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Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses

Herder et al., PLOS Biology, doi:10.1371/journal.pbio.3001065
Dec 2021  
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In vitro study using a 3D respiratory epithelial model and cells from human donors, showing that elevated temperature (39-40°C) restricts SARS-CoV-2 infection and replication independently of interferon-mediated antiviral defenses. Authors found SARS-CoV-2 can still enter respiratory cells at 40°C but viral transcription and replication are inhibited, limiting infectious virus production. This temperature-dependent restriction correlates with altered host gene expression related to antiviral immunity and epigenetic regulation. As fever is a common COVID-19 symptom, the data suggests febrile temperature ranges may confer protection to respiratory tissues by restricting SARS-CoV-2 propagation.
Herder et al., 21 Dec 2021, United Kingdom, peer-reviewed, 22 authors. Contact:,,
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperThermotherapyAll
Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses
Vanessa Herder, Kieran Dee, Joanna K Wojtus, Ilaria Epifano, Daniel Goldfarb, Christoforos Rozario, Quan Gu, Ana Da Silva Filipe, Kyriaki Nomikou, Jenna Nichols, Ruth F Jarrett, Andrew Stevenson, Steven Mcfarlane, Meredith E Stewart, Agnieszka M Szemiel, Rute M Pinto, Andreu Masdefiol Garriga, Chris Davis, Jay Allan, Sheila V Graham, Pablo R Murcia, Chris Boutell
PLOS Biology, doi:10.1371/journal.pbio.3001065
AU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly: The pandemic spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19), represents an ongoing international health crisis. A key symptom of SARS-CoV-2 infection is the onset of fever, with a hyperthermic temperature range of 38 to 41˚C. Fever is an evolutionarily conserved host response to microbial infection that can influence the outcome of viral pathogenicity and regulation of host innate and adaptive immune responses. However, it remains to be determined what effect elevated temperature has on SARS-CoV-2 replication. Utilizing a three-dimensional (3D) air-liquid interface (ALI) model that closely mimics the natural tissue physiology of SARS-CoV-2 infection in the respiratory airway, we identify tissue temperature to play an important role in the regulation of SARS-CoV-2 infection. Respiratory tissue incubated at 40˚C remained permissive to SARS-CoV-2 entry but refractory to viral transcription, leading to significantly reduced levels of viral RNA replication and apical shedding of infectious virus. We identify tissue temperature to play an important role in the differential regulation of epithelial host responses to SARS-CoV-2 infection that impact upon multiple pathways, including intracellular immune regulation, without disruption to general transcription or epithelium integrity. We present the first evidence that febrile temperatures associated with COVID-19 inhibit SARS-CoV-2 replication in respiratory epithelia. Our data identify an important role for tissue temperature in the epithelial restriction of SARS-CoV-2 independently of canonical interferon (IFN)-mediated antiviral immune defenses.
Author Contributions Conceptualization: Vanessa Herder, Kieran Dee, Ruth F. Jarrett, Sheila V. Graham, Pablo R. Murcia, Chris Boutell.
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