{"id":2540,"date":"2021-08-20T20:19:25","date_gmt":"2021-08-20T20:19:25","guid":{"rendered":"http:\/\/wp.cov19longhaulfoundation.org\/?p=2540"},"modified":"2021-08-20T20:19:25","modified_gmt":"2021-08-20T20:19:25","slug":"cytokeratin-18-cell-death-assays-as-biomarkers-for-quantification-of-apoptosis-and-necrosis-in-covid-19-a-prospective-observational-study","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=2540","title":{"rendered":"Cytokeratin 18 cell death assays as biomarkers for quantification of apoptosis and necrosis in COVID-19: a prospective, observational study"},"content":{"rendered":"\n<p>Authors: Brandon Michael Henry<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-1\">1<\/a>,\u00a0<a rel=\"noreferrer noopener\" href=\"http:\/\/orcid.org\/0000-0002-1211-8247\" target=\"_blank\">http:\/\/orcid.org\/0000-0002-1211-8247<\/a>Isaac Cheruiyot<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-2\">2<\/a>,\u00a0Stefanie W Benoit<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-3\">3<\/a>,<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-4\">4<\/a>,\u00a0Fabian Sanchis-Gomar<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-5\">5<\/a>,<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-6\">6<\/a>,\u00a0<a rel=\"noreferrer noopener\" href=\"http:\/\/orcid.org\/0000-0001-9523-9054\" target=\"_blank\">http:\/\/orcid.org\/0000-0001-9523-9054<\/a>Giuseppe Lippi<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-7\">7<\/a>,\u00a0Justin Benoit<a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242#aff-8\">8<\/a>      Correspondence to\u00a0Dr Brandon Michael Henry, Cincinnati Children&#8217;s Hospital Medical Center, Cincinnati, Ohio, USA;<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n\n\n<p id=\"p-2\" style=\"font-size:24px\"><strong>Background<\/strong>&nbsp;The mechanism by which SARS-CoV-2 triggers cell damage and necrosis are yet to be fully elucidated. We sought to quantify epithelial cell death in patients with COVID-19, with an estimation of relative contributions of apoptosis and necrosis.<\/p>\n\n\n\n<p id=\"p-3\" style=\"font-size:24px\"><strong>Methods<\/strong>&nbsp;Blood samples were collected prospectively from adult patients presenting to the emergency department. Circulating levels of caspase-cleaved (apoptosis) and total cytokeratin 18 (CK-18) (total cell death) were determined using M30 and M65 enzyme assays, respectively. Intact CK-18 (necrosis) was estimated by subtracting M30 levels from M65.<\/p>\n\n\n\n<p id=\"p-4\" style=\"font-size:24px\"><strong>Results<\/strong>&nbsp;A total of 52 COVID-19 patients and 27 matched sick controls (with respiratory symptoms not due to COVID-19) were enrolled. Compared with sick controls, COVID-19 patients had higher levels of M65 (p\u2009=\u20090.046, total cell death) and M30 (p\u2009=\u20090.0079, apoptosis). Hospitalised COVID-19 patients had higher levels of M65 (p=\u20090.014) and intact CK-18 (p=\u20090.004, necrosis) than discharged patients. Intensive care unit (ICU)-admitted COVID-19 patients had higher levels of M65 (p=\u20090.004), M30 (p=\u20090.004) and intact CK-18 (p=\u20090.033) than hospitalised non-ICU admitted patients. In multivariable logistic regression, elevated levels of M65, M30 and intact CK-18 were associated with increased odds of ICU admission (OR=22.05, p=0.014, OR=19.71, p=0.012\u2009and OR=14.12, p=0.016, respectively).<\/p>\n\n\n\n<p id=\"p-5\" style=\"font-size:24px\"><strong>Conclusion<\/strong>\u00a0Necrosis appears to be the main driver of hospitalization, whereas apoptosis and necrosis appear to drive ICU admission. Elevated levels CK-18 levels are independent predictors of severe disease, and could be useful for risk stratification of COVID-19 patients and in assessment of therapeutic efficacy in early-phase COVID-19 clinical trials.<\/p>\n\n\n\n<p class=\"has-large-font-size\">For More Information: <a href=\"https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/jcp.bmj.com\/content\/early\/2021\/03\/30\/jclinpath-2020-207242<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Authors: Brandon Michael Henry1,\u00a0http:\/\/orcid.org\/0000-0002-1211-8247Isaac Cheruiyot2,\u00a0Stefanie W Benoit3,4,\u00a0Fabian Sanchis-Gomar5,6,\u00a0http:\/\/orcid.org\/0000-0001-9523-9054Giuseppe Lippi7,\u00a0Justin Benoit8 Correspondence to\u00a0Dr Brandon Michael Henry, Cincinnati Children&#8217;s Hospital Medical Center, Cincinnati, Ohio, USA; Abstract Background&nbsp;The mechanism by which SARS-CoV-2 triggers [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":2541,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26,774,300,301,892],"tags":[],"class_list":["post-2540","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-apoptosis","category-cytokeratin-ck-18","category-m30-enzyme-assay","category-m65-enzyme-assay","category-necrosis"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/2540","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2540"}],"version-history":[{"count":0,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/2540\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/2541"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2540"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2540"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2540"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}