| 1. |
- Rosengren, Annika, 1951, et al.
(författare)
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Severe COVID-19 in people 55 and older during the first year of the pandemic in Sweden
- 2022
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796 .- 0955-7873. ; 292:4, s. 641-653
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Tidskriftsartikel (refereegranskat)abstract
- Background Exposure to many contacts is the main risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while risk of serious disease and death is chiefly determined by old age and comorbidities. Relative and population-attributable fractions (PAFs) of multiple medical and social exposures for COVID-19 outcomes have not been evaluated among older adults. Objectives We describe the effect of multiple exposures on the odds of testing positive for the virus and of severe disease (hospital care or death) and PAFs in Swedish citizens aged 55 years and above. Methods We used national registers to follow all citizens aged 55 years and above with respect to (1) testing positive, (2) hospitalization, and (3) death between 31 January 2020 and 1 February 2021. Results Of 3,410,241 persons, 156,017 (4.6%, mean age 68.3 years) tested positive for SARS-CoV-2, while 35,999 (1.1%, mean age 76.7 years) were hospitalized or died (12,384 deaths, 0.4%, mean age 84.0 years). Among the total cohort, the proportion living without home care or long-term care was 98.8% among persons aged 55-64 and 22.1% of those aged 95 and above. After multiple adjustment, home care and long-term care were associated with odds ratios of 7.9 (95% confidence interval [CI] 6.8-9.1) and 22.5 (95% CI 19.6-25.7) for mortality, with PAFs of 21.9% (95% CI 20.9-22.9) and 33.3% (95% CI 32.4-34.3), respectively. Conclusion Among Swedish residents aged 55 years and above, those with home care or long-term care had markedly increased risk for COVID-19 death during the first year of the pandemic, with over 50% of deaths attributable to these factors.
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| 2. |
- Andersson, T, et al.
(författare)
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Syndromic surveillance for local outbreak detection and awareness : evaluating outbreak signals of acute gastroenteritis in telephone triage, web-based queries and over-the-counter pharmacy sales
- 2014
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Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 142:2, s. 303-313
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Tidskriftsartikel (refereegranskat)abstract
- For the purpose of developing a national system for outbreak surveillance, local outbreak signals were compared in three sources of syndromic data - telephone triage of acute gastroenteritis, web queries about symptoms of gastrointestinal illness, and over-the-counter (OTC) pharmacy sales of antidiarrhoeal medication. The data sources were compared against nine known waterborne and foodborne outbreaks in Sweden in 2007-2011. Outbreak signals were identified for the four largest outbreaks in the telephone triage data and the two largest outbreaks in the data on OTC sales of antidiarrhoeal medication. No signals could be identified in the data on web queries. The signal magnitude for the fourth largest outbreak indicated a tenfold larger outbreak than officially reported, supporting the use of telephone triage data for situational awareness. For the two largest outbreaks, telephone triage data on adult diarrhoea provided outbreak signals at an early stage, weeks and months in advance, respectively, potentially serving the purpose of early event detection. In conclusion, telephone triage data provided the most promising source for surveillance of point-source outbreaks.
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| 3. |
- Andreasson, Anna Nixon, et al.
(författare)
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Inflammation and positive affect are associated with subjective health in women of the general population
- 2013
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Ingår i: Journal of Health Psychology. - : SAGE Publications. - 1359-1053 .- 1461-7277. ; 18:3, s. 311-320
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Tidskriftsartikel (refereegranskat)abstract
- Poor subjective health has been associated with higher levels of inflammatory cytokines. We investigated whether such an association would apply to women of the general population. Levels of cytokines, affect and subjective health were assessed in 347 women of the general population aged 45 to 90 years. Higher levels of interleukin-6 were associated with poor subjective health, especially in participants over 65 years of age. Positive affect was a more robust determinant of subjective health than negative affect. The presence of low-grade inflammation and absence of positive affect, rather than presence of negative affect, may be important determinants of subjective health.
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| 4. |
- Zeng, Hong-Li, et al.
(författare)
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Global analysis of more than 50,000 SARS-CoV-2 genomes reveals epistasis between eight viral genes
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:49, s. 31519-31526
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide epistasis analysis is a powerful tool to infer gene interactions, which can guide drug and vaccine development and lead to deeper understanding of microbial pathogenesis. We have considered all complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes deposited in the Global Initiative on Sharing All Influenza Data (GISAID) repository until four different cutoff dates, and used direct coupling analysis together with an assumption of quasi-linkage equilibrium to infer epistatic contributions to fitness from polymorphic loci. We find eight interactions, of which three are between pairs where one locus lies in gene ORF3a, both loci holding nonsynonymous mutations. We also find interactions between two loci in gene nsp13, both holding nonsynonymous mutations, and four interactions involving one locus holding a synonymous mutation. Altogether, we infer interactions between loci in viral genes ORF3a and nsp2, nsp12, and nsp6, between ORF8 and nsp4, and between loci in genes nsp2, nsp13, and nsp14. The paper opens the prospect to use prominent epistatically linked pairs as a starting point to search for combinatorial weaknesses of recombinant viral pathogens.
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| 5. |
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| 6. |
- Karshikoff, Bianka, et al.
(författare)
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Why sickness hurts : A central mechanism for pain induced by peripheral inflammation
- 2016
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 57, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women's pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fifty-one participants (29 women) were injected with 0.6ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response. The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2h after injection, and blood was sampled for cytokine analysis. The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostral anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disorders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders.
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| 7. |
- Lasselin, Julie, et al.
(författare)
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Sick for science : experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression
- 2020
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 3672-3683
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Tidskriftsartikel (refereegranskat)abstract
- Depression is one of the global leading causes of disability, but treatments remain limited and classical antidepressants were found to be ineffective in a substantial proportion of patients. Thus, novel effective therapies for the treatment of depression are urgently needed. Given the emerging role of inflammation in the etiology and pathophysiology of affective disorders, we herein illustrate how experimental endotoxemia, a translational model of systemic inflammation, could be used as a tool to develop and test new therapeutic options against depression. Our concept is based on the striking overlap of inflammatory, neural, and affective characteristics in patients with inflammation-associated depression and in endotoxin-challenged healthy subjects. Experimental administration of endotoxin in healthy volunteers is safe, well-tolerated, and without known long-term health risks. It offers a highly standardized translational approach to characterize potential targets of therapies against inflammation-associated depression, as well as to identify characteristics of patients that would benefit from these interventions, and, therefore, could contribute to improve personalization of treatment and to increase the overall rate of responders.
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| 8. |
- Lundberg, Christina, et al.
(författare)
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Age and sex differences in cause-specific excess mortality and years of life lost associated with COVID-19 infection in the Swedish population
- 2023
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Ingår i: European Journal of Public Health. - : OXFORD UNIV PRESS. - 1101-1262 .- 1464-360X. ; 33:5, s. 916-22
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Tidskriftsartikel (refereegranskat)abstract
- Background Estimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic. Methods In this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017-19 in the whole Swedish population. Results COVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65-110 years and women aged 75-110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020. Conclusions Compared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19.
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| 9. |
- Rysz, S, et al.
(författare)
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COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2417-
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
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| 10. |
- Vaivade, Aina, et al.
(författare)
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Autologous hematopoietic stem cell transplantation significantly alters circulating ceramides in peripheral blood of relapsing-remitting multiple sclerosis patients
- 2023
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Ingår i: Lipids in Health and Disease. - : BioMed Central (BMC). - 1476-511X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The common inflammatory disease multiple sclerosis (MS) is a disease of the central nervous system. For more than 25 years autologous hematopoietic stem cell transplantation (AHSCT) has been used to treat MS. It has been shown to be highly effective in suppressing inflammatory activity in relapsing-remitting MS (RRMS) patients. This treatment is thought to lead to an immune system reset, inducing a new, more tolerant system; however, the precise mechanism behind the treatment effect in MS patients is unknown. In this study, the effect of AHSCT on the metabolome and lipidome in peripheral blood from RRMS patients was investigated.Methods: Peripheral blood samples were collected from 16 patients with RRMS at ten-time points over the five months course of AHSCT and 16 MS patients not treated with AHSCT. Metabolomics and lipidomics analysis were performed using liquid-chromatography high-resolution mass spectrometry. Mixed linear models, differential expression analysis, and cluster analysis were used to identify differentially expressed features and groups of features that could be of interest. Finally, in-house and in-silico libraries were used for feature identification, and enrichment analysis was performed.Results: Differential expression analysis found 657 features in the lipidomics dataset and 34 in the metabolomics dataset to be differentially expressed throughout AHSCT. The administration of cyclophosphamide during mobilization and conditioning was associated with decreased concentrations in glycerophosphoinositol species. Thymoglobuline administration was associated with an increase in ceramide and glycerophosphoethanolamine species. After the conditioning regimen, a decrease in glycerosphingoidlipids concentration was observed, and following hematopoietic stem cell reinfusion glycerophosphocholine concentrations decreased for a short period of time. Ceramide concentrations were strongly associated with leukocyte levels during the procedure. The ceramides Cer(d19:1/14:0) and Cer(d20:1/12:0) were found to be increased (P < .05) in concentration at the three-month follow-up compared to baseline. C16 ceramide, Cer(D18:2/16:0), and CerPE(d16:2(4E,6E)/22:0) were found to be significantly increased in concentration after AHSCT compared to prior to treatment as well as compared to newly diagnosed RRMS patients.Conclusion: AHSCT had a larger impact on the lipids in peripheral blood compared to metabolites. The variation in lipid concentration reflects the transient changes in the peripheral blood milieu during the treatment, rather than the changes in the immune system that are assumed to be the cause of clinical improvement within RRMS patients treated with AHSCT. Ceramide concentrations were affected by AHSCT and associated with leukocyte counts and were altered three months after treatment, suggesting a long-lasting effect.
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