{"id":16032,"date":"2026-10-21T06:00:00","date_gmt":"2026-10-21T10:00:00","guid":{"rendered":"https:\/\/cov19longhaulfoundation.org\/?p=16032"},"modified":"2026-09-07T11:03:02","modified_gmt":"2026-09-07T15:03:02","slug":"sars-cov-2-mesenteric-vascular-injury-and-ischemic-enterocolitis","status":"publish","type":"post","link":"https:\/\/cov19longhaulfoundation.org\/?p=16032","title":{"rendered":"SARS-CoV-2, Mesenteric Vascular Injury and Ischemic Enterocolitis"},"content":{"rendered":"\n<p class=\"has-small-font-size wp-block-paragraph\">John Murphy, CEO The COVID-19 Long haul Foundation<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Abstract<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">SARS-CoV-2 infection can produce clinically important gastrointestinal vascular injury, including acute mesenteric ischaemia, mesenteric arterial and venous thrombosis, non-occlusive mesenteric ischaemia, intestinal microvascular thrombosis, ischaemic colitis, gastrointestinal haemorrhage, bowel infarction, transmural necrosis and perforation. Although these complications are uncommon relative to the overall burden of COVID-19, their pathological consequences can be catastrophic.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The emerging evidence is particularly notable because severe intestinal injury can occur in the absence of an obstructing thrombus in the superior mesenteric artery or other major mesenteric vessels. Systematic imaging reviews identify non-occlusive mesenteric ischaemia as a frequent phenotype, whereas surgical and pathological studies demonstrate fibrin microthrombi in small mucosal and submucosal vessels, endothelial injury, vascular congestion, haemorrhage and necrosis. In a clinicopathological series of 28 bowel resection specimens from 22 patients with COVID-19-associated ischaemic enterocolitis, small-vessel fibrin thrombi were identified in 24 of 25 cases with acute ischaemia, and more than half demonstrated extension of necrosis into the muscularis propria. Perforation was identified grossly in 11% of specimens.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The colon is particularly important because ischaemic injury can produce mucosal friability, ulceration, haemorrhagic necrosis and ultimately full-thickness wall destruction. These lesions may culminate in microscopic or macroscopic perforation, faecal contamination, peritonitis, sepsis and death. Case reports document actual colonic perforations with histologically demonstrated necrosis and mesenteric microcirculatory thrombosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The pathophysiological model is multifactorial: endothelial dysfunction, platelet activation, complement activation, neutrophil extracellular traps, coagulation activation, microvascular thrombosis, systemic hypotension, vasoconstriction and impaired oxygen delivery may converge on the intestinal microcirculation. Large-vessel thrombosis is therefore only one mechanism. The presence of a patent superior mesenteric artery on CT or autopsy does not exclude severe intestinal vascular injury.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-associated gastrointestinal haemorrhage represents a second, partially overlapping phenotype. Meta-analyses estimate gastrointestinal bleeding in approximately 2\u20133% of hospitalised or studied COVID populations, although estimates are highly heterogeneous and confounded by disease severity, anticoagulation and selection of patients.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The available evidence supports a causal relationship between severe SARS-CoV-2 infection and a subset of mesenteric and intestinal vascular injuries, but does not establish that every intestinal haemorrhage, ischaemic event or colonic perforation occurring after COVID is caused by the virus. Differentiation among macrovascular occlusion, microvascular thrombosis, non-occlusive ischaemia, anticoagulant-associated bleeding, critical-illness injury and unrelated gastrointestinal disease is essential.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">Introduction<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-19 was initially regarded principally as a respiratory disease. It is now established as a systemic disorder involving the vascular, coagulation, renal, neurological, cardiac and gastrointestinal systems.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Among the most severe extrapulmonary manifestations is <strong>acute mesenteric ischaemia (AMI)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The clinical spectrum extends from relatively subtle mucosal injury to:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>intestinal hypoperfusion;<\/li>\n\n\n\n<li>ischaemic colitis;<\/li>\n\n\n\n<li>mesenteric arterial thrombosis;<\/li>\n\n\n\n<li>mesenteric venous thrombosis;<\/li>\n\n\n\n<li>microvascular thrombosis;<\/li>\n\n\n\n<li>mucosal haemorrhage;<\/li>\n\n\n\n<li>haemorrhagic infarction;<\/li>\n\n\n\n<li>deep ulceration;<\/li>\n\n\n\n<li>transmural necrosis;<\/li>\n\n\n\n<li>bowel-wall disruption;<\/li>\n\n\n\n<li>pneumatosis;<\/li>\n\n\n\n<li>perforation;<\/li>\n\n\n\n<li>peritonitis;<\/li>\n\n\n\n<li>sepsis;<\/li>\n\n\n\n<li>multiorgan failure.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A systematic review of 47 studies involving 75 patients found small-bowel ischaemia in 46.7% and ischaemic colitis in 37.3% of reported COVID-associated AMI cases. Importantly, non-occlusive mesenteric ischaemia accounted for 67.9%, suggesting that large-vessel obstruction is not required for severe intestinal injury.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The pathological significance of this observation is profound.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The bowel can infarct even when the principal mesenteric artery remains open.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">1. The Mesenteric Circulation as a Target of COVID-19<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The gastrointestinal tract receives a large fraction of cardiac output.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The intestine consequently has little tolerance for prolonged reductions in perfusion.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Three vascular compartments must be considered:<\/p>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li><strong>large mesenteric arteries and veins<\/strong>;<\/li>\n\n\n\n<li><strong>medium-sized intramural vessels<\/strong>;<\/li>\n\n\n\n<li><strong>the mucosal and submucosal microcirculation<\/strong>.<\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\">Conventional acute mesenteric ischaemia usually evokes the image of an embolus or thrombus occluding the SMA.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-19 has complicated that model.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The available pathological evidence indicates that injury can occur predominantly at the <strong>microvascular level<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>normal or patent SMA \u2260 normal intestinal perfusion.<\/strong><\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">2. Epidemiological and Imaging Evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The updated systematic review of 75 COVID-associated AMI cases found:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>small-bowel ischaemia: 46.67%;<\/li>\n\n\n\n<li>ischaemic colitis: 37.3%;<\/li>\n\n\n\n<li>non-occlusive mesenteric ischaemia: 67.9%;<\/li>\n\n\n\n<li>bowel-wall thickening\/edema: 50.9%;<\/li>\n\n\n\n<li>bowel hypoperfusion: 20.7%;<\/li>\n\n\n\n<li>ileal involvement: 32.07%;<\/li>\n\n\n\n<li>colonic involvement: 32.07%;<\/li>\n\n\n\n<li>SMA involvement: 24.9%;<\/li>\n\n\n\n<li>SMV involvement: 14.3%.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Approximately half of patients treated conservatively in that literature review died.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">These numbers should not be interpreted as population incidence because the literature is enriched for severe cases. They nevertheless establish that intestinal ischaemia is a reproducible clinical phenotype.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">3. Macrovascular Mesenteric Arterial Thrombosis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The most straightforward mechanism is thrombosis of a major mesenteric artery.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The proposed sequence is:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>SARS-CoV-2 infection<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 systemic inflammation<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 endothelial activation<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 platelet activation<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 coagulation activation<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 thrombus formation<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 SMA obstruction<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 intestinal hypoperfusion<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 mucosal injury<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 transmural infarction.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Published cases demonstrate SMA thrombosis followed by bowel infarction requiring emergency surgery. The original systematic imaging literature identified nine patients with arterial compromise caused by superior mesenteric thromboembolism.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This phenotype is readily visible on CT angiography.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">But it is only part of the story.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">4. Mesenteric Microvascular Thrombosis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The more unusual and potentially more important mechanism is microvascular thrombosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The intestinal mucosa receives blood through a dense network of small vessels.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-associated endothelial dysfunction and coagulation activation may produce fibrin deposition in these vessels.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The consequences can be severe despite preservation of flow through the major mesenteric arteries.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The updated systematic review identified microvascular thrombi in six patients whose major vessels showed no abnormalities on imaging.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The pathological implication is crucial:<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>The disease may be a disorder of intestinal microcirculation rather than simply an obstructive disease of the SMA.<\/strong><\/p>\n<\/blockquote>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">5. Direct Clinicopathological Evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">One of the most informative studies examined <strong>28 bowel resection specimens from 22 patients<\/strong> with COVID-associated ischaemic enterocolitis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The specimens included:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>small intestine;<\/li>\n\n\n\n<li>terminal ileum;<\/li>\n\n\n\n<li>colon;<\/li>\n\n\n\n<li>combined small bowel and colon.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The gross findings were striking.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">External examination<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Serosal discoloration occurred in <strong>25 of 28 specimens (89%)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Other findings included:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>bowel dilatation: 32%;<\/li>\n\n\n\n<li>pneumatosis: 14%;<\/li>\n\n\n\n<li>perforation: 11%;<\/li>\n\n\n\n<li>serosal adhesions: 32%;<\/li>\n\n\n\n<li>serosal exudate: 29%.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The internal surface was abnormal in <strong>93%<\/strong>, with mucosal discoloration.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Some segments were:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>dusky red;<\/li>\n\n\n\n<li>purple;<\/li>\n\n\n\n<li>black;<\/li>\n\n\n\n<li>tan-yellow;<\/li>\n\n\n\n<li>green;<\/li>\n\n\n\n<li>grey-brown.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">These are not merely radiological abnormalities.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">They represent gross pathological evidence of intestinal tissue injury.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">6. Histopathology of COVID-Associated Ischaemic Enterocolitis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The microscopic findings provide even stronger evidence.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Among the specimens with acute ischaemia:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>mucosal necrosis was present;<\/li>\n\n\n\n<li>necrosis could be coagulative, haemorrhagic or purulent;<\/li>\n\n\n\n<li>muscularis propria involvement occurred in more than half;<\/li>\n\n\n\n<li>52% had patchy or multifocal mucosal necrosis;<\/li>\n\n\n\n<li>pneumatosis-type changes were identified histologically in 60%.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Most strikingly:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>small-vessel fibrin thrombi occurred in 24 of 25 cases (96%).<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">These thrombi were located predominantly in:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>submucosal vessels;<\/li>\n\n\n\n<li>mucosal vessels.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">They were generally situated beneath areas of necrotic mucosa.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This provides a compelling pathological bridge between COVID-associated coagulopathy and intestinal tissue destruction.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">7. Endothelial Injury<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The same study found abnormalities of small-vessel walls.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In 23 of 25 cases, markedly oedematous submucosal areas contained small vessels with:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>fibrinous degeneration;<\/li>\n\n\n\n<li>perivascular neutrophils;<\/li>\n\n\n\n<li>changes resembling leukocytoclastic vasculitis.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Importantly, the authors did <strong>not<\/strong> identify well-formed thromboemboli within the mesenteric vessels.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This observation reinforces the concept of a <strong>microvascular process<\/strong> rather than conventional large-vessel embolism.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">8. The Colon: Why It Matters<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The colon is not simply an innocent bystander.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-associated ischaemic injury can involve:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>caecum;<\/li>\n\n\n\n<li>ascending colon;<\/li>\n\n\n\n<li>transverse colon;<\/li>\n\n\n\n<li>descending colon;<\/li>\n\n\n\n<li>sigmoid colon;<\/li>\n\n\n\n<li>rectum.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The distribution can be focal, multifocal or extensive.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ischaemic colitis can develop even when the celiac, SMA and inferior mesenteric arteries appear patent.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">One reported patient had inflammatory changes from the rectum to the splenic flexure despite patent major mesenteric arteries. Endoscopy demonstrated severely oedematous, ulcerated and friable mucosa, while biopsy showed crypt abnormalities, loss of goblet cells, lamina-propria hyalinization and mucosal haemorrhage.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is precisely the pattern expected from <strong>intramural or microvascular ischaemia<\/strong>.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">9. From Ischemia to Hemorrhage<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Ischaemia and bleeding are not mutually exclusive.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Indeed, severe ischaemia can generate haemorrhage.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The mechanism is:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>vascular insufficiency<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 epithelial hypoxia<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 endothelial injury<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 capillary leakage<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 mucosal breakdown<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 haemorrhage.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Reperfusion can amplify the injury.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>ischaemia \u2192 vascular injury \u2192 reperfusion \u2192 haemorrhagic mucosal necrosis.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Histologically, the resulting tissue may contain both necrosis and blood.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The clinicopathological series demonstrated coagulative, haemorrhagic and purulent patterns of mucosal necrosis.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">10. COVID-19 and Gastrointestinal Hemorrhage<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Gastrointestinal bleeding has been documented repeatedly in COVID-19.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A systematic review and meta-analysis including 91,887 patients identified 534 bleeding events, corresponding to 0.6% in the pooled underlying populations; after adjustment for outlying studies, the pooled estimate was approximately 2%, with substantial heterogeneity. Lower gastrointestinal bleeding accounted for a smaller proportion than upper gastrointestinal bleeding.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A subsequent meta-analysis of 33 studies including 134,905 patients estimated a pooled gastrointestinal bleeding prevalence of <strong>3.05%<\/strong>, increasing to approximately <strong>6.2% among patients receiving anticoagulants<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">These estimates require caution because:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>disease severity differs substantially among studies;<\/li>\n\n\n\n<li>anticoagulant exposure is a major confounder;<\/li>\n\n\n\n<li>critically ill patients undergo more procedures;<\/li>\n\n\n\n<li>upper and lower gastrointestinal bleeding have different mechanisms;<\/li>\n\n\n\n<li>published cohorts may preferentially capture severe cases.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Nevertheless, bleeding is a recognized COVID-associated gastrointestinal complication.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">11. Lower Gastrointestinal Bleeding and Ischemic Colitis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Lower gastrointestinal bleeding is particularly important when accompanied by:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>abdominal pain;<\/li>\n\n\n\n<li>diarrhoea;<\/li>\n\n\n\n<li>urgency;<\/li>\n\n\n\n<li>haematochezia;<\/li>\n\n\n\n<li>elevated lactate;<\/li>\n\n\n\n<li>high D-dimer;<\/li>\n\n\n\n<li>CT evidence of colonic-wall injury.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">In COVID-associated ischaemic colitis, endoscopy can demonstrate:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>oedema;<\/li>\n\n\n\n<li>erythema;<\/li>\n\n\n\n<li>petechiae;<\/li>\n\n\n\n<li>mucosal friability;<\/li>\n\n\n\n<li>longitudinal ulceration;<\/li>\n\n\n\n<li>cratered ulcers;<\/li>\n\n\n\n<li>necrotic mucosa.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Biopsy may demonstrate:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>crypt withering;<\/li>\n\n\n\n<li>loss of goblet cells;<\/li>\n\n\n\n<li>lamina-propria hyalinization;<\/li>\n\n\n\n<li>mucosal haemorrhage;<\/li>\n\n\n\n<li>coagulative necrosis.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">12. The &#8220;Visceral Tear&#8221; Question<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The term <strong>visceral tear<\/strong> is not normally used in the pathology literature to describe COVID-associated intestinal injury.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The corresponding pathological terms are:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>mucosal laceration;<\/li>\n\n\n\n<li>mucosal ulceration;<\/li>\n\n\n\n<li>transmural necrosis;<\/li>\n\n\n\n<li>bowel-wall disruption;<\/li>\n\n\n\n<li>perforation;<\/li>\n\n\n\n<li>haemorrhagic infarction.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The distinction matters.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A mechanically torn colon and an ischaemically destroyed colon are different lesions.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In COVID-associated vascular injury, the sequence may be:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>microvascular thrombosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>mucosal ischaemia<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>mucosal necrosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>ulceration<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>submucosal and muscular injury<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>transmural necrosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>loss of mechanical integrity<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2193<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>perforation.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therefore the final &#8220;tear&#8221; may actually represent the end-stage of <strong>vascular infarction<\/strong>, rather than a primary traumatic rupture.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">13. Documented Colonic Perforation<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">There are multiple reports of actual colonic perforation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In one case of severe COVID-19, CT demonstrated free air and wall defects of the transverse colon. Emergency laparotomy revealed two perforations measuring approximately 25 mm and 7 mm. Histology showed necrosis around the perforations, while microcirculatory thrombosis was identified in mesenteric vessels.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Another report described COVID-associated haemorrhagic colitis complicated by colonic perforation. Resection demonstrated:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>nonviable colon;<\/li>\n\n\n\n<li>haemorrhage;<\/li>\n\n\n\n<li>pericolonic fat necrosis;<\/li>\n\n\n\n<li>acute serositis;<\/li>\n\n\n\n<li>surface adhesions.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Subsequent operations demonstrated necrotic omental tissue, marked inflammation and haemorrhage, followed by feculent drainage and intra-abdominal abscesses.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">These observations demonstrate a plausible continuum from vascular injury to bowel-wall destruction and contamination.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">14. Transmural Necrosis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Transmural necrosis represents the point at which the injury progresses through:<\/p>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li>mucosa;<\/li>\n\n\n\n<li>submucosa;<\/li>\n\n\n\n<li>muscularis propria;<\/li>\n\n\n\n<li>serosa.<\/li>\n<\/ol>\n\n\n\n<p class=\"wp-block-paragraph\">At that stage the bowel wall can no longer maintain structural integrity.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The clinicopathological series demonstrated muscularis propria involvement in more than half of acutely ischaemic specimens.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Another surgical pathology series of four COVID patients demonstrated disease ranging from superficial mucosal ischaemia to <strong>frank transmural ischaemic colitis<\/strong>, with pneumatosis and perforation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This progression is clinically consequential because transmural necrosis greatly increases the risk of:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>perforation;<\/li>\n\n\n\n<li>bacterial translocation;<\/li>\n\n\n\n<li>peritonitis;<\/li>\n\n\n\n<li>sepsis;<\/li>\n\n\n\n<li>multiorgan failure.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">15. Pneumatosis Intestinalis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Pneumatosis intestinalis is gas within the bowel wall.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In COVID-associated intestinal ischaemia it may arise when:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>mucosal injury + increased intraluminal pressure + bacterial gas production<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">permit gas to enter damaged bowel-wall layers.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Pneumatosis was identified grossly in 14% of specimens in the major clinicopathological series and histologically in 60% of acutely ischaemic cases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Its significance depends on context.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Pneumatosis accompanied by:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>portal venous gas;<\/li>\n\n\n\n<li>absent bowel-wall enhancement;<\/li>\n\n\n\n<li>elevated lactate;<\/li>\n\n\n\n<li>peritonitis;<\/li>\n\n\n\n<li>severe abdominal pain;<\/li>\n\n\n\n<li>shock<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">should raise major concern for transmural infarction.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">16. Perforation Is the Final Structural Failure<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Perforation can occur by at least two mechanisms.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Mechanism A: Ischaemic wall destruction<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Microvascular thrombosis causes progressive necrosis until the wall becomes discontinuous.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Mechanism B: Pressure plus compromised wall<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Severe bowel distension or ileus increases intraluminal pressure while the ischaemic wall becomes progressively weaker.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The combination can produce focal rupture.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The clinical result is the same:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>intestinal contents escape into the peritoneal cavity.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This produces:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>chemical peritonitis;<\/li>\n\n\n\n<li>bacterial contamination;<\/li>\n\n\n\n<li>sepsis;<\/li>\n\n\n\n<li>abscess formation;<\/li>\n\n\n\n<li>septic shock.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">17. Colonic Distension as a Potential Amplifier<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">A particularly interesting phenotype is COVID-associated colonic ileus and distension.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Severe inflammation can impair motility.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The resulting:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>ileus \u2192 distension \u2192 increased intraluminal pressure \u2192 reduced mural perfusion<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">can amplify an already compromised microcirculation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">One published case described marked colonic dilatation, wall thickening and inflammatory changes, with mucosal biopsy demonstrating substantial haemorrhage and possible vascular thrombi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus, intestinal vascular injury and mechanical pressure may reinforce each other.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">18. Autopsy Evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The autopsy literature provides an important confirmation because it removes some of the uncertainty inherent in imaging.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Two recent fatal COVID cases demonstrated extensive intestinal ischaemia.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In one, extensive small- and large-intestinal ischaemic changes occurred despite a <strong>widely patent SMA and major branches<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Histology showed:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>acute mucosal inflammation;<\/li>\n\n\n\n<li>mucosal necrosis;<\/li>\n\n\n\n<li>intramucosal haemorrhage;<\/li>\n\n\n\n<li>fibrin thrombi in intramucosal and submucosal vessels.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The second case involved abdominal pain followed by melaena and bright-red rectal bleeding. Autopsy demonstrated focal transmural inflammation of the small bowel with multiple fibrin microthrombi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is perhaps the strongest evidence that COVID-associated intestinal infarction can occur through <strong>microvascular rather than macrovascular disease<\/strong>.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">19. Endothelial Dysfunction<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The intestinal vascular endothelium may be central to the disease.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">SARS-CoV-2-associated inflammation can activate endothelial cells and produce:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>endothelial swelling;<\/li>\n\n\n\n<li>altered permeability;<\/li>\n\n\n\n<li>platelet adhesion;<\/li>\n\n\n\n<li>leukocyte adhesion;<\/li>\n\n\n\n<li>coagulation activation;<\/li>\n\n\n\n<li>complement activation.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The intestinal microvascular bed can consequently become dysfunctional even without a large-vessel occlusion.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A multicentre pathological study found endothelial shrinkage, leukocyte adhesion and partial vascular-wall destruction in colonic and small-intestinal specimens.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">20. NETosis and Immunothrombosis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-19 is characterized by immunothrombosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Neutrophils release extracellular DNA\/protein networks known as NETs.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">NETs can:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>activate platelets;<\/li>\n\n\n\n<li>concentrate tissue factor;<\/li>\n\n\n\n<li>activate coagulation;<\/li>\n\n\n\n<li>trap erythrocytes;<\/li>\n\n\n\n<li>promote fibrin formation.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">This produces a self-amplifying loop:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>inflammation \u2192 NETosis \u2192 coagulation \u2192 microthrombus \u2192 tissue hypoxia \u2192 tissue injury \u2192 further inflammation.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The intestinal microcirculation is particularly vulnerable because its extensive capillary network provides abundant opportunity for microscopic vascular obstruction.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">21. Complement<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Complement activation can contribute to endothelial injury and thrombosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The conceptual pathway is:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>SARS-CoV-2\/inflammatory activation \u2192 complement activation \u2192 endothelial injury \u2192 platelet\/coagulation activation \u2192 microvascular thrombosis.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Complement-mediated vascular injury is therefore another plausible contributor to intestinal microangiopathy.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The evidence, however, is less specific than the histological evidence for fibrin microthrombi.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">22. Hypoperfusion and Non-Occlusive Mesenteric Ischemia<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Not every COVID-associated intestinal infarction is thrombotic.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Severe COVID can produce:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>hypotension;<\/li>\n\n\n\n<li>shock;<\/li>\n\n\n\n<li>hypoxaemia;<\/li>\n\n\n\n<li>myocardial dysfunction;<\/li>\n\n\n\n<li>vasopressor exposure;<\/li>\n\n\n\n<li>systemic inflammatory vasoconstriction.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The result can be <strong>NOMI<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The updated systematic review identified NOMI as the most frequent pattern in reported COVID-associated AMI.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This mechanism is especially important in ICU patients.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">23. The Colon Versus the Small Intestine<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Different patient populations appear to demonstrate different distributions.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The systematic literature contains both:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>small-bowel infarction;<\/li>\n\n\n\n<li>colonic ischaemia.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">A review of 89 reported patients found that among ICU patients, the large bowel alone was involved in 56%, with an additional 24% involving both large and small bowel. The authors associated this phenotype with microvascular thrombosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus, in critically ill patients, <strong>colonic ischaemia may be an especially important manifestation<\/strong>.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">24. Why the Colon Can Bleed Before It Perforates<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The mucosa is the first layer to become hypoxic.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Consequently:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>microvascular injury \u2192 epithelial necrosis \u2192 capillary leakage \u2192 mucosal haemorrhage \u2192 haematochezia.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">At this stage, the muscular wall may remain intact.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">If perfusion is restored, the mucosa can heal.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">If the process continues:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>mucosal injury \u2192 submucosal injury \u2192 muscularis necrosis \u2192 serosal injury \u2192 perforation.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus, rectal bleeding can potentially represent an <strong>early clinical marker of intestinal vascular injury<\/strong>, while perforation represents a late structural consequence.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">25. Why a Negative CTA Does Not Always End the Investigation<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">CT angiography is essential but has limitations.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A CTA can demonstrate:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>SMA occlusion;<\/li>\n\n\n\n<li>SMV thrombosis;<\/li>\n\n\n\n<li>bowel-wall hypoenhancement;<\/li>\n\n\n\n<li>bowel-wall thickening;<\/li>\n\n\n\n<li>pneumatosis;<\/li>\n\n\n\n<li>portal venous gas;<\/li>\n\n\n\n<li>free air.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">But microvascular thrombosis may be below its resolution.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The pathological literature demonstrates exactly this phenomenon.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therefore:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>patent SMA + abnormal bowel does not equal &#8220;no vascular injury.&#8221;<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">When clinical suspicion remains high, the bowel itself must be evaluated.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">26. Endoscopic Findings<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Colonoscopy or flexible sigmoidoscopy may demonstrate:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>oedema;<\/li>\n\n\n\n<li>erythema;<\/li>\n\n\n\n<li>petechiae;<\/li>\n\n\n\n<li>friability;<\/li>\n\n\n\n<li>ulceration;<\/li>\n\n\n\n<li>sharply demarcated ischaemic segments;<\/li>\n\n\n\n<li>necrotic mucosa.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">In one COVID-associated ischaemic colitis report, endoscopy showed severe oedema, ulceration and friability extending from the rectum proximally. Biopsy confirmed mucosal haemorrhage and characteristic ischaemic changes.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Another multicentre study reported oedematous mucosa with ischaemic ulcerations and petechiae. Histology demonstrated coagulative epithelial necrosis, ulceration and intramucosal haemorrhagic foci.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">27. Laboratory Correlates<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Potential laboratory warning signals include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>rising D-dimer;<\/li>\n\n\n\n<li>elevated CRP;<\/li>\n\n\n\n<li>leukocytosis;<\/li>\n\n\n\n<li>elevated lactate;<\/li>\n\n\n\n<li>metabolic acidosis;<\/li>\n\n\n\n<li>LDH elevation;<\/li>\n\n\n\n<li>falling haemoglobin when haemorrhage occurs.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">In the multicentre series of 24 patients with intestinal ischaemia, CRP was substantially elevated in all patients and D-dimer was markedly elevated in those in whom it was measured.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">None of these tests, however, is specific.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A normal lactate does not exclude early mesenteric ischaemia.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">28. Mortality<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The combination of ischaemia, necrosis, perforation and critical illness is highly lethal.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In the 24-patient multicentre series, bowel necrosis accompanied death in <strong>15 patients (62.5%)<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In the systematic imaging review, mortality among medically managed patients was approximately 50%.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">These figures cannot be extrapolated to all patients with COVID-19 because the studies are enriched for severe, surgically selected cases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">They nevertheless demonstrate that once COVID-associated bowel infarction becomes clinically apparent, it is a life-threatening emergency.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">29. Differential Diagnosis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">A rigorous evaluation must distinguish COVID-associated vascular injury from:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>conventional atherosclerotic mesenteric ischemia;<\/li>\n\n\n\n<li>atrial-fibrillation embolism;<\/li>\n\n\n\n<li>mesenteric venous thrombosis;<\/li>\n\n\n\n<li>hypotension;<\/li>\n\n\n\n<li>vasopressor-induced NOMI;<\/li>\n\n\n\n<li>volvulus;<\/li>\n\n\n\n<li>mechanical obstruction;<\/li>\n\n\n\n<li>diverticular disease;<\/li>\n\n\n\n<li>inflammatory bowel disease;<\/li>\n\n\n\n<li>infectious colitis;<\/li>\n\n\n\n<li>C. difficile;<\/li>\n\n\n\n<li>cytomegalovirus in immunocompromised patients;<\/li>\n\n\n\n<li>gastrointestinal malignancy;<\/li>\n\n\n\n<li>anticoagulant-associated bleeding;<\/li>\n\n\n\n<li>peptic ulcer disease;<\/li>\n\n\n\n<li>angiodysplasia;<\/li>\n\n\n\n<li>abdominal trauma.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The temporal presence of COVID is insufficient by itself.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">30. Anticoagulation: The Double-Edged Sword<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID introduced an important therapeutic paradox.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The disease increases thrombotic risk.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Clinicians consequently frequently use anticoagulation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">But anticoagulation can increase the probability or severity of gastrointestinal haemorrhage.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The meta-analysis of gastrointestinal bleeding found a higher pooled bleeding prevalence among patients receiving anticoagulants.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Therefore:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>COVID \u2192 thrombosis risk<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">and simultaneously<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>COVID + anticoagulation \u2192 bleeding risk.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A patient presenting with gastrointestinal haemorrhage therefore requires evaluation of both mechanisms.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">31. A Unified Pathophysiological Model<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The available evidence supports a multifactorial model:<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase I: Viral infection<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">SARS-CoV-2 infection activates innate and adaptive immunity.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase II: Endothelial activation<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Endothelial cells become pro-inflammatory and prothrombotic.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase III: Immunothrombosis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Platelets, neutrophils, complement and coagulation pathways interact.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase IV: Microvascular obstruction<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Fibrin thrombi develop within mucosal and submucosal vessels.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase V: Tissue hypoxia<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The mucosa becomes ischaemic.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase VI: Hemorrhagic injury<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Endothelial breakdown and reperfusion produce mucosal haemorrhage.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase VII: Ulceration<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Necrotic mucosa separates from viable tissue.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase VIII: Transmural progression<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The injury extends through the muscularis.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase IX: Wall failure<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The bowel becomes structurally incompetent.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase X: Perforation<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">A full-thickness defect develops.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase XI: Peritonitis<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Enteric bacteria and intestinal contents enter the peritoneal cavity.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Phase XII: Sepsis and multiorgan failure<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The patient may develop septic shock and death.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">32. The Significance of a &#8220;Patent&#8221; Mesenteric Artery<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Perhaps the most important conceptual lesson from the pathology literature is that <strong>mesenteric vascular disease in COVID cannot be defined solely by angiographic occlusion<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">A patient can have:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>patent SMA<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>patent SMV<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>severe bowel necrosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">because the pathological lesion exists in the microcirculation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The autopsy evidence described above is particularly persuasive in this regard.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This mechanism resembles a systemic microangiopathic process more than classical embolic mesenteric infarction.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">33. Could COVID Produce a &#8220;Visceral Tear&#8221;?<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">In the literal sense of a traumatic tear, evidence is limited.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">But COVID-associated intestinal vascular injury can clearly produce <strong>structural disruption of the visceral bowel wall<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The continuum is:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>vascular occlusion\/microthrombosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 <strong>mucosal necrosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 <strong>deep ulcer<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 <strong>transmural necrosis<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 <strong>serosal destruction<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 <strong>focal wall discontinuity<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u2192 <strong>perforation.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus, if &#8220;visceral tear&#8221; refers to spontaneous disruption of the colon or intestine following an ischaemic\/haemorrhagic event, the medical literature provides documented examples.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The appropriate pathology term would generally be <strong>perforation secondary to transmural ischaemic necrosis<\/strong>, rather than simply &#8220;tear.&#8221;<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">34. A Particularly Important Pathological Observation<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The clinicopathological series deserves emphasis because it connects almost every step of this proposed mechanism.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The investigators observed:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>gross bowel discoloration;<\/li>\n\n\n\n<li>mucosal discoloration;<\/li>\n\n\n\n<li>mucosal necrosis;<\/li>\n\n\n\n<li>haemorrhagic necrosis;<\/li>\n\n\n\n<li>muscularis involvement;<\/li>\n\n\n\n<li>pneumatosis;<\/li>\n\n\n\n<li>perforation;<\/li>\n\n\n\n<li>small-vessel fibrin thrombi;<\/li>\n\n\n\n<li>vascular-wall fibrinous degeneration.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">This combination makes it difficult to explain the disease simply as nonspecific abdominal symptoms accompanying critical illness.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">There is demonstrable structural intestinal vascular injury in a subset of patients.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">35. Causal Inference<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The strength of evidence varies according to phenotype.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Strong evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-19 can be associated causally with acute mesenteric ischaemia in a subset of severely affected patients.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Strong pathological evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-associated intestinal ischaemia can involve microvascular fibrin thrombosis and endothelial injury.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Strong evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID can be associated with ischaemic colitis.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Strong evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID-associated intestinal ischaemia can progress to necrosis and perforation.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Moderate evidence<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">COVID can contribute to gastrointestinal haemorrhage through ischaemic injury, endothelial dysfunction and systemic coagulopathy.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Less certain<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">SARS-CoV-2 directly infecting intestinal vascular cells as the principal mechanism of every vascular lesion.<\/p>\n\n\n\n<h5 class=\"wp-block-heading\">Not established<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Every episode of gastrointestinal bleeding or colonic perforation occurring after COVID is caused by SARS-CoV-2.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The distinction is essential.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">36. Implications for Pathologists<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">When a patient with recent or active COVID undergoes bowel resection for unexplained ischaemia, pathology should include careful evaluation of:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>mucosal necrosis;<\/li>\n\n\n\n<li>depth of necrosis;<\/li>\n\n\n\n<li>haemorrhage;<\/li>\n\n\n\n<li>fibrin thrombi;<\/li>\n\n\n\n<li>small-vessel injury;<\/li>\n\n\n\n<li>medium-vessel thrombosis;<\/li>\n\n\n\n<li>vasculitis;<\/li>\n\n\n\n<li>pneumatosis;<\/li>\n\n\n\n<li>bacterial invasion;<\/li>\n\n\n\n<li>fungal infection;<\/li>\n\n\n\n<li>cytomegalovirus where relevant;<\/li>\n\n\n\n<li>serosal inflammation;<\/li>\n\n\n\n<li>perforation margins.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Where clinically justified, additional investigations could include:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>SARS-CoV-2 molecular testing;<\/li>\n\n\n\n<li>endothelial markers;<\/li>\n\n\n\n<li>fibrin stains;<\/li>\n\n\n\n<li>platelet markers;<\/li>\n\n\n\n<li>complement deposition studies;<\/li>\n\n\n\n<li>microbiological cultures.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The distinction between <strong>vasculitis and thrombosis<\/strong> is especially important.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">37. Implications for Radiology<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">Radiologists evaluating a COVID patient with severe abdominal pain should examine not only the SMA but also:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>SMV;<\/li>\n\n\n\n<li>portal vein;<\/li>\n\n\n\n<li>bowel-wall enhancement;<\/li>\n\n\n\n<li>bowel-wall thickness;<\/li>\n\n\n\n<li>mesenteric edema;<\/li>\n\n\n\n<li>pneumatosis;<\/li>\n\n\n\n<li>portal venous gas;<\/li>\n\n\n\n<li>free intraperitoneal air;<\/li>\n\n\n\n<li>ascites;<\/li>\n\n\n\n<li>focal transition points;<\/li>\n\n\n\n<li>segmental distribution.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The combination of:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>severe pain + elevated D-dimer + bowel hypoenhancement + pneumatosis \u00b1 portal venous gas<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">should prompt urgent consideration of intestinal infarction.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">38. Implications for Clinical Medicine<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The clinical threshold for investigation should be low when a patient with current or recent COVID develops:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>severe abdominal pain;<\/li>\n\n\n\n<li>new abdominal distension;<\/li>\n\n\n\n<li>unexplained gastrointestinal bleeding;<\/li>\n\n\n\n<li>haematochezia;<\/li>\n\n\n\n<li>melena;<\/li>\n\n\n\n<li>unexplained falling haemoglobin;<\/li>\n\n\n\n<li>lactic acidosis;<\/li>\n\n\n\n<li>rapidly increasing D-dimer;<\/li>\n\n\n\n<li>peritoneal signs.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">The presence of respiratory improvement does not necessarily eliminate gastrointestinal vascular risk.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Indeed, some reported cases developed abdominal complications days after respiratory disease had begun to improve.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">39. The Need to Distinguish COVID From COVID-Associated Treatment Effects<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">A rigorous causal analysis must also examine:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>anticoagulants;<\/li>\n\n\n\n<li>corticosteroids;<\/li>\n\n\n\n<li>immunomodulators;<\/li>\n\n\n\n<li>vasopressors;<\/li>\n\n\n\n<li>mechanical ventilation;<\/li>\n\n\n\n<li>hypotension;<\/li>\n\n\n\n<li>bacterial sepsis;<\/li>\n\n\n\n<li>fungal infection.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Some intestinal catastrophes occurring during COVID may therefore be <strong>multifactorial<\/strong> rather than attributable to the virus alone.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">This is especially important in ICU patients.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">40. Conclusion<\/h5>\n\n\n\n<p class=\"wp-block-paragraph\">The accumulated clinical, radiological, surgical, histopathological and autopsy evidence establishes that SARS-CoV-2 infection can be associated with a severe intestinal vascular phenotype.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The spectrum includes:<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>mesenteric arterial thrombosis \u2192 mesenteric venous thrombosis \u2192 microvascular thrombosis \u2192 non-occlusive ischaemia \u2192 ischaemic colitis \u2192 mucosal haemorrhage \u2192 ulceration \u2192 transmural necrosis \u2192 bowel-wall disruption \u2192 perforation \u2192 peritonitis \u2192 sepsis and death.<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The most consequential discovery is that <strong>large-vessel occlusion is not necessary<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Pathological examination has demonstrated fibrin microthrombi in mucosal and submucosal vessels, endothelial injury, haemorrhagic necrosis and transmural damage even when major mesenteric vessels are patent.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The colon is particularly important. COVID-associated ischaemic colitis can produce mucosal oedema, friability, haemorrhage and deep ulceration; when vascular insufficiency persists, the injury can progress through the muscularis to transmural necrosis and ultimately perforation. Documented cases include actual transverse-colon and sigmoid-colon perforations, with pathology demonstrating nonviable bowel, haemorrhage and necrosis.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Thus, what might clinically appear initially as &#8220;abdominal pain and bleeding&#8221; can, in selected patients, represent the beginning of a vascular catastrophe.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The most useful conceptual model is not simply <strong>COVID causes thrombosis<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">It is:<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p class=\"wp-block-paragraph\"><strong>SARS-CoV-2 infection can create a prothrombotic, endothelial and inflammatory environment in which macrovascular occlusion, microvascular thrombosis, hypoperfusion and haemorrhagic injury interact to produce intestinal infarction. When the ischaemic process becomes transmural, the bowel wall can lose its structural integrity and perforate.<\/strong><\/p>\n<\/blockquote>\n\n\n\n<p class=\"wp-block-paragraph\">This model explains why severe intestinal injury can occur despite a patent SMA, why bleeding and infarction can coexist, why pathological examination can reveal extensive microvascular thrombosis that was invisible on CT angiography, and why colonic perforation can represent the terminal event of an evolving vascular process rather than an isolated mechanical tear.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h5 class=\"wp-block-heading\">References<\/h5>\n\n\n\n<ol start=\"1\" class=\"wp-block-list\">\n<li>Ojha V, Mani A, Mukherjee A, et al. Mesenteric ischemia in patients with COVID-19: an updated systematic review of abdominal CT findings in 75 patients. <em>Abdom Radiol<\/em>. 2022;47:1565\u20131602.<\/li>\n\n\n\n<li>Keshavarz P, Rafiee F, Kavandi H, et al. Ischemic gastrointestinal complications of COVID-19: a systematic review on imaging presentation. <em>Clin Imaging<\/em>. 2021;73:86\u201395.<\/li>\n\n\n\n<li>Patel S, Parikh C, Verma D, et al. Bowel ischemia in COVID-19: a systematic review. <em>Int J Clin Pract<\/em>. 2021;75.<\/li>\n\n\n\n<li>Marasco G, Maida M, Morreale GC, et al. Gastrointestinal bleeding in COVID-19 patients: a systematic review with meta-analysis. <em>Gastroenterol Res Pract<\/em>. 2021;2021:2534975.<\/li>\n\n\n\n<li>D&#8217;Ardes D, Boccatonda A, Cocco G, et al. Acute mesenteric ischemia in COVID-19 patients. Review of clinical, laboratory and imaging findings.<\/li>\n\n\n\n<li>COVID-19 and Intestinal Ischemia: A Multicenter Case Series. <em>Front Med<\/em>. 2022.<\/li>\n\n\n\n<li>Clinicopathological findings in patients with COVID-19-associated ischaemic enterocolitis. <em>J Pathol Clin Res<\/em>. 2021.<\/li>\n\n\n\n<li>Gastrointestinal Manifestations of COVID-19 Infection: Clinicopathologic Findings in Intestinal Resections Performed at Single Institution.<\/li>\n\n\n\n<li>COVID-19-associated ischemic colitis: a rare manifestation of COVID-19 infection\u2014case report and review.<\/li>\n\n\n\n<li>Colon perforation as a complication of COVID-19: a case report.<\/li>\n\n\n\n<li>Colonic perforation secondary to COVID-19-induced hemorrhagic colitis in a patient heterozygous for Factor V Leiden.<\/li>\n\n\n\n<li>Ischemic and hemorrhagic abdominal complications in COVID-19 patients: experience from the first Italian wave.<\/li>\n\n\n\n<li>Severe colon ischemia in patients with severe coronavirus-19 (COVID-19).<\/li>\n\n\n\n<li>Intestinal ischemic manifestations of SARS-CoV-2: results from the ABDOCOVID multicentre study.<\/li>\n\n\n\n<li>Lethal gastrointestinal manifestations of COVID-19 infection at autopsy. Recent autopsy report documenting extensive small- and large-intestinal ischaemia, intramucosal\/submucosal fibrin thrombi and intestinal haemorrhage despite patent major mesenteric vessels.<\/li>\n\n\n\n<li>The prevalence of gastrointestinal bleeding in COVID-19 patients: a systematic review and meta-analysis.<\/li>\n\n\n\n<li>Acute gastrointestinal bleeding in COVID-19 patients: a systematic review and meta-analysis.<\/li>\n\n\n\n<li>Pathological findings in organs and tissues of patients with COVID-19: a systematic review.<\/li>\n\n\n\n<li>Deshmukh V, Motwani R, Kumar A, et al. Histopathological observations in COVID-19: a systematic review. <em>J Clin Pathol<\/em>. 2021;74:76\u201383.<\/li>\n\n\n\n<li>Predictors of bowel necrosis in patients with acute mesenteric ischemia: systematic review and meta-analysis.<\/li>\n\n\n\n<li>Colonic perforation in critically ill COVID-19 patients: a case series highlighting surgical management and outcomes.<\/li>\n\n\n\n<li>Ischemic colitis and small bowel ischemia in a vaccinated patient with mild COVID-19 infection: a case report.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>John Murphy, CEO The COVID-19 Long haul Foundation Abstract SARS-CoV-2 infection can produce clinically important gastrointestinal vascular injury, including acute mesenteric ischaemia, mesenteric arterial and venous thrombosis, non-occlusive mesenteric ischaemia, [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":16089,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1279,90,92,1564,187,210,224,1565,1566,313,1029,1326,1413,892,1534,616],"tags":[],"class_list":["post-16032","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-avascular-necrosis","category-clots-bleeds","category-coagulation","category-enterocolitis","category-gastrointestinal","category-hemorrhage","category-hypercoagulation","category-mesenteric","category-mesenteric-artery","category-mesentery","category-micro-clots","category-microvascular-damage","category-microvascular-injury","category-necrosis","category-vascular-dysfunction","category-vascular-system"],"_links":{"self":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/16032","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=16032"}],"version-history":[{"count":4,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/16032\/revisions"}],"predecessor-version":[{"id":16036,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/posts\/16032\/revisions\/16036"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=\/wp\/v2\/media\/16089"}],"wp:attachment":[{"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=16032"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=16032"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cov19longhaulfoundation.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=16032"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}