Background Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. Methods The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. Findings The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent ( p < 0.01), whereas altered consciousness/confusion were more frequent ( p < 0.01). Risk factors for hospitalization and mortality were similar to the general population 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 in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: 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 medical complications and mortality, especially from age 40. Funding Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.

healing does not augment WIHN in these IL-6 KO mice (data not shown) as it does in WT mice (Nelson et al., 2015), suggesting that STAT3 pathway activation is already sufficient for WIHN and WIHN cannot be enhanced further. Dimerization with gp130 to elicit activation of the JAK/STAT3 pathway is common to IL-6 family members. Ciliary neurotrophic factor and leukemia inhibitory factor have also been linked to tissue regeneration, suggesting that the activity of gp130 is the critical key player in this pathway (Heinrich et al., 2003).

Polygenic approaches often access more variance of complex traits than is possible by single variant approaches. For genotype data, genetic risk scores (GRS) are widely used for risk prediction as well as in association and interaction studies. Recently, interest has been growing in transferring GRS approaches to DNA methylation data (methylation risk scores, MRS), which can be used 1) as biomarkers for environmental exposures, 2) in association analyses in which single CpG sites do not achieve significance, 3) as dimension reduction approach in interaction and mediation analyses, and 4) to predict individual risks of disease or treatment success. Most GRS approaches can directly be transferred to methylation data. However, since methylation data is more sensitive to confounding, e.g. by age and tissue, it is more complex to find appropriate external weights. In this review, we will outline the adaption of current GRS approaches to methylation data and highlight occurring challenges.