Lars Heggelund

Lars Heggelund
  • Doctor of Medicine, PhD
  • Consultant at Vestre Viken Hospital Trust

About

109
Publications
22,583
Reads
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2,959
Citations
Introduction
Various aspects of airway infections, etiology, New etiological diagnostic methods including molecular microbiological analysis. Evaluation of inflammatory responses and biomarkers with predictive value. Studies on both short- and long-term prognosis.
Current institution
Vestre Viken Hospital Trust
Current position
  • Consultant
Additional affiliations
February 2019 - present
Vestre Viken Hospital Trust
Position
  • Consultant
January 2013 - present
Drammen Sykehus
Position
  • Consultant
December 2011 - December 2012
University of Oslo
Position
  • Professor (Associate)

Publications

Publications (109)
Article
Full-text available
There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were...
Article
Full-text available
Importance Lower respiratory tract (LRT) infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. Molecular tests have the potential to optimize treatment decisions and management of CAP, but limited evidence exists to support their routine use. Objective To determine whether the judicious...
Article
Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID‐19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID‐19, we examined circulating levels of mediators involved in va...
Article
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Purpose: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. Materials and methods: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to e...
Article
Background COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HIC). Objectives The main aims were to compare the frequency of coagulopathy complications in developing countries (...
Article
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Background: In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The...
Article
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Objectives: Explore the role of fungal burden in risk stratification of non-HIV patients with Pneumocystis pneumonia (PCP). Methods: Retrospective analysis of characteristics associated with 30-day mortality in patients with positive P. jirovecii PCR in BALF between 2006 and 2017 in a multicenter cohort from Central Norway. Fungal burden was ind...
Article
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Background and aims: To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19). Methods: We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID...
Article
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Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these co...
Article
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Background: The iron-regulatory hormone hepcidin is a promising biomarker to differentiate anemia of inflammation from iron deficiency. Plasma hepcidin concentrations increase substantially during inflammation, and the amount of smaller, non-biologically active isoforms of hepcidin increase in inflammatory conditions. These smaller isoforms are me...
Article
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Abstract Background Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce. Methods Rectal swabs for gut microbiota analyses were collected within 48 h after hospit...
Article
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Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to Ma...
Preprint
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Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from t...
Article
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Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus ) and explores the feasibility of evaluation in a randomised controlled trial. Patients prese...
Article
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Background Community-acquired pneumonia (CAP) is the most frequent infection diagnosis in hospitals. Antimicrobial therapy for CAP is depicted in clinical practice guidelines, but adherence data and effect of antibiotic stewardship measures are lacking. Methods A dedicated antibiotic team pointed out CAP as a potential target for antimicrobial ste...
Article
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Background: Bloodstream infections (BSI) occur frequently and are associated with severe outcomes. In this study we aimed to investigate proportions of patients that received discordant empirical antimicrobial therapy and its association to mortality. Methods: A retrospective cohort study model was undertaken to outline BSI in an intensive care,...
Article
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Background: The COVID-19 pandemic was met with strict containment measures. We hypothesized that societal infection control measures would impact the number of hospital admissions for respiratory tract infections, as well as, the spectrum of pathogens detected in patients with suspected community acquired pneumonia (CAP). Methods: This study is...
Article
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Background Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in...
Article
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Background Community-acquired pneumonia (CAP) causes a large burden of disease. Due to difficulties in obtaining representative respiratory samples and insensitive standard microbiological methods, the microbiological aetiology of CAP is difficult to ascertain. With a few exceptions, standard-of-care diagnostics are too slow to influence initial de...
Article
Full-text available
Background: T-cell activation is associated with an adverse outcome in COVID-19, but whether T-cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown. Objectives: To investigate whether T-cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hosp...
Article
Full-text available
Background Immune dysregulation is a major factor in the development of severe Covid-19. The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in SARS-CoV-2 infection is limited. We thus investigated the levels of these chemokines in Covid-19 patients. Methods Serial blood...
Article
Full-text available
Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respirat...
Article
Full-text available
The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World...
Article
Full-text available
Background Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients. Method...
Article
Full-text available
Objectives : To determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients, and the impact of dexamethasone as standard therapy. Methods : This multicentre, observational, retrospective study included patients ≥ 18 years admitted from March 1st 2020 to January 31st 2021 with COVID-19 infection who r...
Preprint
Full-text available
Background Community acquired pneumonia (CAP) causes a large burden of disease. Due to difficulties in obtaining representative respiratory samples and insensitive standard microbiological methods, the microbiological aetiology of CAP is difficult to ascertain. With a few exceptions, standard of care diagnostics are too slow to influence initial de...
Article
Full-text available
Purpose Studies on aetiology of community-acquired pneumonia (CAP) vary in terms of microbial sampling methods, anatomical locations, and laboratory analyses, since no gold standard exists. In this large, multicentre, retrospective, regional study from Norway, our primary objective was to report the results of a strategic diagnostic stewardship int...
Article
Full-text available
Background: Virtually all living organisms, including microbes and humans, depend on iron to survive and grow. During an infection, the plasma level of iron and several iron-related proteins change substantially. We hypothesized that iron and iron-related proteins could predict short- and long-term outcomes in community-acquired pneumonia. Method...
Article
Full-text available
Purpose Reactive oxygen species (ROS) are an important part of the inflammatory response during infection but can also promote DNA damage. Due to the sustained inflammation in severe Covid-19, we hypothesized that hospitalized Covid-19 patients would be characterized by increased levels of oxidative DNA damage and dysregulation of the DNA repair ma...
Article
Full-text available
The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DL CO ), and chest-CT were performed at 23 Norwegian hospitals included in the...
Preprint
Full-text available
PurposeStudies on aetiology of community-acquired pneumonia (CAP) vary in terms of microbial sampling methods, anatomical locations, and laboratory analyses, since no gold standard exists. In this large, multicentre, retrospective, regional study from Norway, our primary objective was to report the results of a strategic diagnostic stewardship inte...
Article
Full-text available
Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission f...
Article
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Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruit...
Preprint
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BacgroundSuper-infections in COVID-19 patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation were initially reported to be rare. Little is known of their incidence after dexamethasone was introduced as standard care. We aimed to determine the incidence and characteristics of superinfections in mechanically ventilated COV...
Preprint
Full-text available
Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population control...
Article
Full-text available
Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospit...
Article
Full-text available
Background Iron is crucial for survival and growth of microbes. Consequently, limiting iron availability is a human antimicrobial defense mechanism. We explored iron and iron-related proteins as potential biomarkers in community-acquired pneumonia and hypothesized that infection-induced changes in these potential biomarkers differ between groups of...
Article
Full-text available
In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. In this study we analyzed plasma cytokines in COVID-19 patients and investigated their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Hospitalized patients (n = 34...
Article
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Background: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associate...
Article
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Background: The pathogenesis of COVID-19 is still incompletely understood, but seems to involve immune activation and immune dysregulation. Objective: We examined parameters of activation of different leukocyte subsets in COVID-19 infected patients in relation to disease severity. Methods: We analyzed plasma levels of myeloperoxidase (MPO, neu...
Article
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Significance The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there i...
Preprint
Full-text available
Objective To test the hypotheses that serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury b...
Preprint
Full-text available
Background: In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment. Objectives: Analyze plasma cytokines in COVID-19 patients and investigate their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Method: Hospitalized pa...
Article
Full-text available
Background: Biomarkers may facilitate clinical decisions in order to guide antimicrobial treatment and prediction of prognosis in community-acquired pneumonia (CAP). We measured serum C-reactive protein, procalcitonin (PCT) and calprotectin levels, and plasma pentraxin 3 (PTX3) and presepsin levels, along with whole-blood white cell counts, at thre...
Article
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Background Disease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity a...
Article
Full-text available
Background: The inflammatory response in community-acquired pneumonia (CAP) is orchestrated through activation of cytokine networks and the complement system. We examined the association of multiple cytokines and the terminal complement complex (TCC) with microbial etiology, disease severity and short-term outcome. Materials and methods: Plasma...
Article
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Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with ch...
Article
Full-text available
Low vitamin D status has been associated with short-term (30-day) mortality in hospitalized adults with community-acquired pneumonia (CAP). Data on its prevalence in these patients are scarce, and impact on long-term prognosis is unknown. We examined the prevalence of vitamin D deficiency and inadequacy and their effect on long-term mortality in ho...
Data
Minimal data set underlying the findings in the study. Variable instructions are in sheet 2. (XLSX)
Data
Identification of confounders in the association between vitamin D status (25-hydroxyvitamin D 30–49 nmol/L or <30 nmol/L versus ≥50 nmol/L [reference category]) and long-term all-cause mortality after hospitalization for CAP. (DOCX)
Data
Identification of potential confounders: Univariable associations between long-term all-cause mortality after hospitalization for CAP and factors found to have a significant association with vitamin D status. (DOCX)
Data
Causes of death and vitamin D status measured at admission in 72 patients who died during long-term follow-up after hospitalization for CAP. (DOCX)
Data
The inclusion process for the study population. (DOCX)
Data
Summary of microbiological specimen collection and methods. (DOCX)
Article
Full-text available
Background: Contributors to long-term mortality in patients with community-acquired pneumonia (CAP) remain unclear, with little attention paid to pneumonia etiology. We examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for CAP, with emphasis on demographic, clinical,...
Data
The inclusion process for the study population. (DOCX)
Data
Minimal data set underlying the findings in the study. Variable instructions are in sheet 2. (XLSX)
Data
Plot of the Cox-Snell residuals from the model. The curve is very close to the diagonal indicating a good model fit. (EPS)
Data
Microbial findings in 162 hospital survivors with an etiologically established diagnosis of community-acquired pneumonia. (DOCX)
Article
Background and aims: On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier. Methods: In 2004-2006 we conducted...
Article
Full-text available
Despite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields. 267 CAP patients were enrolled consecutively o...
Article
Full-text available
We present a case of Corynebacterium pseudotuberculosis pneumonia in a veterinary student, with molecular genetic evidence of acquisition during laboratory work, an observation relevant for laboratory personnel working with C pseudotuberculosis isolates. The patient was clinically cured with 14 months trimethoprim/sulfamethoxazole and rifampicin co...
Article
Full-text available
To determine the prevalence and predictors of positive interferon-gamma release assays (IGRAs) and tuberculin skin tests (TSTs) in human immunodeficiency virus (HIV) infected patients in Norway, a low tuberculosis (TB) endemic country. Multicentre cross-sectional study of 298 HIV patients tested with QuantiFERON®-TB Gold In-Tube (QFT-GIT), T-SPOT®....
Article
Full-text available
Article
CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19...
Article
While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CX...
Article
The CCR7 ligands, CCL19 and CCL21, coordinate lymph node homing of naive and central memory T cells. In untreated HIV-infected patients, serum levels of CCL19 and CCL21 showed a biphasic pattern during progression; a marked increase was followed by a decline in patients with advanced immunodeficiency. During highly active antiretroviral therapy, a...
Conference Paper
Background: CCL19 and CCL21 not only orchestrate lymphocyte and dendritic cell migration, but seem also to regulate their immunogenic potential. HIV infection is characterized by a persistent and inappropriate immune activation. Based on the inflammatory properties of CCL19 and CCL21, we hypothesized a pathogenic role of these chemokines in HIV inf...
Article
Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by diffe...
Article
Staphylococcus aureus, including methicillin-resistant strains (MRSA), may cause a wide range of infections involving skin and soft tissue, as well as bone, airways, and endovascular grafts.
Article
Increasing data support the involvement of chemokines in atherogenesis. However, although several studies have shown increased chemokine levels in adult patients, the literature is virtually devoid of data on chemokines in children with hypercholesterolemia. We examined the gene expression of chemokines in peripheral blood mononuclear cells (PBMCs)...
Article
Mannose-binding lectin (MBL) is a soluble receptor of the innate immune system, probably contributing to antimicrobial defence. The possible role of MBL in HIV infection is unclear. Peripheral blood mononuclear cells (PBMCs) from 28 HIV-infected patients and 13 healthy controls were stimulated with MBL and costimulated with HIV-1 gp120 or mannan fr...
Article
The importance of the innate immune system, including mannose-binding lectin and the complement system, in common variable immunodeficiency is unclear. The objective of this study was to evaluate mannose-binding lectin and the complement system in relation to clinical and immunological parameters in patients with common variable immunodeficiency. C...

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