A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia

Abstract Introduction A neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in t...

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Autores principales:	Brian S. Bull, Karen L. Hay
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	blood tissues human animals infections viral retroviral Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/efe90c0de1c14836a85b3ca2ed874f86
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spelling	oai:doaj.org-article:efe90c0de1c14836a85b3ca2ed874f862021-11-12T19:57:14ZA macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia2050-452710.1002/iid3.482https://doaj.org/article/efe90c0de1c14836a85b3ca2ed874f862021-12-01T00:00:00Zhttps://doi.org/10.1002/iid3.482https://doaj.org/toc/2050-4527Abstract Introduction A neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in tissue factor—a thromboplastin. This prothrombotic aspect likely explains how a respiratory virus whose malign effects should be confined to the oropharynx, bronchi and lungs, can cause a panoply of extra‐pulmonary organ disorders. Elevated ferritin levels in ICU Covid 19 patients, and elevated acute phase proteins suggest immune overreaction. Elevated d‐dimers implicate clotting as well. This evidence links hyperactive innate immunity (macrophage lung infiltrates) with the elevated levels of oligomeric fibrin present in the bloodstream of these patients. Methods An in‐house assay measuring oligomeric (soluble) fibrin (also referred to as soluble fibrin monomer complexes or SFMC) in whole blood, previously developed for monitoring incipient disseminated intravascular coagulation (DIC) during liver transplantation, was made available to COVID ICU attendings. Since SFMC constitutes the input to intravascular fibrin clots and d‐dimer reflects fibrin clot dissolution, it was thought that the two tests, run in tandem along with assays of immune activation, might clarify the frequency and possibly the cause of DIC in patients with severe COVID‐19 pneumonia. Results Classical DIC with intravascular clotting and thrombocytopenia was documented only rarely. However, early in the pandemic shortly after the assay was made available, it identified three patients undergoing acute defibrination. In each patient virtually all of the body's fibrinogen was transformed into SFMC over 3–4 days and deposited somewhere in the vasculature without any gross clots being detected. Conclusions Three COVID‐19 patients with evidence of a hyperactive immune response (elevated ferritin and acute phase proteins) defibrinated while blood levels of SFMC were being monitored. SFMC levels that were five times higher than normal appeared in the circulation during the defibrination process. SFMC at these levels may precipitate as showers of microclots, damaging heart, kidney, brain, and so forth.Brian S. BullKaren L. HayWileyarticleblood tissueshuman animalsinfectionsviral retroviralImmunologic diseases. AllergyRC581-607ENImmunity, Inflammation and Disease, Vol 9, Iss 4, Pp 1336-1342 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	blood tissues human animals infections viral retroviral Immunologic diseases. Allergy RC581-607
spellingShingle	blood tissues human animals infections viral retroviral Immunologic diseases. Allergy RC581-607 Brian S. Bull Karen L. Hay A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia
description	Abstract Introduction A neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in tissue factor—a thromboplastin. This prothrombotic aspect likely explains how a respiratory virus whose malign effects should be confined to the oropharynx, bronchi and lungs, can cause a panoply of extra‐pulmonary organ disorders. Elevated ferritin levels in ICU Covid 19 patients, and elevated acute phase proteins suggest immune overreaction. Elevated d‐dimers implicate clotting as well. This evidence links hyperactive innate immunity (macrophage lung infiltrates) with the elevated levels of oligomeric fibrin present in the bloodstream of these patients. Methods An in‐house assay measuring oligomeric (soluble) fibrin (also referred to as soluble fibrin monomer complexes or SFMC) in whole blood, previously developed for monitoring incipient disseminated intravascular coagulation (DIC) during liver transplantation, was made available to COVID ICU attendings. Since SFMC constitutes the input to intravascular fibrin clots and d‐dimer reflects fibrin clot dissolution, it was thought that the two tests, run in tandem along with assays of immune activation, might clarify the frequency and possibly the cause of DIC in patients with severe COVID‐19 pneumonia. Results Classical DIC with intravascular clotting and thrombocytopenia was documented only rarely. However, early in the pandemic shortly after the assay was made available, it identified three patients undergoing acute defibrination. In each patient virtually all of the body's fibrinogen was transformed into SFMC over 3–4 days and deposited somewhere in the vasculature without any gross clots being detected. Conclusions Three COVID‐19 patients with evidence of a hyperactive immune response (elevated ferritin and acute phase proteins) defibrinated while blood levels of SFMC were being monitored. SFMC levels that were five times higher than normal appeared in the circulation during the defibrination process. SFMC at these levels may precipitate as showers of microclots, damaging heart, kidney, brain, and so forth.
format	article
author	Brian S. Bull Karen L. Hay
author_facet	Brian S. Bull Karen L. Hay
author_sort	Brian S. Bull
title	A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia
title_short	A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia
title_full	A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia
title_fullStr	A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia
title_full_unstemmed	A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia
title_sort	macrophage attack culminating in microthromboses characterizes covid 19 pneumonia
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/efe90c0de1c14836a85b3ca2ed874f86
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A macrophage attack culminating in microthromboses characterizes COVID 19 pneumonia

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