key: cord-0890568-qmh3wtqo
authors: Evans, Scott E.; Tseng, Chien-Te K.; Scott, Brenton L.; Höök, A. Magnus; Dickey, Burton F.
title: Inducible Epithelial Resistance against Coronavirus Pneumonia in Mice
date: 2020-10-03
journal: Am J Respir Cell Mol Biol
DOI: 10.1165/rcmb.2020-0247le
sha: e8805931aceac4c67e5f1883000eecda8361f82a
doc_id: 890568
cord_uid: qmh3wtqo

nan

, a single PUL-042 treatment significantly improved survival of otherwise lethal SARS-CoV infection and significantly reduced the lung MERS-CoV burden 3 days after challenge, congruent with our prior work demonstrating a consistent correlation between survival advantage and reduced pathogen burden. Of note, the relationship between host survival and pathogen burden in respiratory viral infections can be very steep, with a 1.6-fold increase in the viral load resulting in a decrease in mouse survival from 80% to 20% in one model (15) .

Considerable attention has been paid recently to attenuating the host response in COVID-19, with an intent to improve patient survival by reducing immunopathology. Here, we show an example of how inducing early, effective, proinflammatory responses can protect against pathogenic CoV pneumonia. The similarity of the pathogenic CoVs, together with our demonstrations of protection against other respiratory viruses, suggest this approach can also protect against SARS-CoV-2. As such, PUL-042 is under investigation in two U.S. Food and Drug Administration-approved randomized multicenter clinical trials to reduce pneumonia severity and mortality in patients with early COVID-19 (NCT 04312997) or in COVID-19-exposed healthcare workers and personal contacts (NCT 04313023).

The urgent, ongoing need to test interventions against SARS-CoV-2 precludes our immediate ability to do additional studies of SARS-CoV or MERS-CoV; thus, these results must be interpreted in view of this limitation. Nonetheless, these data suggest this host-focused strategy can be used in patients with suspected COVID-19 without requiring delays for confirmatory testing, as it is well tolerated by humans (NCT 02124278) and has broad activity against other infectious agents. Although it is suspected that a second pandemic wave may arise concurrently with seasonal influenza, a patient with a virus-like illness can be preemptively treated with PUL-042 with the expectation that she or he will appreciate a benefit, whether the syndrome results from SARS-CoV-2, influenza A, both viruses, or another pathogen. CoVs possess the capacity to jump species boundaries, making it highly likely that more pathogenic CoVs will emerge. However, this same strategy of manipulating lung epithelial responses can be anticipated to also protect against future emergent viruses. n

To the Editor:

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the latest threat to global health security, and the pressure to identify effective therapeutics during this pandemic is immense. This stress has led to the use of unproven therapies with greater than minimal risk. One example is the use of IL-6 receptor antagonists. After an early report of a "cytokine storm" in patients with coronavirus disease (COVID-19) , there is increased interest in anti-IL-6 therapy as a treatment option, with ill-defined criteria for use (1). 

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