ABSTRACT
OBJECTIVES: COVID-19 vaccine responses in rare autoimmune rheumatic diseases (RAIRD) remain poorly understood, in particular there is little known about whether people develop effective T cell responses. We conducted an observational study to evaluate the short-term humoral and cell-mediated T cell response after the second SARS-CoV-2 vaccination in RAIRD patients compared with healthy controls (HC). METHODS: Blood samples were collected after the second dose and anti-spike, anti-nucleocapsid antibody levels and SARS-CoV-2 specific T cell responses were measured and compared with HC. Activation induced marker and deep phenotyping assays were used to identify differences in T cells between high and low/no antibody groups, followed by multi-dimensional clustering. RESULTS: 50 patients with RAIRD were included (31 with AAV, 4 with other systemic vasculitis, 9 with SLE and 6 with myositis). Median anti-spike levels were significantly lower in RAIRD compared with HC (p< 0.0001). 15 (33%) patients had undetectable and 26 (57%) had lower levels than the lowest HC. Rituximab in the last 12 months (p= 0.003) was associated with reduced immunogenicity compared with a longer pre-vaccination period. There was a significant difference in B cell percentages (p= 0.03) and spike-specific CD4+ T cells (p= 0.02) between no/low antibody vs. high antibody groups. Patients in the no/low antibody group had a higher percentage of terminally differentiated (exhausted) T cells. CONCLUSIONS: Following two doses, most RAIRD patients have lower antibody levels than the lowest HC and lower anti-spike T cells. RAIRD patients with low/no antibodies have diminished numbers and poor quality of memory T cells which lack proliferative and functional capacities.
ABSTRACT
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.
ABSTRACT
COVID-19 affects the paediatric population less frequently than adults. A retrospective study was performed in a tertiary paediatric hospital in Mexico City in children <18 years of age who were hospitalized with a positive reverse transcription-polymerase chain reaction for SARS-CoV-2. Included in the study were 86 patients with a median age of 10 years old (IQR 2.6-14.3 years), who were classified in three groups: previously healthy, with chronic disease and immunosuppressed patients. The principal signs and symptoms were fever (81%), cough (51%) and headache (35%). A total of 20 patients (23%) required management in the paediatric intensive care unit (PICU) and 17% needed mechanical ventilation for an average of 12.7 days (IQR 2-29 days). There was no statistically significant difference between the three clinical classification groups in those patients admitted to the PICU, most of which were previously healthy patients. The mortality rate was 5% (four patients). Given that the paediatric population is susceptible to infection, potential transmitters and to clinical presentations with variable degrees of severity, it is important to continue reinforcing social distancing measures.