{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:18:27Z","timestamp":1780391907769,"version":"3.54.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, and is caused by overactivation of the alternative complement pathway. A 13-year-old Japanese boy with an unremarkable medical history developed symptoms of TMA following coronavirus disease 2019 (COVID-19) infection with mild respiratory symptoms. He was eventually diagnosed with aHUS with a gain-of-function <jats:italic>C3<\/jats:italic> variant. He improved with supportive therapy and plasma exchange, and did not require anti-C5 antibody therapy. In the literature, more than 20 cases of <jats:italic>de novo<\/jats:italic> or relapsed aHUS have been described following COVID-19. It has been shown that the complement lectin pathway can be activated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and N proteins, and the alternative pathway can be activated by the SARS-CoV-2 spike protein. The current case highlights the possibility that COVID-19, even when respiratory symptoms are not severe, can trigger aHUS.<\/jats:p>","DOI":"10.3389\/fped.2025.1507727","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T07:00:03Z","timestamp":1737615603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Atypical hemolytic uremic syndrome with a C3 variant following COVID-19: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Masato","family":"Ando","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kubota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Kadowaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minako","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Nagaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Miwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Ohnishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.5551\/jat.RV17026","article-title":"Pathogenesis of atypical hemolytic uremic syndrome","volume":"26","author":"Yoshida","year":"2019","journal-title":"J Atheroscler Thromb"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s10875-022-01289-3","article-title":"Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee","volume":"42","author":"Tangye","year":"2022","journal-title":"J Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11307","DOI":"10.3390\/ijms231911307","article-title":"Coronavirus disease 2019-associated thrombotic microangiopathy: literature review","volume":"23","author":"Vre\u010dko","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3134","DOI":"10.1016\/j.ekir.2024.07.034","article-title":"Systematic review of individual patient data COVID-19 infection and vaccination-associated thrombotic microangiopathy","volume":"9","author":"Moradiya","year":"2024","journal-title":"Kidney Int Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e2020016774","DOI":"10.1542\/peds.2020-016774","article-title":"Toddler with new onset diabetes and atypical hemolytic-uremic syndrome in the setting of COVID-19","volume":"147","author":"Alizadeh","year":"2021","journal-title":"Pediatrics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"11795565211049897","DOI":"10.1177\/11795565211049897","article-title":"Thrombotic microangiopathy in a severe pediatric case of COVID-19","volume":"15","author":"Dalk\u0131ran","year":"2021","journal-title":"Clin Med Insights Pediatr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1007\/s00467-021-05390-4","article-title":"Anti-factor H antibody associated hemolytic uremic syndrome following SARS-CoV-2 infection","volume":"37","author":"Khandelwal","year":"2022","journal-title":"Pediatr Nephrol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1007\/s00467-022-05457-w","article-title":"Pathology findings in pediatric patients with COVID-19 and kidney dysfunction","volume":"37","author":"Nomura","year":"2022","journal-title":"Pediatr Nephrol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1007\/s00467-022-05566-6","article-title":"Atypical hemolytic uremic syndrome induced by SARS-CoV2 infection in infants with EXOSC3 mutation","volume":"37","author":"Quekelberghe","year":"2022","journal-title":"Pediatr Nephrol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3811170","DOI":"10.1155\/2022\/3811170","article-title":"Coronavirus disease 2019 (COVID-19) associated hemolytic uremic syndrome in a toddler","volume":"2022","author":"Searcy","year":"2022","journal-title":"Case Rep Pediatr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1092860","DOI":"10.3389\/fped.2023.1092860","article-title":"Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: an instructive case report of a previously healthy toddler and review of literature","volume":"11","author":"Mato\u0161evi\u0107","year":"2023","journal-title":"Front Pediatr"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.3390\/diagnostics13071228","article-title":"Pitfalls of thrombotic microangiopathies in children: two case reports and literature review","volume":"13","author":"Mocanu","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1111\/nep.14225","article-title":"COVID-19 associated thrombotic microangiopathy","volume":"28","author":"Yilmaz","year":"2023","journal-title":"Nephrology (Carlton)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"251","DOI":"10.24953\/turkjpediatr.2024.4524","article-title":"A pediatric case with hemolytic uremic syndrome associated with COVID-19, which progressed to end-stage kidney disease","volume":"66","author":"D\u00f6ven","year":"2024","journal-title":"Turk J Pediatr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.24875\/BMHIM.21000061","article-title":"Thrombotic thrombocytopenic purpura associated with COVID-19 in a critically ill child: a Peruvian case report","volume":"79","author":"Dom\u00ednguez-Rojas","year":"2022","journal-title":"Bol Med Hosp Infant Mex"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e812","DOI":"10.1097\/MPH.0000000000002370","article-title":"Unusual presentation of thrombotic thrombocytopenic purpura in a newly diagnosed pediatric patient with systemic lupus erythematosus in the setting of MIS-C","volume":"44","author":"Al-Antary","year":"2022","journal-title":"J Pediatr Hematol Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1007\/s00467-022-05701-3","article-title":"Acute kidney injury following multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis","volume":"38","author":"Tripathi","year":"2023","journal-title":"Pediatr Nephrol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"692256","DOI":"10.3389\/fped.2021.692256","article-title":"Acute kidney injury in pediatric acute SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C): is there a difference?","volume":"9","author":"Grewal","year":"2021","journal-title":"Front Pediatr"},{"key":"B19","doi-asserted-by":"publisher","first-page":"760070","DOI":"10.3389\/fped.2021.760070","article-title":"Hematuria as an early sign of multisystem inflammatory syndrome in children: a case report of a boy with multiple comorbidities and review of literature","volume":"9","author":"Generali\u0107","year":"2021","journal-title":"Front Pediatr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1007\/s10157-018-1549-3","article-title":"Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome","volume":"22","author":"Fujisawa","year":"2018","journal-title":"Clin Exp Nephrol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.2215\/CJN.06281208","article-title":"A large family with a gain-of-function mutation of complement C3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure","volume":"4","author":"Lhotta","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00467-010-1708-6","article-title":"Eculizumab induces long-term remission in recurrent post-transplant HUS associated with C3 gene mutation","volume":"26","author":"Al-Akash","year":"2011","journal-title":"Pediatr Nephrol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3399","DOI":"10.1093\/ndt\/gfr422","article-title":"Thrombotic microangiopathy mimicking membranoproliferative glomerulonephritis","volume":"26","author":"Brackman","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4182","DOI":"10.1182\/blood-2011-10-383281","article-title":"A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function","volume":"119","author":"Roumenina","year":"2012","journal-title":"Blood"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1007\/s00467-012-2183-z","article-title":"Novel C3 mutation p.Lys65Gln in aHUS affects complement factor H binding","volume":"27","author":"Volokhina","year":"2012","journal-title":"Pediatr Nephrol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.molimm.2012.12.006","article-title":"Analysis of genetic and predisposing factors in Japanese patients with atypical hemolytic uremic syndrome","volume":"54","author":"Fan","year":"2013","journal-title":"Mol Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1681\/ASN.2012090884","article-title":"Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype","volume":"24","author":"Bresin","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s12185-014-1655-2","article-title":"Analysis of patients with atypical hemolytic uremic syndrome treated at the mie university hospital: concentration of C3 p.I1157T mutation","volume":"100","author":"Matsumoto","year":"2014","journal-title":"Int J Hematol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s00467-015-3267-3","article-title":"aHUS associated with C3 gene mutation: a case with numerous relapses and favorable 20-year outcome","volume":"31","author":"Siomou","year":"2016","journal-title":"Pediatr Nephrol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.1097\/MPH.0000000000000505","article-title":"Disease recurrence after early discontinuation of eculizumab in a patient with atypical hemolytic uremic syndrome with complement C3 I1157T mutation","volume":"38","author":"Toyoda","year":"2016","journal-title":"J Pediatr Hematol Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1007\/s00431-017-2856-5","article-title":"Occurrence of atypical HUS associated with influenza B","volume":"176","author":"van Hoeve","year":"2017","journal-title":"Eur J Pediatr"},{"key":"B32","doi-asserted-by":"publisher","first-page":"178","DOI":"10.11406\/rinketsu.59.178","article-title":"Atypical hemolytic uremic syndrome with C3 p.I1157T missense mutation successfully treated with eculizumab","volume":"59","author":"Okano","year":"2018","journal-title":"Rinsho Ketsueki"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1177\/1076029618771750","article-title":"Clinical manifestation of patients with atypical hemolytic uremic syndrome with the C3 p.I1157T variation in the kinki region of Japan","volume":"24","author":"Matsumoto","year":"2018","journal-title":"Clin Appl Thromb Hemost"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1159\/000502289","article-title":"Life-threatening extrarenal manifestations in an infant with atypical hemolytic uremic syndrome caused by a complement 3-gene mutation","volume":"44","author":"Han","year":"2019","journal-title":"Kidney Blood Press Res"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.3389\/fimmu.2020.01348","article-title":"The relevance of the MCP risk polymorphism to the outcome of aHUS associated with C3 mutations. A case report","volume":"11","author":"Lumbreras","year":"2020","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"917","DOI":"10.2169\/internalmedicine.5716-20","article-title":"Renal damage in recurrent atypical hemolytic uremic syndrome associated with C3 p.Ile1157Thr gene mutation","volume":"60","author":"Okabe","year":"2021","journal-title":"Intern Med"},{"key":"B37","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s12882-021-02293-2","article-title":"Eculizumab therapy on a patient with co-existent lupus nephritis and C3 mutation-related atypical haemolytic uremic syndrome: a case report","volume":"22","author":"Kim","year":"2021","journal-title":"BMC Nephrol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1016\/j.ekir.2021.03.897","article-title":"Kidney thrombotic microangiopathy after COVID-19 associated with C3 gene mutation","volume":"6","author":"Mat","year":"2021","journal-title":"Kidney Int Rep"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e244190","DOI":"10.1136\/bcr-2021-244190","article-title":"Atypical haemolytic uraemic syndrome: a case of rare genetic mutation","volume":"14","author":"Sangeetha","year":"2021","journal-title":"BMJ Case Rep"},{"key":"B40","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1053\/j.ajkd.2022.07.012","article-title":"Atypical hemolytic uremic syndrome occurring after receipt of mRNA-1273 COVID-19 vaccine booster: a case report","volume":"81","author":"Claes","year":"2023","journal-title":"Am J Kidney Dis"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1007\/s40620-023-01595-y","article-title":"Relapse of atypical hemolytic uremic syndrome triggered by COVID-19: a lesson for the clinical nephrologist","volume":"36","author":"Uwatoko","year":"2023","journal-title":"J Nephrol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1007\/s40620-023-01646-4","article-title":"Atypical HUS with multiple complement system mutations triggered by synthetic psychoactive drug abuse: a case report","volume":"36","author":"Jelicic","year":"2023","journal-title":"J Nephrol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/s41590-021-01114-w","article-title":"Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules","volume":"23","author":"Stravalaci","year":"2022","journal-title":"Nat Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"714511","DOI":"10.3389\/fimmu.2021.714511","article-title":"Lectin pathway mediates complement activation by SARS-CoV-2 proteins","volume":"12","author":"Ali","year":"2021","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s41392-022-01133-5","article-title":"Highly pathogenic coronavirus N protein aggravates inflammation by MASP-2-mediated lectin complement pathway overactivation","volume":"7","author":"Gao","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.3324\/haematol.2021.279155","article-title":"Complement dysregulation is associated with severe COVID-19 illness","volume":"107","author":"Yu","year":"2022","journal-title":"Haematologica"},{"key":"B47","doi-asserted-by":"publisher","first-page":"eabd4570","DOI":"10.1126\/science.abd4570","article-title":"Inborn errors of type I IFN immunity in patients with life-threatening COVID-19","volume":"370","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"B48","doi-asserted-by":"publisher","first-page":"eabd4585","DOI":"10.1126\/science.abd4585","article-title":"Autoantibodies against type I IFNs in patients with life-threatening COVID-19","volume":"370","author":"Bastard","year":"2020","journal-title":"Science"},{"key":"B49","doi-asserted-by":"publisher","first-page":"eabo3627","DOI":"10.1126\/science.abo3627","article-title":"Inborn errors of OAS\u2013RNase L in SARS-CoV-2\u2013related multisystem inflammatory syndrome in children","volume":"379","author":"Lee","year":"2023","journal-title":"Science"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1507727\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T07:00:06Z","timestamp":1737615606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1507727\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,23]]},"references-count":49,"alternative-id":["10.3389\/fped.2025.1507727"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1507727","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,23]]},"article-number":"1507727"}}