Value of the Lymphocyte Transformation Test for the Diagnosis of Drug-Induced Hypersensitivity Reactions in Hospitalized Patients with Severe COVID-19

Abstract

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays for PBMCs. We included five nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT result for at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT result. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

Keywords

• delayed drug hypersensitivity
• skin reaction
• SARS-CoV-2
• LTT
• interleukins