{"id":38103,"date":"2020-06-01T07:22:38","date_gmt":"2020-06-01T07:22:38","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=38103"},"modified":"2020-06-01T16:02:01","modified_gmt":"2020-06-01T16:02:01","slug":"autopsies-show-how-covid-19-damages-lungs-more-than-flu","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/38103","title":{"rendered":"Autopsies show how COVID-19 damages lungs more than flu"},"content":{"rendered":"

Mark Mascolini for NATAP.org<\/span><\/strong><\/p>\n

COVID-19 wreaks more havoc in the lung than influenza A(H1N1), according to an autopsy comparison by German researchers. [1]<\/span><\/strong><\/p>\n

The greater damage with COVID-19 included widespread thrombosis with microangiopathy, 9-fold more prevalent alveolar capillary microthrombi, and almost 3-fold more aberrant angiogenesis (new blood vessel growth) than seen with influenza A.<\/span><\/p>\n

Researchers at the University of Witten-Herdecke and colleagues at other centers note that respiratory disease is the hallmark of infection with SARS-CoV-2, the virus that causes COVID-19, but the precise morphologic (structural) and molecular changes remain poorly defined. To address that gap, they compared 3 sets of lung biopsies from (1) 7 people who died from COVID-19 respiratory failure, (2) 7 people who died from acute respiratory distress syndrome (ARDS) caused by influenza A(H1N1), and 10 age-matched uninfected control lungs. They used several methods to analyse lung biopsies: 7-color immunohistochemical analysis, microcomputed tomographic imaging, scanning electron microscopy, corrosion casting, and direct multiplexed measurement of gene expression.<\/span><\/p>\n

In people who died from COVID-19 or influenza A, the peripheral lung histologic (microscopic anatomy) pattern was diffuse alveolar damage and perivascular T-cell infiltration. In people with COVID-19, the researchers characterised alveolar damage as necrosis of alveolar lining cells, pneumocyte type 2 hyperplasia, and linear intraalveolar fibrin deposition. In flu patients, \u201cflorid diffuse\u201d alveolar damage was marked by \u201cmassive interstitial edema and extensive fibrin deposition.\u201d\u00a0<\/span><\/p>\n

The researchers found no angiotensin-converting enzyme 2 (ACE2)-positive lymphocytes in perivascular tissue or alveoli of uninfected control lungs, but they did find ACE2-positive lymphocytes in the COVID-19 group and the influenza A group. CD4 T cells proved more numerous in COVID-19 lungs than in flu lungs (average 13.6 versus 5.8 within a 200-\u03bcm radius of precapillary and postcapillary vessel walls in 20 fields of examination per patient,\u00a0p=0.04). But COVID-19 lung had significantly fewer CD8 T cells than flu lungs (average 5.3 versus 11.6,\u00a0p=0.008).<\/span><\/p>\n

Alveolar capillary microthrombi proved more than 9 times more prevalent with COVID-19 than with influenza A (average 159 versus 16 thrombi per square centimeter of vascular lumen area,\u00a0p=0.002). But in postcapillary venules less than 1 mm in diameter, COVID-19 lungs had fewer thrombi than flu lungs (average 12 versus 35,\u00a0p=0.02). Three-dimensional microCT showed that lung in both groups had \u201cnearly total occlusions of precapillary and postcapillary vessels.\u201d<\/span><\/p>\n

Imaging showed structurally deformed capillaries in COVID-19 lung, marked by \u201csudden changes in caliber and the presence of intussusceptive pillars* in capillaries.\u201d In the COVID-19 group, transmission electron microscopy showed ultrastructural damage to the endothelium and both intracellular and extracellular SARS-CoV-2.\u00a0<\/span><\/p>\n

The researchers found 2.7-fold greater density of intussusceptive angiogenic features* in COVID-19 lungs (average 60.7 features per field) than in flu lungs (average 22.5) or uninfected control lungs (average 2.1) (p<0.001 for both comparisons). In people with COVID-19, degree of intussusceptive angiogenesis increased significantly with longer time in the hospital (p<0.001). In contrast, flu patients had no increase in intussusceptive angiogenesis over time.<\/span><\/p>\n

The investigators summarised three features that distinguished COVID-19 lungs from influenza A lungs: <\/span><\/p>\n

    \n
  1. Severe endothelial injury associated with intracellular SARS-CoV-2 virus and disrupted endothelial cell membranes,\u201d <\/span><\/li>\n
  2. Widespread vascular thrombosis with microangiopathy and occlusion of alveolar capillaries, and <\/span><\/li>\n
  3. Significant new vessel growth through a mechanism of intussusceptive angiogenesis.<\/span><\/li>\n<\/ol>\n

    The authors call this last finding unexpected and suggest that more endothelialitis and thrombosis may contribute to the intussusceptive angiogenesis documented in COVID-19 lungs. They caution that how their findings affect the clinical course of COVID-19 remains to be defined.<\/span><\/p>\n

    *Compared with normal sprouting angiogenesis, intussusceptive angiogenesis is a \u201csplitting process\u201d marked by invasion of existing blood vessels by other tissues, forming damaging \u201ctissue pillars\u201d. [2]<\/span><\/p>\n

    References<\/span><\/p>\n

      \n
    1. Ackermann\u00a0\u00a0M,\u00a0Verleden\u00a0SE, Kuehnel\u00a0M, et al.\u00a0Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020 May 21.\u00a0doi: 10.1056\/NEJMoa2015432.<\/span>
      \nhttps:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2015432<\/a><\/span><\/li>\n
    2. Adair TH, Montani JP. Angiogenesis. San Rafael (CA): Morgan & Claypool Life Sciences. 2010.\u00a0<\/span>
      \n      https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK53238<\/a><\/span><\/li>\n<\/ol>\n

      \u00a0<\/span><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"

      Mark Mascolini for NATAP.org COVID-19 wreaks more havoc in the lung than influenza A(H1N1), according to an autopsy comparison by German researchers. [1] The greater damage with COVID-19 included widespread thrombosis with microangiopathy, 9-fold more prevalent alveolar capillary microthrombi, and …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[290,278],"tags":[],"class_list":["post-38103","post","type-post","status-publish","format-standard","hentry","category-covid-19-pathogenesis","category-covid-19"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38103","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=38103"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38103\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=38103"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=38103"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=38103"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}