Distinctive features of severe SARS-CoV-2 pneumonia
G.R. Scott Budinger, Alexander V. Misharin, Karen M. Ridge, Benjamin D. Singer, Richard G. Wunderink
G.R. Scott Budinger, Alexander V. Misharin, Karen M. Ridge, Benjamin D. Singer, Richard G. Wunderink
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Review

Distinctive features of severe SARS-CoV-2 pneumonia

Abstract

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.

Authors

G.R. Scott Budinger, Alexander V. Misharin, Karen M. Ridge, Benjamin D. Singer, Richard G. Wunderink

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Figure 2

A model for SARS-CoV-2 infection explains the prolonged clinical course and spatial heterogeneity.

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A model for SARS-CoV-2 infection explains the prolonged clinical course ...
(i) SARS-CoV-2 spares alveolar epithelial cells that do not express ACE2 (ii) and infects ACE2-expressing alveolar epithelial cells (iii), allowing uptake by alveolar macrophages (iv). Alveolar macrophages harboring viruses release chemokines that recruit T cells and monocytes to the alveolus (v). T cells induce macrophage apoptosis, further driving the recruitment of MoAMs (vi). These recruited macrophages take up SARS-CoV-2, resulting in self-sustaining inflammatory circuits. Macrophages harboring virus can migrate to adjacent alveoli (vii), where they can initiate inflammatory circuits with T cells and infect ACE2-expressing epithelial cells (viii), whereupon the process repeats itself from steps v–viii. AT1, type 1 alveolar epithelial cell.