The emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant global morbidity, mortality, and societal disruption. A better understanding of virus-host interactions may potentiate therapeutic insights toward limiting this infection. Here we investigated the dynamics of the systemic response to SARS-CoV-2 in hamsters by histological analysis and transcriptional profiling. Infection resulted in consistently high levels of virus in the upper and lower respiratory tracts and sporadic occurrence in other distal tissues. A longitudinal cohort revealed a wave of inflammation, including a type I interferon (IFN-I) response, that was evident in all tissues regardless of viral presence but was insufficient to prevent disease progression. Bolstering the antiviral response with intranasal administration of recombinant IFN-I reduced viral disease, prevented transmission, and lowered inflammation in vivo. This study defines the systemic host response to SARS-CoV-2 infection and supports use of intranasal IFN-I as an effective means of early treatment.

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的出现和传播导致了严重的全球发病率、死亡率和社会混乱。更好地了解病毒与宿主的相互作用可能会加强对限制这种感染的治疗见解。在这里，我们通过组织学分析和转录谱研究了仓鼠对 SARS-CoV-2 的全身反应的动态。感染导致上呼吸道和下呼吸道中的病毒水平持续偏高，而其他远端组织中则偶有发生。一个纵向队列揭示了一波炎症，包括 I 型干扰素 (IFN-I) 反应，这在所有组织中都很明显，无论是否存在病毒，但不足以阻止疾病进展。体内。这项研究定义了宿主对 SARS-CoV-2 感染的全身反应，并支持使用鼻内 IFN-I 作为早期治疗的有效手段。