Development of an effective immune response in adults with Down Syndrome after SARS-CoV-2 vaccination (preprint)

Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to COVID-19 and may impair the generation of protective immunity after vaccine administration. The cellular and humoral responses of 55 DS patients who received a complete SARS-CoV-2 vaccination regime at one to three (V1) and six (V2) months were characterised. SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1, and increased at V2. Likewise, a sustained increase of SARS-CoV-2-specific circulating Tfh (cTfh) cells was observed one to three months after vaccine administration. Specific IgG antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, though IgG titers decreased significantly between both timepoints.

Comparison of the Characteristics, Morbidity, and Mortality of COVID-19 and Other Viral and Bacterial Pneumonia in Individuals with Down Syndrome: A Retrospective Cohort Study in Spain (preprint)

Background: Individuals with Down syndrome (DS) have an increased risk for coronavirus disease 2019 (COVID-19) hospitalization and death. Whether these outcomes are COVID-19-specific, or also occur in hospitalized individuals with DS and non-COVID-19 pneumonias, is unknown.Methods: This retrospective cohort study compared COVID-19 cases in persons with DS hospitalized in Spain reported to the Trisomy 21 Research Society COVID-19 survey, with admissions for viral or bacterial pneumonias from a retrospective clinical database of the Spanish Ministry of Health.Findings: 89 of 150 patients with COVID-19 and 2832 patients with non-COVID-19 pneumonias were hospitalised in Spain during the respective study periods. Patients with DS admitted for COVID-19 were significantly older and had more frequently obesity or dementia than patients with non-COVID-19 pneumonias. The mean length of stay of COVID-19 patients who died during their admission was significantly shorter than those who survived or those with non-COVID-19 pneumonias (p < 0·001). In-hospital mortality rates were significantly higher for COVID-19 patients (26·7% vs. 9·4%), especially among individuals over 40 (59% vs. 15·3%).Interpretation: Acute SARS-CoV-2 infection leads to higher mortality rates than non-COVID-19 pneumonias in individuals with DS. The length of stay of deceased COVID-19 patients was significantly shorter than those who survived the admission or those with non-COVID-19 pneumonias.Funding: Down Syndrome Affiliates in Action, Down Syndrome Medical Interest Group-USA, GiGi’s Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, National Down Syndrome Society, National Task Group on Intellectual Disabilities and Dementia Practices.Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Hospital del Mar institutional review board (CEIC Parc de Salut Mar, ref. code 2020/9197)

An international survey on the impact of COVID-19 in individuals with Down syndrome (preprint)

Background: Health conditions and immune dysfunction associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19 once infected by SARS-CoV-2. Methods: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers/family members on patients with COVID-19 and DS (N=1046). De-identified survey data collected between April and October 2020 were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. COVID-19 patients with DS from the ISARIC4C survey (ISARIC4C DS cases=100) were matched to a random set of patients without DS (ISARIC4C controls=400) and hospitalized DS cases in the T21RS survey (T21RS DS cases=100) based on age, gender, and ethnicity. Findings: The mean age in the T21RS survey was 29 years (SD=18), 73% lived with their family. Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Pain and nausea were reported less frequently (p<0.01), whereas altered consciousness/confusion were reported more frequently (p<0.01). Risk factors for hospitalization and mortality were similar to the general population (age, male gender, diabetes, obesity, dementia) with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher than for controls (T21RS DS versus controls: risk ratio (RR)=3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus controls: RR=2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. Interpretation: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of mortality, especially from age 40. Funding: Down Syndrome Affiliates in Action, Down Syndrome Medical Interest Group-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, Matthews Foundation, National Down Syndrome Society, National Task Group on Intellectual Disabilities and Dementia Practices.