Editors' ChoiceCORONAVIRUS

The story of COVID-19: A comparative analysis

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Science Translational Medicine  10 Jun 2020:
Vol. 12, Issue 547, eabc8943
DOI: 10.1126/scitranslmed.abc8943


COVID-19 induces a distinct host transcriptome.

The host-pathogen interactions following viral infections shape patient outcomes. Blanco-Melo et al. set out to understand how the SARS-CoV-2 virus affects the host transcriptome and, more importantly, whether and how this host response differs from that induced by other viruses. Their goal was to define the therapeutic challenges and opportunities unique to coronavirus disease 2019 (COVID-19).

The authors derived the key characteristics of the host response to SARS-CoV-2 by analyzing the changes in the transcriptome in human primary lung epithelial cell lines, in a longitudinal study in an animal model using ferrets, and in patient samples (both lung samples from autopsies and serum from patients with mild infection) in response to the virus. Further, the nonclinical samples were infected with not only SARS-CoV-2 but also other common human respiratory pathogens that are known to cause significant morbidity. This helped to identify common pathways activated by viral pathogens as well as pathways that are unique to SARS-CoV-2.

Remarkably, the transcriptomic signature was distinct from other highly pathogenic viruses that infect humans. These studies revealed that infection with SARS-CoV-2 appears to elicit a modest interferon or antiviral response but a longer and exuberant proinflammatory signal in the form of chemokines, which in turn attract effector cells to the lungs to perpetuate the immunopathology. This proinflammatory environment may account for the lung immunopathology and protracted course of illness that we have come to associate with COVID-19. The low interferon response could be overcome in cell cultures with extremely high doses of SARS-CoV-2; this effect was independent of the eventual viral replication titers. However, this observation was not testable in the clinical samples. The strength of the study lies in using several different model systems to check for consistency. The concordance of the results thus not only strengthens the validity of the findings but also demonstrates that these model systems can be reliably used to study this unique pathogen.

The current study provides unique insights into this novel pathogen. The translational relevance of these pathways makes a stronger case for directing therapeutic strategies against the proinflammatory milieu rather than the more classical antiviral response.

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