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.

Parsonage Turner syndrome of the brachial plexus secondary to Covid-19 vaccine: A case report (preprint)

Parsonage Turner syndrome (PTS) is a peripheral inflammatory neuropathy of unknown etiology. We present a rare case of a patient with PTS post-covid-19 BNT162b2 mRNA vaccine. Symptoms occurred fifteen days after the second dose. The patient was treated with corticosteroids, analgesics and physical rehabilitation with a partial recovery.

The use of oocyte cryopreservation for fertility preservation in patients with sex chromosome disorders: a case series describing outcomes.

PURPOSE: Characterize outcomes among adolescents and young adults (AYAs) with sex chromosome disorders (SCDs) after oocyte cryopreservation (OC) consultation. METHODS: Retrospective case series of all AYA (< 25 years) patients with SCDs seen for OC consultation from 2011 to 2019 at a large, urban, academic fertility center. All AYA patients with an SCD seen for OC consult in the study time period were reviewed and included. Data collected included patient age, SCD type, number of patients who attempted OC, number of cycles attempted, and cycle outcomes. RESULTS: Twenty-two patients were included: 9 with Turner syndrome, 12 with mosaic Turner syndrome, and 1 with 47,XXX. Mean age at consult was 14.7 ± 3.5 years. Fourteen patients elected for OC: 5 with Turner syndrome, 8 with mosaic Turner syndrome, and 1 47,XXX who pursued 31 OC cycles total. Of those 14 patients, 10 underwent retrieval, 9 froze oocytes, and 8 froze mature (MII) oocytes. Seven patients underwent > 1 cycle and 7 had ≥ 1 cancelation. 3/3 patients who pursued cycles after 1st cancelation never got to retrieval. Age, SCD type, and baseline FSH did not predict ability to freeze MIIs. One patient returned after OC and attempted 4 ovulation induction cycles and 2 IVF cycles; all were canceled for low response. CONCLUSIONS: AYA patients with SCDs have a high risk of poor response and cycle cancelation but the majority froze MIIs. Thus, setting expectations is important. A larger sample size is needed to evaluate possible clinical predictors of success.

Immune defects and cardiovascular risk in X chromosome monosomy mosaicism mediated by loss of chromosome Y. A risk factor for SARS-CoV-2 vulnerability in elderly men? (preprint)

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) has an estimated overall case fatality ratio of 1.38% in China, being 53% higher in males and increasing exponentially with age. Mosaicism for X chromosome monosomy (XCM) shows a similar increase in aging population mostly driven by loss of chromosome Y in males (LOY), and is associated with a raise in all-cause mortality. Using comparative transcriptomic data, we have defined that XCM/LOY is associated with abnormal peripheral blood cell counts with decreased progenitor cells and multiple biomarkers of immune system dysfunction, pro-coagulation activity and increased cardiovascular risk. Several differentially down-regulated genes in XCM/LOY individuals are involved in the initial immune response to SARS-CoV-2 (OR of enrichment=7.23, p=1.5x10-7), mainly interferon-induced genes that code for inhibitors of viral processes. Thus, our data suggest that XCM mosaicism underlies at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential relevance for modulating prognosis and therapeutic response, we propose that evaluation of LOY and XCM by currently established methods should be implemented as biomarkers in infected patients, including currently ongoing clinical trials with different medications and vaccines for COVID-19. Testing for LOY/XCM at large scale among elderly people may also be helpful to identify still unexposed people who may be especially vulnerable to severe Covid-19 disease.