{"id":23743,"date":"2021-11-24T02:45:30","date_gmt":"2021-11-24T02:45:30","guid":{"rendered":"https:\/\/evaggelatos.com\/?p=23743"},"modified":"2021-11-24T02:55:12","modified_gmt":"2021-11-24T02:55:12","slug":"23743","status":"publish","type":"post","link":"https:\/\/evaggelatos.com\/?p=23743","title":{"rendered":"\u03a4\u03b9 \u03c1\u03cc\u03bb\u03bf \u03c0\u03b1\u03af\u03b6\u03b5\u03b9 \u03bf \u03a0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03c2 \u0395\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c4\u03c9\u03bd \u0391\u03b9\u03bc\u03bf\u03c0\u03b5\u03c4\u03b1\u03bb\u03af\u03c9\u03bd (PAF) \u03c9\u03c2 \u03b4\u03c5\u03bd\u03b7\u03c4\u03b9\u03ba\u03cc\u03c2 \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1\u03c2 \u03c0\u03bf\u03c5 \u03c3\u03c5\u03bd\u03b5\u03b9\u03c3\u03c6\u03ad\u03c1\u03b5\u03b9 \u03c3\u03c4\u03b7 \u03bd\u03bf\u03c3\u03b7\u03c1\u03cc\u03c4\u03b7\u03c4\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7 \u03b8\u03bd\u03b7\u03c3\u03b9\u03bc\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c0\u03bf\u03c5 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c3\u03bf\u03b2\u03b1\u03c1\u03ae \u03bd\u03cc\u03c3\u03bf COVID-19."},"content":{"rendered":"<header class=\"post-header\">\n<h1 class=\"entry-title nom font-size-32 times\">\u039d\u03b5\u03cc\u03c4\u03b5\u03c1\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19 \u03bc\u03ad\u03c3\u03b1 \u03b1\u03c0\u03cc \u03bc\u03b9\u03b1 \u03ac\u03bb\u03bb\u03b7 \u2013 \u03bd\u03ad\u03b1 \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03b8\u03ad\u03bc\u03b1\u03c4\u03bf\u03c2<\/h1>\n<div class=\"post-meta georgia\">YgeiaNews | <a href=\"mailto:info@ygeianews.gr\">info@ygeianews.gr<\/a> | 23\/11\/2021 &#8211; 09:40<\/div>\n<\/header>\n<div id=\"PostImage\" class=\"maskimage article-image\"><img decoding=\"async\" class=\"imagefit\" src=\"https:\/\/www.ygeiamasnews.gr\/wp-content\/uploads\/2021\/11\/covid-1-768x450-1.jpg\" alt=\"\u039d\u03b5\u03cc\u03c4\u03b5\u03c1\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19 \u03bc\u03ad\u03c3\u03b1 \u03b1\u03c0\u03cc \u03bc\u03b9\u03b1 \u03ac\u03bb\u03bb\u03b7 \u2013 \u03bd\u03ad\u03b1 \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03b8\u03ad\u03bc\u03b1\u03c4\u03bf\u03c2\" \/><\/div>\n<div class=\"post-body\">\n<div class=\"article-wrapper georgia\">\n<div class=\"addthis_inline_share_toolbox_wfii\"><\/div>\n<div class=\"content-wrap\">\n<p><strong>\u0388\u03c7\u03bf\u03c5\u03bd \u03c0\u03b5\u03c1\u03ac\u03c3\u03b5\u03b9\u00a0 \u03b4\u03cd\u03bf \u03c0\u03b5\u03c1\u03af\u03c0\u03bf\u03c5 \u03c7\u03c1\u03cc\u03bd\u03b9\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03b5\u03bc\u03c6\u03ac\u03bd\u03b9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c0\u03c1\u03c9\u03c4\u03cc\u03b3\u03bd\u03c9\u03c1\u03b7\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b1\u03bd\u03b5\u03c0\u03c4\u03c5\u03b3\u03bc\u03ad\u03bd\u03bf \u03ba\u03cc\u03c3\u03bc\u03bf \u03c0\u03b1\u03bd\u03b4\u03b7\u03bc\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd, \u03ad\u03c7\u03bf\u03c5\u03bd \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03c4\u03b1 \u03ba\u03b1\u03c4\u03ac\u03bb\u03bb\u03b7\u03bb\u03b1 \u03b5\u03bc\u03b2\u03cc\u03bb\u03b9\u03b1 \u03ba\u03b1\u03b9 \u03c0\u03b1\u03c1\u03bf\u03c5\u03c3\u03b9\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03ae\u03b4\u03b7 \u03c4\u03b1 \u03c0\u03c1\u03ce\u03c4\u03b1 \u03c6\u03ac\u03c1\u03bc\u03b1\u03ba\u03b1, \u03b1\u03bb\u03bb\u03ac \u03b4\u03b5\u03bd \u03ad\u03c7\u03b5\u03b9 \u03b1\u03ba\u03cc\u03bc\u03b1 \u03b4\u03b9\u03b5\u03c5\u03ba\u03c1\u03b9\u03bd\u03b9\u03c3\u03c4\u03b5\u03af \u03c0\u03bb\u03ae\u03c1\u03c9\u03c2 \u03bf \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc\u03c2 \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03c0\u03c1\u03cc\u03ba\u03bb\u03b7\u03c3\u03b7\u03c2 \u03b1\u03c0\u03cc \u03b1\u03c5\u03c4\u03cc\u03bd \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19<\/strong>.<\/p>\n<p>\u038c\u03c0\u03c9\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03ba\u03b1\u03c4\u03b1\u03bd\u03bf\u03b7\u03c4\u03cc,<strong> \u03b7 \u03b4\u03b9\u03b1\u03bb\u03b5\u03cd\u03ba\u03b1\u03bd\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03bf\u03cd \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03bc\u03b9\u03b1\u03c2 \u03c0\u03b1\u03b8\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ae\u03c2 \u03ba\u03b1\u03c4\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7\u03c2 \u03b5\u03af\u03bd\u03b1\u03b9 \u03c0\u03c1\u03c9\u03c4\u03b1\u03c1\u03c7\u03b9\u03ba\u03ae\u03c2 \u03c3\u03b7\u03bc\u03b1\u03c3\u03af\u03b1\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03b1\u03c0\u03bf\u03bb\u03cd\u03c4\u03c9\u03c2 \u03b5\u03c0\u03b9\u03c4\u03c5\u03c7\u03ae \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03ae \u03c4\u03b7\u03c2,<\/strong> \u03ad\u03c3\u03c4\u03c9 \u03ba\u03b1\u03b9 \u03b1\u03bd \u03ad\u03c7\u03bf\u03c5\u03bd \u03c5\u03c0\u03ac\u03c1\u03be\u03b5\u03b9<strong> \u03ba\u03ac\u03c0\u03bf\u03b9\u03bf\u03b9 \u03c4\u03c1\u03cc\u03c0\u03bf\u03b9 \u03bc\u03b5\u03c1\u03b9\u03ba\u03ae\u03c2 \u03b1\u03bd\u03c4\u03b9\u03bc\u03b5\u03c4\u03ce\u03c0\u03b9\u03c3\u03ae\u03c2 \u03c4\u03b7\u03c2<\/strong>.<\/p>\n<p><strong>\u03a4\u03bf\u03bd \u039d\u03bf\u03ad\u03bc\u03b2\u03c1\u03b9\u03bf \u03c4\u03bf\u03c5 2021 \u03b4\u03b7\u03bc\u03bf\u03c3\u03b9\u03b5\u03cd\u03c4\u03b7\u03ba\u03b5 \u03c3\u03c4\u03bf \u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03bf\u03bd\u03b9\u03ba\u03cc \u03c0\u03b5\u03c1\u03b9\u03bf\u03b4\u03b9\u03ba\u03cc <em>Clinical and Applied Thrombosis\/Hemostasis <\/em>\u03ad\u03bd\u03b1 \u03ac\u03c1\u03b8\u03c1\u03bf \u03b1\u03bd\u03b1\u03c3\u03ba\u03cc\u03c0\u03b7\u03c3\u03b7\u03c2<\/strong> \u03ba\u03b1\u03b8\u03b7\u03b3\u03b7\u03c4\u03ce\u03bd \u03c4\u03bf\u03c5 \u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03af\u03bf\u03c5 \u03c4\u03b7\u03c2 \u039c\u03b9\u03bd\u03b5\u03c3\u03cc\u03c4\u03b1\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03bf\u03c5 Veterans Affairs Health care System \u03c4\u03b7\u03c2 \u039c\u03b9\u03bd\u03b5\u03ac\u03c0\u03bf\u03bb\u03b7\u03c2 \u03c4\u03c9\u03bd \u0397\u03a0\u0391 \u03bc\u03b5 \u03c4\u03af\u03c4\u03bb\u03bf <em>\u201c<strong>\u0391\u03bd\u03b1\u03c3\u03ba\u03cc\u03c0\u03b7\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03a0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 \u0395\u03bd\u03b5\u03c1\u03b3\u03bf\u03c0\u03bf\u03af\u03b7\u03c3\u03b7\u03c2 \u03c4\u03c9\u03bd \u0391\u03b9\u03bc\u03bf\u03c0\u03b5\u03c4\u03b1\u03bb\u03af\u03c9\u03bd (PAF) \u03c9\u03c2 \u03b4\u03c5\u03bd\u03b7\u03c4\u03b9\u03ba\u03bf\u03cd \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 \u03c0\u03bf\u03c5 \u03c3\u03c5\u03bd\u03b5\u03b9\u03c3\u03c6\u03ad\u03c1\u03b5\u03b9 \u03c3\u03c4\u03b7 \u03bd\u03bf\u03c3\u03b7\u03c1\u03cc\u03c4\u03b7\u03c4\u03b1 \u03ba\u03b1\u03b9 \u03c3\u03c4\u03b7 \u03b8\u03bd\u03b7\u03c3\u03b9\u03bc\u03cc\u03c4\u03b7\u03c4\u03b1 \u03c0\u03bf\u03c5 \u03c3\u03c7\u03b5\u03c4\u03af\u03b6\u03b5\u03c4\u03b1\u03b9 \u03bc\u03b5 \u03c3\u03bf\u03b2\u03b1\u03c1\u03ae \u03bd\u03cc\u03c3\u03bf COVID-19<\/strong>\u201d (A Review of Platelet-ActivatingFactorAs a Potential Contributorto Morbidity\u00a0 and Mortality Associate dwith Severe COVID-19).<\/em><\/p>\n<p>\u03a4<strong>\u03bf \u03ac\u03c1\u03b8\u03c1\u03bf \u03b1\u03c5\u03c4\u03cc, \u03c3\u03c4\u03bf \u03c0\u03bb\u03b1\u03af\u03c3\u03b9\u03bf \u03c4\u03b7\u03c2 \u03b4\u03b9\u03b5\u03c1\u03b5\u03cd\u03bd\u03b7\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03c0\u03b9\u03b8\u03b1\u03bd\u03bf\u03cd \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03bf\u03cd \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd, \u03b1\u03bd\u03b1\u03c6\u03ad\u03c1\u03b5\u03c4\u03b1\u03b9 \u03c3\u03c4\u03bf \u03c1\u03cc\u03bb\u03bf \u03c4\u03c9\u03bd \u03c6\u03bb\u03b5\u03b3\u03bc\u03bf\u03bd\u03c9\u03b4\u03ce\u03bd \u03c0\u03b1\u03c1\u03b1\u03b3\u03cc\u03bd\u03c4\u03c9\u03bd<\/strong> \u03ba\u03b1\u03b9 <strong>\u03c3\u03c5\u03b3\u03ba\u03b5\u03ba\u03c1\u03b9\u03bc\u03ad\u03bd\u03b1 \u03c4\u03bf\u03c5 PAF \u03b5\u03c0\u03b9\u03c3\u03b7\u03bc\u03b1\u03af\u03bd\u03bf\u03bd\u03c4\u03b1\u03c2 \u03c4\u03b9\u03c2 \u03bf\u03bc\u03bf\u03b9\u03cc\u03c4\u03b7\u03c4\u03b5\u03c2 \u03c4\u03c9\u03bd \u03b2\u03b9\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ce\u03bd \u03b4\u03c1\u03ac\u03c3\u03b5\u03c9\u03bd \u03c4\u03bf\u03c5 PAF \u03bc\u03b5 \u03c4\u03b9\u03c2 \u03ba\u03bb\u03b9\u03bd\u03b9\u03ba\u03ad\u03c2 \u03b5\u03c0\u03b9\u03c0\u03bb\u03bf\u03ba\u03ad\u03c2 \u03c0\u03bf\u03c5 \u03c0\u03b1\u03c1\u03bf\u03c5\u03c3\u03b9\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03c3\u03c4\u03b7 \u03c3\u03bf\u03b2\u03b1\u03c1\u03ae \u03bd\u03cc\u03c3\u03bf COVID-19. <\/strong><\/p>\n<p>\u039a\u03b1\u03b9 <strong>\u03ba\u03b1\u03c4\u03b1\u03bb\u03ae\u03b3\u03b5\u03b9 \u03c3\u03c4\u03bf \u03c3\u03c5\u03bc\u03c0\u03ad\u03c1\u03b1\u03c3\u03bc\u03b1 \u03cc\u03c4\u03b9 \u03b4\u03c5\u03c3\u03bb\u03b5\u03b9\u03c4\u03bf\u03c5\u03c1\u03b3\u03af\u03b5\u03c2 \u03ae\/\u03ba\u03b1\u03b9 \u03b1\u03c0\u03bf\u03c1\u03c1\u03cd\u03b8\u03bc\u03b9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03b5\u03c4\u03b1\u03b2\u03bf\u03bb\u03b9\u03c3\u03bc\u03bf\u03cd \u03c4\u03bf\u03c5 PAF \u03b1\u03c0\u03cc \u03c4\u03bf\u03bd \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03cc \u03bc\u03c0\u03bf\u03c1\u03b5\u03af \u03bd\u03b1 \u03c0\u03c1\u03bf\u03ba\u03b1\u03bb\u03bf\u03cd\u03bd \u03b1\u03c5\u03c4\u03ad\u03c2 \u03c4\u03b9\u03c2 \u03c0\u03b1\u03b8\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ad\u03c2 \u03ba\u03b1\u03c4\u03b1\u03c3\u03c4\u03ac\u03c3\u03b5\u03b9\u03c2<\/strong>.<\/p>\n<p><strong>\u0397 \u03bd\u03ad\u03b1 \u03b1\u03c5\u03c4\u03ae \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03c4\u03b7 \u03b4\u03b9\u03b1\u03bb\u03b5\u03cd\u03ba\u03b1\u03bd\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03bf\u03cd \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd \u03bc\u03ad\u03c3\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03b4\u03c1\u03ac\u03c3\u03b7 \u03c4\u03bf\u03c5 PAF \u03ad\u03c7\u03b5\u03b9 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03ad\u03c3\u03b5\u03b9 \u03b8\u03ad\u03bc\u03b1 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b7\u03c2, \u03b1\u03c0\u03cc \u03c4\u03bf 2020, \u03c4\u03b7\u03c2 \u03b5\u03c1\u03b5\u03c5\u03bd\u03b7\u03c4\u03b9\u03ba\u03ae\u03c2 \u03bf\u03bc\u03ac\u03b4\u03b1\u03c2 \u03c0\u03bf\u03c5 \u03b1\u03c0\u03bf\u03c4\u03b5\u03bb\u03b5\u03af\u03c4\u03b1\u03b9 \u03b1\u03c0\u03cc \u03c4\u03bf\u03bd \u039f\u03bc\u03cc\u03c4\u03b9\u03bc\u03bf \u039a\u03b1\u03b8\u03b7\u03b3\u03b7\u03c4\u03ae \u0392\u03b9\u03bf\u03c7\u03b7\u03bc\u03b5\u03af\u03b1\u03c2 &amp; \u03a7\u03b7\u03bc\u03b5\u03af\u03b1\u03c2 \u03a4\u03c1\u03bf\u03c6\u03af\u03bc\u03c9\u03bd \u03c4\u03bf\u03c5 \u03a4\u03bc\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u03a7\u03b7\u03bc\u03b5\u03af\u03b1\u03c2<\/strong> \u03c4\u03bf\u03c5 \u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03af\u03bf\u03c5 \u0391\u03b8\u03b7\u03bd\u03ce\u03bd <strong>\u039a. \u0391. \u0394\u03b7\u03bc\u03cc\u03c0\u03bf\u03c5\u03bb\u03bf<\/strong>, \u03c4\u03b7\u03bd \u039a\u03b1\u03b8\u03b7\u03b3\u03ae\u03c4\u03c1\u03b9\u03b1 \u0392\u03b9\u03bf\u03c7\u03b7\u03bc\u03b5\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03a4\u03bc\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u0395\u03c0\u03b9\u03c3\u03c4\u03ae\u03bc\u03b7\u03c2 \u0394\u03b9\u03b1\u03b9\u03c4\u03bf\u03bb\u03bf\u03b3\u03af\u03b1\u03c2-\u0394\u03b9\u03b1\u03c4\u03c1\u03bf\u03c6\u03ae\u03c2 \u03c4\u03bf\u03c5 \u03a7\u03b1\u03c1\u03bf\u03ba\u03bf\u03c0\u03b5\u03af\u03bf\u03c5 \u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03af\u03bf\u03c5 <strong>\u03a3. \u0391\u03bd\u03c4\u03c9\u03bd\u03bf\u03c0\u03bf\u03cd\u03bb\u03bf\u03c5, \u03c4\u03b7\u03bd \u03a0\u03c1\u03bf\u03ca\u03c3\u03c4\u03b1\u03bc\u03ad\u03bd\u03b7 \u03c4\u03bf\u03c5 \u03a4\u03bc\u03ae\u03bc\u03b1\u03c4\u03bf\u03c2 \u039a\u03bb\u03b9\u03bd\u03b9\u03ba\u03ae\u03c2 \u0394\u03b9\u03b1\u03c4\u03c1\u03bf\u03c6\u03ae\u03c2 \u03c3\u03c4\u03bf \u0393\u039d\u0391 \u039a\u03bf\u03c1\u03b3\u03b9\u03b1\u03bb\u03ad\u03bd\u03b5\u03b9\u03bf \u2013 \u039c\u03c0\u03b5\u03bd\u03ac\u03ba\u03b5\u03b9\u03bf\u00a0 \u0394\u03c1. \u03a0. \u039d\u03c4\u03b5\u03c4\u03bf\u03c0\u03bf\u03cd\u03bb\u03bf\u03c5 <\/strong><strong>\u03ba\u03b1\u03b9 \u03c4\u03bf\u03bd <\/strong>\u039a\u03b1\u03b8\u03b7\u03b3\u03b7\u03c4\u03ae \u03c4\u03bf\u03c5 \u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03af\u03bf\u03c5 Tufts \u03c4\u03b7\u03c2 \u0392\u03bf\u03c3\u03c4\u03cc\u03bd\u03b7\u03c2 <strong>\u0398\u03b5\u03bf\u03c7\u03ac\u03c1\u03b7 \u0398\u03b5\u03bf\u03c7\u03b1\u03c1\u03af\u03b4\u03b7<\/strong>.<\/p>\n<p><strong>\u039c\u03b5 5 \u03b4\u03b7\u03bc\u03bf\u03c3\u03b9\u03b5\u03cd\u03c3\u03b5\u03b9\u03c2 \u03c0\u03bf\u03c5 \u03ad\u03b3\u03b9\u03bd\u03b1\u03bd \u03c3\u03b5 \u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03bf\u03bd\u03b9\u03ba\u03ac \u03c0\u03b5\u03c1\u03b9\u03bf\u03b4\u03b9\u03ba\u03ac \u03c3\u03c4\u03bf \u03b4\u03b9\u03ac\u03c3\u03c4\u03b7\u03bc\u03b1 2020 \u2013 2021 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u0395\u03bb\u03bb\u03b7\u03bd\u03b9\u03ba\u03ae \u03bf\u03bc\u03ac\u03b4\u03b1, \u03ad\u03c7\u03b5\u03b9 \u03c0\u03b5\u03c1\u03b9\u03b3\u03c1\u03b1\u03c6\u03b5<\/strong>\u03af (\u03bc\u03ad\u03c3\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b7 \u03bd\u03ad\u03b1 \u03b1\u03c5\u03c4\u03ae \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03b5\u03bc\u03c0\u03bb\u03bf\u03ba\u03ae \u03c4\u03bf\u03c5 PAF) <strong>\u03bc\u03af\u03b1 \u03c0\u03b9\u03b8\u03b1\u03bd\u03ae \u03b2\u03b9\u03bf\u03c7\u03b7\u03bc\u03b9\u03ba\u03ae \u03c0\u03bf\u03c1\u03b5\u03af\u03b1 \u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03bf\u03bd\u03b9\u03ba\u03ac \u03bf\u03bb\u03bf\u03ba\u03bb\u03b7\u03c1\u03c9\u03bc\u03ad\u03bd\u03b7 \u03ba\u03b1\u03b9 \u03b2\u03b9\u03b2\u03bb\u03b9\u03bf\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03ac \u03c4\u03b5\u03ba\u03bc\u03b7\u03c1\u03b9\u03c9\u03bc\u03ad\u03bd\u03b7 \u03bc\u03b5 \u03c4\u03b7\u03bd \u03bf\u03c0\u03bf\u03af\u03b1 \u03c3\u03c5\u03bc\u03c0\u03bb\u03b7\u03c1\u03ce\u03bd\u03b5\u03c4\u03b1\u03b9 \u03bf \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc\u03c2 \u03b5\u03b9\u03c3\u03cc\u03b4\u03bf\u03c5 \u03c4\u03bf\u03c5 \u03b9\u03bf\u03cd \u03c3\u03c4\u03b1 \u03ba\u03cd\u03c4\u03c4\u03b1\u03c1\u03b1, \u03b1\u03bb\u03bb\u03ac \u03ba\u03b1\u03b9 \u03b5\u03be\u03b7\u03b3\u03bf\u03cd\u03bd\u03c4\u03b1\u03b9\u00a0 \u03bf\u03b9 \u03b5\u03c0\u03b9\u03c0\u03bb\u03bf\u03ba\u03ad\u03c2 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19<\/strong>.<\/p>\n<p>\u0391\u03ba\u03cc\u03bc\u03b1 <strong>\u03b5\u03c0\u03b9\u03c3\u03b7\u03bc\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03b7 \u03c0\u03b9\u03b8\u03b1\u03bd\u03ae \u03b5\u03c5\u03b5\u03c1\u03b3\u03b5\u03c4\u03b9\u03ba\u03ae \u03b4\u03c1\u03ac\u03c3\u03b7 \u03c4\u03c9\u03bd 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\u03c6\u03bb\u03b5\u03b3\u03bc\u03bf\u03bd\u03ce\u03b4\u03bf\u03c5\u03c2 \u03c0\u03b1\u03c1\u03ac\u03b3\u03bf\u03bd\u03c4\u03b1 PAF \u03ad\u03c7\u03b5\u03b9 \u03b1\u03bd\u03b1\u03ba\u03b1\u03bb\u03c5\u03c6\u03b8\u03b5\u03af \u03b1\u03c0\u03cc \u03c4\u03bf\u03bd \u039a. \u0391. \u0394\u03b7\u03bc\u03cc\u03c0\u03bf\u03c5\u03bb\u03bf\u00a0 \u03c4\u03bf 1979 \u03c3\u03c4\u03bf University of Texasat San Antonio.<\/strong><\/p>\n<p><strong>\u03a4\u03bf \u03ac\u03c1\u03b8\u03c1\u03bf \u03b1\u03c5\u03c4\u03cc \u03c4\u03c9\u03bd \u0391\u03bc\u03b5\u03c1\u03b9\u03ba\u03b1\u03bd\u03ce\u03bd \u03ba\u03b1\u03b8\u03b7\u03b3\u03b7\u03c4\u03ce\u03bd \u03cc\u03c7\u03b9 \u03bc\u03cc\u03bd\u03bf<\/strong> <strong>\u03b1\u03c0\u03bf\u03b4\u03ad\u03c7\u03b5\u03c4\u03b1\u03b9 \u03c4\u03b1 \u03cc\u03c3\u03b1 \u03ad\u03c7\u03b5\u03b9 \u03ae\u03b4\u03b7 \u03b4\u03b7\u03bc\u03bf\u03c3\u03b9\u03b5\u03cd\u03c3\u03b5\u03b9 \u03b7 \u0395\u03bb\u03bb\u03b7\u03bd\u03b9\u03ba\u03ae \u03bf\u03bc\u03ac\u03b4\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03b5\u03bc\u03c0\u03bb\u03bf\u03ba\u03ae \u03c4\u03bf\u03c5 PAF \u03c3\u03c4\u03b7\u03bd \u03bd\u03cc\u03c3\u03bf COVID-19<\/strong> (\u03b1\u03bd\u03b1\u03c6\u03ad\u03c1\u03bf\u03bd\u03c4\u03b1\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03b9\u03c2 \u03c3\u03c7\u03b5\u03c4\u03b9\u03ba\u03ad\u03c2 \u03b4\u03b7\u03bc\u03bf\u03c3\u03b9\u03b5\u03cd\u03c3\u03b5\u03b9\u03c2 \u03c4\u03b7\u03c2 \u0395\u03bb\u03bb\u03b7\u03bd\u03b9\u03ba\u03ae\u03c2 \u03bf\u03bc\u03ac\u03b4\u03b1\u03c2) <strong>\u03b1\u03bb\u03bb\u03ac \u03b5\u03bd\u03b9\u03c3\u03c7\u03cd\u03b5\u03b9, \u03b5\u03c0\u03b9\u03b2\u03b5\u03b2\u03b1\u03b9\u03ce\u03bd\u03b5\u03b9 \u03ba\u03b1\u03b9 \u03b5\u03c0\u03b9\u03c7\u03b5\u03b9\u03c1\u03b7\u03bc\u03b1\u03c4\u03bf\u03bb\u03bf\u03b3\u03b5\u03af \u03b3\u03b9\u03b1 \u03cc\u03bb\u03b1 \u03b1\u03c5\u03c4\u03ac \u03c0\u03bf\u03c5 \u03b5\u03af\u03c7\u03b5 \u03b4\u03b7\u03bc\u03bf\u03c3\u03b9\u03b5\u03cd\u03c3\u03b5\u03b9 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03b8\u03ad\u03bc\u03b1 \u03b1\u03c5\u03c4\u03cc \u03b7 \u0395\u03bb\u03bb\u03b7\u03bd\u03b9\u03ba\u03ae \u03bf\u03bc\u03ac\u03b4\u03b1 \u03ba\u03b1\u03b9 \u03b5\u03c0\u03b9\u03c0\u03bb\u03ad\u03bf\u03bd \u03b1\u03c0\u03bf\u03b4\u03af\u03b4\u03b5\u03b9 \u03c3\u03c4\u03bf\u03c5\u03c2 \u03b1\u03bd\u03b1\u03c3\u03c4\u03bf\u03bb\u03b5\u03af\u03c2 \u03c4\u03bf\u03c5 PAF \u03ba\u03b1\u03b9 \u03c0\u03b9\u03b8\u03b1\u03bd\u03ae \u03b5\u03c5\u03b5\u03c1\u03b3\u03b5\u03c4\u03b9\u03ba\u03ae \u03c6\u03b1\u03c1\u03bc\u03b1\u03ba\u03bf\u03bb\u03bf\u03b3\u03b9\u03ba\u03ae \u03b4\u03c1\u03ac\u03c3\u03b7.<\/strong><\/p>\n<p>\u039c\u03ad\u03c7\u03c1\u03b9 \u03c3\u03c4\u03b9\u03b3\u03bc\u03ae\u03c2<strong> \u03ad\u03c7\u03b5\u03b9 \u03b1\u03c0\u03bf\u03b4\u03b5\u03b9\u03c7\u03b8\u03b5\u03af \u03b7 \u03b5\u03c5\u03b5\u03c1\u03b3\u03b5\u03c4\u03b9\u03ba\u03ae \u03b4\u03c1\u03ac\u03c3\u03b7 \u03c4\u03b7\u03c2 \u039c\u03b5\u03c3\u03bf\u03b3\u03b5\u03b9\u03b1\u03ba\u03ae\u03c2 \u03b4\u03af\u03b1\u03b9\u03c4\u03b1\u03c2 \u03ad\u03bd\u03b1\u03bd\u03c4\u03b9 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19, \u03b1\u03c0\u03cc \u03c0\u03b5\u03b9\u03c1\u03b1\u03bc\u03b1\u03c4\u03b9\u03ba\u03ad\u03c2 \u03bc\u03b5\u03bb\u03ad\u03c4\u03b5\u03c2 \u03a0\u03b1\u03bd\u03b5\u03c0\u03b9\u03c3\u03c4\u03b7\u03bc\u03af\u03c9\u03bd \u03c4\u03b7\u03c2 \u0395\u03c5\u03c1\u03ce\u03c0\u03b7\u03c2 \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u0391\u03bc\u03b5\u03c1\u03b9\u03ba\u03ae\u03c2<\/strong>.<\/p>\n<p><strong>\u039c\u03ad\u03bd\u03b5\u03b9 \u03bd\u03b1 \u03b1\u03c0\u03bf\u03b4\u03b5\u03b9\u03c7\u03b8\u03b5\u03af \u03c0\u03b5\u03b9\u03c1\u03b1\u03bc\u03b1\u03c4\u03b9\u03ba\u03ac \u03ba\u03b1\u03b9 \u03bf \u03c0\u03b9\u03b8\u03b1\u03bd\u03cc\u03c2 \u03c1\u03cc\u03bb\u03bf\u03c2 \u03c4\u03bf\u03c5 PAF \u03c3\u03c4\u03bf \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd. <\/strong><\/p>\n<p><strong>\u03a4\u03bf \u03b8\u03ad\u03bc\u03b1 \u03cc\u03bc\u03c9\u03c2 \u03c6\u03b1\u03af\u03bd\u03b5\u03c4\u03b1\u03b9 \u03bd\u03b1 \u03b5\u03af\u03bd\u03b1\u03b9, \u03cc\u03c7\u03b9 \u03c4\u03bf \u03c0\u03bf\u03c3\u03bf\u03c3\u03c4\u03cc \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03bf\u03c7\u03ae\u03c2 \u03c4\u03bf\u03c5 PAF, \u03b1\u03bb\u03bb\u03ac \u03bf \u03c4\u03c1\u03cc\u03c0\u03bf\u03c2 \u03c3\u03c5\u03bc\u03bc\u03b5\u03c4\u03bf\u03c7\u03ae\u03c2 \u03c4\u03bf\u03c5,<\/strong> \u03b3\u03b9\u03b1\u03c4\u03af <strong>\u03b1\u03bd \u03bf PAF \u03b5\u03af\u03bd\u03b1\u03b9 \u201c\u03c4\u03bf \u03b5\u03bd\u03b1\u03c1\u03ba\u03c4\u03ae\u03c1\u03b9\u03bf \u03bb\u03ac\u03ba\u03c4\u03b9\u03c3\u03bc\u03b1\u201d \u03b3\u03b9\u03b1 \u03c4\u03b9\u03c2 \u03c0\u03b1\u03c1\u03b5\u03bd\u03ad\u03c1\u03b3\u03b5\u03b9\u03b5\u03c2-\u03bd\u03bf\u03c3\u03b7\u03c1\u03cc\u03c4\u03b7\u03c4\u03b1\u00a0 \u03c4\u03b7\u03c2 \u03c3\u03bf\u03b2\u03b1\u03c1\u03ae\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19, \u03c4\u03cc\u03c4\u03b5 \u03b1\u03c5\u03c4\u03cc \u03b5\u03af\u03bd\u03b1\u03b9 \u03c3\u03b7\u03bc\u03b1\u03bd\u03c4\u03b9\u03ba\u03cc.<\/strong><\/p>\n<p>\u03a0\u0397\u0393\u0397:https:\/\/www.ygeiamasnews.gr\/astheneies\/epidimies\/73080\/neotera-gia-to-mixanismo-drasis-tou-koronoiou-kai-tis-nosou-covid-19-mesa-apo-mia-alli-nea-proseggisi-tou-thematos\/<\/p>\n<p>\u03a0\u03b9\u03bf \u03ba\u03ac\u03c4\u03c9 \u03b7 \u03b2\u03b9\u03b2\u03bb\u03b9\u03bf\u03b3\u03c1\u03b1\u03c6\u03b9\u03ba\u03ad\u03c2 \u03b1\u03bd\u03b1\u03c6\u03bf\u03c1\u03ad\u03c2:<\/p>\n<\/div>\n<div data-module-name=\"article-badge-bar\">\n<div class=\"articleMeta ja\">\n<div class=\"hlFld-Title\">\n<div class=\"publicationContentTitle\">\n<h1>A Review of Platelet-Activating Factor As a Potential Contributor to Morbidity and Mortality Associated with Severe COVID-19<\/h1>\n<\/div>\n<\/div>\n<div class=\"copyrightStatement\"><\/div>\n<div class=\"articleMetaDrop publicationContentDropZone\" data-pb-dropzone=\"articleMetaDropZone\"><\/div>\n<div class=\"publicationContentAuthors\">\n<div class=\"author-container js__articleAuthorContainer\" data-max-authors=\"5\" data-authorname-selector=\".contribDegrees &gt; .entryAuthor\" data-author-container-selector=\".NLM_contrib-group\">\n<div class=\"authors\">\n<div class=\"hlFld-ContribAuthor\"><span class=\"contribDegrees\"><a class=\"entryAuthor\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764\" aria-label=\"Open contributor information pop-up for Mark Klein\"> Mark Klein<\/a><span class=\"degreesComma\">, <\/span>MD<a id=\"corresp1-10760296211051764\" class=\"ref corresp\" tabindex=\"-1\"><\/a><a href=\"https:\/\/orcid.org\/0000-0003-3457-6879\" target=\"_blank\" rel=\"noopener\"><img decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/templates\/jsp\/images\/orcid.png\" \/><\/a><\/span>, <span class=\"contribDegrees\"><a class=\"entryAuthor\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764\" aria-label=\"Open contributor information pop-up for Vinh Dao\"> Vinh Dao<\/a><span class=\"degreesComma\">, <\/span>PharmD, BCPS<a href=\"https:\/\/orcid.org\/0000-0002-2704-2222\" target=\"_blank\" rel=\"noopener\"><img decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/templates\/jsp\/images\/orcid.png\" \/><\/a><\/span>, <span class=\"contribDegrees\"><a class=\"entryAuthor\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764\" aria-label=\"Open contributor information pop-up for Fatima Khan\"> Fatima Khan<\/a><span class=\"degreesComma\">, <\/span>MD, MPH<\/span><\/div>\n<\/div>\n<\/div>\n<\/div>\n<p><span class=\"publicationContentEpubDate dates\"> <b>First Published <\/b> November 10, 2021 <\/span> <span class=\"ArticleType\"> Research Article <\/span> <span class=\"crossMark\"> <a id=\"crossMark\" href=\"https:\/\/crossmark.crossref.org\/dialog?doi=10.1177%2F10760296211051764&amp;domain=journals.sagepub.com&amp;uri_scheme=https%3A&amp;cm_version=v2.0\" rel=\"noopener\" data-item-name=\"crossmark\" data-doi=\"10.1177\/10760296211051764\" data-target=\"crossmark\"> <img decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/templates\/jsp\/images\/CROSSMARK_Color_horizontal.svg\" width=\"100\" \/> <\/a> <\/span><\/p>\n<div class=\"articleMetaDrop publicationContentDropZone publicationContentDropZone1\" data-pb-dropzone=\"articleMetaDropZone1\">\n<div id=\"66028d4c-d8fb-4855-92bd-8d3e954d6d44\" class=\"widget doiWidget none widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<div class=\"doiWidgetContainer\"><a class=\"doiWidgetLink\" href=\"https:\/\/doi.org\/10.1177%2F10760296211051764\" rel=\"noopener\">https:\/\/doi.org\/10.1177\/10760296211051764<\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"80078b98-037a-4dab-b149-628ef0ecefc6\" class=\"widget layout-one-column none widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<div class=\"pb-columns row-fluid\">\n<div class=\"width_1_1\">\n<div data-pb-dropzone=\"center\">\n<div id=\"de1d8314-cfbd-4c21-ae0c-fd75561d30c2\" class=\"widget layout-inline-content none badgeBar widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<div class=\"inline-dropzone\" data-pb-dropzone=\"content\">\n<div id=\"65b729d8-216d-444f-b58b-df8e513bd058\" class=\"widget general-html-asset none widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<table class=\"badge-bar\">\n<tbody>\n<tr>\n<td class=\"articleInfoLink\"><a tabindex=\"0\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-item-name=\"article-info\">Article information\u00a0<span id=\"authorInfoArrow\" class=\"arrow-down indicator\"><\/span> <\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"b271a0d4-9500-4879-a880-60e90df38c35\" class=\"widget sageConditionalDisplayWidget none pull-right widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<div data-pb-dropzone=\"conditional\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"868f5842-72e5-40fa-8c2c-fce25e31057f\" class=\"widget sageConditionalDisplayWidget none pull-right widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<div data-pb-dropzone=\"conditional\">\n<div id=\"d872e956-9550-45ce-98e7-7cab12211a3b\" class=\"widget articleBadges none articleBadges widget-none widget-compact-all\">\n<div class=\"wrapped \">\n<div class=\"widget-body body body-none body-compact-all\">\n<div class=\"content \"><img decoding=\"async\" class=\"accessIcon openAccess\" title=\"Open Access\" src=\"https:\/\/journals.sagepub.com\/templates\/jsp\/_style2\/_sage\/images\/openAccess.gif\" alt=\"Open Access\" \/><a class=\"creative-commons-badge cc-by-nc\" title=\"creative commons licence\" href=\"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/\" rel=\"noopener\"><img decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/templates\/jsp\/_style2\/_sage\/images\/creativecommons\/cc-by-nc.png\" alt=\"Creative Commons Attribution, Non Commercial 4.0 License\" \/><\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"publication-tabs ja publication-tabs-dropdown\">\n<div class=\"tabs tabs-widget\">\n<div class=\"tab-content \">\n<div class=\"tab tab-pane active\">\n<article class=\"article\">\n<div class=\"hlFld-Abstract\">\n<div class=\"sectionInfo abstractSectionHeading\">\n<h2 class=\"sectionHeading\">Abstract<\/h2>\n<\/div>\n<div class=\"abstractSection abstractInFull\">\n<p>The precise mechanisms of pathology in severe COVID-19 remains elusive. Current evidence suggests that inflammatory mediators are responsible for the manifestation of clinical symptoms that precedes a fatal response to infection. This review examines the nature of platelet activating factor and emphasizes the similarities between the physiological effects of platelet activating factor and the clinical complications of severe COVID-19.<\/p>\n<\/div>\n<\/div>\n<div class=\"abstractKeywords\">\n<div class=\"hlFld-KeywordText\">\n<p><b>Keywords <\/b><\/p>\n<div lang=\"\"><span class=\"kwd\"><a class=\"attributes\" href=\"https:\/\/journals.sagepub.com\/keyword\/Platelet+Activating+Factor\">platelet activating factor<\/a>, <\/span><span class=\"kwd\"><a class=\"attributes\" href=\"https:\/\/journals.sagepub.com\/keyword\/COVID-19\">COVID-19<\/a>, <\/span><span class=\"kwd\"><a class=\"attributes\" href=\"https:\/\/journals.sagepub.com\/keyword\/Thrombosis\">thrombosis<\/a><\/span><\/div>\n<\/div>\n<\/div>\n<div class=\"hlFld-Fulltext\">\n<div id=\"section1-10760296211051764\" class=\"NLM_sec NLM_sec-type_intro NLM_sec_level_1\">\n<p><a name=\"_i1\"><\/a><\/p>\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">Introduction<\/h2>\n<\/div>\n<p>The novel SARS-CoV-2 virus has created a worldwide pandemic which has claimed over four million lives globally.<sup><a id=\"focusIdbibr1-10760296211051764201\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr1-10760296211051764\" data-ref-text=\"1\" data-reflink=\"bibr1-10760296211051764\" data-referenceslink=\"1 Corona Virus Resource Center. Global Deaths Data. John Hopkins University of Medicine; 2021. Available at https:\/\/coronavirus.jhu.edu.\">1<\/a><\/sup> The severity of COVID-19 remains a key predictor for the risk of morbidity and mortality.<sup><a id=\"focusIdbibr2-10760296211051764202\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr2-10760296211051764\" data-ref-text=\"2\" data-reflink=\"bibr2-10760296211051764\" data-referenceslink=\"2 Jehi L, Ji X, Milinovich A, et al. Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19. PLoS One. 2020;15(8).\">2<\/a>,<a id=\"focusIdbibr3-10760296211051764203\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr3-10760296211051764\" data-ref-text=\"3\" data-reflink=\"bibr3-10760296211051764\" data-referenceslink=\"3 Berlin DA, Gulick RM, Martinez FJ. Severe covid-19. N Engl J Med. 2020;383(25):2451\u20132460.\">3<\/a><\/sup> Despite ongoing research, scientists have yet to unlock the precise mechanisms of pathology that leads to the high rate of mortality seen in severe COVID-19. Efforts to understand the causes of morbidity and mortality in severe COVID-19 are plagued by the inability to pinpoint clear mechanistic interrelations among potential pathological mechanisms and organ systems impacted by the SARS-CoV-2 virus. Morbidity and mortality associated with COVID-19 has been attributed to a wide range of physiological effects and critical events that involves multiple organ systems and has bewildered clinicians that are fighting to curtail the rate of fatality (<span id=\"ref-fig1-10760296211051764\" class=\"figure refFigure figuresContent\"><a class=\"showFiguresEEvent figure-no-fig1-10760296211051764\" title=\"Open Figure Viewer\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-attr-fig-id=\"fig1-10760296211051764\">Figure 1<\/a><\/span>).<sup><a id=\"focusIdbibr4-10760296211051764205\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr4-10760296211051764\" data-ref-text=\"4\" data-reflink=\"bibr4-10760296211051764\" data-referenceslink=\"4 Center for Disease Control and Prevention, National Center for Health Statistics (2020), Provisional Death Counts for Coronavirus Disease 2019 (COVID-19), Weekly Updates by Select Demographic and Geographic Characteristics, Atlanta, GA. Available at https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid_weekly\/index.htm.\">4<\/a><\/sup> COVID-19 mortality has been directly linked to a myriad of sequelae including pneumonia, respiratory distress, hemodynamic instability, thrombotic events, cardiovascular disease, acute renal insufficiency, and other multi-organ failures.<sup><a id=\"focusIdbibr3-10760296211051764206\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr3-10760296211051764\" data-ref-text=\"3\" data-reflink=\"bibr3-10760296211051764\" data-referenceslink=\"3 Berlin DA, Gulick RM, Martinez FJ. Severe covid-19. N Engl J Med. 2020;383(25):2451\u20132460.\">3<\/a>,<a id=\"focusIdbibr4-10760296211051764207\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr4-10760296211051764\" data-ref-text=\"4\" data-reflink=\"bibr4-10760296211051764\" data-referenceslink=\"4 Center for Disease Control and Prevention, National Center for Health Statistics (2020), Provisional Death Counts for Coronavirus Disease 2019 (COVID-19), Weekly Updates by Select Demographic and Geographic Characteristics, Atlanta, GA. Available at https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid_weekly\/index.htm.\">4<\/a><\/sup> Aside from COVID-19 infection itself, a commonality among the various causes of morbidity and mortality has not been identified. Moreover, anecdotal evidence suggests a high variation of symptomatic presentation and severity of disease in the general population whereby some individuals remain asymptomatic while others will develop a fatal response.<\/p>\n<div id=\"fig1-10760296211051764\" class=\"figure\">\n<div class=\"holder\">\n<p><a class=\"thumbnail showFiguresEEvent\" title=\"Open Figure Viewer\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-attr-fig-id=\"fig1-10760296211051764\"><img decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/na101\/home\/literatum\/publisher\/sage\/journals\/content\/cata\/2021\/cata_27\/10760296211051764\/20211109\/images\/medium\/10.1177_10760296211051764-fig1.gif\" alt=\" figure \" \/><\/a><\/p>\n<div class=\"caption\">\n<p><span class=\"captionLabel\">Figure 1.<\/span> Rate of Complications Contributing to Mortality in COVID-19 (as of November 2020).<sup><a id=\"focusIdbibr4-10760296211051764214\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr4-10760296211051764\" data-ref-text=\"4\" data-reflink=\"bibr4-10760296211051764\" data-referenceslink=\"4 Center for Disease Control and Prevention, National Center for Health Statistics (2020), Provisional Death Counts for Coronavirus Disease 2019 (COVID-19), Weekly Updates by Select Demographic and Geographic Characteristics, Atlanta, GA. Available at https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid_weekly\/index.htm.\">4<\/a><\/sup><\/p>\n<div id=\"footer\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<p>The purpose of this article is to introduce platelet activating factor (PAF) as a biomolecular entity with a potential role in the physiological processes which dictate a severe response to COVID-19. PAF exists as a potent phospholipid mediator that is highly involved in many complex biological processes. As PAF has not commanded the same level of attention as other biochemical mediators and pathways, it is easy to overlook the role that PAF may have as a contributor to pathogenesis. However, there is growing interest and ongoing research into PAF as an important mediator of normal physiological function. Conversely, dysfunction or dysregulation of PAF pathways can result in pathogenic effects.<\/p>\n<\/div>\n<div id=\"section2-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<p><a name=\"_i3\"><\/a><\/p>\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">The Biological Role of Platelet Activating Factor<\/h2>\n<\/div>\n<p>The synthesis of PAF is not unique to any particular cell line and production occurs within multiple cell families which includes inflammatory cells, mast cells, endothelial cells, platelets, and some organ tissues.<sup><a id=\"focusIdbibr5-10760296211051764216\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764217\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> The physiological effect of PAF is typically localized to the region of synthesis, and activity is dependent on the precise cellular group(s) involved. PAF synthesis begins when cellular membrane phospholipids are catalyzed by the enzyme phospholipase A2 into Lyso-PAF, the intermediary predecessor to PAF.<sup><a id=\"focusIdbibr5-10760296211051764218\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764219\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> Acetyl-CoA acetyltransferase is a thiolase enzyme that preforms the rate-limiting step to complete the conversion of Lyso-PAF into PAF (<span id=\"ref-fig2-10760296211051764\" class=\"figure refFigure figuresContent\"><a class=\"showFiguresEEvent figure-no-fig2-10760296211051764\" title=\"Open Figure Viewer\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-attr-fig-id=\"fig2-10760296211051764\">Figure 2<\/a><\/span>).<sup><a id=\"focusIdbibr5-10760296211051764221\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764222\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup><\/p>\n<div id=\"fig2-10760296211051764\" class=\"figure\">\n<div class=\"holder\">\n<p><a class=\"thumbnail showFiguresEEvent\" title=\"Open Figure Viewer\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-attr-fig-id=\"fig2-10760296211051764\"><img decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/na101\/home\/literatum\/publisher\/sage\/journals\/content\/cata\/2021\/cata_27\/10760296211051764\/20211109\/images\/medium\/10.1177_10760296211051764-fig2.gif\" alt=\" figure \" \/><\/a><\/p>\n<div class=\"caption\">\n<p><span class=\"captionLabel\">Figure 2.<\/span> Intracellular biosynthesis of platelet activating factor.<\/p>\n<div id=\"footer\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<p>Endogenously, PAF is an agonist at platelet activating factor receptor sites expressed on the surface of leukocytes, endothelial cells, platelets, and a host of other cell types. PAF promotes chemotaxis of leukocytes and is a potent mediator of inflammation, particularly in response to microbial or viral infectious processes.<sup><a id=\"focusIdbibr5-10760296211051764229\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764230\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> PAF is also an important contributor to the physiological response of allergy and anaphylactic reactions in the presence of allergens and allergic stimuli. Synthesis of PAF within platelet cells promotes platelet aggregation and clot formation as activation of the G protein-coupled platelet activating factor receptor signals intracellular integrin \u03b1<sub>IIb<\/sub>\u03b2<sub>3,<\/sub> thromboxane A2 synthesis, and promotes binding of fibrinogen.<sup><a id=\"focusIdbibr6-10760296211051764231\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> Researchers have also examined the role of PAF in the support of brain function, glycogen degradation, and reproductive integrity.<sup><a id=\"focusIdbibr5-10760296211051764232\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764233\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> PAF production by endothelial cells, which comprises the inner lining of the vasculature, results in either vasoconstriction or vasodilation, the extent of which is dependent on the affected vascular bed and the presence of leukocyte infiltration. The downstream effect of platelet activating factor receptor activation is mediated by diverse intracellular signaling pathways and alterations in mRNA transcription.<sup><a id=\"focusIdbibr6-10760296211051764234\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> Termination of PAF activity occurs when PAF is recycled back into Lyso-PAF by acetylhydrolases for subsequent incorporation back into the cell membrane as phospholipids.<sup><a id=\"focusIdbibr5-10760296211051764235\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764236\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup><\/p>\n<\/div>\n<div id=\"section3-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">Platelet Activating Factor Pathogenesis<\/h2>\n<\/div>\n<p>Although<strong> PAF promotes a natural inflammatory response to allergens and infectious processes, researchers have hypothesized that PAF-mediated physiological actions could become pathogenic in the presence of excessive activity or dysregulation.<\/strong> The presence of inflammation and leukocytes stimulates the PAF production cycle.<sup><a id=\"focusIdbibr6-10760296211051764238\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> The risk of pathogenicity arises when PAF synthesis or termination cycles are altered as a result of disease or individual genetic variation in physiology. As PAF promotes localized inflammation, it becomes a \u201cbeacon\u201d for further recruitment of granulocytes, monocytes, and macrophages. The migration of leukocytes to the affected area further perpetuates the PAF synthesis cycle, creating a surge which can overwhelm innate regulatory mechanisms designed to inhibit PAF.<sup><a id=\"focusIdbibr6-10760296211051764239\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup><\/p>\n<p>Infection or allergic stimuli are potent catalysts of PAF mediated increases in vascular permeability that induces localized swelling, edema, hypotension, and cytokine release.<sup><a id=\"focusIdbibr6-10760296211051764240\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> Pathogenicity can occur when these responses are exaggerated in vital organ systems. Such examples include the respiratory system where vascular permeability promotes pulmonary edema and infiltration thereby compromising pulmonary function. Similar to hemodynamic instability that occurs in situations of sepsis or anaphylaxis, reflexive vascular response to PAF signaling may lead to the development of hypotensive shock. However, the detrimental effects of PAF are not restricted or confined to the vasculature. Other mechanisms of pathogenicity explored include atherogenesis, gastrointestinal ulceration, pancreatitis, renal impairment, inflammatory skin, and autoimmune disorders.<sup><a id=\"focusIdbibr5-10760296211051764241\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr5-10760296211051764\" data-ref-text=\"5\" data-reflink=\"bibr5-10760296211051764\" data-referenceslink=\"5 Prescott SM, Zimmerman GA, McIntyre TM, et al. Platelet-Activating factor and related lipid mediators annual review of biochemistry. Annu Rev Biochem. 2000;69(1):419-445.\">5<\/a>,<a id=\"focusIdbibr6-10760296211051764242\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup><\/p>\n<\/div>\n<div id=\"section4-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">PAF in Acute Respiratory Distress Syndrome<\/h2>\n<\/div>\n<p>One of the earliest clinically recognized manifestations of COVID-19 was severe pneumonia leading to Acute Respiratory Distress Syndrome (ARDS) requiring mechanical ventilation.<sup><a id=\"focusIdbibr4-10760296211051764244\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr4-10760296211051764\" data-ref-text=\"4\" data-reflink=\"bibr4-10760296211051764\" data-referenceslink=\"4 Center for Disease Control and Prevention, National Center for Health Statistics (2020), Provisional Death Counts for Coronavirus Disease 2019 (COVID-19), Weekly Updates by Select Demographic and Geographic Characteristics, Atlanta, GA. Available at https:\/\/www.cdc.gov\/nchs\/nvss\/vsrr\/covid_weekly\/index.htm.\">4<\/a><\/sup> Data from a study conducted by Feng et al. cited the prevalence of severe pneumonia in COVID-19 at 10 % and noted that this may be an underestimation when compared to previously published studies.<sup><a id=\"focusIdbibr7-10760296211051764245\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr7-10760296211051764\" data-ref-text=\"7\" data-reflink=\"bibr7-10760296211051764\" data-referenceslink=\"7 Feng Z, Yu Q, Yao S, et al. Early prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics. Nat Commun. 2020;11(1):4968.\">7<\/a><\/sup> The prevalence of clinically milder pneumonia is expected to be considerably higher than what was reported by Feng et al. who had only examined the rate of severe pneumonia. While the role of PAF in ARDS secondary to COVID-19 remains unexplored, numerous studies have investigated the role of PAF as an instigator of acute lung injury and ARDS in the context of bacterial sepsis.<sup><a id=\"focusIdbibr8-10760296211051764246\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr8-10760296211051764\" data-ref-text=\"8\" data-reflink=\"bibr8-10760296211051764\" data-referenceslink=\"8 Makristathis A, Stauffer F, Feistauer SM, et al. Bacteria induce release of platelet-activating factor (PAF) from polymorphonuclear neutrophil granulocytes: possible role for PAF in pathogenesis of experimentally induced bacterial pneumonia. Infect Immun. 1993;61(5):1996-2002.\">8<\/a>,<a id=\"focusIdbibr9-10760296211051764247\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr9-10760296211051764\" data-ref-text=\"9\" data-reflink=\"bibr9-10760296211051764\" data-referenceslink=\"9 Clavijo LC, Carter MB, Matheson PJ, et al. Platelet-activating factor and bacteremia-induced pulmonary hypertension. J Surg Res. 2000;88(2):173-180.\">9<\/a><\/sup> In vitro experiments have shown that exogenously administered PAF increases vascular permeability and pulmonary edema in animal models.<sup><a id=\"focusIdbibr9-10760296211051764248\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr9-10760296211051764\" data-ref-text=\"9\" data-reflink=\"bibr9-10760296211051764\" data-referenceslink=\"9 Clavijo LC, Carter MB, Matheson PJ, et al. Platelet-activating factor and bacteremia-induced pulmonary hypertension. J Surg Res. 2000;88(2):173-180.\">9<\/a><\/sup> Moreover, the inhibition of PAF activity reduces the development of pulmonary edema in similar animal models.<sup><a id=\"focusIdbibr9-10760296211051764249\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr9-10760296211051764\" data-ref-text=\"9\" data-reflink=\"bibr9-10760296211051764\" data-referenceslink=\"9 Clavijo LC, Carter MB, Matheson PJ, et al. Platelet-activating factor and bacteremia-induced pulmonary hypertension. J Surg Res. 2000;88(2):173-180.\">9<\/a><\/sup> The implications of these findings for human patients remains to be determined.<\/p>\n<p>Previous studies have also examined the nature of PAF acetylhydrolase deficiency and its relationship to asthmatic symptoms.<sup><a id=\"focusIdbibr10-10760296211051764250\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr10-10760296211051764\" data-ref-text=\"10\" data-reflink=\"bibr10-10760296211051764\" data-referenceslink=\"10 Miwa M, Miyake T, Yamanaka T, et al. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children. J Clin Invest. 1988;82(6):1983-1991.\">10<\/a><\/sup> As previously discussed, acetylhydrolase is an enzyme tasked with terminating the action of PAF by recycling PAF back into its intermediary precursor, Lyso-PAF. Masao et al. and colleagues examined PAF acetylhydrolase deficiency in Japanese children as a result of autosomal recessive heredity and determined that the prevalence of serum PAF acetylhydrolase deficiency was significantly higher in those individuals who experienced severe asthma symptoms.<sup><a id=\"focusIdbibr10-10760296211051764251\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr10-10760296211051764\" data-ref-text=\"10\" data-reflink=\"bibr10-10760296211051764\" data-referenceslink=\"10 Miwa M, Miyake T, Yamanaka T, et al. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children. J Clin Invest. 1988;82(6):1983-1991.\">10<\/a><\/sup> In addition, PAF has also been shown to promote bronchoconstriction, mucus secretion, and inflammation of bronchi in asthmatic patients.<sup><a id=\"focusIdbibr10-10760296211051764252\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr10-10760296211051764\" data-ref-text=\"10\" data-reflink=\"bibr10-10760296211051764\" data-referenceslink=\"10 Miwa M, Miyake T, Yamanaka T, et al. Characterization of serum platelet-activating factor (PAF) acetylhydrolase. Correlation between deficiency of serum PAF acetylhydrolase and respiratory symptoms in asthmatic children. J Clin Invest. 1988;82(6):1983-1991.\">10<\/a>,<a id=\"focusIdbibr11-10760296211051764253\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr11-10760296211051764\" data-ref-text=\"11\" data-reflink=\"bibr11-10760296211051764\" data-referenceslink=\"11 Hsieh KH, Ng CK. Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy. J Allergy Clin Immunol. 199;91(2):650-657.\">11<\/a><\/sup> The severity of asthmatic symptoms may also be influenced by commonplace anti-inflammatory medications, many of which are available for over-the-counter purchase. It has been suggested that the use of systemic non-steroidal anti-inflammatory drugs (NSAIDs) could exacerbate asthma symptoms as inhibition of cyclooxygenase enzymes shifts arachidonic acid down the parallel lipoxygenase pathway that results in the synthesis of leukotrienes responsible for bronchial inflammation and asthmatic symptoms.<sup><a id=\"focusIdbibr12-10760296211051764254\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr12-10760296211051764\" data-ref-text=\"12\" data-reflink=\"bibr12-10760296211051764\" data-referenceslink=\"12 Kowalski ML, Agache I, Bavbek S, et al. Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)-a EAACI position paper. Allergy. 2019;74(1):28-39.\">12<\/a>,<a id=\"focusIdbibr13-10760296211051764255\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr13-10760296211051764\" data-ref-text=\"13\" data-reflink=\"bibr13-10760296211051764\" data-referenceslink=\"13 Busse WW. Leukotrienes and inflammation. Am J Respir Crit Care Med. 1998;157(6 Pt 1):S210-S213.\">13<\/a><\/sup> Although there was early speculation that systemic NSAIDs could worsen the outcomes of severe COVID-19, further research has since disproved this hypothesis.<sup><a id=\"focusIdbibr14-10760296211051764256\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr14-10760296211051764\" data-ref-text=\"14\" data-reflink=\"bibr14-10760296211051764\" data-referenceslink=\"14 Moore N, Carleton B, Blin P, et al. Does ibuprofen worsen COVID-19? Drug Saf. 2020;43(7):611-614.\">14<\/a><\/sup> The role of inflammatory cytokines in COVID-19 morbidity and mortality remains a significant topic of research.<\/p>\n<\/div>\n<div id=\"section5-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">PAF in Acute Cardiovascular Events and Thrombosis<\/h2>\n<\/div>\n<p>Patients with COVID-19 have a high incidence of both arterial and venous thrombotic complications. In a large New York City health system, thrombotic events occurred in 16% of hospitalized COVID-19 patients.<sup><a id=\"focusIdbibr15-10760296211051764258\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr15-10760296211051764\" data-ref-text=\"15\" data-reflink=\"bibr15-10760296211051764\" data-referenceslink=\"15 Bilaloglu S, Aphinyanaphongs Y, Jones S, et al. Thrombosis in hospitalized patients With COVID-19 in a New York city health system. JAMA. 2020;324(8):799-801.\">15<\/a><\/sup> The all-cause mortality in the described population was 24.5% and was higher in those with thrombotic events (43.2% vs 21.0%; <i>P<\/i> &lt; 0.001).<sup><a id=\"focusIdbibr15-10760296211051764259\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr15-10760296211051764\" data-ref-text=\"15\" data-reflink=\"bibr15-10760296211051764\" data-referenceslink=\"15 Bilaloglu S, Aphinyanaphongs Y, Jones S, et al. Thrombosis in hospitalized patients With COVID-19 in a New York city health system. JAMA. 2020;324(8):799-801.\">15<\/a><\/sup> Other studies have estimated rates of thrombotic events as high as 49% in severe COVID-19.<sup><a id=\"focusIdbibr16-10760296211051764260\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr16-10760296211051764\" data-ref-text=\"16\" data-reflink=\"bibr16-10760296211051764\" data-referenceslink=\"16 Hajra A, Mathai SV, Ball S, et al. Management of thrombotic complications in COVID-19: an update. Drugs. 2020;80(15):1553-1562.\">16<\/a><\/sup> Thrombotic events, in these studies, included a wide range of diagnoses including acute coronary syndrome, deep vein thrombosis, pulmonary embolism, and cerebrovascular events.<sup><a id=\"focusIdbibr16-10760296211051764261\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr16-10760296211051764\" data-ref-text=\"16\" data-reflink=\"bibr16-10760296211051764\" data-referenceslink=\"16 Hajra A, Mathai SV, Ball S, et al. Management of thrombotic complications in COVID-19: an update. Drugs. 2020;80(15):1553-1562.\">16<\/a>,<a id=\"focusIdbibr17-10760296211051764262\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr17-10760296211051764\" data-ref-text=\"17\" data-reflink=\"bibr17-10760296211051764\" data-referenceslink=\"17 Piazza G, Campia U, Hurwitz S, et al. Registry of arterial and venous thromboembolic complications in patients With COVID-19. J Am Coll Cardiol. 2020;76(18):2060-2072.\">17<\/a><\/sup> Although most of the initial research in COVID-19 associated thrombosis focused on the existence of an underlying hypercoagulable state, there is increasing evidence to suggest the presence of endothelial damage and vascular injury as essential contributors to the activation of the coagulation cascade.<sup><a id=\"focusIdbibr16-10760296211051764263\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr16-10760296211051764\" data-ref-text=\"16\" data-reflink=\"bibr16-10760296211051764\" data-referenceslink=\"16 Hajra A, Mathai SV, Ball S, et al. Management of thrombotic complications in COVID-19: an update. Drugs. 2020;80(15):1553-1562.\">16<\/a>,<a id=\"focusIdbibr17-10760296211051764264\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr17-10760296211051764\" data-ref-text=\"17\" data-reflink=\"bibr17-10760296211051764\" data-referenceslink=\"17 Piazza G, Campia U, Hurwitz S, et al. Registry of arterial and venous thromboembolic complications in patients With COVID-19. J Am Coll Cardiol. 2020;76(18):2060-2072.\">17<\/a><\/sup> We have previously discussed the action of PAF as a provocateur of vascular permeability, microvascular leakage, and progression of atherosclerosis in the vasculature. Insult to the vascular system intensifies when sustained vascular injury is accompanied by recruitment of leukocytes, platelets, and mast cells to the damaged site which further potentiates the activation of PAF.<sup><a id=\"focusIdbibr18-10760296211051764265\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr18-10760296211051764\" data-ref-text=\"18\" data-reflink=\"bibr18-10760296211051764\" data-referenceslink=\"18 Palur Ramakrishnan AV, Varghese TP, Vanapalli S, et al. Platelet activating factor: a potential biomarker in acute coronary syndrome? Cardiovasc Ther. 2017;35(1):64-70.\">18<\/a><\/sup> The net result is a nocuous medley of platelet reactivity, aggregation, and release of pro-inflammatory vascular cytokines that promotes the construction of atherosclerotic plaques.<sup><a id=\"focusIdbibr18-10760296211051764266\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr18-10760296211051764\" data-ref-text=\"18\" data-reflink=\"bibr18-10760296211051764\" data-referenceslink=\"18 Palur Ramakrishnan AV, Varghese TP, Vanapalli S, et al. Platelet activating factor: a potential biomarker in acute coronary syndrome? Cardiovasc Ther. 2017;35(1):64-70.\">18<\/a><\/sup> Interleukin-1\u03b2, a potent inflammatory cytokine produced by activated platelets, is abundant in platelet-fibrin thrombi and substantiates a potential link between inflammatory mediators and thrombosis.<sup><a id=\"focusIdbibr6-10760296211051764267\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr6-10760296211051764\" data-ref-text=\"6\" data-reflink=\"bibr6-10760296211051764\" data-referenceslink=\"6 Zimmerman GA, McIntyre TM, Prescott SM, et al. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294-S301.\">6<\/a><\/sup> Furthermore, PAF derives its nomenclature from earlier human and animal experiments that identified PAF as a potent mediator of platelet aggregation in vitro.<sup><a id=\"focusIdbibr19-10760296211051764268\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr19-10760296211051764\" data-ref-text=\"19\" data-reflink=\"bibr19-10760296211051764\" data-referenceslink=\"19 Marcus AJ, Safier LB, Ullman HL, et al. Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro. Blood. 1981;58(5):1027-1031.\">19<\/a>,<a id=\"focusIdbibr20-10760296211051764269\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr20-10760296211051764\" data-ref-text=\"20\" data-reflink=\"bibr20-10760296211051764\" data-referenceslink=\"20 Cazenave JP, Benveniste J, Mustard JF. Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs. Lab Invest. 1979;41(3):275-285.\">20<\/a><\/sup> When human platelet-rich plasma is exposed to PAF in vitro, researchers have observed concentration dependent reversible and irreversible platelet aggregation.<sup><a id=\"focusIdbibr19-10760296211051764270\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr19-10760296211051764\" data-ref-text=\"19\" data-reflink=\"bibr19-10760296211051764\" data-referenceslink=\"19 Marcus AJ, Safier LB, Ullman HL, et al. Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro. Blood. 1981;58(5):1027-1031.\">19<\/a><\/sup> In vivo, studies have demonstrated that exogenously administered PAF antagonists suppresses platelet activation and aggregation in rabbit and canine models.<sup><a id=\"focusIdbibr21-10760296211051764271\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr21-10760296211051764\" data-ref-text=\"21\" data-reflink=\"bibr21-10760296211051764\" data-referenceslink=\"21 Golino P, Ambrosio G, Ragni M, et al. Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation. Circulation. 1993;88(3):1205-1214.\">21<\/a><\/sup> Researchers have also postulated that PAF can increase reactive nitrogen and oxygen species which incites vascular permeability.<sup><a id=\"focusIdbibr18-10760296211051764272\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr18-10760296211051764\" data-ref-text=\"18\" data-reflink=\"bibr18-10760296211051764\" data-referenceslink=\"18 Palur Ramakrishnan AV, Varghese TP, Vanapalli S, et al. Platelet activating factor: a potential biomarker in acute coronary syndrome? Cardiovasc Ther. 2017;35(1):64-70.\">18<\/a><\/sup> Moreover, certain reactive nitrogen species may inhibit acetylhydrolases and enhance the activity of PAF under conditions of oxidative stress.<sup><a id=\"focusIdbibr18-10760296211051764273\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr18-10760296211051764\" data-ref-text=\"18\" data-reflink=\"bibr18-10760296211051764\" data-referenceslink=\"18 Palur Ramakrishnan AV, Varghese TP, Vanapalli S, et al. Platelet activating factor: a potential biomarker in acute coronary syndrome? Cardiovasc Ther. 2017;35(1):64-70.\">18<\/a><\/sup> Preliminary research has reported that COVID-19 patients who were taking low-dose aspirin, an irreversible inhibitor of platelet aggregation, were at reduced risk for placement of mechanical ventilation, or transfer to intensive care units.<sup><a id=\"focusIdbibr22-10760296211051764274\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr22-10760296211051764\" data-ref-text=\"22\" data-reflink=\"bibr22-10760296211051764\" data-referenceslink=\"22 Chow JH, Khanna AK, Kethireddy S, et al. Aspirin Use is associated with decreased mechanical ventilation, ICU admission, and In-hospital mortality in hospitalized patients with COVID-19. Anesth Analg. 2020;132(4):930-941.\">22<\/a><\/sup> Data from studies conducted in China demonstrated that mean plasma concentration of PAF levels in patients with coronary heart disease reached 49.7 pg\/ml, which was higher than the 23.8 pg\/ml observed in controls.<sup><a id=\"focusIdbibr18-10760296211051764275\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr18-10760296211051764\" data-ref-text=\"18\" data-reflink=\"bibr18-10760296211051764\" data-referenceslink=\"18 Palur Ramakrishnan AV, Varghese TP, Vanapalli S, et al. Platelet activating factor: a potential biomarker in acute coronary syndrome? Cardiovasc Ther. 2017;35(1):64-70.\">18<\/a><\/sup> More research is needed to discern whether thrombosis in COVID-19 is a unilateral process attributed solely to a hypercoagulable state or whether those thrombotic events involves a myriad of processes that includes platelet aggregation. Hottz et al. observed increased platelet activation and platelet-monocyte aggregate activity in patients with severe COVID-19 compared to milder cases. Their conclusions were based on amplification in the surface expression of P-selectin and CD63, markers indicating platelet activation, and confirmed by measuring plasma levels of thromboxane B2.<sup><a id=\"focusIdbibr23-10760296211051764276\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr23-10760296211051764\" data-ref-text=\"23\" data-reflink=\"bibr23-10760296211051764\" data-referenceslink=\"23 Hottz ED, Azevedo-Quintanilha IG, Palhinha L, et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood. 2020;136(11):1330-1341.\">23<\/a><\/sup> There continues to be heightened interest in the role of PAF as a mechanism of thrombosis in primary acute coronary syndrome. Subsequently, PAF emerges as an intriguing mechanism that may be linked to the incidence of coronary events and thrombosis seen with severe COVID-19.<\/p>\n<\/div>\n<div id=\"section6-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">PAF in Hemodynamic Instability<\/h2>\n<\/div>\n<p>Another notable symptom of severe COVID-19 is hemodynamic instability and the presence of hypotensive shock reminiscent of sepsis or anaphylactic reactions. In septic or anaphylactic shock, a cascade of inflammatory mediators increases vascular permeability and vasodilation leading to hypotension and hypoperfusion of vital organs.<sup><a id=\"focusIdbibr24-10760296211051764278\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr24-10760296211051764\" data-ref-text=\"24\" data-reflink=\"bibr24-10760296211051764\" data-referenceslink=\"24 Beltran-Garcia J, Osca-Verdegal R, Pallardo FV, et al. Sepsis and coronavirus disease 2019: common features and anti-inflammatory therapeutic approaches. Crit Care Med. 2020;48(12):1841-1844.\">24<\/a><\/sup> Furthermore, compensatory mechanisms designed to maintain hemodynamic stability can amplify myocardial strain, thereby provoking a coronary event as the imbalance between oxygen availability and oxygen requirements widens. Research has suggested that PAF serves a pivotal role in the clinical presentation of anaphylaxis. Vadas et al. found that serum levels of PAF in anaphylactic individuals reached 805\u2009\u00b1\u2009595 pg\/ml, concentrations far higher than the 23.8 pg\/ml reported in controls.<sup><a id=\"focusIdbibr25-10760296211051764279\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr25-10760296211051764\" data-ref-text=\"25\" data-reflink=\"bibr25-10760296211051764\" data-referenceslink=\"25 Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358(1):28-35.\">25<\/a><\/sup> The higher levels of serum PAF were also found to be directly correlated with increased severity of anaphylactic response.<sup><a id=\"focusIdbibr25-10760296211051764280\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr25-10760296211051764\" data-ref-text=\"25\" data-reflink=\"bibr25-10760296211051764\" data-referenceslink=\"25 Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358(1):28-35.\">25<\/a><\/sup> The elimination of PAF receptors results in diminished anaphylactic reactions in genetically modified animal models.<sup><a id=\"focusIdbibr26-10760296211051764281\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr26-10760296211051764\" data-ref-text=\"26\" data-reflink=\"bibr26-10760296211051764\" data-referenceslink=\"26 Munoz-Cano RM, Casas-Saucedo R, Valero Santiago A, et al. Platelet-Activating factor (PAF) in allergic rhinitis: clinical and therapeutic implications. J Clin Med. 2019;8(9):1338.\">26<\/a><\/sup> In vitro, rupatadine is a second-generation antihistamine with demonstrated anti-PAF activity, that appears to block cytokine production and degranulation in select types of mast cells.<sup><a id=\"focusIdbibr26-10760296211051764282\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr26-10760296211051764\" data-ref-text=\"26\" data-reflink=\"bibr26-10760296211051764\" data-referenceslink=\"26 Munoz-Cano RM, Casas-Saucedo R, Valero Santiago A, et al. Platelet-Activating factor (PAF) in allergic rhinitis: clinical and therapeutic implications. J Clin Med. 2019;8(9):1338.\">26<\/a><\/sup> Contrarily, these inhibitory effects were not seen in antihistamines without anti-PAF activity.<sup><a id=\"focusIdbibr26-10760296211051764283\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr26-10760296211051764\" data-ref-text=\"26\" data-reflink=\"bibr26-10760296211051764\" data-referenceslink=\"26 Munoz-Cano RM, Casas-Saucedo R, Valero Santiago A, et al. Platelet-Activating factor (PAF) in allergic rhinitis: clinical and therapeutic implications. J Clin Med. 2019;8(9):1338.\">26<\/a><\/sup> These findings have led to interest in PAF inhibitors as a potential treatment for allergy mediated symptoms such as allergic rhinitis and chronic urticaria.<sup><a id=\"focusIdbibr27-10760296211051764284\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr27-10760296211051764\" data-ref-text=\"27\" data-reflink=\"bibr27-10760296211051764\" data-referenceslink=\"27 Palgan K, Bartuzi Z. Platelet activating factor in allergies. Int J Immunopathol Pharmacol. 2015;28(4):584-589.\">27<\/a><\/sup> An expansion of this concept is that progressive mast cell activity in direct response to the presence of PAF has been examined as a highly plausible pathway in the pathophysiology of anaphylactic shock.<sup><a id=\"focusIdbibr25-10760296211051764285\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr25-10760296211051764\" data-ref-text=\"25\" data-reflink=\"bibr25-10760296211051764\" data-referenceslink=\"25 Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358(1):28-35.\">25<\/a>,<a id=\"focusIdbibr28-10760296211051764286\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr28-10760296211051764\" data-ref-text=\"28\" data-reflink=\"bibr28-10760296211051764\" data-referenceslink=\"28 Kajiwara N, Sasaki T, Bradding P, et al. Activation of human mast cells through the platelet-activating factor receptor. J Allergy Clin Immunol. 2010;125(5):1137-1145.\">28<\/a><\/sup> Mechanisms of mast cell degranulation become more intriguing relative to COVID-19 morbidity when we consider that initial mast cell activation and PAF synthesis at focal sites can rapidly evolve into an amplification loop that triggers mast cell degranulation at more distal sites (ie, pulmonary structures) as some researchers have suggested.<sup><a id=\"focusIdbibr28-10760296211051764287\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr28-10760296211051764\" data-ref-text=\"28\" data-reflink=\"bibr28-10760296211051764\" data-referenceslink=\"28 Kajiwara N, Sasaki T, Bradding P, et al. Activation of human mast cells through the platelet-activating factor receptor. J Allergy Clin Immunol. 2010;125(5):1137-1145.\">28<\/a><\/sup> Hemodynamic compromise may be at least partly a consequence of unbridled vasodilation and increased capillary permeability provoked by mast cell degranulation and inflammatory cytokines.<sup><a id=\"focusIdbibr25-10760296211051764288\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr25-10760296211051764\" data-ref-text=\"25\" data-reflink=\"bibr25-10760296211051764\" data-referenceslink=\"25 Vadas P, Gold M, Perelman B, et al. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis. N Engl J Med. 2008;358(1):28-35.\">25<\/a><\/sup><\/p>\n<\/div>\n<div id=\"section7-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">PAF in Multi-Organ Failure<\/h2>\n<\/div>\n<p>Morbidity and mortality associated with severe COVID-19 has also been characterized by vital organ failure, or in some instances, multiple-organ failure.<sup><a id=\"focusIdbibr29-10760296211051764290\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr29-10760296211051764\" data-ref-text=\"29\" data-reflink=\"bibr29-10760296211051764\" data-referenceslink=\"29 Mokhtari T, Hassani F, Ghaffari N, et al. COVID-19 and multiorgan failure: a narrative review on potential mechanisms. J Mol Histol. 2020;51(6):613-628.\">29<\/a>,<a id=\"focusIdbibr30-10760296211051764291\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr30-10760296211051764\" data-ref-text=\"30\" data-reflink=\"bibr30-10760296211051764\" data-referenceslink=\"30 Zaim S, Chong JH, Sankaranarayanan V, et al. COVID-19 and multiorgan response. Curr Probl Cardiol. 2020;45(8):100618.\">30<\/a><\/sup> The diversity of organ systems involved has perplexed both scientists and medical personnel alike. Acute renal dysfunction has been a reported sequelae in 3 to 9% of COVID-19 infections.<sup><a id=\"focusIdbibr31-10760296211051764292\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr31-10760296211051764\" data-ref-text=\"31\" data-reflink=\"bibr31-10760296211051764\" data-referenceslink=\"31 Raza A, Estepa A, Chan V, et al. Acute renal failure in critically Ill COVID-19 patients With a focus on the role of renal replacement therapy: a review of what We know So Far. Cureus. 2020;12(6):e8429. Published 2020; Jun 3.\">31<\/a><\/sup> The presence of acute kidney injury is also associated with poor prognostic outcomes and increased mortality rate.<sup><a id=\"focusIdbibr2-10760296211051764293\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr2-10760296211051764\" data-ref-text=\"2\" data-reflink=\"bibr2-10760296211051764\" data-referenceslink=\"2 Jehi L, Ji X, Milinovich A, et al. Development and validation of a model for individualized prediction of hospitalization risk in 4,536 patients with COVID-19. PLoS One. 2020;15(8).\">2<\/a><\/sup> Previous research in human patients has shown that both serum and urine PAF levels are elevated under conditions of corresponding acute renal failure.<sup><a id=\"focusIdbibr32-10760296211051764294\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr32-10760296211051764\" data-ref-text=\"32\" data-reflink=\"bibr32-10760296211051764\" data-referenceslink=\"32 Mariano F, Guida G, Donati D, et al. Production of platelet-activating factor in patients with sepsis-associated acute renal failure. Nephrol Dial Transplant. 1999;14(5):1150-1157.\">32<\/a><\/sup> Mariano et al. reported that plasma PAF levels collected from patients with acute renal failure in the setting of sepsis were significantly higher than PAF levels seen in controls on the first day of observation (244.4\u2009\u00b1\u2009105.1 pg\/ml vs 6.6\u2009\u00b1\u20094.7 pg\/ml; <i>P<\/i> &lt; 0.05).<sup><a id=\"focusIdbibr32-10760296211051764295\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr32-10760296211051764\" data-ref-text=\"32\" data-reflink=\"bibr32-10760296211051764\" data-referenceslink=\"32 Mariano F, Guida G, Donati D, et al. Production of platelet-activating factor in patients with sepsis-associated acute renal failure. Nephrol Dial Transplant. 1999;14(5):1150-1157.\">32<\/a><\/sup> Mariano et al. collected additional data over four consecutive days and concluded that PAF levels in septic patients with acute renal failure were similarly elevated each of the four days when compared to controls.<sup><a id=\"focusIdbibr32-10760296211051764296\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr32-10760296211051764\" data-ref-text=\"32\" data-reflink=\"bibr32-10760296211051764\" data-referenceslink=\"32 Mariano F, Guida G, Donati D, et al. Production of platelet-activating factor in patients with sepsis-associated acute renal failure. Nephrol Dial Transplant. 1999;14(5):1150-1157.\">32<\/a><\/sup> Other investigators have demonstrated that activation of PAF receptors in renal tissue increases kidney inflammation and fibrosis in animal models.<sup><a id=\"focusIdbibr33-10760296211051764297\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr33-10760296211051764\" data-ref-text=\"33\" data-reflink=\"bibr33-10760296211051764\" data-referenceslink=\"33 Correa-Costa M, Andrade-Oliveira V, Braga TT, et al. Activation of platelet-activating factor receptor exacerbates renal inflammation and promotes fibrosis. Lab Invest. 2014;94(4):455-466.\">33<\/a><\/sup><\/p>\n<p><strong>The association between PAF and systemic inflammatory response syndrome (SIRS) in the setting of acute pancreatitis has been previously recognized.<sup><a id=\"focusIdbibr34-10760296211051764298\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr34-10760296211051764\" data-ref-text=\"34\" data-reflink=\"bibr34-10760296211051764\" data-referenceslink=\"34 Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48(1):62-69.\">34<\/a><\/sup> The release of proinflammatory cytokines, anti-inflammatory cytokines, and tumor necrosis factor \u03b1 mediates the development of SIRS and systemic multi-organ failure in acute pancreatitis.<sup><a id=\"focusIdbibr34-10760296211051764299\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr34-10760296211051764\" data-ref-text=\"34\" data-reflink=\"bibr34-10760296211051764\" data-referenceslink=\"34 Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48(1):62-69.\">34<\/a><\/sup> This \u201cinflammatory soup\u201d also includes PAF which establishes a link between PAF and the manifestation of SIRS in pancreatic disease.<\/strong><sup><a id=\"focusIdbibr34-10760296211051764300\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr34-10760296211051764\" data-ref-text=\"34\" data-reflink=\"bibr34-10760296211051764\" data-referenceslink=\"34 Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48(1):62-69.\">34<\/a><\/sup> However, Johnson et al. failed to demonstrate that antagonism of PAF activity reduces morbidity or prevents multi-organ failure in individuals hospitalized with acute pancreatitis.<sup><a id=\"focusIdbibr34-10760296211051764301\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr34-10760296211051764\" data-ref-text=\"34\" data-reflink=\"bibr34-10760296211051764\" data-referenceslink=\"34 Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48(1):62-69.\">34<\/a><\/sup> The connection between PAF and SIRS is intriguing none the less.<\/p>\n<p>It is widely accepted that diabetes is an independent risk factor for the development of sepsis and SIRS.<sup><a id=\"focusIdbibr34-10760296211051764302\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr34-10760296211051764\" data-ref-text=\"34\" data-reflink=\"bibr34-10760296211051764\" data-referenceslink=\"34 Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48(1):62-69.\">34<\/a><\/sup> International studies have confirmed that diabetes is also a significant risk factor of mortality in severe COVID-19. Available data suggests that diabetes (type I or type II), with the latter being most prominent, is present in approximately one-third of mortality cases associated with COVID-19.<sup><a id=\"focusIdbibr35-10760296211051764303\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr35-10760296211051764\" data-ref-text=\"35\" data-reflink=\"bibr35-10760296211051764\" data-referenceslink=\"35 Ganesan SK, Venkatratnam P, Mahendra J, et al. Increased mortality of COVID-19 infected diabetes patients: role of furin proteases. Int J Obes. 2020;44(12):2486-2488.\">35<\/a>,<a id=\"focusIdbibr36-10760296211051764304\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr36-10760296211051764\" data-ref-text=\"36\" data-reflink=\"bibr36-10760296211051764\" data-referenceslink=\"36 Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in england: a whole-population study. Lancet Diabetes Endocrinol. 2020;8(10):813-822.\">36<\/a><\/sup> If diabetes does increase either the incidence of SIRS, or sets into motion another inflammatory cascade that ultimately leads to multi-organ failure with severe COVID-19, then the potential role of PAF as a progenitor of COVID-19 morbidity and mortality becomes more tangible.<\/p>\n<\/div>\n<div id=\"section8-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">Similarities of Symptomatic Presentations Between Severe COVID-19 and Dengue<\/h2>\n<\/div>\n<p>Early detection of COVID-19 infection is vital to both the timeliness of treatment initiation for individual patients as well as contact tracing to reduce spread of infection within the general population. Efforts to distinguish the earlier non-specific clinical stages of COVID-19 from other diseases has been a priority from the beginning of the pandemic, especially in geographical regions with a higher prevalence rate of other viral illnesses that exhibit similar symptoms to COVID-19 and can undermine COVID-19 early detection efforts. Such research has led to a direct comparison between the symptomatic presentation found in COVID-19 to symptoms that are seen in dengue, a mosquito-borne viral illness that can result in fatal hemorrhagic fever.<sup><a id=\"focusIdbibr37-10760296211051764306\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> Henrina et al. reported that COVID-19 and dengue share a remarkable resemblance in clinical presentation, particularly when examining the earlier stages of COVID-19.<sup><a id=\"focusIdbibr37-10760296211051764307\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> The presence of fever is the most common symptom shared between COVID-19 and dengue.<sup><a id=\"focusIdbibr37-10760296211051764308\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> The symptomatic similarities between COVID \u221219 and dengue do not end there and expand to include headache and myalgias.<sup><a id=\"focusIdbibr37-10760296211051764309\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> Manifestation of pulmonary symptoms which includes cough or respiratory distress can occur in both COVID-19 and dengue as well.<sup><a id=\"focusIdbibr37-10760296211051764310\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> Nausea, vomiting, abdominal pain, diarrhea, and acute liver injury comprise the list of gastrointestinal symptoms akin to either syndrome.<sup><a id=\"focusIdbibr37-10760296211051764311\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> Although less common, individuals infected by COVID-19 or dengue virus may also experience the precipitous appearance of a cutaneous rash.<sup><a id=\"focusIdbibr37-10760296211051764312\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> Applied laboratory analysis of serum samples collected from individuals infected by COVID-19 or dengue virus have also demonstrated similar abnormalities in hematologic indexes. Thrombocytopenia, leukopenia, and elevated D-dimer as identified by hematologic panels can be present in both COVID-19 and dengue.<sup><a id=\"focusIdbibr37-10760296211051764313\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup> The similarities of clinical presentation between COVID-19 and dengue is so pronounced that it can be difficult to distinguish between these two pathologies, particularly in the early stages of infection, and has resulted in COVID-19 cases that were initially misdiagnosed as dengue.<sup><a id=\"focusIdbibr37-10760296211051764314\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr37-10760296211051764\" data-ref-text=\"37\" data-reflink=\"bibr37-10760296211051764\" data-referenceslink=\"37 Henrina J, Putra ICS, Lawrensia S, et al. Coronavirus disease of 2019: a mimicker of dengue infection? SN Compr Clin Med. 2020:1-11.\">37<\/a><\/sup><\/p>\n<p>The telltale signs of severe dengue infections are thrombocytopenia, hemorrhage, increased vascular permeability, shock, and excessive cytokine activity.<sup><a id=\"focusIdbibr38-10760296211051764315\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr38-10760296211051764\" data-ref-text=\"38\" data-reflink=\"bibr38-10760296211051764\" data-referenceslink=\"38 Souza DG, Fagundes CT, Sousa LP, et al. Essential role of platelet-activating factor receptor in the pathogenesis of dengue virus infection. Proc Natl Acad Sci U S A. 2009;106(33):14138-14143.\">38<\/a><\/sup> Evidence from animal models has shown that deletion of PAF receptor genes and administration of PAF receptor antagonists results in lower severity of disease following exposure to dengue virus.<sup><a id=\"focusIdbibr38-10760296211051764316\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr38-10760296211051764\" data-ref-text=\"38\" data-reflink=\"bibr38-10760296211051764\" data-referenceslink=\"38 Souza DG, Fagundes CT, Sousa LP, et al. Essential role of platelet-activating factor receptor in the pathogenesis of dengue virus infection. Proc Natl Acad Sci U S A. 2009;106(33):14138-14143.\">38<\/a><\/sup> These findings appear to support at least a partial role of PAF in the pathogenesis of dengue infections. Sousa et al. noted that in murine models, deletion or inhibition of PAF activity reduced the production of inflammatory cytokines and tumor necrosis factor \u03b1.<sup><a id=\"focusIdbibr38-10760296211051764317\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr38-10760296211051764\" data-ref-text=\"38\" data-reflink=\"bibr38-10760296211051764\" data-referenceslink=\"38 Souza DG, Fagundes CT, Sousa LP, et al. Essential role of platelet-activating factor receptor in the pathogenesis of dengue virus infection. Proc Natl Acad Sci U S A. 2009;106(33):14138-14143.\">38<\/a><\/sup> If there truly exists a communal inflammatory pathway resulting in the manifestation of similar clinical presentation in both COVID-19 and dengue, then it is plausible that PAF plays a significant role in the pathogenesis of COVID-19 as well.<a name=\"_i11\"><\/a><\/p>\n<\/div>\n<div id=\"section9-10760296211051764\" class=\"NLM_sec NLM_sec-type_discussion NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">Discussion<\/h2>\n<\/div>\n<p><strong>COVID-19 can present with a myriad of clinical symptoms.<\/strong> There is significant overlap between the clinical manifestations of COVID-19 and other well-established clinical syndromes such as allergy and anaphylactic reactions, thrombotic events, and viral illnesses like dengue. Our existing knowledge regarding the latter syndromes suggests the potential role of PAF in COVID-19 as a mediator within the inflammatory cascade which promotes the development of inflammation, thrombosis, and hemodynamic compromise (<a class=\"ref showTableEvent\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-id=\"table1-10760296211051764\">Table 1<\/a>). As we identify key similarities in pathogenesis between COVID-19 and other disease states to affirm the role of PAF in COVID-19, we can apply the same principles of speculative comparison to treatments with proven efficacy in medical conditions of which we have familiarity and experience. In the case of severe allergy, anaphylaxis, and septic shock, the administration of corticosteroids has been demonstrated to improve disease outcomes.<sup><a id=\"focusIdbibr39-10760296211051764320\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr39-10760296211051764\" data-ref-text=\"39\" data-reflink=\"bibr39-10760296211051764\" data-referenceslink=\"39 Lian XJ, Huang DZ, Cao YS, et al. Reevaluating the role of corticosteroids in septic shock: an updated meta-analysis of randomized controlled trials. Biomed Res Int. 2019:3175047.\">39<\/a><\/sup> Available evidence suggests that corticosteroids can also improve outcomes in severe COVID-19 disease igniting the acceptance of corticosteroids as a viable treatment modality for severe COVID-19.<sup><a id=\"focusIdbibr40-10760296211051764321\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr40-10760296211051764\" data-ref-text=\"40\" data-reflink=\"bibr40-10760296211051764\" data-referenceslink=\"40 Prescott HC, Rice TW. Corticosteroids in COVID-19 ARDS: evidence and hope during the pandemic. JAMA. 2020;324(13):1292-1295.\">40<\/a><\/sup> A review of the PAF synthesis pathway and corticosteroid pharmacodynamics reveals that corticosteroids inhibit the activity of phospholipase A2, an enzyme responsible for the conversion of cell membrane phospholipids to Lyso-PAF, the progenitor of PAF, and thereby reducing downstream production of PAF itself.<sup><a id=\"focusIdbibr41-10760296211051764322\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr41-10760296211051764\" data-ref-text=\"41\" data-reflink=\"bibr41-10760296211051764\" data-referenceslink=\"41 Ericson-Neilsen W, Kaye AD. Steroids: pharmacology, complications, and practice delivery issues. Ochsner J. 2014;14(2):203-207.\">41<\/a><\/sup> If PAF indeed activates physiological pathways that contribute to the pathogenic effects of COVID-19, it is conceivable that pharmacological agents which directly inhibit the activity of PAF, or modulate the cycle of PAF synthesis and degradation may reduce morbidity and mortality associated with COVID-19.<sup><a id=\"focusIdbibr42-10760296211051764323\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr42-10760296211051764\" data-ref-text=\"42\" data-reflink=\"bibr42-10760296211051764\" data-referenceslink=\"42 Shamizadeh S, Brockow K, Ring J. Rupatadine: efficacy and safety of a non-sedating antihistamine with PAF-antagonist effects. Allergo J Int. 2014;23(3):87-95.\">42<\/a>\u2013<a id=\"focusIdbibr42-10760296211051764324\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr42-10760296211051764\" data-ref-text=\"45\" data-reflink=\"bibr42-10760296211051764\" data-referenceslink=\"42 Shamizadeh S, Brockow K, Ring J. Rupatadine: efficacy and safety of a non-sedating antihistamine with PAF-antagonist effects. Allergo J Int. 2014;23(3):87-95.\">45<\/a><\/sup> This speculative concept is shared by others.<sup><a id=\"focusIdbibr46-10760296211051764325\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr46-10760296211051764\" data-ref-text=\"46\" data-reflink=\"bibr46-10760296211051764\" data-referenceslink=\"46 Demopoulos CA. Is platelet-activating factor (PAF) a missing link for elucidating the mechanism of action of the coronavirus SARS-CoV-2 and explaining the Side effects-complications of COVID-19 disease? Preprints. 2020:2020060253\">46<\/a>,<a id=\"focusIdbibr47-10760296211051764326\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr47-10760296211051764\" data-ref-text=\"47\" data-reflink=\"bibr47-10760296211051764\" data-referenceslink=\"47 Demopoulos CA, Antonopoulou S, Theoharides TC. COVID-19, microthromboses, inflammation, and platelet activating factor. Biofactors. 2020;42(10):1850-1852.\">47<\/a><\/sup> Moreover, scientists continue to explore whether pharmacological agents that demonstrate PAF inhibition, such as rupatadine, are viable treatments for COVID-19.<sup><a id=\"focusIdbibr47-10760296211051764327\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr47-10760296211051764\" data-ref-text=\"47\" data-reflink=\"bibr47-10760296211051764\" data-referenceslink=\"47 Demopoulos CA, Antonopoulou S, Theoharides TC. COVID-19, microthromboses, inflammation, and platelet activating factor. Biofactors. 2020;42(10):1850-1852.\">47<\/a>,<a id=\"focusIdbibr48-10760296211051764328\" class=\"ref showRefEvent2\" role=\"button\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-rid=\"bibr48-10760296211051764\" data-ref-text=\"48\" data-reflink=\"bibr48-10760296211051764\" data-referenceslink=\"48 Theoharides TC, Antonopoulou S, Demopoulos CA. Coronavirus 2019, microthromboses, and platelet activating factor. Clin Ther. 2020;42(10):1850-1852.\">48<\/a><\/sup><\/p>\n<p>&nbsp;<\/p>\n<table id=\"table1-10760296211051764\" border=\"0\" width=\"95%\" cellspacing=\"0\" cellpadding=\"0\">\n<tbody>\n<tr bgcolor=\"#e1e1e1\">\n<td>\n<table class=\"showtable_wrap\" cellspacing=\"2\" cellpadding=\"2\">\n<tbody>\n<tr bgcolor=\"#e1e1e1\">\n<td align=\"center\" valign=\"top\" bgcolor=\"#ffffff\">\n<div id=\"table1-10760296211051764\" class=\"table\"><a class=\"showFiguresEEvent\" href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764#\" data-id=\"table1-10760296211051764\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/journals.sagepub.com\/templates\/jsp\/images\/dummy_table_thumb.gif\" alt=\"Table\" width=\"150\" height=\"100\" align=\"bottom\" border=\"1\" \/><\/a><\/div>\n<\/td>\n<td align=\"left\" valign=\"top\">\n<div class=\"short-legend\">\n<p><span class=\"captionLabel\">Table 1.<\/span> Categorization of pathology that contributes to morbidity and mortality in severe COVID-19 with a direct comparison to the known physiological effects of Platelet Activating Factor in human or animal models.<\/p>\n<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<div id=\"div-table1-10760296211051764\" class=\"tableWrapper visuallyhidden\">\n<div class=\"tableViewerNav\"><\/div>\n<div class=\"NLM_table-wrap\">\n<div class=\"caption\">\n<p><span class=\"captionLabel\">Table 1.<\/span> Categorization of pathology that contributes to morbidity and mortality in severe COVID-19 with a direct comparison to the known physiological effects of Platelet Activating Factor in human or animal models.<\/p>\n<\/div>\n<p><img decoding=\"async\" id=\"_i12\" src=\"https:\/\/journals.sagepub.com\/na101\/home\/literatum\/publisher\/sage\/journals\/content\/cata\/2021\/cata_27\/10760296211051764\/20211109\/images\/medium\/10.1177_10760296211051764-table1.gif\" alt=\"\" \/><\/p>\n<\/div>\n<div class=\"tableViewerLargeImage\"><a tabindex=\"0\" href=\"https:\/\/journals.sagepub.com\/na101\/home\/literatum\/publisher\/sage\/journals\/content\/cata\/2021\/cata_27\/10760296211051764\/20211109\/images\/large\/10.1177_10760296211051764-table1.jpeg\" target=\"_blank\" rel=\"noopener\"><strong>View larger version<\/strong><\/a><\/div>\n<\/div>\n<\/div>\n<div id=\"section10-10760296211051764\" class=\"NLM_sec NLM_sec_level_1\">\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">Conclusion<\/h2>\n<\/div>\n<p>Our understanding of COVID-19 remains limited and the pathologic mechanisms which contribute to disease development are likely multi-factorial and complex. PAF represents a potential pathophysiologic mechanism for severe COVID-19 due to its prominent role in signaling of inflammatory and thrombotic pathways. Even if PAF does indeed play a role in the pathogenesis of severe COVID-19, it is unlikely that it is a sole player in the cascade of events that leads to the culmination of the clinically varied and complex presentation of COVID-19. <strong>Additional research is needed to validate both the relationship between PAF and COVID-19 as well as the extent to which PAF may increase morbidity and mortality in severe COVID-19.<\/strong><\/p>\n<\/div>\n<div class=\"acknowledgement\">\n<div class=\"sectionInfo\">\n<h2 class=\"section-heading-2\">Acknowledgements<\/h2>\n<\/div>\n<p>MK, VD, and FM are all employees of the Minneapolis VA Healthcare System. This material is based upon work supported by the Department of Veterans Affairs (specifically the Veterans Health Administration).<\/p>\n<\/div>\n<div class=\"fn-group\">\n<p><span class=\"fn-label\">Funding<\/span><br \/>\nThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.<\/p>\n<p><span class=\"fn-label\">Conflict of Interest Statement<\/span><br \/>\nThe Author(s) declare(s) that there is no conflict of interest<\/p>\n<p><span class=\"fn-label\">Ethics and Patient Consent<\/span><br \/>\nThis is a review article. Our institution does not require ethics approval for a review article. Patient consent is not applicable to this article.<\/p>\n<p><span class=\"fn-label\">Author Contributions<\/span><br \/>\nF.K., V.D., and M.K. came up with the concept for the manuscript. V.D. did the initial literature search, and F.K. and M.K. confirmed the appropriateness of the sources. All authors wrote the manuscript.<\/p>\n<p><span class=\"fn-label\">Declaration of Conflicting Interests<\/span><br \/>\nThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.<\/p>\n<p><span class=\"fn-label\">Funding<\/span><br \/>\nThe author(s) received no financial support for the research, authorship and\/or publication of this article.<\/p>\n<p><span class=\"fn-label\">ORCID iDs<\/span><br \/>\nMark Klein <a class=\"ext-link\" href=\"https:\/\/orcid.org\/0000-0003-3457-6879\" target=\"_blank\" rel=\"noopener\">https:\/\/orcid.org\/0000-0003-3457-6879<\/a><\/p>\n<p>Vinh Dao <a class=\"ext-link\" href=\"https:\/\/orcid.org\/0000-0002-2704-2222\" target=\"_blank\" rel=\"noopener\">https:\/\/orcid.org\/0000-0002-2704-2222<\/a><\/p>\n<\/div>\n<p><a name=\"_i15\"><\/a><\/p>\n<div class=\"sectionInfo\">\n<h2 class=\"sectionHeading\">References<\/h2>\n<\/div>\n<table class=\"references\" border=\"0\">\n<tbody>\n<tr id=\"bibr1-10760296211051764\">\n<td class=\"refnumber\">1.<\/td>\n<td valign=\"top\">Corona Virus Resource Center . 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Indian J Otolaryngol Head Neck Surg. <span class=\"NLM_year\">2009<\/span>;61(4):<span class=\"NLM_fpage\">320<\/span>&#8211;<span class=\"NLM_lpage\">332<\/span>.<br \/>\n<span class=\"ref-google\"><a class=\"google-scholar\" href=\"http:\/\/scholar.google.com\/scholar_lookup?hl=en&amp;volume=61&amp;publication_year=2009&amp;pages=320-332&amp;issue=4&amp;author=M+Sudhakara+Rao&amp;author=D+Dwarakanatha+Reddy&amp;author=PS+Murthy&amp;title=Rupatadine%3A+pharmacological+profile+and+its+use+in+the+treatment+of+allergic+rhinitis\">Google Scholar<\/a><\/span><span class=\"ref-xLink\"> | <a href=\"https:\/\/journals.sagepub.com\/servlet\/linkout?suffix=bibr43-10760296211051764&amp;dbid=16&amp;doi=10.1177%2F10760296211051764&amp;key=10.1007%2Fs12070-009-0091-8\">Crossref<\/a> | <a href=\"https:\/\/journals.sagepub.com\/servlet\/linkout?suffix=bibr43-10760296211051764&amp;dbid=8&amp;doi=10.1177%2F10760296211051764&amp;key=23120659\">Medline<\/a><\/span><\/p>\n<hr aria-hidden=\"true\" \/>\n<\/td>\n<\/tr>\n<tr id=\"bibr44-10760296211051764\">\n<td class=\"refnumber\">44.<\/td>\n<td valign=\"top\">Papakonstantinou, V, Lagopati, N, Tsilibary, EC, <span class=\"NLM_etal\">et al.<\/span> <span class=\"NLM_article-title\">A review on platelet activating factor inhibitors: could a New class of potent metal-based anti-inflammatory drugs induce anticancer properties?<\/span> Bioinorg Chem Appl. <span class=\"NLM_year\">2017<\/span>.<br \/>\n<span class=\"ref-google\"><a class=\"google-scholar\" href=\"http:\/\/scholar.google.com\/scholar_lookup?hl=en&amp;publication_year=2017&amp;author=V+Papakonstantinou&amp;author=N+Lagopati&amp;author=EC+Tsilibary&amp;title=A+review+on+platelet+activating+factor+inhibitors%3A+could+a+New+class+of+potent+metal-based+anti-inflammatory+drugs+induce+anticancer+properties%3F\">Google Scholar<\/a><\/span><span class=\"ref-xLink\"> | <a href=\"https:\/\/journals.sagepub.com\/servlet\/linkout?suffix=bibr44-10760296211051764&amp;dbid=16&amp;doi=10.1177%2F10760296211051764&amp;key=10.1155%2F2017%2F6947034\">Crossref<\/a> | <a href=\"https:\/\/journals.sagepub.com\/servlet\/linkout?suffix=bibr44-10760296211051764&amp;dbid=8&amp;doi=10.1177%2F10760296211051764&amp;key=28458618\">Medline<\/a><\/span><\/p>\n<hr aria-hidden=\"true\" \/>\n<\/td>\n<\/tr>\n<tr id=\"bibr45-10760296211051764\">\n<td class=\"refnumber\">45.<\/td>\n<td valign=\"top\">Peplow, PV . <span class=\"NLM_article-title\">Regulation of platelet-activating factor (PAF) activity in human diseases by phospholipase A2 inhibitors, PAF acetylhydrolases, PAF receptor antagonists and free radical scavengers<\/span>. 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Biofactors. <span class=\"NLM_year\">2020<\/span>;42(10):<span class=\"NLM_fpage\">1850<\/span>&#8211;<span class=\"NLM_lpage\">1852<\/span>.<br \/>\n<span class=\"ref-google\"><a class=\"google-scholar\" href=\"http:\/\/scholar.google.com\/scholar_lookup?hl=en&amp;volume=42&amp;publication_year=2020&amp;pages=1850-1852&amp;issue=10&amp;author=CA+Demopoulos&amp;author=S+Antonopoulou&amp;author=TC+Theoharides&amp;title=COVID-19%2C+microthromboses%2C+inflammation%2C+and+platelet+activating+factor\">Google Scholar<\/a><\/span><\/p>\n<hr aria-hidden=\"true\" \/>\n<\/td>\n<\/tr>\n<tr id=\"bibr48-10760296211051764\">\n<td class=\"refnumber\">48.<\/td>\n<td valign=\"top\">Theoharides, TC, Antonopoulou, S, Demopoulos, CA. <span class=\"NLM_article-title\">Coronavirus 2019, microthromboses, and platelet activating factor<\/span>. Clin Ther. <span class=\"NLM_year\">2020<\/span>;42(10):<span class=\"NLM_fpage\">1850<\/span>&#8211;<span class=\"NLM_lpage\">1852<\/span>.<br \/>\n<span class=\"ref-google\"><a class=\"google-scholar\" href=\"http:\/\/scholar.google.com\/scholar_lookup?hl=en&amp;volume=42&amp;publication_year=2020&amp;pages=1850-1852&amp;issue=10&amp;author=TC+Theoharides&amp;author=S+Antonopoulou&amp;author=CA+Demopoulos&amp;title=Coronavirus+2019%2C+microthromboses%2C+and+platelet+activating+factor\">Google Scholar<\/a><\/span><span class=\"ref-xLink\"> | <a href=\"https:\/\/journals.sagepub.com\/servlet\/linkout?suffix=bibr48-10760296211051764&amp;dbid=16&amp;doi=10.1177%2F10760296211051764&amp;key=10.1016%2Fj.clinthera.2020.08.006\">Crossref<\/a> | <a href=\"https:\/\/journals.sagepub.com\/servlet\/linkout?suffix=bibr48-10760296211051764&amp;dbid=8&amp;doi=10.1177%2F10760296211051764&amp;key=32883529\">Medline<\/a><\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"response\">\n<div class=\"sub-article-title\">\u03a0\u0397\u0393\u0397:https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/10760296211051764<\/div>\n<\/div>\n<p class=\"bioTitle\">Author biography<\/p>\n<p><b>Dr. Mark Klein<\/b> is a Staff Physician at the Minneapolis VA Healthcare System and Associate Professor at the University of Minnesota.<\/p>\n<p><b>Vinh Dao<\/b> is a pharmacist in the Pain Center at the Minneapolis VA Healthcare System.<\/p>\n<p><b>Dr. Fatima Khan<\/b> is a Staff Physician at the Minneapolis VA Healthcare System and Assistant Professor at the University of Minnesota.<\/p>\n<\/article>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>\u039d\u03b5\u03cc\u03c4\u03b5\u03c1\u03b1 \u03b3\u03b9\u03b1 \u03c4\u03bf \u03bc\u03b7\u03c7\u03b1\u03bd\u03b9\u03c3\u03bc\u03cc \u03b4\u03c1\u03ac\u03c3\u03b7\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd \u03ba\u03b1\u03b9 \u03c4\u03b7\u03c2 \u03bd\u03cc\u03c3\u03bf\u03c5 COVID-19 \u03bc\u03ad\u03c3\u03b1 \u03b1\u03c0\u03cc \u03bc\u03b9\u03b1 \u03ac\u03bb\u03bb\u03b7 \u2013 \u03bd\u03ad\u03b1 \u03c0\u03c1\u03bf\u03c3\u03ad\u03b3\u03b3\u03b9\u03c3\u03b7 \u03c4\u03bf\u03c5 \u03b8\u03ad\u03bc\u03b1\u03c4\u03bf\u03c2 YgeiaNews | info@ygeianews.gr | 23\/11\/2021 &#8211; 09:40 \u0388\u03c7\u03bf\u03c5\u03bd \u03c0\u03b5\u03c1\u03ac\u03c3\u03b5\u03b9\u00a0 \u03b4\u03cd\u03bf \u03c0\u03b5\u03c1\u03af\u03c0\u03bf\u03c5 \u03c7\u03c1\u03cc\u03bd\u03b9\u03b1 \u03b1\u03c0\u03cc \u03c4\u03b7\u03bd \u03b5\u03bc\u03c6\u03ac\u03bd\u03b9\u03c3\u03b7 \u03c4\u03b7\u03c2 \u03c0\u03c1\u03c9\u03c4\u03cc\u03b3\u03bd\u03c9\u03c1\u03b7\u03c2 \u03b3\u03b9\u03b1 \u03c4\u03bf\u03bd \u03b1\u03bd\u03b5\u03c0\u03c4\u03c5\u03b3\u03bc\u03ad\u03bd\u03bf \u03ba\u03cc\u03c3\u03bc\u03bf \u03c0\u03b1\u03bd\u03b4\u03b7\u03bc\u03af\u03b1\u03c2 \u03c4\u03bf\u03c5 \u03ba\u03bf\u03c1\u03c9\u03bd\u03bf\u03ca\u03bf\u03cd, \u03ad\u03c7\u03bf\u03c5\u03bd \u03b2\u03c1\u03b5\u03b8\u03b5\u03af \u03c4\u03b1 \u03ba\u03b1\u03c4\u03ac\u03bb\u03bb\u03b7\u03bb\u03b1 \u03b5\u03bc\u03b2\u03cc\u03bb\u03b9\u03b1 \u03ba\u03b1\u03b9 \u03c0\u03b1\u03c1\u03bf\u03c5\u03c3\u03b9\u03ac\u03b6\u03bf\u03bd\u03c4\u03b1\u03b9 \u03ae\u03b4\u03b7 \u03c4\u03b1 \u03c0\u03c1\u03ce\u03c4\u03b1 \u03c6\u03ac\u03c1\u03bc\u03b1\u03ba\u03b1, &hellip; <\/p>\n<p><a class=\"more-link btn\" href=\"https:\/\/evaggelatos.com\/?p=23743\">\u03a3\u03c5\u03bd\u03ad\u03c7\u03b5\u03b9\u03b1 \u03b1\u03bd\u03ac\u03b3\u03bd\u03c9\u03c3\u03b7\u03c2<\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[85],"tags":[250,75],"class_list":["post-23743","post","type-post","status-publish","format-standard","hentry","category-85","tag-250","tag-75","item-wrap"],"_links":{"self":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts\/23743","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=23743"}],"version-history":[{"count":4,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts\/23743\/revisions"}],"predecessor-version":[{"id":23747,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=\/wp\/v2\/posts\/23743\/revisions\/23747"}],"wp:attachment":[{"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=23743"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=23743"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/evaggelatos.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=23743"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}