Previous research suggests decreased immune function and increased risk of infections in individuals with insomnia. We examined the effect of insomnia symptoms on risk of bloodstream infections (BSIs) and BSI-related mortality in a population-based prospective study. A total of 53,536 participants in the second Norwegian Nord-Trøndelag Health Study (HUNT2) were linked to prospective data on clinically relevant BSIs until 2011. In Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for a first-time BSI and for BSI-related mortality (BSI registered ≤30 days prior to death) associated with insomnia symptoms. Compared with participants who reported "no symptoms", participants reporting having "difficulty initiating sleep" (DIS) often/almost every night had a HR for a first-time BSI of 1.14 (95% CI 0.96-1.34). Participants reporting "difficulties maintaining sleep" (DMS) often/almost every night had a HR of 1.19 (95% CI 1.01-1.40), whereas those having a feeling of "non-restorative sleep" once a week or more had a HR of 1.23 (95% CI 1.04-1.46). Participants frequently experiencing all three of the above symptoms had a HR of 1.39 (1.04-1.87), whilst those who had both DIS and DMS had a

Objective: Previous research suggest decreased immune function and increased risk of infections in persons with insomnia. We examined the effect of insomnia symptoms on risk of bloodstream infections (BSI) and BSI–related mortality in a population–based prospective study. Methods: A total of 53,536 participants in the Norwegian HUNT2 study (1995–97) were linked to prospective data on clinically relevant BSIs until 2011. In Cox regression, we estimated hazard ratios (HRs) with 95% confidence interval (CI) for a first–time BSI and for BSI related mortality (BSI registered ≤30 days prior to death) associated with insomnia symptoms. Results: Compared with participants who reported ″no symptoms of insomnia ″, participants reporting having ″difficulty initiating sleep ″ often/almost every night had a HR for a first-time BSI of 1.14 (95% CI 0.96–1.34). Participants reporting ″difficulties maintaining sleep ″ often/almost every night had a HR of 1.19 (95% CI 1.01–1.40), whereas those having a ″feeling of non–restorative sleep ″ once a week or more had a HR of 1.23 (95% CI 1.04–1.46). Participants experiencing all three above insomnia symptoms frequently had a HR of 1.39 (1.04–1.87) and being troubled by insomnia to a degree that affected work performance was associated with a HR of 1.41 (95% CI 1.08–1.84). The HRs for BSI related mortality suggest an increased risk with increasing insomnia symptoms, but confidence intervals are wide and inconclusive. Conclusions: We found that frequent insomnia symptoms and insomnia symptoms that affected work performance was associated with a weak positive increased risk of BSI.

ImportanceInsomnia has been associated with altered inflammatory response as well as increased risk of infections and sepsis in observational studies. However, these studies are prone to bias, such as residual confounding. To further understand the potential causal association between insomnia and sepsis risk, a 2-sample Mendelian randomization (MR) approach should be explored.ObjectiveTo evaluate whether genetically predicted insomnia is associated with risk of sepsis.Design, Setting, and ParticipantsTwo-sample MR was performed to estimate the association between genetically predicted insomnia and sepsis risk. Data were obtained from a genome-wide association study identifying 555 independent genetic variants (R2 < 0.01) strongly associated with insomnia (P < 5 × 10−8). Sensitivity analyses were conducted to address bias due to pleiotropy and sample overlap, along with mediation analyses and sex-stratified analyses. The insomnia data set included 2.4 million individuals of European ancestry from the UK Biobank and 23andMe. For sepsis, 462 918 individuals of European ancestry from the UK Biobank were included. Data were extracted between February and December 2022 and analyzed between March 2022 and March 2023.ExposureGenetically predicted insomnia.Main Outcome and MeasureSepsis.ResultsThere were 593 724 individuals with insomnia and 10 154 cases of sepsis. A doubling in the population prevalence of genetically predicted insomnia was associated with an odds ratio of 1.37 (95% CI, 1.19-1.57; P = 7.6 × 10−6) for sepsis. Sensitivity analyses supported this observation. One-third of the association between genetically predicted insomnia and risk of sepsis was mediated through a combination of cardiometabolic risk factors for sepsis (body mass index, type 2 diabetes, smoking, or cardiovascular disease; overall proportion, 35.2%; 95% CI, 5.1-76.9). The association between insomnia and sepsis was more pronounced among women compared with men (women: odds ratio, 1.44; 95% CI, 1.24-1.68; men: OR, 1.10; 95% CI, 0.86-1.40).Conclusions and RelevanceThe concordance between these findings and previous observational studies supports that insomnia is potentially causally associated with the risk of sepsis. Thus, insomnia is a potential preventable risk factor of sepsis that should be further investigated, also in non-European populations.

Objective Previous studies on thyroid function and risk of infection is conflicting and often stem from intensive care cohorts were nonthyroidal illness syndrome (NTIS) may be present. The objective of this study was to identify the risk of bloodstream infections (BSI) and BSI‐related mortality with thyroid‐stimulating hormone (TSH) levels within the reference range in a general population. Design Prospective follow‐up. Participants The HUNT2 (1995‐97) included 34,619 participants with information on TSH levels. Measurements Hazard ratios (HRs) with 95% confidence interval (CI) confirmed BSIs and BSI‐related mortality until 2011. Results During a median follow‐up of 14.5 years, 1179 experienced at least one episode of BSI and 208 died within 30 days after a BSI. TSH levels within the reference range of 0.5–4.5 mU/L were not associated with the risk of first‐time BSI, with an HR of 0.97 (95% CI: 0.90–1.04) per mU/L. Stratified by baseline age < or ≥65 years, TSH was inversely associated with the risk of BSI (HR: 0.88; 95% CI: 0.78–1.00 per mU/L) in the youngest age group only. Persons with any baseline thyroid disease had a 30% risk and the hyperthyroid subgroup a 57%, and hypothyroidism a 20% increased risk of BSI. TSH levels were not clearly associated with BSI mortality, but the HRs were imprecise due to few BSI‐related deaths. Conclusion There was some evidence of a weak inverse association between TSH levels and the risk of BSI in persons below 65 years of age. The increased risk seen in persons with thyroid illness is probably explained by confounding by concurrent ill health.

Objective: Research suggest insomnia can decrease immune function and increase risk of infections. We investigated whether insomnia increase risk of sepsis by using mendelian randomization (MR). Methods: Two sample MR was used to estimate the association between insomnia and risk of sepsis. In total 203 genetic variants associated with insomnia, was obtained from a genome-wide association study (GWAS) evaluating 1.3 million subjects from the UK Biobank and 23andMe. Results: Insomnia was found to be associated with a 7% (95% CI 2–13%, P=0.01) increased odds of genetically-predicted sepsis. Conclusions: Our results show that insomnia is causally associated with increased risk of insomnia.