Publications by authors named "Lars-Magnus Andersson"

44 Publications

Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up.

EBioMedicine 2021 Aug 29;70:103512. Epub 2021 Jul 29.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19.

Methods: Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15).

Findings: One hundred patients with mild (n = 24), moderate (n = 28), and severe (n = 48) COVID-19 were followed for a median (IQR) of 225 (187-262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r = 0·53, p < 0·001) and GFAp (r = 0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n = 40), "brain-fog" (n = 29), and changes in cognition (n = 25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.

Interpretation: The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury.

Funding: The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.
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http://dx.doi.org/10.1016/j.ebiom.2021.103512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320425PMC
August 2021

Risk factors for norovirus infection in healthcare workers during nosocomial outbreaks: a cross-sectional study.

Antimicrob Resist Infect Control 2021 07 22;10(1):107. Epub 2021 Jul 22.

Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.

Background: Norovirus outbreaks cause severe medico-socio-economic problems affecting healthcare workers and patients. The aim of the study was to investigate prevalence of norovirus infection and risk factors for infection in healthcare workers during nosocomial outbreaks.

Methods: A cross-sectional study of norovirus infections in healthcare workers was performed in seven outbreak wards in a large university hospital. Packs (swab for rectal sampling, and questionnaire) were posted to healthcare workers on notification of a ward outbreak. Rectal samples were examined with norovirus-specific real-time PCR. Replies from questionnaires were analysed using logistic regression models with norovirus genogroup (G)II positive findings as dependent variable. The results are expressed as odds ratios (OR) with 95% confidence intervals (CI). Sequencing and phylogenetic analyses (1040 nucleotides) were used to characterize norovirus strains from healthcare workers. Cluster analyses included norovirus GII.4 strains detected in ward patients during the ongoing outbreaks.

Results: Of 308 packs issued to healthcare workers, 129 (42%) were returned. norovirus GII was detected in 26 healthcare workers (20.2%). Work in cohort care (OR 4.8, 95% CI 1.4-16.3), work in wards for patients with dementia (OR 13.2, 95% CI 1.01-170.7), and having diarrhoea, loose stools or other gastrointestinal symptoms the last week (OR 7.7, 95% CI 2.5-27.2) were associated with increased norovirus prevalence in healthcare workers. Sequencing revealed norovirus GII.4 in healthcare workers samples, and strains detected in healthcare workers and ward patients during a given ward outbreak showed ≥ 99% similarity.

Conclusion: Norovirus positive findings in healthcare workers were strongly associated with symptomatic infection, close contact with sick patients, and dementia nursing.
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http://dx.doi.org/10.1186/s13756-021-00979-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299649PMC
July 2021

COMP: A Potential Early Biomarker of RAS After Lung Transplantation.

Transplant Direct 2021 Aug 19;7(8):e730. Epub 2021 Jul 19.

Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Background: Chronic rejection, defined as chronic lung allograft dysfunction (CLAD), is the major factor limiting long-term survival after lung transplantation (LTx). A specific subgroup of CLAD is restrictive allograft syndrome (RAS). CLAD's pathogenesis is largely unknown, but previous findings suggest that it is associated with increased fibrosis in the transplanted lung. Cartilage oligomeric matrix protein (COMP) has been associated with multiple fibrotic conditions. The current study aimed to explore the relation between COMP serum levels and development of CLAD, and RAS in particular, in a retrospective cohort of LTx patients.

Methods: This study included retrospective data from patients who underwent LTx during 2009-2011. Blood samples and spirometry data were obtained at follow-up visits 1, 3, 6, 9, and 12 mo after transplantation. Serum samples were analyzed for COMP. CLAD and RAS were defined according to the 2019 International Society for Heart and Lung Transplantation consensus document.

Results: Data from 38 patients (19 men and women, respectively) were collected. Twenty-three patients (60.5%) developed CLAD, of whom 6 (26.1 %) fulfilled the criteria for RAS. Patients who developed RAS had higher mean COMP levels between 1 and 3 mo after LTx than those who did not develop RAS (10.9 [3.9-17.5] U/L vs 7.4 [3.9-10.8] U/L,  = 0.008). RAS was also associated with shorter survival. We found no association between COMP levels and CLAD of other types than RAS.

Conclusions: Serum level of COMP early after LTx seems to be associated with RAS development and might serve as a biomarker suitable for clinical use in the LTx setting.
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http://dx.doi.org/10.1097/TXD.0000000000001189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291357PMC
August 2021

Comparable endemic coronavirus nucleoprotein-specific antibodies in mild and severe Covid-19 patients.

J Med Virol 2021 09 3;93(9):5614-5617. Epub 2021 May 3.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

The severity of disease of Covid-19 is highly variable, ranging from asymptomatic to critical respiratory disease and death. Potential cross-reactive immune responses between SARS-CoV-2 and endemic coronavirus (eCoV) may hypothetically contribute to this variability. We herein studied if eCoV nucleoprotein (N)-specific antibodies in the sera of patients with mild or severe Covid-19 are associated with Covid-19 severity. There were comparable levels of eCoV N-specific antibodies early and during the first month of infection in Covid-19 patients with mild and severe symptoms, and healthy SARS-CoV-2-negative subjects. These results warrant further studies to investigate the potential role of eCoV-specific antibodies in immunity to SARS-CoV-2 infection.
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http://dx.doi.org/10.1002/jmv.27038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242474PMC
September 2021

Healthcare utilization and costs of psychiatric and somatic comorbidities associated with newly diagnosed adult ADHD.

Acta Psychiatr Scand 2021 07 4;144(1):50-59. Epub 2021 May 4.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Psychiatric and somatic problems in young adulthood have been found to be main drivers of costs in individuals with childhood ADHD. However, knowledge of the patterns of healthcare utilization and costs of comorbidities in middle-aged adults with newly diagnosed ADHD is very limited.

Method: We studied individuals born 1966-1978 (from the Swedish Total Population Register) with newly diagnosed ADHD between the ages of 30-45 years and individuals without ADHD matched on birthdate, birth county, and sex. Healthcare utilization and expenditure for psychiatric and somatic disorders were obtained over four years (two years pre- and post-initial ADHD diagnosis).

Results: Middle-aged adults with newly diagnosed ADHD showed higher levels of healthcare utilization and costs (outpatient, inpatient, medications) for psychiatric and somatic comorbidities relative to adults without ADHD, both before and after the initial diagnosis. Females showed greater average group differences across the study period for medication prescriptions than males. Total incremental annual costs per capita were €2478.76 in adults with ADHD relative to those without, and costs were mainly driven by inpatient care. Psychiatric outpatient visits were statistically significantly higher the year before the ADHD diagnosis compared with two years before and after the diagnosis.

Conclusion: This study demonstrates the substantial burden of psychiatric and somatic comorbidities in middle-aged adults newly diagnosed with ADHD. Psychiatric outpatient visits peaked in the year leading up to the ADHD diagnosis. Findings further suggested that females with ADHD may seek more treatment for comorbidities than males, which may reflect a general female tendency.
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http://dx.doi.org/10.1111/acps.13297DOI Listing
July 2021

Proteomic blood profiling in mild, severe and critical COVID-19 patients.

Sci Rep 2021 03 18;11(1):6357. Epub 2021 Mar 18.

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.

The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.
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http://dx.doi.org/10.1038/s41598-021-85877-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973581PMC
March 2021

Higher plasma drug levels in elderly people living with HIV treated with darunavir.

PLoS One 2021 4;16(2):e0246171. Epub 2021 Feb 4.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: The proportion of elderly people living with HIV-1 (PLHIV) is rising. In older patients, comorbidities and concomitant medications are more frequent, increasing the risk of potential drug-drug interactions (PDDIs). Data on the pharmacokinetics of ART in individuals aged ≥ 65 years of age are scarce. We compared plasma drug levels of ART, PDDIs, and side-effects in PLHIV aged ≥ 65 years of age, with controls ≤ 49 years of age.

Methods: Patients ≥ 65 years of age and controls ≤ 49 years of age, all of whom were on stable treatment with atazanavir (ATV), darunavir (DRV), or efavirenz (EFV) were included cross-sectionally. Plasma drug levels of ART were analyzed, comorbidities, concomitant medication, adherence, and side-effects recorded, and PDDIs analyzed using drug interactions databases.

Results: Between 2013 and 2015, we included 100 individuals ≥ 65 years of age (study group) and 99 controls (≤ 49 years of age). Steady-state DRV concentrations were significantly higher in the study group than in the control group (p = 0.047). In the ATV group there was a trend towards a significant difference (p = 0.056). No significant differences were found in the EFV arm. The DRV arm had a higher frequency of reported side-effects than the ATV and EFV arms in the study group (36.7% vs. 0% and 23.8% respectively (p = 0.014), with significant differences between DRV vs. ATV, and EFV vs. ATV).

Conclusions: Higher steady-state plasma levels of DRV and ATV (but not EFV) were found in PLHIV aged ≥ 65 years of age, compared to controls ≤ 49 years of age.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246171PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861408PMC
July 2021

Early detection of sepsis using artificial intelligence: a scoping review protocol.

Syst Rev 2021 01 16;10(1):28. Epub 2021 Jan 16.

Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, 412 96, Sweden.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. To decrease the high case fatality rates and morbidity for sepsis and septic shock, there is a need to increase the accuracy of early detection of suspected sepsis in prehospital and emergency department settings. This may be achieved by developing risk prediction decision support systems based on artificial intelligence.

Methods: The overall aim of this scoping review is to summarize the literature on existing methods for early detection of sepsis using artificial intelligence. The review will be performed using the framework formulated by Arksey and O'Malley and further developed by Levac and colleagues. To identify primary studies and reviews that are suitable to answer our research questions, a comprehensive literature collection will be compiled by searching several sources. Constrictions regarding time and language will have to be implemented. Therefore, only studies published between 1 January 1990 and 31 December 2020 will be taken into consideration, and foreign language publications will not be considered, i.e., only papers with full text in English will be included. Databases/web search engines that will be used are PubMed, Web of Science Platform, Scopus, IEEE Xplore, Google Scholar, Cochrane Library, and ACM Digital Library. Furthermore, clinical studies that have completed patient recruitment and reported results found in the database ClinicalTrials.gov will be considered. The term artificial intelligence is viewed broadly, and a wide range of machine learning and mathematical models suitable as base for decision support will be evaluated. Two members of the team will test the framework on a sample of included studies to ensure that the coding framework is suitable and can be consistently applied. Analysis of collected data will provide a descriptive summary and thematic analysis. The reported results will convey knowledge about the state of current research and innovation for using artificial intelligence to detect sepsis in early phases of the medical care chain.

Ethics And Dissemination: The methodology used here is based on the use of publicly available information and does not need ethical approval. It aims at aiding further research towards digital solutions for disease detection and health innovation. Results will be extracted into a review report for submission to a peer-reviewed scientific journal. Results will be shared with relevant local and national authorities and disseminated in additional appropriate formats such as conferences, lectures, and press releases.
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http://dx.doi.org/10.1186/s13643-020-01561-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811741PMC
January 2021

Serum neopterin levels in relation to mild and severe COVID-19.

BMC Infect Dis 2020 Dec 10;20(1):942. Epub 2020 Dec 10.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19.

Methods: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion.

Results: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases.

Conclusions: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.
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http://dx.doi.org/10.1186/s12879-020-05671-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726600PMC
December 2020

Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.

PLoS One 2020 21;15(10):e0241104. Epub 2020 Oct 21.

Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.

Methods: SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.

Results: Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.

Conclusions: Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241104PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577439PMC
November 2020

Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019.

J Infect Dis 2021 01;223(1):15-18

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
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http://dx.doi.org/10.1093/infdis/jiaa632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665561PMC
January 2021

CSF Biomarkers in Patients With COVID-19 and Neurologic Symptoms: A Case Series.

Neurology 2021 01 1;96(2):e294-e300. Epub 2020 Oct 1.

From the Department of Infectious Diseases (A.E., N.K., L.H., L.-M.A., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg; Region Västra Götaland (A.E., N.K., L.H., L.-M.A., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden; Institutes of Medical Biochemistry (J.G.) and Biological Chemistry (D.F.), Medical University of Innsbruck, Biocenter, Austria; Department of Neurology (R.W.P.), University of California San Francisco; Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology; and UK Dementia Research Institute at UCL (H.Z.), London.

Objective: To explore whether hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neurologic symptoms have evidence of CNS infection, inflammation, and injury using CSF biomarker measurements.

Methods: We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β-microglobulin, and immunoglobulin G index), blood-brain barrier integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe coronavirus disease 2019 (COVID-19) and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4 of 6), suspected meningitis (1 of 6), and dysgeusia (1 of 6). SARS-CoV-2 infection was confirmed by real-time PCR analysis of nasopharyngeal swabs.

Results: SARS-CoV-2 RNA was detected in the plasma of 2 patients (cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in 1 but not in a second real-time PCR assay. CSF neopterin (median 43.0 nmol/L) and β-microglobulin (median 3.1 mg/L) were increased in all. Median immunoglobulin G index (0.39), albumin ratio (5.35), and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.

Conclusion: Our results in patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
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http://dx.doi.org/10.1212/WNL.0000000000010977DOI Listing
January 2021

Does extraction of cardiac implantable electronic devices improve outcome in patients with bacteraemia?

Infect Dis (Lond) 2020 Nov - Dec;52(12):877-882. Epub 2020 Jul 31.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: bacteraemia (SAB) is recognized as an infection that is difficult to treat and with high risk of device related infection. Extraction/explantation of cardiac implantable electronic devices (CIED) is recommended in SAB patients but studies evaluating long-term prognosis are scarce.

Materials And Methods: In this retrospective cohort study, 626 consecutive SAB patients were identified in routine diagnostics (November 2014-October 2016). Patient characteristic, infective endocarditis (IE) incidence and mortality were compared for patients with and without CIED.

Results: SAB patients with CIED ( = 33) compared to non-CIED patients ( = 593) were older (83 versus 70 years,  = .0001), had a higher 30-day mortality (12/33, 36% versus 119/593, 20%,  = .044) and higher incidence of IE (9/33, 27% versus 41/593, 7%,  = .0006). One-year mortality was 19/33 (58%) among the SAB CIED patients. Echocardiography was performed in all nine patients with CIED-IE but only in 14/24 (58%) of the 24 SAB CIED patients that were considered not having IE. However, if patients with very early mortality were excluded, echocardiography was performed in 14/17 (82%) of SAB CIED-non-IE patients. CIED extraction/explantation during intravenous antibiotic treatment was only performed in three patients with SAB CIED-IE and in one non-IE patient. One year post treatment initiation, 14 out of 33 SAB CIED patients were alive of whom only one had CIED extraction/explantation performed as part of treatment.

Conclusion: bacteraemia in CIED patients is associated with poor prognosis but in a subgroup of patients survival beyond one year was seen despite retainment of the electronic device.
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http://dx.doi.org/10.1080/23744235.2020.1799070DOI Listing
May 2021

Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19.

Neurology 2020 09 16;95(12):e1754-e1759. Epub 2020 Jun 16.

From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.

Objective: To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.

Methods: We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.

Results: The patients with severe COVID-19 had higher plasma concentrations of GFAp ( = 0.001) and NfL ( < 0.001) than controls, while GFAp was also increased in patients with moderate disease ( = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up ( < 0.01), while NfL showed a sustained increase from first to last follow-up ( < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.

Conclusion: We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19-related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.
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http://dx.doi.org/10.1212/WNL.0000000000010111DOI Listing
September 2020

Extensive Hospital In-Ward Clustering Revealed By Molecular Characterization of Influenza A Virus Infection.

Clin Infect Dis 2020 12;71(9):e377-e383

Department of Clinical Microbiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Nosocomial transmission of influenza A virus (InfA) infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with InfA infections during an entire season and to investigate in-ward transmission at a large, acute-care hospital.

Methods: During the 2016-17 season, all hospitalized patients ≥18 years old with laboratory-verified (real-time polymerase chain reaction) InfA were identified. Cases were characterized according to age; sex; comorbidity; antiviral therapy; viral load, expressed as cycle threshold values; length of hospital stay; 30-day mortality; and whether the InfA infection met criteria for a health care-associated influenza A infection (HCAI). Respiratory samples positive for InfA that were collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and a phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included.

Results: We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs 4.6% among non-HCAI patients), although the difference was not statistically significant in a multivariable analysis, where age was the only independent risk factor for death (P < .05). We identified 8 closely related clusters (involving ≥3 cases) and another 10 pairs of strains, supporting in-ward transmission.

Conclusions: We found that the in-ward transmission of InfA occurs frequently and that HCAI may have severe outcomes. WGS may be used for outbreak investigations, as well as for evaluations of the effects of preventive measures.
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http://dx.doi.org/10.1093/cid/ciaa108DOI Listing
December 2020

Pollen exposure weakens innate defense against respiratory viruses.

Allergy 2020 03 7;75(3):576-587. Epub 2019 Nov 7.

Chair and Institute of Environmental Medicine, UNIKA-T, Technical University of Munich and Helmholtz Zentrum München, Augsburg, Germany.

Background: Hundreds of plant species release their pollen into the air every year during early spring. During that period, pollen allergic as well as non-allergic patients frequently present to doctors with severe respiratory tract infections. Our objective was therefore to assess whether pollen may interfere with antiviral immunity.

Methods: We combined data from real-life human exposure cohorts, a mouse model and human cell culture to test our hypothesis.

Results: Pollen significantly diminished interferon-λ and pro-inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with respiratory syncytial virus, co-exposure to pollen caused attenuated antiviral gene expression and increased pulmonary viral titers. In non-allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to downregulation of type I and -III interferons in nasal mucosa. In a large patient cohort, numbers of rhinoviruspositive cases were correlated with airborne birch pollen concentrations.

Conclusion: The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high-risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.
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http://dx.doi.org/10.1111/all.14047DOI Listing
March 2020

Burden of rotavirus infection in hospitalized elderly individuals prior to the introduction of rotavirus vaccination in Sweden.

J Clin Virol 2019 10 18;119:1-5. Epub 2019 Jul 18.

Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Diagnosvägen 21, 41650 Gothenburg, Sweden.

Background: Rotavirus gastroenteritis (GE) in the elderly has been much less studied than in children.

Objectives: The aim of this study was to determine the morbidity and mortality for elderly hospitalized patients with rotavirus GE prior to the introduction of rotavirus vaccination in Sweden, and to investigate the epidemiology of rotavirus genotypes in these patients.

Study Design: All patients 60 years or older who were hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, and were rotavirus positive in a clinical diagnostic test from 2009 to 2016, were included. Medical records were reviewed and rotavirus genotyping real-time PCR was performed.

Results: One hundred and fifty-nine patients were included, corresponding to an annual incidence of hospitalization due to rotavirus GE of 16/100 000 inhabitants aged 60 years or older. G2P[4] was the most common genotype, followed by G1P[8] and G4P[8]. The majority of patients had community-onset of symptoms and no or few pre-existing health disorders. Four patients (2.5%) died within 30 days of sampling. Patients with hospital-onset rotavirus GE had a longer median length of stay following diagnosis compared with patients with community-onset of symptoms (19 vs. 5 days, p = 0.001) and higher 30-day mortality (8.6% (3/35) vs. < 1% (1/124), p = 0.03).

Conclusions: Hospitalization due to rotavirus GE among the elderly seems to mainly affect otherwise healthy individuals and is associated with low 30-day mortality.
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http://dx.doi.org/10.1016/j.jcv.2019.07.005DOI Listing
October 2019

Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections.

Euro Surveill 2019 Apr;24(17)

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from breakthrough infections was identified. Our results indicate that a high risk of onward transmission is limited to naïve infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.
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http://dx.doi.org/10.2807/1560-7917.ES.2019.24.17.1900114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628760PMC
April 2019

CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection.

Neurol Neuroimmunol Neuroinflamm 2019 01 7;6(1):e512. Epub 2018 Nov 7.

Department of Infectious Diseases (M.G., A.Y., L.-M.A., L.H.), Institute of Biomedicine, the Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Molecular Neuroscience (A.H., E.V., H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (A.H., E.V., H.Z.), London, United Kingdom; Department of Neurology and Center for Neuroepidemiology and Clinical Neurological Research (S.S.), Yale University, New Haven, CT; Division of Biological Chemistry (D.F.), Biocenter, Medical University of Innsbruck, Austria; Department of Neurology (R.W.P.), University of California San Francisco; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.

Objective: To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection.

Methods: In this retrospective cross-sectional study, we measured concentrations of the macrophage/microglial activation marker sTREM2 in CSF samples from 121 HIV-1-infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury.

Results: CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1-infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4 T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls.

Conclusions: Elevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4 T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection.
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http://dx.doi.org/10.1212/NXI.0000000000000512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278890PMC
January 2019

PCR Detection of Respiratory Pathogens in Asymptomatic and Symptomatic Adults.

J Clin Microbiol 2019 01 2;57(1). Epub 2019 Jan 2.

Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.

The frequency of viral respiratory pathogens in asymptomatic subjects is poorly defined. The aim of this study was to explore the prevalence of respiratory pathogens in the upper airways of asymptomatic adults, compared with a reference population of symptomatic patients sampled in the same centers during the same period. Nasopharyngeal (NP) swab samples were prospectively collected from adults with and without ongoing symptoms of respiratory tract infection (RTI) during 12 consecutive months, in primary care centers and hospital emergency departments, and analyzed for respiratory pathogens by a PCR panel detecting 16 viruses and four bacteria. Altogether, 444 asymptomatic and 75 symptomatic subjects completed sampling and follow-up (FU) at day 7. In the asymptomatic subjects, the detection rate of viruses was low (4.3%), and the most common virus detected was rhinovirus (3.2%). was found in 5.6% of the asymptomatic subjects and in 1.4%. The only factor independently associated with low viral detection rate in asymptomatic subjects was age ≥65 years ( = 0.04). An increased detection rate of bacteria was seen in asymptomatic subjects who were currently smoking ( < 0.01) and who had any chronic condition ( < 0.01). We conclude that detection of respiratory viruses in asymptomatic adults is uncommon, suggesting that a positive PCR result from a symptomatic patient likely is relevant for ongoing respiratory symptoms. Age influences the likelihood of virus detection among asymptomatic adults, and smoking and comorbidities may increase the prevalence of bacterial pathogens in the upper airways.
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http://dx.doi.org/10.1128/JCM.00716-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322459PMC
January 2019

Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation.

Transplant Direct 2018 Aug 11;4(8):e370. Epub 2018 Jul 11.

Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, University of Gothenburg, Sweden.

Background: Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development.

Method: Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded.

Results: Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development ( = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment.

Conclusions: This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.
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http://dx.doi.org/10.1097/TXD.0000000000000808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092179PMC
August 2018

Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation.

Open Forum Infect Dis 2018 Apr 6;5(4):ofy050. Epub 2018 Mar 6.

Department of Infectious Diseases/Clinical Virology, Institute of Biomedicine, Gothenburg, Sweden.

Background: Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients.

Methods: This prospective single-center study included 98 patients followed for 2 years after transplantation. Bacterial infections, fungal infections, viral respiratory infections (VRTI), cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV levels, were monitored.

Results: The levels of torque teno virus DNA increased rapidly after transplantation, likely due to immunosuppressive treatment. A modest increase in levels of Epstein-Barr virus DNA was also observed after transplantation. There were no associations between either TTV or EBV and infectious events or acute rejection, respectively, during follow-up. When Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were significantly elevated 6-24 months after transplantation as compared with Cyclosporine treatment.

Conclusions: Although replication of TTV, but not EBV, appears to reflect the functionality of the immune system, depending on the type of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has limited potential for defining the net state of immune suppression.
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http://dx.doi.org/10.1093/ofid/ofy050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888719PMC
April 2018

Incidence, Etiology, and Outcomes of Community-Acquired Pneumonia: A Population-Based Study.

Open Forum Infect Dis 2018 Feb 8;5(2):ofy010. Epub 2018 Feb 8.

Faculty of Medicine, University of Iceland, Reykjavik.

Background: The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies.

Methods: Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality.

Results: The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. was the most common pathogen (61 of 310, 20%; incidence: 4.1/10000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10000), were identified in 12% (36 of 310; incidence: 2.4/10000), and multiple pathogens were identified in 10% (30 of 310; incidence: 2.0/10000). Recent antimicrobial therapy was associated with increased detection of ( < .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of ( = .02). Symptoms and outcomes were similar irrespective of microbial etiology.

Conclusions: Pneumococci, , and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified.
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http://dx.doi.org/10.1093/ofid/ofy010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804852PMC
February 2018

Tidig infektionskonsult gav effekt vid Staphylococcus aureus-bakteriemi - Konsultationen minskade återinläggningsfrekvens och mortalitet, visar retrospektiv studie.

Lakartidningen 2018 01 16;115. Epub 2018 Jan 16.

Ostra sjukhuset - Infektion Göteborg, Sweden Ostra sjukhuset - Infektion Göteborg, Sweden.

Automatic infectious disease consultant alert is associated with decreased mortality and readmission rate in Staphylococcus aureus bacteriemia A management plan was implemented at a 2000 bed teaching hospital where positive blood cultures with growth of Staphylococcus aureus were reported simultaneously to the ordering unit and to the Infectious Disease Consultant. Readmission rate and 30-day mortality were compared one year before and one year after introduction of the management plan. Out of totally 320 respectively 321 patients with SAB 252 and 244 were included in the study. 30-day mortality decreased from 26/252 (10%) to 14/244 (5,7%) (p=0.059) when all patients with SAB were included and to 9/193 (4,7%) (p=0,026) when only patients who received a formal consultation after introduction of the management plan were included. The rate of readmission within 30 days declined from 38/227 (17%) in 2014-2015 to 24/230 (10%) in 2015-2016 (p=0,049).
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January 2018

Slow Clearance of Norovirus following Infection with Emerging Variants of Genotype GII.4 Strains.

J Clin Microbiol 2017 05 8;55(5):1533-1539. Epub 2017 Mar 8.

Department of Infectious diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

The emergence of new norovirus genotype GII.4 strains is associated with widespread norovirus epidemics. Extended periods of viral shedding can contribute to the epidemic potential of norovirus. To describe the duration of viral shedding in infections with novel emerging GII.4 strains versus infections with previously circulating strains, we performed a prospective cohort study of patients hospitalized with norovirus gastroenteritis during separate winter seasons. Rectal swab samples were obtained at the time of inclusion and weekly during follow-ups. The subgenotype strain was determined from capsid sequences. The outcome was defined by the detection of virus for >14 days (slow clearance) or by the detection of negative samples within 14 days (rapid clearance). Two major epidemic GII.4 strains emerged during the study period, GII.4 New Orleans 2009, in 2010, and GII.4 Sydney 2012, in 2012. From these two seasons, sequences were available from 24 cases where the duration of shedding could be determined. The median age of the patients was 83 years and 50% were women. The majority of patients were infected with virus that clustered with the respective season's epidemic strain ( = 19), whereas 5 patients had previously circulating strains (3 were Den Haag 2006b, in 2010, and 2 were New Orleans 2009, in 2012). Among the patients infected with an epidemic strain, the proportion who shed virus for >14 days was significantly higher (16/19 [84%] versus 1/5 [20%], = 0.01). In summary, a slow clearance of norovirus from stool was more common in infections with novel epidemic GII.4 strains. This suggests that the average duration of shedding may be longer during seasons when new GII.4 strains have emerged.
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http://dx.doi.org/10.1128/JCM.00061-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405271PMC
May 2017

A four year seasonal survey of the relationship between outdoor climate and epidemiology of viral respiratory tract infections in a temperate climate.

J Clin Virol 2016 11 7;84:59-63. Epub 2016 Oct 7.

Department of Infectious Diseases/Clinical Virology, University of Gothenburg, Sweden.

Background: The relation between weather conditions, viral transmission and seasonal activity of respiratory viruses is not fully understood.

Objectives: To investigate the impact of outdoor weather in a temperate climate setting on the seasonal epidemiology of viruses causing respiratory tract infections, particularly influenza A (IFA).

Study Design: In total, 20,062 clinical nasopharyngeal swab samples referred for detection of respiratory pathogens using a multiplex PCR panel, between October 2010 and July 2013, were included. Results of PCR detection were compared with local meteorological data for the same period.

Results: Low temperature and vapor pressure (VP) were associated with weekly incidence of IFA, respiratory syncytial virus, metapneumovirus, bocavirus and adenovirus but no association with relative humidity was found. The incidence of human rhinovirus and enterovirus was independent of temperature. During seasonal IFA outbreaks, the weekly drop of average temperature (compared with the week before) was strongly associated with the IFA incidence recorded the following week.

Conclusion: A sudden drop in outdoor temperature might activate the annual influenza epidemic in a temperate climate by facilitating aerosol spread in dry air. These conditions also seem to affect the incidence of other respiratory pathogens but not human rhino- or enterovirus, suggesting that routes of infection other than aerosol may be relevant for these agents.
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http://dx.doi.org/10.1016/j.jcv.2016.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106483PMC
November 2016

Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.

PLoS One 2016 21;11(7):e0158973. Epub 2016 Jul 21.

Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objective: To investigate the role of homocysteine in neuronal injury in HIV infection.

Methods: Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation.

Results: A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016).

Conclusion: A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158973PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956037PMC
July 2017

Flocked nasal swab versus nasopharyngeal aspirate in adult emergency room patients: similar multiplex PCR respiratory pathogen results and patient discomfort.

Infect Dis (Lond) 2016 15;48(3):246-50. Epub 2015 Oct 15.

a Department of Clinical Sciences , Infectious Disease Research Unit, Skåne University Hospital , Malmö , Sweden.

Fifty adult emergency room patients with symptoms of respiratory tract infections or acute onset of extreme fatigue were sampled by both nasopharyngeal aspirate (NPA) and flocked nasal swab (fNS). Respiratory agents were detected by a qualitative influenza PCR and an 18-valent multiplex PCR in 20 of 29 patients with a clinical diagnosis of respiratory tract infection, and in 3 of 21 without such a diagnosis. PCR detected influenza A and B in NPA samples from 11 patients and in fNS samples from 10 patients. Little or no discomfort was perceived by 60% of the patients when sampled by NPA and by 66% when sampled by fNS. We conclude that NPA and fNS were equally sensitive for detection of respiratory agents by multiplex PCR, and the two sampling methods did not differ significantly regarding discomfort perceived by patients (p = 0.171, Wilcoxon signed rank test). Hence less invasive sampling by fNS might be preferable in certain settings and situations.
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http://dx.doi.org/10.3109/23744235.2015.1096956DOI Listing
June 2016

Low serum levels of CCL5 are associated with longer duration of viral shedding in norovirus infection.

J Clin Virol 2015 Aug 19;69:133-7. Epub 2015 Jun 19.

Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Diagnosvägen 21, Gothenburg SE-416 50, Sweden. Electronic address:

Background: The mechanisms that determine the duration of fecal shedding of norovirus in humans have not been described in detail.

Objectives: We investigated serum inflammatory mediator levels in relation to the duration of viral shedding in norovirus infection.

Study Design: A prospective cohort study of patients hospitalized with acute norovirus genogroup II infection. Rectal swab samples were obtained at inclusion and day 7, 14, 21 and 28. Serum levels of 42 inflammatory mediators were determined with a Luminex-based cytokine assay. Sera from 20 healthy blood donors served as controls.

Results: Altogether, 28 patients (54% women, median age 83 years, median duration of symptoms 3 days) were included. Twelve subjects cleared the virus within 14 days and 16 were norovirus-RNA positive for >21 days, constituting the two study groups ("rapid" vs. "slow" clearance). Individuals with norovirus infection had higher levels of IL-18, CXCL9, CXCL10, soluble IL-2 receptor and macrophage migration inhibitory factor (MIF), compared to controls (p<0.05), with the highest median concentrations in the slow clearance group. In contrast, CCL5 levels were lower in the slow compared to the rapid clearance group (median 54 vs. 134 ng/mL, p<0.05), and lower in norovirus-infected patients than in controls.

Conclusion: Low levels of CCL5 were associated with longer duration of viral shedding, suggesting that CCL5 may influence the clearance of norovirus.
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http://dx.doi.org/10.1016/j.jcv.2015.06.088DOI Listing
August 2015
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