Fruit and vegetable consumption and its contribution to inequalities in life expectancy and disability-free life expectancy in ten European countries

ObjectivesTo assess to what extent educational differences in total life expectancy (TLE) and disability-free life expectancy (DFLE) could be reduced by improving fruit and vegetable consumption in ten European countries.MethodsData from national census or registries with mortality follow-up, EU-SILC, and ESS were used in two scenarios to calculate the impact: the upward levelling scenario (exposure in low educated equals exposure in high educated) and the elimination scenario (no exposure in both groups). Results are estimated for men and women between ages 35 and 79years.ResultsVarying by country, upward levelling reduced inequalities in DFLE by 0.1-1.1years (1-10%) in males, and by 0.0-1.3years (0-18%) in females. Eliminating exposure reduced inequalities in DFLE between 0.6 and 1.7years for males (6-15%), and between 0.1years and 1.8years for females (3-20%).ConclusionsUpward levelling of fruit and vegetable consumption would have a small, positive effect on both TLE and DFLE, and could potentially reduce inequalities in TLE and DFLE.Peer reviewe

SARS-CoV-2 Vaccination Safety in Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Multifocal Motor Neuropathy

Background and ObjectivesThere are concerns on the safety of SARS-CoV-2 vaccination in patients with a history of Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). The aim of this study was to determine the risk of recurrence of GBS and exacerbations of CIDP or MMN after SARS-CoV-2 vaccination.MethodsWe conducted a prospective, multicenter cohort study from January 2021 to August 2021. Patients known in 1 of 3 Dutch University Medical Centers with research focus on immune-mediated neuropathy and members of the Dutch Patient Association for Neuromuscular Diseases were invited to participate if they were 18 years or older and diagnosed with GBS, CIDP, or MMN. Participants completed a series of questionnaires at 4 different time points: study baseline (1), within 48 hours before any SARS-CoV-2 vaccination (2 and 3, if applicable), and 6 weeks after their last vaccination (4). Participants unwilling to get vaccinated completed the last questionnaire (4) 4 months after study baseline. We assessed recurrences of GBS, any worsening of CIDP or MMN-related symptoms, treatment alterations, and hospitalization.ResultsOf 1,152 individuals to whom we sent the questionnaires, 674 (59%) signed informed consent. We excluded 153 individuals, most often because they had already received a SARS-CoV-2 vaccination or had had the infection (84%) before study baseline. Of 521 participants included in analyses, 403 (81%) completed the last questionnaire (time point 4). None of 162 participants with a history of GBS had a recurrence after vaccination. Of 188 participants with CIDP, 10 participants (5%) reported a worsening of symptoms within 6 weeks after vaccination. In 5 (3%) of these patients, maintenance treatment was modified. Two of 53 participants with MMN (4%) reported a worsening of symptoms, and treatment modification was reported by 1 participant.DiscussionWe found no increased risk of GBS recurrence and a low to negligible risk of worsening of CIDP or MMN-related symptoms after SARS-CoV-2 vaccination. Based on our data, SARS-CoV-2 vaccination in patients with these immune-mediated neuropathies seems to be safe

mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8⁺ T cell responses

SARS-CoV-2-specific CD8+ T cells recognize conserved viral peptides and in the absence of cross-reactive antibodies form an important line of protection against emerging viral variants as they ameliorate disease severity. SARS-CoV-2 mRNA vaccines induce robust spike-specific antibody and T cell responses in healthy individuals, but their effectiveness in patients with chronic immune-mediated inflammatory disorders (IMIDs) is less well defined. These patients are often treated with systemic immunosuppressants, which may negatively affect vaccine-induced immunity. Indeed, TNF inhibitor (TNFi)-treated inflammatory bowel disease (IBD) patients display reduced ability to maintain SARS-CoV-2 antibody responses post-vaccination, yet the effects on CD8+ T cells remain unclear. Here, we analyzed the impact of IBD and TNFi treatment on mRNA-1273 vaccine-induced CD8+ T cell responses compared to healthy controls in SARS-CoV-2 experienced and inexperienced patients. CD8+ T cells were analyzed for their ability to recognize 32 SARS-CoV-2-specific epitopes, restricted by 10 common HLA class I allotypes using heterotetramer combinatorial coding. This strategy allowed in-depth ex vivo profiling of the vaccine-induced CD8+ T cell responses using phenotypic and activation markers. mRNA vaccination of TNFi-treated and untreated IBD patients induced robust spike-specific CD8+ T cell responses with a predominant central memory and activated phenotype, comparable to those in healthy controls. Prominent non-spike-specific CD8+ T cell responses were observed in SARS-CoV-2 experienced donors prior to vaccination. Non-spike-specific CD8+ T cells persisted and spike-specific CD8+ T cells notably expanded after vaccination in these patient cohorts. Our data demonstrate that regardless of TNFi treatment or prior SARS-CoV-2 infection, IBD patients benefit from vaccination by inducing a robust spike-specific CD8+ T cell response.</p

Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: a cohort study

Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders. Methods: We did a cohort study in participants treated in outpatient clinics in seven university hospitals and one rheumatology treatment centre in the Netherlands as well as participants included in two national cohort studies on COVID-19-related disease severity. We included patients aged older than 18 years, diagnosed with any of the prespecified immune-mediated inflammatory disorders, who were able to understand and complete questionnaires in Dutch. Participants with immune-mediated inflammatory disorders who were not on systemic immunosuppressants and healthy participants were included as controls. Anti-receptor binding domain IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses—ie, vaccination after previous SARS-CoV-2 infection—were studied as a proxy for recall responses. Findings: Between Feb 2 and Aug 1, 2021, we included 3222 participants in our cohort. Sera from 2339 participants, 1869 without and 470 participants with previous SARS-CoV-2 infection were analysed (mean age 49·9 years [SD 13·7]; 1470 [62·8%] females and 869 [37·2%] males). Humoral responses did not differ between disorders. Anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks for reaching seroconversion following standard vaccination (0·32 [95% CI 0·19–0·49] for anti-CD20 therapy, 0·35 [0·21–0·55] for S1P modulators, and 0·61 [0·40–0·90] for mycophenolate mofetil combined with corticosteroids). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments (from 52·6% after the second vaccination to 89·5% after the third) but not significantly for anti-CD20 therapies (from 36·8% to 45·6%) and S1P modulators (from 35·5% to 48·4%). Most other immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment. Interpretation: Humoral responses following vaccination are impaired by specific immunosuppressants. After standard vaccination regimens, patients with immune-mediated inflammatory disorders taking most immunosuppressants show similar seroconversion to controls, although antibody titres might be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate to loss of (short-term) protection. In patients on immunosuppressants showing poor humoral responses after standard vaccination regimens, a third vaccination resulted in additional seroconversion in patients taking mycophenolate mofetil combination treatments, whereas the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited. Funding: ZonMw (The Netherlands Organization for Health Research and Development)

Disease activity in patients with immune-mediated inflammatory diseases after SARS-CoV-2 vaccinations

For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine. Patients reported changes in disease activity on a five-point Likert scale every 60 days for up to twelve months after first vaccination. In case of self-reported increased activity, hospital records were screened whether the treating physician reported increased activity, and for potential intensification of immunosuppressive (ISP) treatment. Mixed models were used to study determinants for self-reported increased disease activity. In total, 2111 patients were included for analysis after primary immunization (mean age 49.7 years [SD 13.7], 1329/2111 (63.0%) female), from which 1266 patients for analysis after first additional vaccination. Increased disease activity at 60 days after start of primary immunization was reported by 223/2111 (10.6%). In 96/223 (43.0%) the increase was confirmed by the treating physician and in 36/223 (16.1%) ISP treatment was intensified. Increased disease activity at seven to 60 days after additional vaccination, was reported by 139/1266 (11.0%). Vaccinations were not temporally associated with self-reported increased disease activity. Conversely, increased disease activity before first vaccination, neuromuscular disease, and multiple sclerosis were associated. Altogether, self-reported increased disease activity after vaccination against SARS-CoV-2 was recorded in a minority of patients and was generally mild. Moreover, multivariate analyses suggest that disease related factors, but not vaccinations are the major determinants for self-reported increased disease activity

Disease activity in patients with immune-mediated inflammatory diseases after SARS-CoV-2 vaccinations

For patients with immune-mediated inflammatory diseases (IMIDs), concerns exist about increased disease activity after vaccination. We aimed to assess changes in disease activity after SARS-CoV-2 vaccination in patients with IMIDs, and determine risk factors for increased disease activity. In this substudy of a prospective observational cohort study (Target-to-B!), we included patients with IMIDs who received a SARS-CoV-2 vaccine. Patients reported changes in disease activity on a five-point Likert scale every 60 days for up to twelve months after first vaccination. In case of self-reported increased activity, hospital records were screened whether the treating physician reported increased activity, and for potential intensification of immunosuppressive (ISP) treatment. Mixed models were used to study determinants for self-reported increased disease activity. In total, 2111 patients were included for analysis after primary immunization (mean age 49.7 years [SD 13.7], 1329/2111 (63.0%) female), from which 1266 patients for analysis after first additional vaccination. Increased disease activity at 60 days after start of primary immunization was reported by 223/2111 (10.6%). In 96/223 (43.0%) the increase was confirmed by the treating physician and in 36/223 (16.1%) ISP treatment was intensified. Increased disease activity at seven to 60 days after additional vaccination, was reported by 139/1266 (11.0%). Vaccinations were not temporally associated with self-reported increased disease activity. Conversely, increased disease activity before first vaccination, neuromuscular disease, and multiple sclerosis were associated. Altogether, self-reported increased disease activity after vaccination against SARS-CoV-2 was recorded in a minority of patients and was generally mild. Moreover, multivariate analyses suggest that disease related factors, but not vaccinations are the major determinants for self-reported increased disease activity

Breakthrough SARS-CoV-2 infections with the delta (B.1.617.2) variant in vaccinated patients with immune-mediated inflammatory diseases using immunosuppressants:a substudy of two prospective cohort studies

Background: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. Methods: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed post-vaccination serum samples for anti-receptor binding domain (RBD) antibodies to assess the humoral vaccination response (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC-COVID study only). We used multivariable logistic regression analyses to explore potential clinical and humoral determinants associated with the odds of breakthrough infections. The T2B! study is registered with the Dutch Trial Register, Trial ID NL8900, and the ARC-COVID study is registered with Dutch Trial Register, trial ID NL8513. Findings: We included 3207 patients with immune-mediated inflammatory diseases who receive immunosuppressants, and 1807 controls (985 patients with immune-mediated inflammatory disease not on immunosuppressants and 822 healthy controls). Among patients receiving immunosuppressants, mean age was 53 years (SD 14), 2042 (64%) of 3207 were female and 1165 (36%) were male; among patients not receiving immunosuppressants, mean age was 54 years (SD 14), 598 (61%) of 985 were female and 387 (39%) were male; and among healthy controls, mean age was 57 years (SD 13), 549 (67%) of 822 were female and 273 (33%) were male. The cumulative incidence of PCR-test or antigen-test confirmed SARS-CoV-2 breakthrough infections was similar in patients on immunosuppressants (148 of 3207; 4·6% [95% CI 3·9-5·4]), patients not on immunosuppressants (52 of 985; 5·3% [95% CI 4·0-6·9]), and healthy controls (33 of 822; 4·0% [95% CI 2·8-5·6]). There was no difference in the odds of breakthrough infection for patients with immune-mediate inflammatory disease on immunosuppressants versus combined controls (ie, patients not on immunosuppressants and healthy controls; adjusted odds ratio 0·88 [95% CI 0·66-1·18]). Seroconversion after vaccination (odds ratio 0·58 [95% CI 0·34-0·98]; T2B! cohort only) and SARS-CoV-2 infection before vaccination (0·34 [0·18-0·56]) were associated with a lower odds of breakthrough infections. Interpretation: The incidence and severity of SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases on immunosuppressants was similar to that in controls. However, caution might still be warranted for those on anti-CD20 therapy and those with traditional risk factors. Funding: ZonMw (the Netherlands Organization for Health Research and Development) and Reade foundation

Risk factors associated with short-term adverse events after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases

BACKGROUND: Studies have suggested incremental short-term adverse events (AE) after repeated vaccination. In this report, we assessed occurrence and risk factors for short-term AEs following repeated SARS-CoV-2 vaccination in patients with various immune-mediated inflammatory diseases (IMIDs). METHODS: Self-reported daily questionnaires on AEs during the first 7 days after vaccination were obtained of 2259 individuals (2081 patients and 178 controls) participating in an ongoing prospective multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B-COVID). Relative risks were calculated for potential risk factors associated with clinically relevant AE (rAE), defined as AE lasting longer than 2 days or impacting daily life. RESULTS: In total, 5454 vaccinations were recorded (1737 first, 1992 second and 1478 third vaccinations). Multiple sclerosis, Crohn’s disease and rheumatoid arthritis were the largest disease groups. rAEs were reported by 57.3% (95% CI 54.8–59.8) of patients after the first vaccination, 61.5% (95% CI 59.2–63.7) after the second vaccination and 58% (95% CI 55.3–60.6) after the third vaccination. At day 7 after the first, second and third vaccination, respectively, 7.6% (95% CI 6.3–9.1), 7.4% (95% CI 6.2–8.7) and 6.8% (95% CI 5.4–8.3) of patients still reported AEs impacting daily life. Hospital admissions and allergic reactions were uncommon (<0.7%). Female sex (aRR 1.43, 95% CI 1.32–1.56), age below 50 (aRR 1.14, 95% CI 1.06–1.23), a preceding SARS-CoV-2 infection (aRR 1.14, 95% CI 1.01–1.29) and having an IMID (aRR 1.16, 95% CI 1.01–1.34) were associated with increased risk of rAEs following a vaccination. Compared to the second vaccination, the first vaccination was associated with a lower risk of rAEs (aRR 0.92, 95% CI 0.84–0.99) while a third vaccination was not associated with increased risk on rAEs (aRR 0.93, 95% CI 0.84–1.02). BNT162b2 vaccines were associated with lower risk on rAEs compared to CX-024414 (aRR 0.86, 95% CI 0.80–0.93). CONCLUSIONS: A third SARS-CoV-2 vaccination was not associated with increased risk of rAEs in IMID patients compared to the second vaccination. Patients with an IMID have a modestly increased risk of rAEs after vaccination when compared to controls. Most AEs are resolved within 7 days; hospital admissions and allergic reactions were uncommon. TRIAL REGISTRATION: NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02310-7