Neutralizing Antibody Titers in Hospitalized Patients with Acute Puumala Orthohantavirus Infection Do Not Associate with Disease Severity

Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.     

Introduction and Rapid Spread of SARS-CoV-2 Omicron Variant and Dynamics of BA.1 and BA.1.1 Sublineages,Finland, December 2021

Multiple introductions of SARS-COV-2 Omicron variant BA.1 and BA.1.1. lineages to Finland were detected in early December 2021. Within 3 weeks, Omicron overtook Delta as the most common variant in the capital region. Sequence analysis demonstrated the emergence and spread through community transmission of a large cluster of BA.1.1 virus.     

Abdominal obesity and alcohol use modify the impact of genetic risk for incident advanced liver disease in the general population

Background & Aims

Genetic variants, abdominal obesity and alcohol use are risk factors for incident liver disease (ILD). We aimed to study whether variants either alone or when aggregated into genetic risk scores (GRSs) associate with ILD, and whether waist-hip ratio (WHR) or alcohol use interacts with this risk.

Methods

Our study included 33 770 persons (mean age 50 years, 47% men) who participated in health-examination surveys (FINRISK 1992–2012 or Health 2000) with data on alcohol use, WHR and 63 genotypes associated with liver disease. Data were linked with national health registers for liver-related outcomes (hospitalizations, malignancies and death). Exclusions were baseline clinical liver disease. Mean follow-up time was 12.2 years. Cox regression analyses between variants and ILD were adjusted for age, sex and BMI.

Results

Variants in PNPLA3, IFNL4, TM6SF2, FDFT1, PPP1R3B, SERPINA1 and HSD17B13 were associated with ILD. GRSs calculated from these variants were not associated with WHR or alcohol use, but were exponentially associated with ILD (up to 25-fold higher risk in high versus low score). The risk of ILD in individuals with high GRS and high WHR or alcohol use compared with those with none of these risk factors was increased by up to 90-fold. GRSs provided new prognostic information particularly in individuals with high WHR.

Conclusions

The effect of multiple genetic variants on the risk of ILD is potentiated by abdominal obesity and alcohol use. Simple GRSs may help to identify individuals with adverse lifestyle who are at a particularly high risk of ILD.     

Persistent organic pollutants associate with liver disease in a Finnish general population sample

Background and Aims

Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population-based data are scarce. In this population-based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease.

Methods

This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health-examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase-alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression.

Results

Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04–0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non-alcoholic fatty liver disease. OCPs, PCBs and perfluoro-octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05–0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21–2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07–2.68, p < 0.05 respectively).

Conclusions

Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease.     

Concurrent changes in dental anxiety and smoking in parents of the FinnBrain Birth Cohort Study

We evaluated associations between changes in dental anxiety and tobacco use, adjusted for general anxiety and depressive symptoms. The FinnBrain Birth Cohort Study data, collected at gestational weeks 14 and 34 and at 3 months postpartum, were used. Questionnaires included the Modified Dental Anxiety Scale (MDAS), the Edinburgh Postnatal Depression Scale (EPDS), and the anxiety subscale of the Symptom Checklist-90 (SCL). Smoking was categorized as “stable non-smoking”, “started smoking”, “quit smoking”, and “stable smoking”. Changes in smoking and dental anxiety were evaluated “during pregnancy” (i.e., from gestational week 14 to gestational week 34) in 2442 women and 1346 men and “after pregnancy” (i.e., from gestational week 34 to 3 months postpartum) in 2008 women and 1095 men. Changes were evaluated in three smoking categories (stable non-smoking, fluctuating, and stable smoking), using data from all three time-points (1979 women and 1049 men). Modeling used repeated measures analysis of covariance. Stable smoking mothers had statistically significantly higher levels of dental anxiety (mean MDAS 12.3–12.6) than non-smoking mothers (mean MDAS 10.1–10.7) or mothers who smoked at some point during pregnancy (mean MDAS 10.8–11.5). A similar tendency was observed in fathers. However, no systematic change in dental anxiety by changes in smoking habits was observed. Those smoking during pregnancy and with high dental anxiety may need special support for smoking cessation.