOH could be used as hallmark for SARS-CoV-2 infection and activation of the autoimmune system. Implications of all the available evidenceOur study comprehensively characterized the heterogeneity of the AABs signature in SARS-CoV-2 convalescent individuals. The results established a list of diagnostic signatures and potential therapeutic targets for long-Covid-19 patients although follow-up long-term studies are required. We believe that our findings will serve as a valuable resource, to drive further exploration of long-COVID syndrome pathogenesis.
Published: 2021
Author Name: Liu, Yunxian
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_yunxian
Author Name: Ebinger, Joseph E
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ebinger_joseph_e
Author Name: Mostafa, Rowann
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mostafa_rowann
Author Name: Budde, Petra
Author link: https://covid19-data.nist.gov/pid/rest/local/author/budde_petra
Author Name: Gajewski, Jana
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gajewski_jana
Author Name: Walker, Brian
Author link: https://covid19-data.nist.gov/pid/rest/local/author/walker_brian
Author Name: Joung, Sandy
Author link: https://covid19-data.nist.gov/pid/rest/local/author/joung_sandy
Author Name: Brutigam, Manuel
Author link: https://covid19-data.nist.gov/pid/rest/local/author/brutigam_manuel
Author Name: Hesping, Franziska
Author link: https://covid19-data.nist.gov/pid/rest/local/author/hesping_franziska
Author Name: Schefer, Elena
Author link: https://covid19-data.nist.gov/pid/rest/local/author/schefer_elena
Author Name: Schubert, Ann Sophie
Author link: https://covid19-data.nist.gov/pid/rest/local/author/schubert_ann_sophie
Author Name: Zucht, Hans Dieter
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zucht_hans_dieter
Author Name: Melmed, Gil Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/melmed_gil_y
Author Name: Sobhani, Kimia
Author link: https://covid19-data.nist.gov/pid/rest/local/author/sobhani_kimia
Author Name: Braun, Jonathan
Author link: https://covid19-data.nist.gov/pid/rest/local/author/braun_jonathan
Author Name: McGovern, Dermot P B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mcgovern_dermot_p_b
Author Name: Eyk, Jennifer E Van
Author link: https://covid19-data.nist.gov/pid/rest/local/author/eyk_jennifer_e_van
Author Name: Cheng, Susan
Author link: https://covid19-data.nist.gov/pid/rest/local/author/cheng_susan
Author Name: Fert Bober, Justyna
Author link: https://covid19-data.nist.gov/pid/rest/local/author/fert_bober_justyna
license: unk
license_url: [unknown license]
source_x: WHO
source_x_url: https://www.who.int/
who_covidence_id: #ppmedrxiv-21263603
has_full_text: FALSE
G_ID: predominance_of_distinct_autoantibodies_in_response_to_sars_cov_2_infection
S2 ID: 237541524