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Pulmonary infarcts in COVID-19

  • Mary M. Salvatore
    Correspondence
    Department of Radiology, Columbia University Irving Medical Center, 630 West 168th Street, New York, NY, United States of America
    Affiliations
    Department of Radiology, Columbia University Medical Center, New York, NY, United States of America
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      Highlights

      • COVID-19 patients have more CT evidence of lung ischemia than non-COVID-19 patients with pulmonary emboli.
      • The bronchial circulation is available to compensate for pulmonary emboli but in COVID-19, the bronchial endothelial cells are vulnerable to infection and may be compromised.
      • The micro-thrombotic disease of COVID-19 effects vessels smaller than 3 mm, which are more often associated with infarction.

      Keywords

      SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) receptors found on vascular endothelial cells among others.
      • Varga Z.
      • Flammer A.J.
      • Steiger P.
      • Haberecker M.
      • Andermatt R.
      • Zinkernagel A.
      • et al.
      Endothelial cell infection and endotheliitis in COVID-19.
      Goshua et al. reported that von Willebrand factor is released by activated vascular endothelial cells and modulates platelet adhesiveness and aggregation; it was most elevated in sickest COVID-19 patients.
      • Goshua G.
      • Pine A.B.
      • Meizlish M.L.
      • Chang C.H.
      • Zhang H.
      • Bahel P.
      • Baluha A.
      • Bar N.
      • Bona R.D.
      • Burns A.J.
      • Dela Cruz C.S.
      • Dumont A.
      • Halene S.
      • Hwa J.
      • Koff J.
      • Menninger H.
      • Neparidze N.
      • Price C.
      • Siner J.M.
      • Tormey C.
      • Rinder H.M.
      • Chun H.J.
      • Lee A.I.
      Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.
      Thus, the endothelial cell infection leads to a hypercoaguable state providing a rationale for the extent of microthrombi seen in those who succumbed to the disease.
      Chest computer tomography (CT) allows the noninvasive evaluation of pulmonary emboli and sequela of endothelial injury. Pulmonary emboli and Hamptons humps (Fig. 1) are known CT findings associated with vascular clotting and parenchymal ischemia and/or infarction.
      • Machin A.
      • Gill G.
      • Pappachan J.M.
      Hampton's hump.
      Larger pulmonary emboli are relatively rare compared to the microthrombotic disease reported in COVID-19.
      • Varga Z.
      • Flammer A.J.
      • Steiger P.
      • Haberecker M.
      • Andermatt R.
      • Zinkernagel A.
      • et al.
      Endothelial cell infection and endotheliitis in COVID-19.
      A recent study found pulmonary emboli in 20% of 51 COVID-19 positive patients and 19% of COVID-19 negative patients.
      • Capaccione K.M.
      • Li G.
      • Salvatore M.M.
      Pulmonary embolism rate in patients infected with SARS-CoV-2.
      However, microthrombi were identified in 90% of autopsies performed on patients with COVID-19.
      • De Michele S.
      • Sun Y.
      • Yilmaz M.M.
      • Katsyv I.
      • Salvatore M.
      • Dzierba A.L.
      • Marboe C.C.
      • Brodie D.
      • Patel N.M.
      • Garcia C.K.
      • Saqi A.
      Forty Postmortem Examinations in COVID-19 Patients.
      Fig. 1
      Fig. 1COVID-19 positive patient with Hampton's hump in the left lower lobe.
      Hampton's humps representing ischemic or infarcted lung are found in less than 36% of patients with pulmonary emboli who do not have COVID-19 infection.
      • Patel U.B.
      • Ward T.J.
      • Kadoch M.A.
      • et al.
      Radiographic features of pulmonary embolism: Hampton's hump.
      The lung is spared in many patients due to its dual blood supply with a bronchial circulation that connects to the pulmonary arterial circulation and responds to ischemia by increasing its volume 300% following pulmonary embolus.

      AA Frazier JR Galvin TJ Franks et al From the archives of the AFIP: pulmonary vasculature: hypertension and infarction. Radiographics. 20 (2): 491–5.

      In contrast, Lax et al. found infarcts at autopsy in 8 of 11(81%) of patients with COVID-19 related pulmonary thrombosis.
      • Lax S.F.
      • Skok K.
      • Zechner P.
      • Kessler H.H.
      • Kaufmann N.
      • Koelblinger C.
      • Vander K.
      • Bargfrieder U.
      • Trauner M.
      Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series.
      The reason for increased infarcts in patients with COVID-19 is likely multifactorial. First, there is a larger clot burden overall increasing the likelihood for infarct or ischemia.
      • Varga Z.
      • Flammer A.J.
      • Steiger P.
      • Haberecker M.
      • Andermatt R.
      • Zinkernagel A.
      • et al.
      Endothelial cell infection and endotheliitis in COVID-19.
      The micro-thrombotic disease of COVID-19 effects vessels smaller than 3 mm, which are more often associated with infarction than large central embolic disease.

      AA Frazier JR Galvin TJ Franks et al From the archives of the AFIP: pulmonary vasculature: hypertension and infarction. Radiographics. 20 (2): 491–5.

      Embolic disease spares the bronchial circulation allowing it to compensate for diminished pulmonary arterial supply. In COVID-19, the bronchial endothelial cells are also vulnerable to infection and may be compromised.
      Autopsies of COVID-19 patients demonstrate a heavy clot burden with significant infarct and ischemia. PE's are not diagnosed more frequently in COVID-19 likely because the micro thrombi are too small. Increased pulmonary infarcts and ischemia were identified at autopsy and should be visible on CT as Hampton's humps. Zhao et al. demonstrated peripheral opacities in 87 of 101 patients (86%) who were infected with SARS-CoV-2.
      • Zhao W.
      • Zhong Z.
      • Xie X.
      • Yu Q.
      • Liu J.
      Relation between chest CT findings and clinical conditions of coronavirus disease (COVID-19) pneumonia: a multicenter study.
      VQ scan and Dual Energy CT could potentially prove if the peripheral opacities of COVID-19 (Fig. 2) represent ischemia suspected with micro thrombotic disease.
      • Lang M.
      • Som A.
      • Carey D.
      • et al.
      Pulmonary vascular manifestations of COVID-19 pneumonia.
      • Khanduri S.
      • Chawla H.
      • Khan A.
      • Ali I.
      • Krishnam A.
      • Malik S.
      • Khan N.
      • Patel Y.D.
      • Surbhi Rehman M.
      Spectrum of chest dual-energy computed tomography findings in COVID patients in North India.
      • Ganti S.
      • Kok S.S.X.
      • Aftab S.
      • Halagatti S.V.
      • Wong S.B.S.
      • Uppaluri A.S.
      Spectrum of lung perfusion changes on dual-energy CT in COVID-19: incremental benefit to conventional CT.
      • Dhawan R.T.
      • Gopalan D.
      • Howard L.
      • Vicente A.
      • Park M.
      • Manalan K.
      • Wallner I.
      • Marsden P.
      • Dave S.
      • Branley H.
      • Russell G.
      • Dharmarajah N.
      • Kon O.M.
      Beyond the clot: perfusion imaging of the pulmonary vasculature after COVID-19.
      19..
      Fig. 2
      Fig. 2COVID-19 positive patient with extensive peripheral consolidation.

      Declaration of competing interest

      Mary Salvatore received lecture fees from Genentech and Boehringer Ingelheim and serves as a consultant for Genentech and Boehringer Ingelheim and has received a research grant from Genentech and Boehringer Ingelheim.

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