{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:23Z","timestamp":1792787603955,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01DK128203,R01DK129522,R01DK109713,R01DK111102,K01DK096127,R01DK126926"],"award-info":[{"award-number":["R01DK128203,R01DK129522,R01DK109713,R01DK111102,K01DK096127,R01DK126926"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["16SDG27500017"],"award-info":[{"award-number":["16SDG27500017"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,22]]},"abstract":"<jats:p>\n                    Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2\/COVID-19 or rhinovirus common cold infection. At low doses, COVID-19 cocktails induced glomerular injury and albuminuria in zinc fingers and homeoboxes 2 (\n                    <jats:italic>Zhx2<\/jats:italic>\n                    ) hypomorph and\n                    <jats:italic>\n                      Zhx2\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice to mimic COVID-19\u2013related proteinuria. Common Cold cocktail induced albuminuria selectively in\n                    <jats:italic>Zhx2<\/jats:italic>\n                    hypomorph mice to model relapse of minimal change disease, which improved after depletion of TNF-\u03b1, soluble IL-4R\u03b1, or IL-6. The\n                    <jats:italic>Zhx2<\/jats:italic>\n                    hypomorph state increased cell membrane to nuclear migration of podocyte ZHX proteins in vivo (both cocktails) and lowered phosphorylated STAT6 activation (COVID-19 cocktail) in vitro. At higher doses, COVID-19 cocktails induced acute heart injury, myocarditis, pericarditis, acute liver injury, acute kidney injury, and high mortality in\n                    <jats:italic>\n                      Zhx2\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice, whereas\n                    <jats:italic>Zhx2<\/jats:italic>\n                    hypomorph mice were relatively protected, due in part to early, asynchronous activation of STAT5 and STAT6 pathways in these organs. Dual depletion of cytokine combinations of TNF-\u03b1 with IL-2, IL-13, or IL-4 in\n                    <jats:italic>\n                      Zhx2\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice reduced multiorgan injury and eliminated mortality. Using genome sequencing and CRISPR\/Cas9, an insertion upstream of\n                    <jats:italic>ZHX2<\/jats:italic>\n                    was identified as a cause of the human\n                    <jats:italic>ZHX2<\/jats:italic>\n                    hypomorph state.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.166012","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T12:00:24Z","timestamp":1681214424000},"source":"Crossref","is-referenced-by-count":13,"title":["Cytokine storm\u2013based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection"],"prefix":"10.1172","volume":"8","author":[{"given":"Maria","family":"Del Nogal Avila","sequence":"first","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7951-4121","authenticated-orcid":true,"given":"Ranjan","family":"Das","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joubert","family":"Kharlyngdoh","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Molina-Jijon","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Donoro Blazquez","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Gambut","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Crowley","sequence":"additional","affiliation":[{"name":"Genomics Core Lab, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0981-169X","authenticated-orcid":true,"given":"David K.","family":"Crossman","sequence":"additional","affiliation":[{"name":"Genomics Core Lab, University of Alabama at Birmingham, Birmingham, Alabama, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasheed A.","family":"Gbadegesin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunveer S.","family":"Chugh","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunjeet S.","family":"Chugh","sequence":"additional","affiliation":[{"name":"Glomerular Disease Therapeutics Laboratory, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Avila-Casado","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, 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