Jiang, Yonghou and Duffy, Fergal and Hadlock, Jennifer and Raappana, Andrew and Styrchak, Sheila and Beck, Ingrid and Mast, Fred D. and Miller, Leslie R. and Chour, William and Houck, John and Armistead, Blair and Duvvuri, Venkata R. and Yeung, Winnie and Haglund, Micaela and Wallner, Jackson and Wallick, Julie A. and Hardy, Samantha and Oldroyd, Alyssa and Ko, Daisy and Gervassi, Ana and Murray, Kim M. and Kaplan, Henry and Aitchison, John D. and Heath, James R. and Sather, D. Noah and Goldman, Jason D. and Frenkel, Lisa and Harrington, Whitney E. (2021) Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection. PLoS ONE, 16 (11). Art. No. e0259902. ISSN 1932-6203. PMCID PMC8598062. doi:10.1371/journal.pone.0259902. https://resolver.caltech.edu/CaltechAUTHORS:20210714-152527909
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Abstract
Background: Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab). Methods: We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls utilizing multivariate logistic and quantile regression adjusted for comorbidities including hypertension, diabetes, and heart disease. Results: There were trends toward increased prevalence (50% vs. 33%, p = 0.1) and level of AT1R-Ab (median 9.8 vs. 6.1 U/mL, p = 0.06) in all cases versus controls. When considered by COVID-19 disease severity, there was a trend toward increased prevalence of AT1R-Ab (55% vs. 31%, p = 0.07), as well as significantly higher AT1R-Ab levels (median 10.7 vs. 5.9 U/mL, p = 0.03) amongst individuals with mild COVID-19 versus matched controls. In contrast, the prevalence (42% vs. 37%, p = 0.9) and level (both medians 6.7 U/mL, p = 0.9) of AT1R-Ab amongst those with severe COVID-19 did not differ from matched controls. Conclusions: These findings support an association between COVID-19 and AT1R-Ab, emphasizing that vascular pathology may be present in individuals with mild COVID-19 as well as those with severe disease.
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| Alternate Title: | AT1R-Ab after SARS-CoV-2 infection | ||||||||||||||||||||||||||||||||||||||
| Additional Information: | © 2021 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: June 11, 2021; Accepted: October 28, 2021; Published: November 17, 2021. This work was supported by Seattle Children’s Research Institute [to LF, WEH, NS, and JDA]; the National Institute of Allergy and Infectious Diseases [K08 AI135072 to WEH]; the Burroughs Wellcome Fund [CAMS 1017213 to WEH]; the Biomedical Advanced Research and Development Authority [HHSO10201600031C to JRH]; and the Swedish Medical Center Foundation [to JDG]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Contributions: Conceptualization: Ana Gervassi, Henry Kaplan, John D. Aitchison, James R. Heath, Jason D. Goldman, Lisa Frenkel, Whitney E. Harrington. Data curation: Yonghou Jiang, Jennifer Hadlock, Ingrid Beck, Fred D. Mast, Leslie R. Miller, John Houck, Blair Armistead, Venkata R. Duvvuri, Winnie Yeung, Micaela Haglund, Julie A. Wallick, Kim M. Murray, Jason D. Goldman, Lisa Frenkel, Whitney E. Harrington. Formal analysis: Yonghou Jiang, Fergal Duffy, Whitney E. Harrington. Funding acquisition: James R. Heath, Jason D. Goldman, Whitney E. Harrington. Investigation: Yonghou Jiang, Fergal Duffy, Andrew Raappana, Sheila Styrchak, Ingrid Beck, Fred D. Mast, Leslie R. Miller, William Chour, Jackson Wallner, Samantha Hardy, Alyssa Oldroyd, Daisy Ko, John D. Aitchison, D. Noah Sather, Whitney E. Harrington. Methodology: Yonghou Jiang, Andrew Raappana, Sheila Styrchak, Ingrid Beck, William Chour, Venkata R. Duvvuri, Ana Gervassi, Henry Kaplan, D. Noah Sather, Lisa Frenkel, Whitney E. Harrington. Project administration: Jennifer Hadlock, Fred D. Mast, John Houck, Winnie Yeung, Micaela Haglund, Jackson Wallner, Julie A. Wallick, Kim M. Murray, Jason D. Goldman, Lisa Frenkel, Whitney E. Harrington. Resources: Lisa Frenkel. Supervision: John D. Aitchison, James R. Heath, D. Noah Sather, Jason D. Goldman, Whitney E. Harrington. Validation: Whitney E. Harrington. Visualization: Yonghou Jiang, Fergal Duffy, Blair Armistead. Writing – original draft: Yonghou Jiang, Fergal Duffy, Jason D. Goldman, Lisa Frenkel, Whitney E. Harrington. Writing – review & editing: Jason D. Goldman, Lisa Frenkel, Whitney E. Harrington. Competing interests: J.D.G. declared research support from Gilead, Lilly, and Regeneron, and Monogram Biosciences and served on advisory board for Gilead. The other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Data Availability: All relevant data are within the manuscript and its Supporting Information files. | ||||||||||||||||||||||||||||||||||||||
| Group: | COVID-19 | ||||||||||||||||||||||||||||||||||||||
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| Issue or Number: | 11 | ||||||||||||||||||||||||||||||||||||||
| PubMed Central ID: | PMC8598062 | ||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1371/journal.pone.0259902 | ||||||||||||||||||||||||||||||||||||||
| Record Number: | CaltechAUTHORS:20210714-152527909 | ||||||||||||||||||||||||||||||||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20210714-152527909 | ||||||||||||||||||||||||||||||||||||||
| Official Citation: | Jiang Y, Duffy F, Hadlock J, Raappana A, Styrchak S, Beck I, et al. (2021) Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection. PLoS ONE 16(11): e0259902. https://doi.org/10.1371/journal.pone.0259902 | ||||||||||||||||||||||||||||||||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||||||||||||||||||||||
| ID Code: | 109806 | ||||||||||||||||||||||||||||||||||||||
| Collection: | CaltechAUTHORS | ||||||||||||||||||||||||||||||||||||||
| Deposited By: | Tony Diaz | ||||||||||||||||||||||||||||||||||||||
| Deposited On: | 14 Jul 2021 18:15 | ||||||||||||||||||||||||||||||||||||||
| Last Modified: | 10 Dec 2021 18:17 |
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