AbstractBackgroundOmalizumab is the recommended treatment for antihistamine‐refractory chronic spontaneous urticaria (CSU) and severe allergic asthma. In addition, it has been shown to reduce the frequency of viral respiratory infections in allergic asthma. Respiratory illness is a known trigger for asthma and CSU.ObjectivesTo explore whether the antiviral effect of omalizumab may be extended to CSU patients independent of their atopic status.MethodsWe conducted a prospective parallel‐group pilot pragmatic trial including 30 non‐allergic and non‐atopic CSU patients (cases) under omalizumab 300 mg Q4‐weeks (due to refractory to H1‐antihistamines) and 30 age‐matched healthy controls. All CSU patients had to have a weekly urticaria activity score UAS7 <15 at least 4 weeks before recruitment. Using the self‐filled validated Jackson scale, we evaluated all study participants for common cold symptoms. All cases and controls rated weekly their respiratory symptoms. An increase in the symptom score of at least 4 points compared to baseline (defined as the minimum weekly report of symptoms) was considered an episode suggestive of a viral infection of the upper respiratory tract (URT). The patients were follow‐up every 4 weeks throughout the study period (10 months).ResultsCSU patients under omalizumab reported fewer episodes suggestive of an URT viral infection than the healthy controls (median of reported episodes: 0 vs. 1, inter‐quartile range 0–1 vs. 1–1, min–max: 0–3 vs. 0–4, respectively;p= 0.0095). The duration of each episode was the same in both cases and controls.ConclusionsOmalizumab can reduce the number of common cold episodes in CSU patients and consequently may minimize viral‐related CSU exacerbations. This beneficial effect is exerted independently of the atopic status, even in non‐asthmatic individuals or non‐allergic patients without any evidence of respiratory susceptibility. Further large‐scale studies are needed to validate the current findings and elucidate the underlying relevant pathophysiology.