In fatal COVID-19, the immune response can control the virus but kill the patient
Tuesday, 2020/12/08 | 09:05:24
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Arturo Casadevall and Liise-anne Pirofski PNAS December 1, 2020 117 (48) 30009-30011
Fig.: Prof. Arturo Casadevall; Johns Hopskins Medecine
COVID-19 is often a biphasic illness with an initial phase of upper respiratory symptoms that can rapidly progress to profound hypoxemia and respiratory failure. Postmortem studies of severe COVID-19 reveal diffuse alveolar damage, hyaline membranes, and thrombi, with varying degrees of inflammation and types of cellular infiltrates. Now, with their autopsy study of early victims of the pandemic in China, Wu et al. (6) provide important insights into the inflammatory pathways that lead to severe COVID-19 pneumonia. Their extensive transcriptional and proteomic analyses of lung tissue from patients with severe pneumonia reveal signatures indicative of a neutrophil-driven inflammatory response without evidence of much active viral proliferation. These findings indicate that the pathogenesis of late severe COVID-19 pneumonia involves a dysregulated immune response, rather than direct viral damage. … In summary, Wu et al. (6) provide insights reinforcing the critical point that, despite controlling the virus, the immune response may also result in irreparable damage that is fatal. Although this notion was already part of the emerging understanding of the pathogenesis of this disease (1), firm evidence from autopsy studies demonstrating that people die with inflammation and a very low viral load moves this concept from hypothesis to fact, with great consequences for directing clinical care and designing new therapies.
See more https://www.pnas.org/content/117/48/30009
Figure: Proposed scheme for the progression and outcomes of COVID-19 from the viewpoint of the damage−response of pathogenesis (24). According to the damage−response framework, the relevant outcome is the amount of host damage endured by the host during the host−microbe interaction. Considering damage as a function of time, death occurs in those individuals who suffer irreparable tissue damage, which appears to be mediated largely by the inflammatory response to SARS-Cov-2. |
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