Type I IFN Signaling Protects Mice from Lethal SARS-CoV-2 Neuroinvasion.

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable for efficient viral clearance at the adaptive phase of SARS-CoV-2 infection. Conversely, we found that in the absence of IFN-I receptor signaling, the extreme animal lethality is consistent with heightened infectious virus and prominent pathological manifestations in the brain. Taken together, our results in this study demonstrate that IFN-I receptor signaling is required for restricting virus neuroinvasion, thereby mitigating COVID-19 severity.

The Impact of Aging in Acute Respiratory Distress Syndrome: A Clinical and Mechanistic Overview.

Acute respiratory distress syndrome (ARDS) is associated with increased morbidity and mortality in the elderly population (≥65 years of age). Additionally, age is widely reported as a risk factor for the development of ARDS. However, the underlying pathophysiological mechanisms behind the increased risk of developing, and increased severity of, ARDS in the elderly population are not fully understood. This is compounded by the significant heterogeneity observed in patients with ARDS. With an aging population worldwide, a better understanding of these mechanisms could facilitate the development of therapies to improve outcomes in this population. In this review, the current clinical evidence of age as a risk factor and prognostic indicator in ARDS and the potential underlying mechanisms that may contribute to these factors are outlined. In addition, research on age-dependent treatment options and biomarkers, as well as future prospects for targeting these underlying mechanisms, are discussed.