{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:49:17Z","timestamp":1788587357669,"version":"build-2803163510"},"posted":{"date-parts":[[2025,2,13]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Many difficult to understand clinical features characterize COVID-19 and Post-Acute Sequelae of COVID-19 (PASC or Long COVID, LC). These can include blood pressure instability, hyperinflammation, coagulopathies, and neuropsychiatric complaints. The pathogenesis of these features remains unclear. The SARS-CoV-2 Spike protein Receptor Binding Domain (RBD) binds Angiotensin Converting Enzyme 2 (ACE2) on the surface of host cells to initiate infection. We hypothesized that some people convalescing from COVID-19 may produce anti-RBD antibodies that resemble ACE2 sufficiently to have ACE2-like catalytic activity, that is they are ACE2-like proteolytic abzymes that may help mediate the pathogenesis of COVID-19 and LC. In previous work, we showed that some people with acute COVID-19 had immunoglobulin-associated ACE2-like proteolytic activity, suggesting that some people with COVID-19 indeed produced ACE2-like abzymes. However, it remained unknown whether ACE2-like abzymes were seen only in acute COVID-19 or whether ACE2-like abzymes could also be identified in people convalescing from COVID-19. Here we show that some people convalescing from COVID-19 attending a clinic for people with persistent pulmonary symptoms also have ACE2-like abzymes and that the presence of ACE2-like catalytic activity correlates with alterations in blood pressure in an exercise test.<\/jats:p>","DOI":"10.1101\/2025.02.12.25322167","type":"posted-content","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T17:30:18Z","timestamp":1739467818000},"source":"Crossref","is-referenced-by-count":2,"title":["ACE-2-like Enzymatic Activity in COVID-19 Convalescents with Persistent Pulmonary Symptoms Associated with Immunoglobulin"],"prefix":"10.64898","author":[{"given":"Yufeng","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Mehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsey M.","family":"Muehling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"Canderan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Enfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Ratcliffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kadl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith A.","family":"Woodfolk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-9260","authenticated-orcid":false,"given":"Steven L.","family":"Zeichner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025060600300548000_2025.02.12.25322167v2.1","unstructured":"Organization WH. WHO COVID-19 dashboard. World Health Organization; 2024 [cited 2024 24 June]; https:\/\/data.who.int\/dashboards\/covid19\/deaths."},{"key":"2025060600300548000_2025.02.12.25322167v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00904-7"},{"key":"2025060600300548000_2025.02.12.25322167v2.3","doi-asserted-by":"crossref","first-page":"1117464","DOI":"10.3389\/fimmu.2023.1117464","article-title":"Long COVID: a review and proposed visualization of the complexity of long COVID","volume":"14","year":"2023","journal-title":"Frontiers in immunology"},{"key":"2025060600300548000_2025.02.12.25322167v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00846-2"},{"key":"2025060600300548000_2025.02.12.25322167v2.5","doi-asserted-by":"crossref","unstructured":"Adjaye-Gbewonyo D , Vahratian A , Perrine CG , Bertolli J. Long COVID in Adults: United States, 2022. 26\/2023.","DOI":"10.15620\/cdc:132417"},{"key":"2025060600300548000_2025.02.12.25322167v2.6","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2076901"},{"key":"2025060600300548000_2025.02.12.25322167v2.7","doi-asserted-by":"crossref","first-page":"1138389","DOI":"10.3389\/fpsyt.2023.1138389","article-title":"Psychiatric symptoms in Long-COVID patients: a systematic review","volume":"14","year":"2023","journal-title":"Frontiers in Psychiatry"},{"key":"2025060600300548000_2025.02.12.25322167v2.8","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.8823"},{"key":"2025060600300548000_2025.02.12.25322167v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00703-9\/ATTACHMENT\/31179DEC-CF64-455B-BD13-6EF0045B7DD6\/MMC1.PDF"},{"key":"2025060600300548000_2025.02.12.25322167v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06651-y"},{"key":"2025060600300548000_2025.02.12.25322167v2.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7942"},{"key":"2025060600300548000_2025.02.12.25322167v2.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"issue":"9","key":"2025060600300548000_2025.02.12.25322167v2.13","doi-asserted-by":"crossref","first-page":"e671","DOI":"10.1016\/S2352-3026(20)30217-9","article-title":"Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study","volume":"7","year":"2020","journal-title":"Lancet Haematol"},{"key":"2025060600300548000_2025.02.12.25322167v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/S41591-020-1051-9"},{"key":"2025060600300548000_2025.02.12.25322167v2.15","doi-asserted-by":"crossref","unstructured":"Yousaf AR , Cortese MM , Taylor AW , Broder KR , Oster ME , Wong JM , Guh AY , McCormick DW , Kamidani S , Schlaudecker EP , Edwards KM , Creech CB , Staat MA , Belay ED , Marquez P , Su JR , Salzman MB , Thompson D , Campbell AP . Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation. Lancet Child Adolesc Health. 2022 Feb 22. PMC8864018","DOI":"10.1016\/S2352-4642(22)00028-1"},{"issue":"4","key":"2025060600300548000_2025.02.12.25322167v2.16","doi-asserted-by":"crossref","first-page":"750","DOI":"10.3390\/v14040750","article-title":"Multisystem Inflammatory Syndrome in Neonates Born to Mothers with SARS-CoV-2 Infection (MIS-N) and in Neonates and Infants Younger Than 6 Months with Acquired COVID-19 (MIS-C): A Systematic Review","volume":"14","year":"2022","journal-title":"Viruses"},{"key":"2025060600300548000_2025.02.12.25322167v2.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.01.039"},{"key":"2025060600300548000_2025.02.12.25322167v2.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb2762"},{"key":"2025060600300548000_2025.02.12.25322167v2.19","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-08193-4"},{"key":"2025060600300548000_2025.02.12.25322167v2.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2023.102619"},{"key":"2025060600300548000_2025.02.12.25322167v2.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2180-5"},{"key":"2025060600300548000_2025.02.12.25322167v2.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.034"},{"key":"2025060600300548000_2025.02.12.25322167v2.23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cca.2021.10.029","article-title":"Angiotensin converting enzyme (ACE)","volume":"524","year":"2022","journal-title":"Clin Chim Acta"},{"key":"2025060600300548000_2025.02.12.25322167v2.24","doi-asserted-by":"crossref","first-page":"170766","DOI":"10.1016\/j.peptides.2022.170766","article-title":"Angiotensin-converting enzyme 2 (ACE2): Two decades of revelations and re-evaluation","volume":"151","year":"2022","journal-title":"Peptides"},{"key":"2025060600300548000_2025.02.12.25322167v2.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.3787261"},{"key":"2025060600300548000_2025.02.12.25322167v2.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.3787262"},{"key":"2025060600300548000_2025.02.12.25322167v2.27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb33195.x"},{"key":"2025060600300548000_2025.02.12.25322167v2.28","doi-asserted-by":"publisher","DOI":"10.1007\/BF02787937"},{"key":"2025060600300548000_2025.02.12.25322167v2.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.19.8876"},{"key":"2025060600300548000_2025.02.12.25322167v2.30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb19963.x"},{"key":"2025060600300548000_2025.02.12.25322167v2.31","doi-asserted-by":"publisher","DOI":"10.1021\/bi7013954"},{"key":"2025060600300548000_2025.02.12.25322167v2.32","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.751"},{"key":"2025060600300548000_2025.02.12.25322167v2.33","doi-asserted-by":"publisher","DOI":"10.1021\/bi2002289"},{"key":"2025060600300548000_2025.02.12.25322167v2.34","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.5.e1"},{"key":"2025060600300548000_2025.02.12.25322167v2.35","doi-asserted-by":"publisher","DOI":"10.1126\/science.1585181"},{"key":"2025060600300548000_2025.02.12.25322167v2.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.25.15257"},{"key":"2025060600300548000_2025.02.12.25322167v2.37","doi-asserted-by":"publisher","DOI":"10.1126\/science.2727702"},{"key":"2025060600300548000_2025.02.12.25322167v2.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509849103"},{"key":"2025060600300548000_2025.02.12.25322167v2.39","doi-asserted-by":"publisher","DOI":"10.1021\/bi992588w"},{"key":"2025060600300548000_2025.02.12.25322167v2.40","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7714"},{"key":"2025060600300548000_2025.02.12.25322167v2.41","doi-asserted-by":"publisher","DOI":"10.1038\/12483"},{"key":"2025060600300548000_2025.02.12.25322167v2.42","doi-asserted-by":"publisher","DOI":"10.1021\/bi050675k"},{"issue":"4","key":"2025060600300548000_2025.02.12.25322167v2.43","doi-asserted-by":"crossref","first-page":"e0054124","DOI":"10.1128\/mbio.00541-24","article-title":"ACE-2-like enzymatic activity is associated with immunoglobulin in COVID-19 patients","volume":"15","year":"2024","journal-title":"mBio"},{"issue":"4","key":"2025060600300548000_2025.02.12.25322167v2.44","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/s41590-025-02110-0","article-title":"Distinct type 1 immune networks underlie the severity of restrictive lung disease after COVID-19","volume":"26","year":"2025","journal-title":"Nat Immunol"},{"key":"2025060600300548000_2025.02.12.25322167v2.45","doi-asserted-by":"publisher","DOI":"10.1159\/000514203"},{"issue":"1","key":"2025060600300548000_2025.02.12.25322167v2.46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s43856-024-00477-z","article-title":"Autoantibodies to ACE2 and immune molecules are associated with COVID-19 disease severity","volume":"4","year":"2024","journal-title":"Communications Medicine"},{"key":"2025060600300548000_2025.02.12.25322167v2.47","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00036.2005"},{"issue":"7","key":"2025060600300548000_2025.02.12.25322167v2.48","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nrcardio.2014.59","article-title":"Angiotensin-converting enzyme 2 and angiotensin 1\u20137: novel therapeutic targets","volume":"11","year":"2014","journal-title":"Nature Reviews Cardiology"},{"key":"2025060600300548000_2025.02.12.25322167v2.49","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10406"},{"key":"2025060600300548000_2025.02.12.25322167v2.50","doi-asserted-by":"publisher","DOI":"10.1042\/CS20130436"},{"key":"2025060600300548000_2025.02.12.25322167v2.51","doi-asserted-by":"crossref","unstructured":"Khajeh Pour S , Ranjit A , Summerill EL , Aghazadeh-Habashi A . Anti-Inflammatory Effects of Ang-(1-7) Bone-Targeting Conjugate in an Adjuvant-Induced Arthritis Rat Model. Pharmaceuticals (Basel). 2022 Sep 17;15(9). PMC9502795","DOI":"10.3390\/ph15091157"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.02.12.25322167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:28:05Z","timestamp":1768508885000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.02.12.25322167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":51,"URL":"https:\/\/doi.org\/10.1101\/2025.02.12.25322167","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1128\/mbio.01735-25","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,2,13]]},"subtype":"preprint"}}