ABSTRACT
Type-I interferons (IFN-I) are critical mediators of innate control of viral infections, but also drive recruitment of inflammatory cells to sites of infection, a key feature of severe COVID-19. Here, and for the first time, IFN-I signaling was modulated in rhesus macaques (RMs) prior to and during acute SARS-CoV-2 infection using a mutated IFN2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. In SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. Notably, IFNmod treatment resulted in a potent reduction in (i) SARS-CoV-2 viral load in Bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes; (ii) inflammatory cytokines, chemokines, and CD163+MRC1-inflammatory macrophages in BAL; and (iii) expression of Siglec-1, which enhances SARS-CoV-2 infection and predicts disease severity, on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. This study, using an intervention targeting both IFN- and IFN-{beta} pathways, shows that excessive inflammation driven by type 1 IFN critically contributes to SARS-CoV-2 pathogenesis in RMs, and demonstrates the potential of IFNmod to limit viral replication, SARS-CoV-2 induced inflammation, and COVID-19 severity.
ABSTRACT
Although uncommon, shark attacks can lead to devastating outcomes for victims. Surgeons also face unique challenges during operative management such as exsanguination, shock, specific injury patterns and infections. This case report presents the management of a 39-year-old previously healthy female attacked by a shark while on vacation in Mexico. The patient sustained severe injuries to her left arm and her left thigh. She was transferred to a Canadian institution after ambiguous operative management in Mexico and presented with no clear antibiotic coverage and a Volkman's contracture of the left upper extremity. In total, the patient underwent four washouts of wounds, two split-thickness skin grafts, one free anterolateral thigh flap, and one free transverse rectus abdominus myocutaneous flap for the reconstruction and salvage of the left lower extremity. This article highlights the specifics of this case and describes important points in managing these devastating injuries.
