Does smoking have an impact on the immunological response to COVID-19 vaccines? Evidence from the VASCO study and need for further studies.

OBJECTIVES: The aim of this study was to investigate the possible impact of smoking on the humoral response to the BNT162b2 mRNA COVID-19 vaccine (also known as the BioNTech-Pfizer COVID-19 vaccine). STUDY DESIGN: A longitudinal sero-epidemiological study was conducted in sample of Italian healthcare workers (HCWs). METHODS: HCWs who were administered two doses of the BNT162b2 mRNA vaccine, 21 days apart, between December 2020 and January 2021, were invited to undergo multiple serology tests to identify SARS-CoV-2 S-RBD-specific immunoglobulin G (IgG) antibodies. Participants also responded to questions about their smoking status (i.e. current smokers vs non-smokers) in a survey. RESULTS: Sixty days after the completion of the vaccination cycle, serological analyses showed a difference in vaccine-induced IgG titre between current smokers and non-smokers, with median antibody titres of 211.80 AU/mL (interquartile range [IQR] 149.80-465.50) and 487.50 AU/mL (IQR 308.45-791.65) [P-value = 0.002], respectively. This significant difference in vaccine-induced IgG titres between current smokers and non-smokers remained after adjusting for age, sex, and previous infection with SARS-CoV-2. CONCLUSIONS: This study observed that vaccine-induced antibody titres decrease faster among current smokers than non-smokers. Further research to investigate the impact of smoking on the immunological response to COVID-19 and non-COVID-19 vaccines is required.

Dipeptidyl peptidase-4 inhibitors and heart failure: Analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System.

BACKGROUND AND AIMS: We tested the possible association between dipeptidyl peptidase-4 inhibitors (DPP-4-I) use and heart failure (HF) occurrence by assessing the publicly available US-FDA Adverse Event Reporting System (FAERS). METHODS: FAERS data reporting HF and DPP-4-Is use in the period from the fourth quarter of 2006 through 2013 were extracted, using the Standardized MedDRA Query "Cardiac failure". Disproportionality (case/non-case method) was implemented by calculating Reporting Odds Ratios (RORs) with 95% Confidence Interval (CI): (1) exploratory analysis on the entire FAERS (using rosiglitazone as positive control); (2) consolidated analyses by therapeutic area (within antidiabetics), correcting for event- and drug-related competition bias and adjusting for co-reported drugs as confounders. RESULTS: HF during DPP4-I use was recorded in 390 reports (4.4% of total reports). In exploratory analysis, statistically significant ROR emerged for DPP-4-I as a class (ROR = 1.17; 95% CI = 1.05-1.29), saxagliptin (1.68; 1.29-2.17), vildagliptin (2.39; 1.38-4.14), and rosiglitazone (13.98; 13.30-14.70). In consolidated analyses, the ROR for saxagliptin (2.60; 1.92-3.50) and vildagliptin (4.07; 2.28-7.27) increased, and became also significant for sitagliptin (1.61; 1.40-1.86). Concomitant drugs were reported in more than 50% of cases; the adjusted RORs of saxagliptin (2.30; 1.70-3.10), vildagliptin (3.15; 1.76-5.63), and sitagliptin (1.48; 1.28-1.71) were nonetheless significant. CONCLUSION: FAERS data are consistent with clinical studies on a possible association between saxagliptin and HF. The disproportionate reporting of HF with sitagliptin, conflicting with a recent phase IV trial, suggests that cardiovascular safety requires close post-marketing vigilance by clinicians of individual DPP-4-I in the community until the issue of class effect is solved.