Immunological evaluation of young unvaccinated patients with Turner syndrome after COVID-19

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de Castro, Mateus V. ; Silva, Monize V. R. ; Oliveira, Luana de M. ; Gozzi-Silva, Sarah C. ; Naslavsky, Michel S. ; Scliar, Marilia O. ; Magalhaes, Monize L. ; da Rocha, Katia M. ; Nunes, Kelly ; Castelli, Erick C. ; Magawa, Jhosiene Y. ; Santos, Keity S. ; Cunha-Neto, Edecio ; Sato, Maria N. ; Zatz, Mayana

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES; v. 129, p. 9-pg., 2023-02-27.

Resumo

Objectives: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. Methods: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic character-ization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed.Results: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-gamma production by cluster of differentiation (CD)4 + and CD8 + T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phor-bol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8 + and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity.Conclusion: Following previous reports in the literature for other conditions, our data showed that pa-tients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/50931-3 - INCT 2014 - Envelhecimento e Doenças Genéticas: Genômica e Metagenômica
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/09702-1 - Estudo de variantes genéticas protetoras em indivíduos nonagenários e centenários resilientes
• Beneficiário: Mateus Vidigal de Castro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado