Sustained impact of subcutaneous immunotherapy among patients with allergic rhinitis who experienced treatment delay due to the COVID-19 pandemic: A multicenter, two-arm, real-world study (preprint)

Background: The aim of this study is to investigate the impact of COVID-19 related treatment delay on subcutaneous immunotherapy (SCIT) efficacy in patients with allergic rhinitis (AR). Methods: The study was performed in 643 patients with SCIT appointments between February 1 and May 31, 2020. The clinical assessment, performed at baseline (V0) and one year later (V1), included visual analogue scale (VAS); daily symptom score (dSS); daily medication score (dMS); combined symptom and medication scores (CSMS); quality of life (QoL); self-rating anxiety scale (SAS); and self-rating depression scale (SDS) for each patient. Results: At V0, 249 patients were treated on schedule, and 394 were delayed (7 ± 4.68 weeks). Among them, 319 patients (105 on schedule, and 214 delayed) also completed the assessments at V1, with the absence of 25.39% patients due to completion of SCIT, and 25.35% patients were withdrawal. The results of all assessments were within the normal range for all patients at V0 and V1, with the exception of a slightly higher SDS score (56.13) at V0. In the SCIT delayed group. there was a significant positive correlation between the length (weeks) of the delay and SDS score, and this was significantly higher in patients with poor control of nasal symptoms. Conclusions: This study showed the long-term efficacy of SCIT for AR patients, including those who have had to delay normal therapy due to the COVID-19 outbreak. The psychological status of SCIT patients in response to lockdown of hospital services during this critical period should be considered.

Discovery of runs-of-homozygosity diplotype clusters and their associations with diseases in UK Biobank (preprint)

Runs of homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE, to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 SNPs and shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended HLA region and autoimmune disorders. We found an association between a diplotype covering the HFE gene and haemochromatosis, even though the well-known causal SNP was not directly genotyped nor imputed. Using genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase of mortality among COVID-19 patients. In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at population scale.