International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.

Emerging variants of concern (VOC) drive the SARS-CoV-2 pandemic1,2. Experimental assessment of replication and transmission of major VOC compared to progenitors are needed to understand successful emerging mechanisms of VOC3. Here, we show that Alpha and Beta spike (S) proteins have a greater affinity to human angiotensin converting enzyme 2 (hACE2) receptor over the progenitor variant (wt-S614G) in vitro. Yet Alpha and wt-S614G had similar replication kinetics in human nasal airway epithelial cultures, whereas Beta was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over the progenitor variant (wt-S614G) in ferrets and two mouse models, where the substitutions in S were major drivers for fitness advantage. In hamsters, supporting high replication levels, Alpha and wt-S614G had comparable fitness. In contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and hACE2-expressing mice. Our study highlights the importance of using multiple models for complete fitness characterization of VOC and demonstrates adaptation of Alpha towards increased upper respiratory tract replication and enhanced transmission in vivo in restrictive models, whereas Beta fails to overcome contemporary strains in naïve animals