Background: Chronic rhinosinusitis with and without nasal polyps (CRSwNP/ CRSsNP) is an inflammatory disease affecting the nasal and sinus mucosal lining. Here, to further characterize this heterogeneous disease, we performed an extended endotyping of CRS using the nasal tissue from CRS-patients and a new approach of expression profiling of chemokines related to Th2-type cytokine IL-5. Methods: In this case-control study, we included 66 patients with CRS (CRSwNP n=26; CRSsNP n=40) diagnosed according to the EPOS 2020 criteria. The control group (n=25) consisted of CRS-free patients scheduled for inferior turbinate surgery. The concentration of following chemokines and cytokines was determined in tissue samples obtained during routine surgery from all subjects: TARC/ CCL17, PARC/ CCL18, eotaxin/ CCL11, MCP-3/ CCL7, MIP-1α/ CCL3, IP-10/ CXCL10, ENA-78/ CCL5, and IL-5. The analysis was performed by partition-based clustering. Results: In CRS tissues, the concentration of eotaxin, TARC, total IgE, IL-5, and ECP was significantly higher than in control (p<0.005). The analysis identified seven clusters. Cluster-1 was IL-5- and inflammatory chemokines-negative (11% CRSwNP). Cluster-2 had low IL-5 concentration and elevated MCP-3/CCL7 (100% CRSsNP). Clusters -3 and -4 expressed IP-10/CXCL10 (type-1-dominated), TARC/CCL17 and eotaxin/CCL11 (both type-2-dominated) (CRSwNP 13-31%). Clusters 5-7 had high concentration of IL-5, TARC/ CCL17, PARC/ CCL18, and eotaxin/CCL11 (type-2-dominated), NP 71-100%, asthma 19-50%, N-ERD 29%. Conclusions: Our chemokine expression-based extended analysis identified distinct CRS endotype clusters, possibly impacting future diagnosis, monitoring, and biologics-based treatment of CRS.

Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome suspected SARS-CoV-2 vaccine hypersensitivity. We present data of 219 individuals, who experienced symptoms suspicious for an allergic reaction after the first (n=214) or the second vaccination (n=5). 195 reactions occurred after the first application of mRNA-based vaccines (157 Comirnaty®, and 38 Spikevax®) and eighteen reactions were reported after first application of a vector vaccine (Vaxzevria®). Of these 162 experienced immediate symptoms. Skin symptoms occurred in 91 cases. The most frequent cutaneous symptom was angioedema (n=45), followed by generalized urticaria (n=36) and generalized erythema/flush (n=20). 70 patients had cardiovascular symptoms, 45 showed respiratory symptoms and gastrointestinal symptoms were recorded in 14 patients. The allergological assessment of 334 individuals (219 with reactions after COVID vaccination and 115 with a history of vaccine related reactions) showed in 17% a suspicion of sensitization against the SARS-CoV-2 vaccine and/or their ingredients defined as one positive skin test and/or BAT. The majority of the SPT/IDT with the vaccines were negative. Of the 214 patients with suspected allergic symptoms after the first vaccination, 67/67 patients tolerated the re-vaccination. In this study, 334 individuals of a cohort resembling >2000 persons presenting for an allergy workup regarding SARS-CoV-2 vaccination only 45 were diagnosed in concordance with the anaphylaxis definition of the Brighton collaboration with anaphylactic immediate hypersensitivity reaction after SARS-CoV-2 vaccination. Identifiable characteristics of these patients with suspected, but also diagnosed SARS-CoV-2 vaccine hypersensitivity were female gender and the symptom angioedema. Overall, IgE-mediated hypersensitivity towards SARS-CoV-2 vaccines is extremely low and not increased in comparison to the reported hypersensitivity for other vaccines.