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Chronic spontaneous urticaria (CSU) is characterized by wheals lasting more than 6 weeks and can be accompanied by angioedema. Treatment of the disease varies depending on the severity and includes first-line therapeutics such as non-sedative antihistamines. Second- and third-line treatments are used in severe and uncontrolled form of CSU. Environmental exposure and infections could trigger worsening symptoms. The goal of this study is to assess the effect of SARS-CoV-2 infection on CSU symptoms and the efficacy of the second- and third-line therapeutics for CSU management in COVID-19 patients. Our findings show that SARS-CoV-2 infection exacerbates CSU symptoms. Worsening of disease was indicated by decreased Urticaria Control Test (UCT) and increased Urticaria Activity Score (UAS). Treatment management was modified by switching to second- and third-line therapeutics; however, therapeutic control was achieved only in one patient. Our data demonstrates that SARS-CoV-2 infection contributes to the severity of CSU. Symptoms of CSU are more challenging to manage and require changes in treatment protocol, including second- and third-line therapeutics. We believe that severe inflammation triggered by SARS-CoV-2 infection contributes to the worsening of CSU symptoms.