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

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 characterization 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-γ 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 phorbol 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 patients 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.

Missed opportunities in the treatment of Turner syndrome: a case discussion and review of the guidelines.

A woman in her 50s with Turner syndrome was referred to the endocrine clinic, having been unaware of her diagnosis until she received a shielding letter from the UK government during the COVID-19 pandemic. Despite a neonatal diagnosis of Turner syndrome on her general practitioner record and despite having undergone laparoscopic examination for absent puberty and primary amenorrhoea aged 18 years, she had not received any prior hormone treatment or cardiovascular screening.Though Turner syndrome is rare, recent data from the UK Biobank suggest that it may be underdiagnosed. Clinicians should be aware of the clinical features and associated complications of Turner syndrome to avoid delayed diagnosis and missed opportunities for treatment.In this report, we discuss the clinical features of this rare syndrome and current guidelines for screening and treatment. We stress the importance of peer-to-peer support and information sharing through patient-led groups, such as the Turner Syndrome Support Society.