SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron.

Background & Objectives: Primary chest wall sarcomas are rare and therapeutically challenging tumors. Herein we report the outcomes of a surgery-based multimodality therapy for these pathologies over an 11-year period. In addition, we present a case that illustrates the surgical challenges that extensive chest wall resection may pose.Methods: Using the Society of Thoracic Surgeons general thoracic surgery database, we have prospectively collected data in our institute on all patients undergoing chest wall resection and reconstruction for primary chest wall sarcomas between June 2008–October 2019.Results: We performed 28 surgical procedures on 25 patients aged 5 to 91 years (median age 33). Eleven tumors were bone- and cartilage-derived and 14 tumors originated from soft tissue elements. Seven patients (7/25, 28%) received neo-adjuvant therapy and 14 patients (14/25, 56%) received adjuvant therapy. The median number of ribs that were resected was 2.5 (range 0 to 6). In 18/28 (64%) of surgeries, additional skeletal or visceral organs were removed, including: diaphragm [1], scapula [2], sternum [2], lung [2], vertebra [1], clavicle [1] and colon [1]. Chest wall reconstruction was deemed necessary in 16/28 (57%) of cases, polytetrafluoroethylene (PTFE) Gore-Tex patches was used in 13/28 (46%) of cases and biological flaps where used in 4/28 (14%) of cases. R0, R1 and R2 resection margins were achieved in 19/28 (68%), 9/28 (32%) and 0/28 (0%) of cases, respectively. The median follow up time was 33 months (range 2 to 138). During the study period, disease recurred in 8/25 (32%) of patients. Of these, 3 were re-operated on and are free of disease. At date of last follow up, 5/25 (20%) of patients have died due to their disease and in contrast, 20/25 (80%) were alive with no evidence of disease.Conclusions: Surgery-based multimodality therapy is an effective treatment approach for primary chest wall sarcomas. Resection of additional skeletal or visceral organs and reconstruction with synthetic and/or biological flaps is often required in order to obtain R0 resection margins. Ultimately, long-term survival in this clinical scenario is an achievable goal.