Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

Comparative safety and effectiveness of inhaled bronchodilators and corticosteroids for treating asthma-COPD overlap: a systematic review and meta-analysis.

OBJECTIVE: To determine the safety and effectiveness of current pharmacotherapies consisting of long-acting beta2-agonist (LABA) and/or inhaled corticosteroids (ICS) in patients with asthma-COPD overlap. DATA SOURCES: A systematic search was conducted using the PubMed, EMBASE, and Web of Science databases up to June 2018. STUDY SELECTIONS: Only studies comparing the safety and effectiveness of LABA and/or ICS in patients with asthma-COPD overlap were included. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) using Inverse Variance Random-effects model. RESULTS: From a total of 3382 articles retrieved, three randomized controlled trials (RCTs), six cohort studies (CS), one nested case control study fulfilled the inclusion criteria for three independent meta-analyses representing 181,603 participants. Three CS results show LABA was associated with decreased risk of myocardial infarction (combined RR: 0.80, 95% CI 0.74-0.87) versus non-LABA use; ICS/LABA was associated with a lower risk of death or hospitalization (combined RR: 0.82, 95% CI 0.75-0.90) compared to no use. Results from RCTs, no clear difference in lung function decline in FEV1 was found (combined mean difference: 0.08, 95% CI 0.15-0.32) in patients receiving ICS and/or LABA compared to placebo. However, due to lack of data, exacerbations, fractures and nontuberculous mycobacterial pulmonary disease outcomes were not meta-analyzed. CONCLUSIONS: Among patients with asthma-COPD overlap, LABA is associated with decreased risk of myocardial infarction; and the combination therapy of ICS/LABA appears to reduce the risk of death or hospitalization. More studies of quality data and larger number of patients are needed. REGISTRATION: PROSPERO (CRD42018090863).

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases.

BACKGROUNDLimited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODSThis observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against SARS-CoV-2 variants, were determined before and after 1 and 2 vaccine doses.RESULTSWe prospectively followed 150 subjects, 26 healthy controls, 9 patients with IMID on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Ab and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in patients with IMID compared with healthy controls. Ab levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF-treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2.CONCLUSIONSOur findings support the need for a third dose of the mRNA vaccine and for continued monitoring of immunity in these patient groups.FUNDINGFunded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR)/COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (to THW and ACG), CIHR FDN-143250 (to THW), GA2-177716 (to VC, ACG, and THW), and GA1-177703 (to ACG) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to ACG).

The effects of recreational cannabis use on glycemic outcomes and self-management behaviours in people with type 1 and type 2 diabetes: a rapid review.

BACKGROUND: Recent surveys of Canadian cannabis users reflect increasing consumption rates, some of whom may have diabetes. However, healthcare providers have limited information resources on the effects of recreational cannabis in people with diabetes. This rapid review was commissioned by Diabetes Canada to synthesize available evidence to guide recommendations for care of people 13 years of age and older who live with diabetes. METHODS: PubMed, Embase and PsycINFO databases were searched from January 2008 to January 2019. Study selection, data abstraction and quality appraisal were completed by pairs of reviewers working independently and discrepancies were resolved by a third reviewer with pilot tests completed before each stage to ensure consistency. Data collected from included studies were tabulated and summarized descriptively. RESULTS: The search resulted in 1848 citations of which 59 publications were selected for screening, resulting in six observational studies (2 full-text articles and 4 conference abstracts) that met the pre-defined criteria for inclusion. Five studies reported higher glycated hemoglobin (HbA1c) in people with type 1 diabetes (T1D) who consumed recreational cannabis. In one study, students aged 17 to 25 years living with T1D self-reported poorer glycemic control and higher HbA1c when smoking cannabis. In one study of adults with T1D, cannabis use within the previous 12 months was associated with almost double the risk of diabetic ketoacidosis compared with no cannabis use (odds ratio [OR] 1.98; confidence interval [CI] [95% CI] 1.01-3.91). Risks for peripheral arterial occlusion and myocardial infarction were found to be higher in people with type 2 diabetes (T2D) who consumed recreational cannabis, and worse renal parameters were also reported in two separate studies of T1D and T2D. CONCLUSIONS: Recreational cannabis use may negatively impact diabetes metabolic factors and self-management behaviours in people with T1D. In people with T2D, recreational cannabis may increase risks for peripheral arterial occlusion, myocardial infarction and renal disease. However, the evidence base of this rapid review was limited to six observational studies of poor to fair methodological quality, and thus, further robust, higher quality research is required to confirm the potential impact of cannabis on diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122829.

Association between early history of asthma and COPD diagnosis in later life: a systematic review and meta-analysis.

Background: Whereas most studies have reported prior history/diagnosis of asthma as an independent risk factor for chronic obstructive pulmonary disease (COPD) development in later life, no systematic review and meta-analysis has been conducted to synthesize these observational studies. The aim of this review is to investigate associations between prior history of asthma and later development of COPD. Methods: We conducted a comprehensive search in PubMed, CINAHL and EMBASE for studies related to prior history of asthma and COPD diagnosis. Articles were screened for relevance by two independent reviewers. Methodological quality was independently assessed and data extracted for qualitative and quantitative review. We explored heterogeneity and performed a publication bias check. Results: From the 1260 articles retrieved, 9 were included in the qualitative review and 7 in the meta-analysis. History of asthma was associated with developing COPD in later life (Inverse Variance Random-effects model, odds ratio: 7.87, 95% confidence interval: 5.40-11.45, p < 0.00001). Conclusions: Studies with high methodological quality provided sufficient evidence to suggest that individuals with previous history of asthma have an increasing likelihood of developing COPD in later life.