Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

By Daniel Blanco-Melo, B. Nilsson-Payant, Wen-Chun Liu, S. Uhl, D. Hoagland, Rasmus Møller, Tristan X. Jordan, K. Oishi, M. Panis, D. Sachs and 5 more. Cell, 2020

3,931 citations recorded by the source corpus.

Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/5b2cf1deadf82dec6fecf86d7f575eef0c84caae

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

In Infectious Diseases

Citations in the corpus

Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis (2020, background): “Moreover, enhanced C3 expression is part of the unique host transcriptional signature in response to SARS–CoV-2 infection (28) and C3aR upregulation in the lung microvascular endothelium was recently correlated with disease severity (29), increased thrombosis, and aberrant angiogenesis in COVID-19 l”
Virology, transmission, and pathogenesis of SARS-CoV-2 (2020, background): “24 25 For example, postmortem histology of lung tissues of patients who died of covid-19 have confirmed the inflammatory nature of the injury, with features of bilateral diffuse alveolar damage, hyaline-membrane formation, interstitialmononuclearinflammatoryinfiltrates,anddesquamation…”
Animal models for COVID-19 (2020, background): “Following mucosal exposure to SARS-CoV-2, clinical alterations in ferrets are undetectable or mild and may include lethargy, nasal discharge, wheezing, oropharyngeal build-up of mucus, sneezing and loose stools 46 .”
SARS-CoV-2 productively infects human gut enterocytes (2020, background): “For a comparison with (33), see Fig S11.”
Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, neutral): “Of note, among several respiratory viruses tested, SARS-CoV-2 has demonstrated to most potently suppress type I and type III IFN expression in both human bronchial epithelial cells and ferrets [81].”