Elder and booster vaccination associates with decreased risk of serious clinical outcomes in comparison of Omicron and Delta variant: A meta-analysis of SARS-CoV-2 infection.

Background: The COVID-19 pandemic brings great pressure to the public health systems. This meta-analysis aimed to compare the clinical outcomes among different virus variants, to clarify their impact on medical resources and to provide evidence for the formulation of epidemic prevention policies. Methods: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the key words "Omicron" and "Delta." The adjusted Risk ratios (RRs), Odds ratios (ORs) and Hazard ratios (HRs) were extracted, and RRs and Rate difference % (RD%) were used to interpret the risk estimates of the outcomes ultimately. Results: Forty-three studies were included, with 3,812,681 and 14,926,841 individuals infected with SARS-CoV-2 Delta and Omicron variant, respectively. The relative risks of hospitalization, death, ICU admission, and mechanical ventilation use after infection with the Omicron variant were all significantly reduced compared those after infection with the Delta variant (RRhospitalization = 0.45, 95%CI: 0.40-0.52; RRdeath = 0.37, 95%CI: 0.30-0.45; RRICU = 0.35, 95%CI: 0.29-0.42; RRmechanical ventilation = 0.33, 95%CI: 0.25-0.44). The change of both absolute and relative risks for hospitalization was more evident (RR = 0.47, 95%CI: 0.42-0.53；RD% =10.61, 95%CI: 8.64-12.59) and a significant increase was observed for the absolute differences in death in the elderly (RD% = 5.60, 95CI%: 4.65-6.55); the change of the absolute differences in the risk of hospitalization and death were most markedly observed in the patients with booster vaccination (RD%hospitalization = 8.60, 95CI%: 5.95-11.24; RD%death = 3.70, 95CI%: 0.34-7.06). Conclusion: The ability of the Omicron variant to cause severe clinical events has decreased significantly, as compared with the Delta variant, but vulnerable populations still need to be vigilant. There was no interaction between the vaccination doses and different variants.

A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level and systemic lupus erythematosus: Mendelian randomization study.

BACKGROUND: Observational studies have suggested a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). In both autoimmunities, 25-hydroxyvitamin D (25-OHD) deficiency is common. However, the causality between T1DM, 25-OHD level and SLE remains largely unknown. METHODS: Independent genetic variants associated with T1DM, 25-OHD level, and SLE from the largest genome-wide association studies were used to conduct two-sample bidirectional Mendelian randomization (BIMR) and two-step Mendelian randomization (MR) analysis to estimate causal relationship between T1DM, 25-OHD level and SLE, and further multivariable Mendelian randomization (MVMR) was used to verify direct causality of T1DM and 25-OHD level on SLE. A series of sensitivity analysis as validation of primary MR results were performed. RESULTS: Consistent with the results of BIMR, there was strong evidence for a direct causal effect of T1DM on the risk of SLE (ORMVMR-IVW = 1.249, 95% CI = 1.148-1.360, PMVMR-IVW = 1.25×10-5), and 25-OHD level was negatively associated with the risk of SLE (ORMVMR-IVW = 0.305, 95% CI = 0.109-0.857, PMVMR-IVW = 0.031). We also observed a negative causal effect of T1DM on 25-OHD level (ORBIMR-IVW = 0.995, 95% CI = 0.991-0.999, PBIMR-IVW = 0.030) while the causal effect of 25-OHD level on the risk of T1DM did not exist (PBIMR-IVW = 0.106). In BIMR analysis, there was no evidence for causal effects of SLE on the risk of T1DM and 25-OHD level (PBIMR-IVW > 0.05, respectively). CONCLUSION: Our MR analysis suggested that there was a network causal relationship between T1DM, 25-OHD level and SLE. T1DM and 25-OHD level both have causal associations with the risk of SLE, and 25-OHD level could be a mediator in the causality of T1DM and SLE.

Genetic estimation of correlations and causalities between multifaceted modifiable factors and gastro-oesophageal reflux disease.

Background: Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal dysfunction that significantly affects the quality of daily life, and health interventions are challenging to prevent the risk of GORD. In this study, we used Mendelian randomization framework to genetically determine the causal associations between multifaceted modifiable factors and the risk of GORD. Materials and methods: Sixty-six exposures with available instrumental variables (IVs) across 6 modifiable pathways were included in the univariable MR analysis (UVMR). Summary-level genome-wide association studies (GWAS) datasets for GORD were retrieved from the Neale Lab (GORD Neale , Ncases = 29975, Ncontrols = 390556) and FinnGen (GORD Finn , Ncases = 13141, Ncontrols = 89695). Using the METAL software, meta-analysis for single nucleotide polymorphisms (SNPs) from GORD Neale and GORD Finn was conducted with an inverse variance weighted (IVW) fixed-effect model. Moreover, we leveraged partition around medoids (PAM) clustering algorithm to cluster genetic correlation subtypes, whose hub exposures were conditioned for multivariable MR (MVMR) analyses. P-values were adjusted with Bonferroni multiple comparisons. Results: Significant causal associations were identified between 26 exposures (15 risk exposures and 11 protective exposures) and the risk of GORD. Among them, 13 risk exposures [lifetime smoking, cigarette consumption, insomnia, short sleep, leisure sedentary behavior (TV watching), body mass index (BMI), body fat percentage, whole body fat mass, visceral adipose tissue, waist circumference, hip circumference, major depressive disorder, and anxious feeling], and 10 protective exposures (leisure sedentary behavior (computer use), sitting height, hand grip strength (left and right), birth weight, life satisfaction, positive affect, income, educational attainment, and intelligence) showed novel significant causal associations with the risk of GORD. Moreover, 13 exposures still demonstrated independent associations with the risk of GORD following MVMR analyses conditioned for hub exposures (educational attainment, smoking initiation and BMI). In addition, 12 exposures showed suggestive causal associations with the risk of GORD. Conclusion: This study systematically elucidated the modifiable factors causally associated with the risk of GORD from multifaceted perspectives, which provided implications for prevention and treatment of GORD.

Predictors of refractory risk in systemic lupus erythematosus-related thrombocytopenia: a dual-centre retrospective study.

OBJECTIVES: Based on clinical and laboratory indicators, this study aimed to establish a multiparametric nomogram to assess the risk of refractory cases of SLE-related thrombocytopenia (SLE-related TP) before systematic treatment. METHODS: From June 2012 to July 2021, a dual-centre retrospective cohort study of prospectively collected data of patients with SLE-related TP was conducted. The cohort data were divided into a developing set, internal validation set and external validation set. Refractory thrombocytopenia (RTP) was defined as failed to prednisone at 1 mg/kg per day with a platelet count cannot achieve or maintain higher than 50×109/L. In the developing set, a nomogram were established to predict RTP risk based on clinical characteristics and laboratory indicators by multivariable logistic regression, and its performance was assessed by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: A total of 1778 patients with SLE were included, and 413 eligible patients were involved in the final analysis with 121 RTPs. The RTP risk assessment (RRA) model was composed of five significant risk variables: pregnancy, severity of TP, complement 3, anticardiolipin antibody-immunoglobulin G and autoimmune haemolytic anaemia. In three datasets, the AUCs were 0.887 (95% CI 0.830 to 0.945), 0.880 (95% CI 0.785 to 0.975) and 0.871 (95% CI 0.793 to 0.949), respectively. The calibration curve, DCA and CIC all showed good performance of the RRA model. CONCLUSION: The RRA model demonstrated good capability for assessing the refractory risk in SLE-related TP, which may be helpful for early identification and intervention.

Myositis-specific autoantibodies in adults with idiopathic inflammatory myopathy: correlations with diagnosis and disease activity.

OBJECTIVE: To determine the relationship of myositis autoantibodies with the diagnosis and severity of idiopathic inflammatory myopathy (IIM) using the 2017 EULAR/ACR idiopathic inflammatory myopathy classification criteria and the myositis disease activity assessment tool (MDAAT). METHODS: Patients who met the new diagnostic criteria were tested for serum myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), and then classified into different subgroups based on autoantibody positivity. Patients were also diagnosed with possible IIM, probable IIM, and definite IIM. The MDAAT was used to evaluate muscular and extramuscular disease activity. The relationships of diagnostic classification with positivity for different myositis autoantibodies were determined. RESULTS: There were 118 patients, and 81% of them had one or more myositis autoantibody. Anti-Jo-1 was the most common MSA, and anti-Ro-52 was the most common MAA. Sixteen patients (14%) had possible IIM, 36 (31%) had probable IIM, and 66 (56%) had definite IIM. MSA-positive patients were significantly more common in the definite IIM group, but MAA positivity was unrelated to diagnostic classification. Positivity for MSAs or MAAs had no correlations with muscle disease activity. Extramuscular disease activity was greater in MSA-positive than MSA-negative patients, but MAA positivity had no significant association with extramuscular disease activity. CONCLUSIONS: MSA positivity aids in the diagnosis of IIM. MSA positivity was associated with greater extramuscular disease activity. Improving the clinical application of MSAs may enhance the individualized treatment of patients with IMM. Key Points • In this paper, we explore the relationships between the myositis autoantibodies and the diagnosis and the disease activity of inflammatory myopathy. • Positive myositis-specific autoantibodies is associated with the establishment of diagnosis and higher extramuscular disease activity. • Thus, more extensive application of myositis autoantibodies maybe the key for further disease assessment and research.