Abstract Introduction Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine central to the pathogenesis of allergic inflammation and asthma. Tezepelumab, a monoclonal antibody that inhibits TSLP, reduces airway inflammation across both T2-high and T2-low asthma phenotypes. Elevated TSLP levels have also been reported in acute COVID-19 infections and are associated with more severe disease and prolonged hospitalization. Pre-existing asthma is associated with a doubling of risk of Long-COVID; in turn, Long-COVID can substantially worsen asthma control. Case Description A 17-year-old male, former competitive baseball player with a history of eczema, allergic rhinitis, and previously well controlled mild persistent asthma, presented with new daily cough and severe exertional dyspnea following COVID-19 infection in December 2020. Symptoms persisted despite treatment with Symbicort 160 mcg (SMART), Spiriva, and Azithromycin. Pulmonary function testing showed mild obstruction with normal exercise spirometry and DLCO. CT chest revealed right lower lobe mosaic attenuation consistent with bronchiolitis obliterans, while VATS biopsy and BAL demonstrated alveolar space enlargement without significant inflammation or infection. Despite maximal therapy, he required daily rescue inhaler use and 10-12 prednisone courses in one year. Immunophenotyping showed eosinophils 80 cells/μL, total IgE 150 kU/L, and FeNO 21 ppb. Tezepelumab was initiated following multidisciplinary discussion given potential for post-viral alterations in TSLP. After seven months of Tezepelumab therapy, the patient reported significant improvement in dyspnea, exercise tolerance, and energy. No further exacerbations requiring systemic corticosteroids occurred, and rescue inhaler use markedly decreased. Discussion This case demonstrates clinical improvement with TSLP inhibition using Tezepelumab in a patient with worsening of asthma control following COVID-19 infection. Post-viral immune dysregulation involving TSLP may contribute to worsening asthma control in Long-COVID. Targeting upstream epithelial cytokines may represent a promising therapeutic strategy for managing Long-COVID-related airway inflammation and asthma refractory to conventional therapy. Consideration should be given to the use of Tezepelumab in Long-COVID associated loss of asthma control. This abstract is funded by: None
Hosinski et al. (Fri,) studied this question.