Value of the Lymphocyte Transformation Test for the Diagnosis of Drug-Induced Hypersensitivity Reactions in Hospitalized Patients with Severe COVID-19. 2023

Carlos Fernández-Lozano, and Emilio Solano Solares, and Isabel Elías-Sáenz, and Isabel Pérez-Allegue, and Monserrat Fernández-Guarino, and Diego Fernández-Nieto, and Laura Díaz Montalvo, and David González-de-Olano, and Ana de Andrés, and Javier Martínez-Botas, and Belén de la Hoz Caballer
Biochemistry-Research Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Carretera de Colmenar Km 9, 28034 Madrid, Spain.

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.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D004342 Drug Hypersensitivity Immunologically mediated adverse reactions to medicinal substances used legally or illegally. Allergy, Drug,Hypersensitivity, Drug,Drug Allergy,Allergies, Drug,Drug Allergies,Drug Hypersensitivities,Hypersensitivities, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000086382 COVID-19 A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent. 2019 Novel Coronavirus Disease,2019 Novel Coronavirus Infection,2019-nCoV Disease,2019-nCoV Infection,COVID-19 Pandemic,COVID-19 Pandemics,COVID-19 Virus Disease,COVID-19 Virus Infection,Coronavirus Disease 2019,Coronavirus Disease-19,SARS Coronavirus 2 Infection,SARS-CoV-2 Infection,Severe Acute Respiratory Syndrome Coronavirus 2 Infection,COVID19,2019 nCoV Disease,2019 nCoV Infection,2019-nCoV Diseases,2019-nCoV Infections,COVID 19,COVID 19 Pandemic,COVID 19 Virus Disease,COVID 19 Virus Infection,COVID-19 Virus Diseases,COVID-19 Virus Infections,Coronavirus Disease 19,Disease 2019, Coronavirus,Disease, 2019-nCoV,Disease, COVID-19 Virus,Infection, 2019-nCoV,Infection, COVID-19 Virus,Infection, SARS-CoV-2,Pandemic, COVID-19,SARS CoV 2 Infection,SARS-CoV-2 Infections,Virus Disease, COVID-19,Virus Infection, COVID-19
D000086402 SARS-CoV-2 A species of BETACORONAVIRUS causing atypical respiratory disease (COVID-19) in humans. The organism was first identified in 2019 in Wuhan, China. The natural host is the Chinese intermediate horseshoe bat, RHINOLOPHUS affinis. 2019 Novel Coronavirus,COVID-19 Virus,COVID19 Virus,Coronavirus Disease 2019 Virus,SARS Coronavirus 2,SARS-CoV-2 Virus,Severe Acute Respiratory Syndrome Coronavirus 2,Wuhan Coronavirus,Wuhan Seafood Market Pneumonia Virus,2019-nCoV,2019 Novel Coronaviruses,COVID 19 Virus,COVID-19 Viruses,COVID19 Viruses,Coronavirus 2, SARS,Coronavirus, 2019 Novel,Coronavirus, Wuhan,Novel Coronavirus, 2019,SARS CoV 2 Virus,SARS-CoV-2 Viruses,Virus, COVID-19,Virus, COVID19,Virus, SARS-CoV-2,Viruses, COVID19
D000086742 COVID-19 Testing Diagnosis of COVID-19 by assaying bodily fluids or tissues for the presence of COVID-19 antibodies, SARS-COV-2 antigens or the VIRAL RNA of SARS-COV-2. 2019 Novel Coronavirus Disease Testing,2019 Novel Coronavirus Testing,2019-nCoV Disease Testing,2019-nCoV Infection Testing,2019-nCoV Testing,COVID-19 Diagnostic Testing,COVID-19 Virus Testing,COVID19 Testing,COVID19 Virus Testing,Coronavirus Disease 2019 Testing,Coronavirus Disease-19 Testing,SARS Coronavirus 2 Testing,SARS-CoV-2 Testing,Severe Acute Respiratory Syndrome Coronavirus 2 Testing,2019 nCoV Disease Testing,2019 nCoV Infection Testing,2019 nCoV Testing,2019-nCoV Disease Testings,2019-nCoV Infection Testings,2019-nCoV Testings,COVID 19 Diagnostic Testing,COVID 19 Testing,COVID 19 Virus Testing,COVID-19 Diagnostic Testings,COVID-19 Testings,COVID-19 Virus Testings,COVID19 Testings,COVID19 Virus Testings,Coronavirus Disease 19 Testing,Coronavirus Disease-19 Testings,Diagnostic Testing, COVID-19,Disease Testing, 2019-nCoV,Infection Testing, 2019-nCoV,SARS CoV 2 Testing,SARS-CoV-2 Testings,Testing, 2019-nCoV,Testing, 2019-nCoV Disease,Testing, 2019-nCoV Infection,Testing, COVID-19,Testing, COVID-19 Virus,Testing, COVID19,Testing, COVID19 Virus,Testing, Coronavirus Disease-19,Testing, SARS-CoV-2,Virus Testing, COVID-19,Virus Testing, COVID19
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D017963 Azithromycin A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Azadose,Azithromycin Dihydrate,Azithromycin Monohydrate,Azitrocin,Azythromycin,CP-62993,Goxal,Sumamed,Toraseptol,Ultreon,Vinzam,Zentavion,Zithromax,Zitromax,CP 62993,CP62993,Dihydrate, Azithromycin,Monohydrate, Azithromycin

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