Background: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established. Objective: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. Methods: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCRconfirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization. Results: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15). Conclusions: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization. (J Allergy Clin Immunol 2020;146:307-14.)

We performed bottom-up engineering of a synthetic pathway in E. coli for the production of eukaryotic trimannosyl chitobiose glycans and the transfer of these glycans to specific asparagine residues in target proteins. Glycan biosynthesis was enabled by four eukaryotic glycosyltransferases, including the yeast uridine diphosphate-N-acetylglucosamine transferases Alg13 and Alg14 and the mannosyltransferases Alg1 and Alg2. By including the bacterial oligosaccharyltransferase PglB from C. jejuni, glycans were successfully transferred to eukaryotic proteins.

Eosinophils are important in the pathogenesis of many diseases, including asthma, eosinophilic esophagitis, and eczema. While IL-5 is crucial for supporting mature eosinophils, the signals that support earlier eosinophil lineage events are less defined. The IL-33 receptor, ST2, is expressed on several inflammatory cells, including eosinophils, and is best characterized for its role during the initiation of allergic responses in peripheral tissues. Recently, ST2 expression was described on hematopoietic progenitor subsets, where its function remains controversial. Our findings demonstrate that IL-33 is required for basal eosinophil homeostasis, since both IL-33– and ST2-deficient mice exhibited diminished peripheral blood eosinophil numbers at baseline. Exogenous IL-33 administration increased mature eosinophils in both the bone marrow and periphery in WT and IL-33–deficient, but not ST2-deficient, mice. Systemic IL-5 was also increased under this treatment, and blocking IL-5 with a neutralizing antibody ablated of the IL-33-induced mature eosinophil expansion. The homeostatic hypereosinophilia seen in IL-5–transgenic mice was significantly lower with ST2 deficiency despite similar elevations in systemic IL-5. Finally, in vitro treatment of bone marrow cells with IL-33, but not IL-5, led to specific early expansion of IL-5Rα–expressing precursor cells. In summary, our findings establish a basal defect in eosinophilopoiesis in IL-33– and ST2-deficient mice and a mechanism whereby IL-33 supports mature eosinophils by driving both systemic IL-5 production and the expansion of IL-5Rα–expressing precursor cells.

The most significant factor contributing to the presence of host cell protein (HCP) impurities in Protein A chromatography eluates is their association with the product monoclonal antibodies (mAbs) has been reported previously, and it has been suggested that more efficacious column washes may be developed by targeting the disruption of the mAbs-HCP interaction. However, characterization of this interaction is not straight forward as it is likely to involve multiple proteins and/or types of interaction. This work is an attempt to begin to understand the contribution of HCP subpopulations and/or mAb interaction propensity to the variability in HCP levels in the Protein A eluate. We performed a flowthrough (FT) recycling study with product respiking using two antibody molecules of apparently different HCP interaction propensities. In each case, the ELISA assay showed depletion of select subpopulations of HCP in Protein A eluates in subsequent column runs, while the feedstock HCP in the FTs remained unchanged from its native harvested cell culture fluid (HCCF) levels. In a separate study, the final FT from each molecule's recycling study was cross-spiked with various mAbs. In this case, Protein A eluate levels remained low for all but two molecules which were known as having high apparent HCP interaction propensity. The results of these studies suggest that mAbs may preferentially bind to select subsets of HCPs, and the degree of interaction and/or identity of the associated HCPs may vary depending on the mAb.

Mast cells and basophils are developmentally related cells whose activation is a hallmark of allergy. Functionally, mast cells and basophils overlap in their ability to produce several mediators, including histamine and granule proteases, but studies have increasingly demonstrated non-redundant roles. To characterize the transcriptional heterogeneity of mast cells and basophils upon their activation, we performed large-scale comparative microarrays of murine bone marrow–derived mast cells (BMMCs) and basophils (BMBs) at rest, upon an adaptive-type activation (IgE crosslinking), or upon an innate-type activation (IL-33 stimulation). Hierarchical clustering demonstrated that BMMCs and BMBs shared specific activation-associated transcriptional signatures but differed in others, both between cell type and between activation mode. In BMMCs, IgE crosslinking upregulated 785 genes including Egr2, Ccl1, and Fxyd6, while IL-33 stimulation induced 823 genes including Ccl1, Egr2, and Il1b. Focused bioinformatics pathway analysis demonstrated that IgE activation aligned with processes such as oxidative phosphorylation, angiogenesis, and the p53 pathway. The IL-33–activated transcriptome was enriched in genes commonly altered by NF-κB in response to TNF, by IL-6 via STAT3, and in response to IFNγ. Furthermore, BMBs activated via IgE crosslinking selectively induced immune response genes Ccl1, Il3, and Il2 compared to IL-33–stimulated BMBs. Principal-component analysis revealed key cell- and activation-specific clustering. Overall, our data demonstrate that mast cells and basophils have cell- and activation-specific transcriptional responses and suggest that context-specific gene networks and pathways may shape how the immune system responds to allergens and innate cytokines.