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- Title
Delayed engagement of host defenses enables SARS-CoV-2 viremia and productive infection of distal organs in the hamster model of COVID-19.
- Authors
Carrau, Lucia; Frere, Justin J.; Golynker, Ilona; Fajardo, Alvaro; Rivera, Cristobal F.; Horiuchi, Shu; Roonprapunt, Tyler; Minkoff, Judith M.; Blanco-Melo, Daniel; TenOever, Benjamin
- Abstract
Clinical presentations that develop in response to infection result from interactions between the pathogen and host defenses. SARS-CoV-2, the etiologic agent of COVID-19, directly antagonizes these defenses, leading to delayed immune engagement in the lungs that materializes only as cells succumb to infection and are phagocytosed. Leveraging the golden hamster model of COVID-19, we sought to understand the dynamics between SARS-CoV-2 infection in the airways and the systemic host response that ensues. We found that early SARS-CoV-2 replication was largely confined to the respiratory tract and olfactory system and, to a lesser extent, the heart and gastrointestinal tract but generated a host antiviral response in every organ as a result of circulating type I and III interferons. Moreover, we showed that diminishing the response in the airways by immunosuppression or administration of SARS-CoV-2 intravenously resulted in decreased immune priming, viremia, and increased viral tropism, including productive infection of the liver, kidney, spleen, and brain. Last, we showed that productive infection of the airways was required for mounting an effective and system-wide antiviral response. Together, these data illustrate how COVID-19 can result in diverse clinical presentations in which disease outcomes can be a by-product of the speed and strength of immune engagement. These studies provide additional evidence for the mechanistic basis of the diverse clinical presentations of COVID-19 and highlight the ability of the respiratory tract to generate a systemic immune defense after pathogen recognition. Editor's summary: SARS-CoV-2 infections can spread from the initial site of infection in the lungs to distal organs. Carrau et al. found that SARS-CoV-2 dissemination depended on the innate immune response in the lungs to infection. Intranasal infection of hamsters with SARS-CoV-2 resulted in high viral titers in the lungs, but not in the blood or distal organs, as well as a systemic interferon response. Animals that were given an immunosuppressant upon intranasal infection or that were infected intravenously showed a decreased systemic interferon response, viremia (the presence of virus in the blood), and infection of distal organs. These results suggest that systemic antiviral signaling induced by SARS-CoV-2 infection in the lungs protects distal, nonpulmonary tissues from subsequent infection. —Wei Wong
- Subjects
LUNGS; SARS-CoV-2; TYPE I interferons; GOLDEN hamster; COVID-19; VIRAL tropism
- Publication
Science Signaling, 2023, Vol 16, Issue 789, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.adg5470