COVID-19 vaccination among health care workers in Finland: coverage, perceptions and attitudes.

AIMS: In this study, we examined the voluntary COVID-19 vaccine coverage among health care workers (HCWs) working in close patient contact. HCWs' beliefs about COVID-19 infection, their opinions of vaccination and reasons for having or declining the COVID-19 vaccination were also evaluated. METHODS: In October 2021, a cross-sectional observational study was carried out in five hospitals in Central and Eastern Finland. The anonymous and voluntary survey was targeted at 5120 doctors and nurses working in close patient contact. RESULTS: Some 1837 responses were included in the study. Ninety-seven per cent of the respondents had received at least one COVID-19 vaccine and 68% of the respondents agreed that all HCWs working in close patient contact should be vaccinated against COVID-19. Vaccination coverage and support for vaccination were higher among older HCWs and doctors. HCWs' main reasons for having the COVID vaccine were willingness to protect themselves, their family and their patients from COVID-19. Concerns about adverse reactions to the COVID-19 vaccine was the main reason for declining it. CONCLUSIONS: The overall COVID-19 vaccination coverage and support for vaccinations among HCWs working in close patient contact were high without actual mandatory policies being introduced. Prioritising HCWs for COVID-19 vaccinations and widespread vaccine availability, as well as low general vaccine hesitancy and high seasonal influenza vaccination coverage among the study population were check marks in achieving high COVID-19 vaccination coverage rapidly.

Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes.

BACKGROUND: The nuclear factor κ light-chain enhancer of activated B cells (NF-κB) signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency. OBJECTIVE: We sought to identify the cause of disease in 3 unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation. METHODS: We applied genetic linkage analysis and next-generation sequencing and functional analyses of NFKB1 and its mutated alleles. RESULTS: In all affected subjects we detected novel heterozygous variants in NFKB1, encoding for p50/p105. Symptoms in variant carriers differed depending on the mutation. Patients harboring a p.I553M variant presented with antibody deficiency, infection susceptibility, and multiorgan autoimmunity. Patients with a p.H67R substitution had antibody deficiency and experienced autoinflammatory episodes, including aphthae, gastrointestinal disease, febrile attacks, and small-vessel vasculitis characteristic of Behçet disease. Patients with a p.R157X stop-gain experienced hyperinflammatory responses to surgery and showed enhanced inflammasome activation. In functional analyses the p.R157X variant caused proteasome-dependent degradation of both the truncated and wild-type proteins, leading to a dramatic loss of p50/p105. The p.H67R variant reduced nuclear entry of p50 and showed decreased transcriptional activity in luciferase reporter assays. The p.I553M mutation in turn showed no change in p50 function but exhibited reduced p105 phosphorylation and stability. Affinity purification mass spectrometry also demonstrated that both missense variants led to altered protein-protein interactions. CONCLUSION: Our findings broaden the scope of phenotypes caused by mutations in NFKB1 and suggest that a subset of autoinflammatory diseases, such as Behçet disease, can be caused by rare monogenic variants in genes of the NF-κB pathway.

Cat scratch disease caused by Bartonella grahamii in an immunocompromised patient.

Bartonella grahamii colonizes rodents worldwide and has been detected in questing Ixodes ricinus ticks. Here, the first human B. grahamii infection confirmed by multilocus sequence typing is reported. The route of transmission and clinical picture of the patient are similar to those seen in patients with cat scratch disease, which is typically diagnosed as a Bartonella henselae infection.

Valvular calcification and its relationship to atherosclerosis in chronic kidney disease.

BACKGROUND AND AIM OF THE STUDY: Cardiovascular calcification is a common complication in patients with chronic kidney disease (CKD). The study aim was to identify the characteristics and risk factors of valvular calcification, and its relationship to atherosclerosis, in CKD. METHODS: In this cross-sectional study, a total of 135 patients with CKD (mean age 52 +/- 11 years) included 58 pre-dialysis patients, 36 dialysis patients, and 41 renal transplant recipients. A control group of 58 subjects was also examined. The characteristics of valvular calcification were assessed using transthoracic echocardiography. RESULTS: The combined prevalences of mitral or aortic valve calcification were 31% in pre-dialysis patients, 50% in dialysis patients, 29% in renal transplant recipients, and 12% in controls (p = 0.001). The prevalences of mitral annular calcification were 17%, 31%, 27% and 2%, respectively (p = 0.001). In multivariate analysis, the risk factors for valvular calcification in CKD were age, duration of dialysis treatment and interleukin-6 level. Mitral annular calcification proved to be five-fold more common in diabetic patients than among non-diabetics. A close association between valvular calcification and patients with or without increased carotid intima-media thickness (44% versus 15%, p < 0.001), carotid plaque (77% versus 49%, p = 0.002), calcified carotid plaque (65% versus 26%, p = 0.001), coronary artery disease (40% versus 15%, p = 0.003) and peripheral arterial disease (46% versus 9%, p < 0.001) was found. CONCLUSION: Valvular calcification is common in CKD, and is closely associated with findings of intimal arterial disease. The presence of inflammation and the duration of dialysis treatment contribute to this complication. Diabetes is also a prominent risk factor for mitral annular calcification in CKD.

The combination of the interleukin-1alpha (IL-1alpha-889) genotype and the interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10 (IL-10) plasma levels in healthy individuals.

Family studies have demonstrated striking differences between individuals in their ability to produce IL-10 following lipopolysaccharide (LPS) stimulation of whole blood cultures in vitro, suggesting that differences in IL-10 production involve a considerable hereditary component. The first aim of this study was to analyse the possible effect of IL-10 genotypes and haplotypes on IL-10 plasma levels in a healthy Finnish population. As previous reports have demonstrated that endogenously produced IL-1 induces LPS-stimulated IL-10 production and that IL-10 inhibits synthesis of IL-1 in human monocytes, it is apparent that these two cytokines form an autoregulatory feedback loop. Secondly, we were interested whether any relationship could be found between IL-10 and IL-1beta in vivo. To examine this, the influence of IL-1alpha -889, IL-1beta -511 and IL-1Ra VNTR genotypes and IL-10 genotypes/haplotypes (ACC, GCC and ATA) on IL-10 plasma levels, and a putative correlation between IL-10 and IL-1alpha plasma levels were analysed. Four hundred adult blood samples were obtained from the Finnish Red Cross Blood Transfusion Centre, Tampere. The IL-10, IL-1alpha, IL-1beta and IL-1Ra gene polymorphisms were analysed using PCR. IL-1beta and IL-10 plasma levels were measured using an ELISA method. Our results indicated that increased IL-10 plasma levels were associated with the ATA haplotype (p = 0.03) and, surprisingly, with the IL-1alpha allele 2 carrier status (p = 0.02) in healthy individuals. This IL-1alpha 2+/ATA+ combination was found in 93 subjects out of 400 analysed (23%) and was associated with significantly high IL-10 plasma levels (p = 0.002). When individuals were classified into three groups, with no detectable IL-10 plasma levels (n = 145), with moderate levels (n = 152) and with high levels (n = 100) of IL-10, the IL-1alpha2+/ATA+ combination was more likely present among those with high levels than among those with undetectable levels of IL-10 (OR = 3.3, 95% CI 1.8 - 6.0, p < 0.001) or those with moderate levels of IL-10 (OR = 2.0, 95% CI 1.2 - 3.6, p = 0.012). Besides the observed association between IL-1alpha genotype and IL-10 levels, a moderate correlation was found between IL-10 and IL-1beta levels (r = 0.6, p = 0.01) among IL-10 producers (n = 252). The present findings suggest that the genotype combination of IL-1alpha 2+/ATA+ has a regulatory effect on basal IL-10 levels and that among individuals with measurable IL-10 plasma levels, IL-1beta and IL-10 basal levels correlate. Until now, data on the feedback loop between IL-1 and IL-10 cytokines have been based on studies in vitro, but now our results suggest that this relationship may also exist in vivo.

The promoter polymorphism of the IL-6 gene is associated with levels of antibodies to 60-kDa heat-shock proteins.

Elevated levels of antibodies to 60 kDa heat shock proteins are associated with severe coronary heart disease and carotid atherosclerosis. The presence of self hsp60-reacting antibodies can only be partially explained by microbial infections and induction by bacterial hsp65 proteins, since important differences (including the epitope specificity and complement activating ability) between hsp60 and hsp65 reacting antibodies have been shown. The aim of this study was to investigate the possible effects of genetic polymorphisms of different genes of proinflammatory cytokines on anti-hsp60 autoantibody levels. One hundred and seventy-six male blood donors were recruited and antibody levels to human hsp60 and Mycobacterium bovis hsp65 were determined by ELISA. Also in these donors, polymorphisms of the promoter of the IL-6 gene at position -174, the biallelic base exchange of the IL-1 beta gene at the -511 position and the IL-1 alpha gene at position -889 were investigated by PCR. A strong association between IL-6 -174 polymorphism and anti-hsp60 antibody levels was seen; the effect on anti-hsp65 antibody was less marked. Carriers of allele C at this position had significantly lower levels of anti-hsp60 and anti-hsp65 antibodies. A lack of associations between IL-1 beta and IL-1 alpha gene polymorphisms and antibody levels was detected. This is the first study in which associations between genetic polymorphisms and autoantibody levels have been described in healthy subjects. Further studies are needed to gain insight into the detailed mechanism of how the IL-6 gene polymorphism at position -174 influences anti-hsp60 autoantibody levels.