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Commentary

In fatal COVID-19, the immune response can control the virus but kill the patient

View ORCID ProfileArturo Casadevall and Liise-anne Pirofski
PNAS December 1, 2020 117 (48) 30009-30011; first published November 11, 2020; https://doi.org/10.1073/pnas.2021128117
Arturo Casadevall
aDepartment of Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Baltimore, MD 21205;
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  • For correspondence: acasadevall@jhu.edu
Liise-anne Pirofski
bDepartment of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461
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  • Transcriptional and proteomic insights into the host response in fatal COVID-19 cases
    - Oct 20, 2020
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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 (1⇓⇓⇓–5). 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.

The identification of neutrophil-driven inflammatory pathways by Wu et al. (6) is consistent with reports of hyaline membrane formation, neutrophils, neutrophil extracellular traps (NETs), and platelet-induced immunopathology in COVID-19 lung damage (7⇓–9). Another critical finding is the paucity of viral sequences in the lung tissues examined, implying little or no viral replication (6). In fact, it is possible that the few viral reads identified represent residual nucleic acid in tissue from nonviable virus. One recent autopsy study did not identify SARS-CoV2 in lung tissue of patients with advanced disease (10), another found virus in the lungs of patients who died during acute disease (11), and another found that viral loads correlated with the inflammatory response and death; those with high viral loads expressed high levels of interferon (IFN)-stimulated genes with minimal lung damage, whereas those with low viral loads had extensive lung damage and low IFN-stimulated gene expression (5). Thus, the immune response during severe COVID-19 pneumonia may progress from inhibition of viral replication …

↵2To whom correspondence may be addressed. Email: acasadevall{at}jhu.edu.

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In fatal COVID-19, the immune response can control the virus but kill the patient
Arturo Casadevall, Liise-anne Pirofski
Proceedings of the National Academy of Sciences Dec 2020, 117 (48) 30009-30011; DOI: 10.1073/pnas.2021128117

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In fatal COVID-19, the immune response can control the virus but kill the patient
Arturo Casadevall, Liise-anne Pirofski
Proceedings of the National Academy of Sciences Dec 2020, 117 (48) 30009-30011; DOI: 10.1073/pnas.2021128117
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