Non-Causal Effects of Asthma on COVID-19 Susceptibility and Severity.

Background: Asthma is observationally associated with an increased risk of COVID-19, but the causality remains unclear. We aim to determine whether there is a casual role of asthma in susceptibility to SARS-CoV-2 infection or COVID-19 severity. Methods: Instrumental variables (IVs) for asthma and moderate-to-severe asthma were obtained from publicly available summary statistics from the most recent and largest genome-wide association study (GWAS), including 394 283 and 57 695 participants of European ancestry, respectively. The corresponding data for COVID-19 susceptibility, hospitalization and severe-disease were derived from the COVID-19 Host Genetics Initiative GWAS meta-analysis of up to 1 683 768 individuals of European descent. Causality was inferred between correlated traits by Mendelian Randomization analyses. Inverse-variance weighted method was used as the primary MR estimates and multiple alternate approaches and several sensitivity analyses were also conducted. Results: Our MR analysis revealed no causal effects of asthma on COVID-19 susceptibility, hospitalization or severe disease, with odds ratio (OR) of 0.994 (95% CI: 0.962-1.027), 1.020 (95% CI: 0.955-1.089), and 0.929 (95% CI: 0.836-1.032), respectively. Furthermore, using genetic variants for moderate-to-severe asthma, a similar pattern of results was observed for COVID-19 susceptibility (OR: 0.988, 95% CI: 0.946-1.031), hospitalization (OR: 0.967, 95% CI: 0.906-1.031), and severe disease (OR: 0.911, 95% CI: 0.823-1.009). The association of asthma and moderate-to-severe asthma with COVID-19 was overall robust to sensitivity analyses. Conclusion: Genetically predicted asthma was not associated with susceptibility to, or severity of, COVID-19 disease, indicating that asthma is unlikely to be a causal factor in the development of COVID-19.

Retraction: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells.

[This retracts the article DOI: 10.1039/C8RA03679A.].

P2X7 receptor: A potential therapeutic target for autoimmune diseases.

P2X7 receptor (P2X7R), a distinct ligand-gated ion channel, is a member of purinergic type 2 receptor family with ubiquitous expression in human body. Previous studies have revealed a pivotal role of P2X7R in innate and adaptive immunity. Once activated, it will meditate some vital cascaded responses including the assembly of nucleotide-binding domain (NOD) like receptor protein 3 (NLRP3) inflammasome, non-classical secretion of IL-1ß, modulation of cytokine-independent pathways in inflammation such as P2X7R- transglutaminase-2 (TG2) and P2X7R-cathepsin pathway, activation and regulation of T cells, etc. In fact, above responses have been identified to be involved in the development of autoimmunity, specifically, the NLRP3 inflammasome could promote inflammation in massive autoimmune diseases and TG2, as well as cathepsin may contribute to joint destruction and degeneration in inflammatory arthritis. Recently, numerous evidences further suggested the significance of P2X7R in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), etc. In this review, we will succinctly discuss the biological characteristics and summarize the recent progress of the involvement of P2X7R in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential.

Retracted Article: ASIC1a involves acidic microenvironment-induced activation and autophagy of pancreatic stellate cells.

Acid-sensing ion channel 1a (ASIC1a), as a member of the proton-gated cation channel family, can be activated by low extracellular pH, and takes part in many acidity-associated physiopathological processes. However, whether ASIC1a is expressed in human pancreatic stellate cells (PSCs) and involved in acid-induced physiopathological events has not been reported yet. In this study, we investigated the expression of ASIC1a in PSCs and its possible role in the activation and autophagy of PSCs evoked by extracellular acid. Our results show that ASIC1a is present in PSCs, and an enhanced expression of ASIC1a occurs under acid stimuli. More importantly, the activation and autophagy of PSCs can be induced in acidic medium, and inhibition of ASIC1a by ASIC1a-specific blocker psalmotoxin-1 (PcTx1) or siRNA knockdown could suppress these two acid-associated processes. Collectively, our present study reports for the first time that ASIC1a is expressed in PSCs, and provides evidence for the involvement of ASIC1a in the acidic microenvironment-induced activation and autophagy of PSCs.

Effects of meteorological factors on incidence of scarlet fever during different periods in different districts of China.

OBJECTIVE: To reveal the difference of meteorological effect on scarlet fever in Beijing and Hong Kong, China, during different periods among 2004-2014. METHODS: The data of monthly incidence of scarlet fever and meteorological variables from 2004 to 2014 in Beijing and Hong Kong were collected from Chinese science data center of public health, meteorological data website and Hong Kong observatory website. The whole study period was separated into two periods by the outbreak year 2011 (Jan 2004-Dec 2010 and Jan 2011-Dec 2014). A generalized additive Poisson model was conducted to estimate the effect of meteorological variables on monthly incidence of scarlet fever during two periods in Beijing and Hong Kong, China. RESULTS: Incidence of scarlet fever in two districts were compared and found the average incidence during period of 2004-2010 were significantly different (Z=203.973, P<0.001) while average incidence became generally equal during 2011-2014 (Z=2.125, P>0.05). There was also significant difference in meteorological variables between Beijing and Hong Kong during whole study period, except air pressure (Z=0.165, P=0.869). After fitting GAM model, it could be found monthly mean temperature showed a negative effect (RR=0.962, 95%CI: 0.933, 0.992) on scarlet fever in Hong Kong during the period of 2004-2010. By comparison, for data in Beijing during the period of 2011-2014, the RRs of monthly mean temperature range growing 1°C and monthly sunshine duration growing 1h was equal to 1.196(1.022, 1.399) and 1.006(1.001, 1.012), respectively. The changes of meteorological effect on scarlet fever over time were not significant both in Beijing and Hong Kong. CONCLUSION: This study suggests that meteorological variables were important factors for incidence of scarlet fever during different period in Beijing and Hong Kong. It also support that some meteorological effects were opposite in different period although these differences might not completely statistically significant.