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Ahmad, I., Edin, A., Granvik, C., Kumm Persson, L., Tevell, S., Månsson, E., . . . Normark, J. (2023). High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19. Frontiers In Public Health, 11, Article ID 1104267.
Open this publication in new window or tab >>High prevalence of persistent symptoms and reduced health-related quality of life 6 months after COVID-19
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2023 (English)In: Frontiers In Public Health, ISSN 2296-2565, Vol. 11, article id 1104267Article in journal (Refereed) Published
Abstract [en]

Background: The long-term sequelae after COVID-19 constitute a challenge to public health and increased knowledge is needed. We investigated the prevalence of self-reported persistent symptoms and reduced health-related quality of life (HRQoL) in relation to functional exercise capacity, 6 months after infection, and explored risk factors for COVID-19 sequalae. Methods: This was a prospective, multicenter, cohort study including 434 patients. At 6 months, physical exercise capacity was assessed by a 1-minute sit-to-stand test (1MSTST) and persistent symptoms were reported and HRQoL was evaluated through the EuroQol 5-level 5-dimension (EQ-5D-5L) questionnaire. Patients with both persistent symptoms and reduced HRQoL were classified into a new definition of post-acute COVID syndrome, PACS+. Risk factors for developing persistent symptoms, reduced HRQoL and PACS+ were identified by multivariable Poisson regression. Results: Persistent symptoms were experienced by 79% of hospitalized, and 59% of non-hospitalized patients at 6 months. Hospitalized patients had a higher prevalence of self-assessed reduced overall health (28 vs. 12%) and PACS+ (31 vs. 11%). PACS+ was associated with reduced exercise capacity but not with abnormal pulse/desaturation during 1MSTST. Hospitalization was the most important independent risk factor for developing persistent symptoms, reduced overall health and PACS+. Conclusion: Persistent symptoms and reduced HRQoL are common among COVID-19 survivors, but abnormal pulse and peripheral saturation during exercise could not distinguish patients with PACS+. Patients with severe infection requiring hospitalization were more likely to develop PACS+, hence these patients should be prioritized for clinical follow-up after COVID-19.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
COVID-19, EQ-5D, long-COVID, PACS, Post COVID-19 condition (PCC), post-acute COVID syndrome (PACS), SARS-CoV-2
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-205360 (URN)10.3389/fpubh.2023.1104267 (DOI)000937266000001 ()36817925 (PubMedID)2-s2.0-85148359690 (Scopus ID)
Funder
Nyckelfonden, OLL-938628Nyckelfonden, OLL-961416Region Västmanland, 20201009Swedish Research Council, 2020-06235Swedish Heart Lung Foundation, 20200325Swedish Heart Lung Foundation, 20210078Knut and Alice Wallenberg Foundation, VC-2020-0015Umeå UniversityRegion Västerbotten, RV-938855Region Värmland, LIVFOU-939646
Available from: 2023-03-29 Created: 2023-03-29 Last updated: 2023-10-30
Björsell, T., Sundh, J., Lange, A., Ahlm, C., Forsell, M. N. E., Tevell, S., . . . Cajander, S. (2023). Risk factors for impaired respiratory function post COVID-19: a prospective cohort study of nonhospitalized and hospitalized patients. Journal of Internal Medicine, 293(5), 600-614
Open this publication in new window or tab >>Risk factors for impaired respiratory function post COVID-19: a prospective cohort study of nonhospitalized and hospitalized patients
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2023 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 293, no 5, p. 600-614Article in journal (Refereed) Published
Abstract [en]

Background: Severe COVID-19 increases the risk for long-term respiratory impairment, but data after mild COVID-19 are scarce. Our aims were to determine risk factors for reduced respiratory function 3–6 months after COVID-19 infection and to investigate if reduced respiratory function would relate to impairment of exercise performance and breathlessness. Methods: Patients with COVID-19 were enrolled at the University Hospitals of Umeå and Örebro, and Karlstad Central Hospital, Sweden. Disease severity was defined as mild (nonhospitalized), moderate (hospitalized with or without oxygen treatment), and severe (intensive care). Spirometry, including diffusion capacity (DLCO), was performed 3–6 months after hospital discharge or study enrollment (for nonhospitalized patients). Breathlessness (defined as ≥1 according to the modified Medical Research Council scale) and functional exercise capacity (1-min sit-to-stand test; 1-MSTST) were assessed. Results: Between April 2020 and May 2021, 337 patients were enrolled in the study. Forced vital capacity and DLCO were significantly lower in patients with severe COVID-19. Among hospitalized patients, 20% had reduced DLCO, versus 4% in nonhospitalized. Breathlessness was found in 40.6% of the participants and was associated with impaired DLCO. A pathological desaturation or heart rate response was observed in 17% of participants during the 1-MSTST. However, this response was not associated with reduced DLCO. Conclusion: Reduced DLCO was the major respiratory impairment 3–6 months following COVID-19, with hospitalization as the most important risk factor. The lack of association between impaired DLCO and pathological physiological responses to exertion suggests that these physiological responses are not primarily related to decreased lung function.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
breathlessness, COVID-19, diffusion capacity, post-acute COVID-19 syndrome, spirometry
National Category
Respiratory Medicine and Allergy General Practice
Identifiers
urn:nbn:se:umu:diva-205377 (URN)10.1111/joim.13614 (DOI)000936826900001 ()36815689 (PubMedID)2-s2.0-85148632325 (Scopus ID)
Funder
Nyckelfonden, OLL-938628Nyckelfonden, OLL-961416Swedish Research Council, 2020-06235Swedish Research Council, 2016-06514Swedish Heart Lung Foundation, 20200325Swedish Heart Lung Foundation, 20210078Knut and Alice Wallenberg Foundation, VC-2020-0015Umeå University, RV‐938855Region Västerbotten, RV-938855Region Värmland, LIVFOU-939646
Available from: 2023-03-24 Created: 2023-03-24 Last updated: 2023-07-14Bibliographically approved
Schagatay, F., Diamant, K., Lidén, M., Edin, A., Athlin, S., Hultgren, O., . . . Cajander, S. (2022). Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19. Frontiers in Immunology, 13, Article ID 945603.
Open this publication in new window or tab >>Serum concentration of extracellular cold-inducible RNA-binding protein is associated with respiratory failure in COVID-19
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2022 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 945603Article in journal (Refereed) Published
Abstract [en]

Uncontrolled release of damage-associated molecular patterns (DAMPs) is suggested to be a major trigger for the dysregulated host immune response that leads to severe COVID-19. Cold-inducible RNA-binding protein (CIRP), is a newly identified DAMP that aggravates inflammation and tissue injury, and induces respiratory failure in sepsis. Whether CIRP contributes to the pathogenesis of respiratory failure in COVID-19 has not yet been explored.

Aim: To investigate if the concentration of extracellular CIRP (eCIRP) in serum associates with respiratory failure and lung involvement by chest computed tomography (CT) in COVID-19.

Methods: Herein we report a prospective observational study of patients with COVID-19 included at two University Hospitals in Sweden between April 2020 and May 2021. Serum from hospitalized patients in Örebro (N=97) were used to assess the association between eCIRP and the level of respiratory support and its correlation with pulmonary involvement on chest CT and inflammatory biomarkers. A cohort of hospitalized and non-hospitalized patients from Umeå (N=78) was used as an external validation cohort. The severity of disease was defined according to the highest degree of respiratory support; mild disease (no oxygen), non-severe hypoxemia (conventional oxygen or high-flow nasal oxygen, HFNO <50% FiO2), and severe hypoxemia (HFNO ≥50% FiO2, mechanical ventilation). Unadjusted and adjusted linear regression was used to evaluate peak eCIRP day 0-4 in respect to severity, age, sex, Charlson comorbidity score, symptom duration, and BMI.

Results: Peak eCIRP concentrations were higher in patients with severe hypoxemia and were independently associated with the degree of respiratory support in both cohorts (Örebro; p=0.01, Umeå; p<0.01). The degree of pulmonary involvement measured by CT correlated with eCIRP, rs=0.30, p<0.01 (n=97).

Conclusion: High serum levels of eCIRP are associated with acute respiratory failure in COVID-19. Experimental studies are needed to determine if treatments targeting eCIRP reduces the risk of acute respiratory failure in COVID-19.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
CIRP, COVID-19, DAMPs, eCIRP, inflammation, severity
National Category
Immunology in the medical area
Research subject
Anaesthesiology
Identifiers
urn:nbn:se:umu:diva-198908 (URN)10.3389/fimmu.2022.945603 (DOI)000840651100001 ()35967397 (PubMedID)2-s2.0-85136034592 (Scopus ID)
Funder
Science for Life Laboratory, SciLifeLab, VC-2020-0015Knut and Alice Wallenberg FoundationRegion VästerbottenSwedish Heart Lung FoundationSwedish Research Council, 2020-06235Region Västmanland
Available from: 2022-09-05 Created: 2022-09-05 Last updated: 2024-01-17Bibliographically approved
Normark, J., Vikström, L., Yong-Dae, G., Persson, I.-L., Edin, A., Björsell, T., . . . Forsell, M. N. E. (2021). Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination [Letter to the editor]. New England Journal of Medicine, 385(11), 1049-1051
Open this publication in new window or tab >>Heterologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination
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2021 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 385, no 11, p. 1049-1051Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Massachusetts Medical Society, 2021
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-187330 (URN)10.1056/NEJMc2110716 (DOI)000674415300001 ()34260850 (PubMedID)2-s2.0-85111281855 (Scopus ID)
Available from: 2021-09-08 Created: 2021-09-08 Last updated: 2022-04-27Bibliographically approved
Edin, A., Eilers, H. & Allard, A. (2020). Evaluation of the Biofire Filmarray Pneumonia panel plus for lower respiratory tract infections. Infectious Diseases, 52(7), 479-488
Open this publication in new window or tab >>Evaluation of the Biofire Filmarray Pneumonia panel plus for lower respiratory tract infections
2020 (English)In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 52, no 7, p. 479-488Article in journal (Refereed) Published
Abstract [en]

Background: Standard diagnostic methods for lower respiratory tract infections are currently too slow and insensitive to guide early clinical decisions concerning treatment and isolation. Syndrome-specific, diagnostic panels have potential to provide information about aetiology quickly. Available panels have been of limited use in lower respiratory tract infections due to slow turn-around-time, lack of quantification of important pathogens and lack of detection of resistance genes.

Materials/methods: We evaluated the newly developed Biofire(R) Filmarray(R) Pneumonia Panel plus (Biomerieux). Eighty-eight consecutive lower respiratory tract samples were analyzed by both standard microbiological methods, as requested by the referring clinician, and by the panel. The agreement with standard methods, empirical treatment coverage and possible impact on isolation practices were assessed by comparing the results from standard diagnostic methods with the panel results in relation to clinical data and information of antimicrobial therapy.

Results: Both qualitative and semi-quantitative results from the panel generally displayed good agreement with standard methods and by combining methods, a possible aetiology was detected in 73% of patients. Due to the panel approach, the panel detected viruses more frequently. In 25% of the 60 patients assessed for empirical treatment coverage, a pathogen not covered by current therapy was detected and in 30% of in-house patients the panel results were found to potentially influence clinical decisions related to isolation care.

Conclusions: The new diagnostic panel shows promise in improving aetiological diagnostics of lower respiratory tract infections. Correctly applied it has potential to offer support in clinical decision-making within hours of sampling.

Place, publisher, year, edition, pages
Taylor & Francis, 2020
Keywords
Lower respiratory tract infections, pneumonia, rapid diagnostics, molecular diagnostics, PCR, clinical impact
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-170517 (URN)10.1080/23744235.2020.1755053 (DOI)000528351600001 ()32319831 (PubMedID)2-s2.0-85083857001 (Scopus ID)
Available from: 2020-05-07 Created: 2020-05-07 Last updated: 2023-03-23Bibliographically approved
Müller, D. C., Kauppi, A., Edin, A., Gylfe, Å., Sjöstedt, A. B. & Johansson, A. (2019). Phospholipid Levels in Blood during Community-Acquired Pneumonia. PLOS ONE, 14(5), Article ID e0216379.
Open this publication in new window or tab >>Phospholipid Levels in Blood during Community-Acquired Pneumonia
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2019 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 5, article id e0216379Article in journal (Refereed) Published
Abstract [en]

Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.

Place, publisher, year, edition, pages
Public Library of Science, 2019
Keywords
Community-acquired pneumonia, phospholipids, infection, diagnosis, metabolomics
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-147058 (URN)10.1371/journal.pone.0216379 (DOI)000467148400025 ()31063483 (PubMedID)2-s2.0-85065767332 (Scopus ID)
Note

Originally included in thesis in manuscript form 

Available from: 2018-04-25 Created: 2018-04-25 Last updated: 2023-03-23Bibliographically approved
Edin, A. (2018). Improved diagnosis and prediction of community-acquired pneumonia. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Improved diagnosis and prediction of community-acquired pneumonia
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Förbättrad diagnostik och prediktion vid samhällsförvärvad pneumoni
Abstract [en]

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Although there is wide variation in the microbial etiology, CAP may manifest with similar symptoms, making institution of proper treatment challenging. Therefore, etiological diagnosis is important to ensure that correct treatment and necessary infection control measures are instituted. This provides a challenge for conventional microbial diagnostic methods, typically based on culture and direct antigen tests. Moreover, existing molecular biomarkers have poor prognostic value. Few studies have investigated the global metabolic response during infection and virtually nothing is known about early responses after the start of antimicrobial treatment. The aim of this work was to improve diagnostic and predictive methods for CAP.

In paper I, a qPCR panel targeting 15 pathogens known to cause CAP was developed and evaluated. It combined identification of bacterial pathogens and viruses in the same diagnostic platform. The method proved to be robust and the results consistent with those obtained by standard methods. The panel approach, compared to conventional, selective diagnostics, detected a larger number of pathogens. In Paper II, whole blood samples from 65 patients with bacteremic sepsis were analyzed for metabolite profiles. Forty-nine patients with symptoms of sepsis, but later attributed to other diagnoses, were matched according to age and sex and served as a control group. Six metabolites were identified, all of which predicted growth of bacteria in blood culture. One of the metabolites, myristic acid, alone predicted bacteremic sepsis with a sensitivity of 100% and a specificity of 95%. Paper III and IV were based on a clinical study enrolling 35 patients with suspected CAP in need of hospital care. The aim was to study the metabolic response during the early phase of acute infection. The qPCR panel developed in Paper I was used to obtain the microbial etiological diagnosis. Paper IV focused on the global metabolic response and highlighted the dynamics of changes in major metabolic pathways during early recovery. A specific metabolite pattern for M. pneumoniae etiology was found. Four metabolites accurately predicted all but one patient as either M. pneumoniae etiology or not. Paper III looked at phospholipid levels during the first 48 hours after hospital admission. It was found that all major phospholipid species, especially the lysophosphatidyl-cholines, were pronouncedly decreased during acute infection. Levels started to increase the day after admission, reaching statistical significance at 48 hours. Paper II-IV showed that metabolomics might be used to study a number of different aspects of infection, such as etiology, disease progress and recovery. Knowledge of the metabolic profiles of patients may not only be utilized for biomarker discovery, as proposed in this work, but also for the future development of targeted therapies and supportive treatment.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2018. p. 80
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1960
Keywords
Community-acquired pneumonia, infection, diagnosis, qPCR, metabolites, metabolomics
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-147064 (URN)978-91-7601-873-6 (ISBN)
Public defence
2018-05-25, Bergasalen (Q0), Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2018-05-04 Created: 2018-04-25 Last updated: 2018-06-09Bibliographically approved
Kauppi, A. M., Edin, A., Ziegler, I., Mölling, P., Sjöstedt, A., Gylfe, Å., . . . Johansson, A. (2016). Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room. PLOS ONE, 11(1), Article ID e0147670.
Open this publication in new window or tab >>Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room
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2016 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 1, article id e0147670Article in journal (Refereed) Published
Abstract [en]

A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69-0.99) and a specificity 0.84 (95% CI 0.58-0.94) with an AUC of 0.93 (95% CI 0.89-1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85-1.00) and specificity of 0.95 (95% CI 0.74-0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.

National Category
Pharmaceutical Sciences Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:umu:diva-130006 (URN)10.1371/journal.pone.0147670 (DOI)000368655300138 ()26800189 (PubMedID)2-s2.0-84958230951 (Scopus ID)
Available from: 2017-01-11 Created: 2017-01-11 Last updated: 2023-03-24Bibliographically approved
Edin, A., Granholm, S., Koskiniemi, S., Allard, A., Sjöstedt, A. & Johansson, A. (2015). Development and Laboratory Evaluation of a Real-Time PCR Assay for Detecting Viruses and Bacteria of Relevance for Community-Acquired Pneumonia. Journal of Molecular Diagnostics, 17(3), 315-324
Open this publication in new window or tab >>Development and Laboratory Evaluation of a Real-Time PCR Assay for Detecting Viruses and Bacteria of Relevance for Community-Acquired Pneumonia
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2015 (English)In: Journal of Molecular Diagnostics, ISSN 1525-1578, E-ISSN 1943-7811, Vol. 17, no 3, p. 315-324Article in journal (Refereed) Published
Abstract [en]

Community-acquired pneumonia may present with similar clinical symptoms, regardless of viral or bacterial cause. Diagnostic assays are needed to rapidly discriminate between causes, because this will guide decisions on appropriate treatment. Therefore, a quantitative real-time PCR (qPCR) assay with duplex reactions targeting eight bacteria and six viruses was developed. Technical performance was examined with linear plasmids. Upper and Lower respiratory tract specimens were used to compare the qPCR assay with standard microbiological methods. The limit of detection was 5 to 20 DNA template copies with approximately 1000-fold differences in concentrations of the two competing templates. SDs for positive controls were <5%. The use of the qPCR assay resulted in 113 positive identifications in 94 respiratory specimens compared with 38 by using standard diagnostics. Diagnostic accuracy of the qPCR assay varied between 60% positive agreement with standard tests for Streptococcus pneumoniae and 100% for Mycoplasma pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Negative percentage of agreement was >95% for M. pneumoniae, Streptococcus pyogenes, respiratory syncytial virus, and influenza A virus; whereas it was only 56% for Haemophilus influenzae. Multiple microbial agents were identified in 19 of 44 sputum and 19 of 50 nasopharynx specimens. We conclude that in parallel qPCR detection of the targeted respiratory bacteria and viruses is feasible. The results indicate good technical performance of the assay in clinical specimens.

National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:umu:diva-103727 (URN)10.1016/j.jmoldx.2015.01.005 (DOI)000353843900011 ()25772704 (PubMedID)2-s2.0-84928153514 (Scopus ID)
Available from: 2015-06-09 Created: 2015-05-28 Last updated: 2023-03-23Bibliographically approved
Edin, A., Kauppi, A. M., Müller, D. C., Gylfe, Å., Sjöstedt, A. & Johansson, A. F.Metabolomic Analysis of Sera from Patients with Community-Acquired Pneumonia.
Open this publication in new window or tab >>Metabolomic Analysis of Sera from Patients with Community-Acquired Pneumonia
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(English)Manuscript (preprint) (Other academic)
Keywords
Community-acquired pneumonia, diagnostics, metabolomics, etiology, metabolic response, infection, metabolite pattern
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-147059 (URN)
Available from: 2018-04-25 Created: 2018-04-25 Last updated: 2018-06-09
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0309-1852

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