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      SARS-CoV-2/COVID-19-Auswirkungen auf die Plazenta Translated title: Impact of SARS-CoV-2/COVID-19 on the placenta

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          Abstract

          Ein besonderes Augenmerk bei der durch das Severe-acute-respiratory-syndrome-Coronavirus‑2 (SARS-CoV-2) hervorgerufenen Coronaviruskrankheit 2019 (COVID-19) wurde von Beginn an auf die Gruppe der Schwangeren gelegt.

          Nach einer Einführung zur Immunabwehr der Plazenta und viralen plazentaren Infektionen, beschreiben wir die morphologischen Veränderungen der Plazenta bei SARS-CoV-2-Infektion der Mutter, ziehen Vergleiche zur SARS-Epidemie und diskutieren die Frage der vertikalen Transmission von SARS-CoV‑2 von der Mutter auf das Neugeborene.

          Die häufigsten pathologischen Befunde der Plazenta bestehen in Zeichen der maternalen und auch fetalen Malperfusion sowie immunologisch bzw. thromboinflammatorisch vermittelten Veränderungen. Es finden sich Infarkte, deziduale Vaskulopathie sowie Thromben im fetalen Kreislauf und Vermehrung avaskulärer Villi. Daneben zeigen sich in einigen Fällen Entzündungsreaktionen mit Villitis und Intervillositis sowie eine Vaskulitis fetaler Gefäße. Zudem konnte der Nachweis erbracht werden, dass SARS-CoV‑2 die Plazenta direkt infizieren kann. Somit ist auch eine vertikale Transmission möglich.

          Ein COVID-19-spezifisches Schädigungsmuster der Plazenta liegt bislang nicht vor, obwohl der Nachweis von fetaler Thrombovaskulitis, Villitis und Intervillositis sowie einer fetalen und maternalen Malperfusion in Analogie zu der bereits bekannten allgemeinen Pathophysiologie von COVID-19 (Entzündungsreaktion und Mikrozirkulationsstörung) interpretiert werden könnte. Der Nachweis viraler RNA in den fetalen Kompartimenten der Plazenta/der Nabelschnur zeugt von der vertikalen SARS-CoV‑2 Transmission.

          Translated abstract

          From the very beginning, special attention regarding severe acute respiratory syndrome-coronavirus‑2 (SARS-CoV-2) and the resulting coronavirus disease-2019 (COVID-19) has been paid to pregnant women.

          In this review, after a short introduction into the immunodefensive role of the placenta and viral infections in general, we describe the morphological changes of the placenta in SARS-CoV-2-infected pregnant women based on our own and other published studies, draw comparisons to the SARS epidemic, and discuss the question of vertical transmission of SARS-CoV‑2 from the mother to the neonate.

          The most common pathological findings of the placenta in SARS-CoV‑2 infection are signs of maternal and fetal malperfusion as well as potentially immunologically and/or thromboinflammation-mediated findings. These manifest as infarcts and decidual vasculopathy as well as thrombi in the fetal circulation and avascular villi. In some cases, there is also an inflammatory reaction with villitis, intervillositis, and fetal vasculitis. In addition, it has been shown that SARS-CoV‑2 can directly infect the placenta, so vertical transmission is possible.

          There is no COVID-19 specific pattern of placental alterations, although the detection of fetal thrombovasculitis, villitis, and intervillositis as well as fetal and maternal malperfusion could be best interpreted as the signature of SARS-CoV‑2 infection – considering the known pathophysiology of COVID-19 regarding other organs (inflammatory reaction and [micro]angiopathy). Detection of viral RNA in the fetal placental tissue and the umbilical cord indicates SARS-CoV‑2 vertical transmission.

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          Most cited references62

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

            Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (Covid-19) pandemic. Despite widespread interest in the pathophysiology of the disease, relatively little is known about the associated morphologic and molecular changes in the peripheral lung of patients who die from Covid-19.
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              Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction

              Aims Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID‐19‐associated organ alterations. Methods and results This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in‐corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open‐source scans in supplementary files. Conclusions This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19. This provides a pathophysiological explanation for higher mortality rates among these patients.
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                Author and article information

                Contributors
                thomas.menter@usb.ch
                Elisabeth.Bruder@usb.ch
                Journal
                Pathologe
                Pathologe
                Der Pathologe
                Springer Medizin (Heidelberg )
                0172-8113
                1432-1963
                11 June 2021
                11 June 2021
                : 1-7
                Affiliations
                GRID grid.6612.3, ISNI 0000 0004 1937 0642, Pathologie, Institut für Medizinische Genetik und Pathologie, Universitätsspital Basel, , Universität Basel, ; Schönbeinstrasse 40, 4031 Basel, Schweiz
                Author notes
                [Herausgeber]

                W. Roth, Mainz

                Article
                952
                10.1007/s00292-021-00952-7
                8193171
                34115179
                69e0c891-d4e1-4016-be8f-be0612c37415
                © The Author(s) 2021

                Open Access Dieser Artikel wird unter der Creative Commons Namensnennung 4.0 International Lizenz veröffentlicht, welche die Nutzung, Vervielfältigung, Bearbeitung, Verbreitung und Wiedergabe in jeglichem Medium und Format erlaubt, sofern Sie den/die ursprünglichen Autor(en) und die Quelle ordnungsgemäß nennen, einen Link zur Creative Commons Lizenz beifügen und angeben, ob Änderungen vorgenommen wurden.

                Die in diesem Artikel enthaltenen Bilder und sonstiges Drittmaterial unterliegen ebenfalls der genannten Creative Commons Lizenz, sofern sich aus der Abbildungslegende nichts anderes ergibt. Sofern das betreffende Material nicht unter der genannten Creative Commons Lizenz steht und die betreffende Handlung nicht nach gesetzlichen Vorschriften erlaubt ist, ist für die oben aufgeführten Weiterverwendungen des Materials die Einwilligung des jeweiligen Rechteinhabers einzuholen.

                Weitere Details zur Lizenz entnehmen Sie bitte der Lizenzinformation auf http://creativecommons.org/licenses/by/4.0/deed.de.

                History
                : 27 April 2021
                Funding
                Funded by: University of Basel
                Categories
                Übersichten

                angiotensin-konvertierendes enzym 2,coronavirusinfektion,plazenta,schwangerschaft,vaskulitis,angiotensin-converting enzyme 2,coronavirus infection,placenta,pregnancy,vasculitis

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