Publications
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Kildal, Anders Benjamin; Ueland, Thor; Mirlashari, Mohammad Reza; Nissen-Meyer, Lise Sofie; Granerud, Beathe Kiland & Riise, Anne Margarita Dyrhol
[Show all 44 contributors for this article]
(2026).
Serial blood serum measurements of calprotectin and deoxyribonuclease in COVID-19 patients during hospitalization and recovery until one year: a prospective, multicenter, observational study.
BMC Infectious Diseases.
26.
doi:
10.1186/s12879-026-12939-x.
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Objectives: To examine circulating calprotectin and deoxyribonuclease (DNase) serum levels during hospitalization in COVID-19 patients, their continuity post-discharge and dynamics in relation to disease severity.
Methods: Serum levels were measured in samples collected from 252 COVID-19 patients during hospitalization (admission, days 3–5 and 7–10), at 3 months and after 1 year, and related to admission to intensive care unit (ICU) or high dependency unit (HDU), and 60-day total mortality.
Results: During hospitalization, calprotectin and DNase levels were significantly elevated compared to healthy controls (HC). Calprotectin was increased in ICU/HDU patients compared to those at wards during hospitalization and in non-survivors compared to survivors during prolonged hospitalization. High calprotectin levels at admission were associated with male sex, PaO2/FiO2 ratio and national COVID-19 wave 2 and 3 compared to wave 1. High admission levels of both calprotectin and ferritin were associated with an approximately twofold higher odds ratio for ICU/HDU admission than either marker alone. DNase was lower at admission in non-survivors compared to survivors. Post-discharge, DNase but not calprotectin levels remained elevated extending to 1-year follow-up compared to HC.
Conclusions: COVID‑19 non‑survivors showed persistently higher calprotectin levels during prolonged hospitalization, and elevated admission calprotectin was associated with later pandemic waves and poorer oxygenation. Incorporating calprotectin with ferritin improved prediction of ICU/HDU admission. DNase levels were lower at admission in non‑survivors, while overall DNase remained elevated from hospitalization through 1‑year follow‑up compared with HC, suggesting a possible role in long‑term COVID‑19–related immune alterations.
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Tøndel, Camilla; Jenum, Synne; Tonby, Kristian; Christensen, Erik Egeland; Cox, Rebecca Jane & Onyango, Therese Bredholt
[Show all 24 contributors for this article]
(2026).
SARS-CoV-2 T-cell vaccine VB10.2210 induces broad T-cell responses in a phase 1/2 open-label clinical trial.
Vaccine.
ISSN 0264-410X.
75.
doi:
10.1016/j.vaccine.2026.128290.
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The repeated emergence of highly transmissive SARS-CoV-2 variants requires a broadly protective vaccine. We developed a T-cell vaccine VB10.2210 that targets SARS-CoV-2 viral antigens to antigen presenting cells comprising 96 validated immunogenic T-cell epitopes covering a global HLA diversity. We report results from a first in human open-label dose-escalation phase 1/2 clinical trial evaluating safety, reactogenicity and immunogenicity of VB10.2210. The study investigated three dose levels (0.3, 1.0 and 3.0 mg), delivered intramuscularly as DNA plasmid by jet injection (NCT05069623), in 34 healthy adults previously vaccinated with mRNA SARS-CoV-2 vaccines. The safety profile was favorable with no observed dose-limiting toxicity. The 3 mg dose elicited the most potent immune response with enhanced breadth and a CD8+ dominated T cell response. T cell responses towards spike protein and de novo responses to non-spike antigens were confirmed by ELISpot. Expansion of VB10.2210 specific T-cell clones was confirmed by TCR sequencing. Further studies are needed to evaluate the clinical benefit of DNA vaccines inducing broad virus specific T-cell immunity in preventing severe COVID-19 or as treatment of patients with persistent infection.
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Granerud, Beathe Kiland; Kaarbø, Mari; Al-Baldawi, Huda; Heggelund, Lars; Tveita, Anders & Müller, Karl Erik
[Show all 42 contributors for this article]
(2025).
Droplet Digital PCR or Real-Time PCR as a Method for Quantifying SARS-CoV-2 RNA in Plasma-Is There a Difference?
Viruses.
17(6).
doi:
10.3390/v17060772.
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The aim of this study is to ascertain whether qRT-PCR (reverse transcriptase real-time PCR) or RT-ddPCR (reverse transcriptase digital droplet PCR) is more effective for detecting SARS-CoV-2 RNA (severe acute respiratory syndrome coronavirus 2 RNA) in blood plasma from COVID-19 (coronavirus infectious disease-19) patients. The E-gene of SARS-CoV-2 RNA was quantified using both methods in 128 plasma samples from 70 hospitalized patients, followed by a statistical analysis to compare the sensitivity and concordance between the methods. Out of the 128 samples, 89 yielded consistent results irrespective of the method used, whereas 39 samples showed discrepancies between the two different methods. RT-ddPCR frequently registered higher viral quantities compared to qRT-PCR; however, the results did not demonstrate a clear superiority in sensitivity for RT-ddPCR. Although RT-ddPCR registered higher viral quantities, this study concludes that both methods provide comparable results for detecting SARS-CoV-2 E-gene RNA in plasma.
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Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine
[Show all 73 contributors for this article]
(2024).
High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial.
Journal of Internal Medicine.
ISSN 0954-6820.
296(3),
p. 249–259.
doi:
10.1111/joim.13820.
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Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.
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Christensen, Erik Egeland; Prebensen, Christian Haugland; Martinsen, Anders B.; Trydal, Elisabet; Hoff, Rune & Kvale, Dag
[Show all 7 contributors for this article]
(2023).
Mortality and Sequential Organ Failure Assessment Score in Patients with Suspected Sepsis: The Impact of Acute and Preexisting Organ Failures and Infection Likelihood.
Critical Care Explorations.
5(2),
p. E0865–E0865.
doi:
10.1097/CCE.0000000000000865.
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IMPORTANCE: The Sequential Organ Failure Assessment (SOFA) was chosen in the definition of sepsis due to superior validity in predicting mortality. However, few studies have assessed the contributions of acute versus chronic organ failures to SOFA for mortality prediction. OBJECTIVES: The main objective in this study was to assess the relative importance of chronic and acute organ failures in mortality prediction in patients with suspected sepsis at hospital admission. We also evaluated how the presence of infection influenced the ability of SOFA to predict 30-day mortality. DESIGN, SETTING, AND PARTICIPANTS: Single-center prospective cohort study including 1,313 adult patients with suspected sepsis in rapid response teams in the emergency department. MAIN OUTCOMES AND MEASURES: The main outcome was 30-day mortality. We measured the maximum total SOFA score during admission (SOFATotal), whereas preexisting chronic organ failure SOFA (SOFAChronic) score was assessed by chart review, allowing calculation of the corresponding acute SOFA (SOFAAcute) score. Likelihood of infection was determined post hoc as “No infection” or “Infection.” RESULTS: SOFAAcute and SOFAChronic were both associated with 30-day mortality, adjusted for age and sex (adjusted odds ratios [AORs], 1.3; 95% CI, 1.3–14 and 1.3; 1.2–1.7), respectively. Presence of infection was associated with lower 30-day mortality (AOR, 0.4; 95% CI, 0.2–0.6), even when corrected for SOFA. In “No infection” patients, SOFAAcute was not associated with mortality (AOR, 1.1; 95% CI, 1.0–1.2), and in this subgroup, neither SOFAAcute greater than or equal to 2 (relative risk [RR], 1.1; 95% CI, 0.6–1.8) nor SOFATotal greater than or equal to 2 (RR, 3.6; 95% CI, 0.9–14.1) was associated with higher mortality. CONCLUSIONS AND RELEVANCE: Chronic and acute organ failures were equally associated with 30-day mortality in suspected sepsis. A substantial part of the total SOFA score was due to chronic organ failure, calling for caution when using total SOFA in defining sepsis and as an outcome in intervention studies. SOFA’s mortality prediction ability was highly dependent on actual presence of infection.
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Olsen, Maria Belland; Huse, Camilla; Sousa, Mirta; Murphy, Sarah Louise Mikalsen; Sarno, Antonio & Obermann, Tobias Sebastian
[Show all 20 contributors for this article]
(2022).
DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients.
Journal of Inflammation Research.
15,
p. 6629–6644.
doi:
10.2147/JIR.S379331.
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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 machinery. Patients and Methods: Levels of the oxidative DNA lesion 8-oxoG and levels of base excision repair (BER) proteins were measured in peripheral blood mononuclear cells (PBMC) from patients (8-oxoG, n = 22; BER, n = 17) and healthy controls (n = 10) (Cohort 1). Gene expression related to DNA repair was investigated in two independent cohorts of hospitalized Covid-19 patients (Cohort 1; 15 patents and 5 controls, Cohort 2; 15 patients and 6 controls), and by publicly available datasets. Results: Patients and healthy controls showed comparable amounts of oxidative DNA damage as assessed by 8-oxoG while levels of several BER proteins were increased in Covid-19 patients, indicating enhanced DNA repair in acute Covid-19 disease. Furthermore, gene expression analysis demonstrated regulation of genes involved in BER and double strand break repair (DSBR) in PBMC of Covid-19 patients and expression level of several DSBR genes correlated with the degree of respiratory failure. Finally, by re-analyzing publicly available data, we found that the pathway Hallmark DNA repair was significantly more regulated in circulating immune cells during Covid-19 compared to influenza virus infection, bacterial pneumonia or acute respiratory infection due to seasonal coronavirus. Conclusion: Although beneficial by protecting against DNA damage, long-term activation of the DNA repair machinery could also contribute to persistent inflammation, potentially through mechanisms such as the induction of cellular senescence. However, further studies that also include measurements of additional markers of DNA damage are required to determine the role and precise molecular mechanisms for DNA repair in SARS-CoV-2 infection.
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Christensen, Erik Egeland; Binde, Christina; Leegaard, Marianne; Tonby, Kristian; Dyrhol-Riise, Anne Ma & Kvale, Dag
[Show all 8 contributors for this article]
(2022).
DIAGNOSTIC ACCURACY and ADDED VALUE of INFECTION BIOMARKERS in PATIENTS with POSSIBLE SEPSIS in the EMERGENCY DEPARTMENT.
Shock.
ISSN 1073-2322.
58(4),
p. 251–259.
doi:
10.1097/SHK.0000000000001981.
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Background: Biomarkers for early recognition of infection are warranted. The hypothesis of this study was that calprotectin, C-reactive protein (CRP), IL-6 and procalcitonin (PCT), alone or in combination, provide clinically useful information to the clinicians for early identification of infection in patients with possible sepsis in the emergency department (ED). Biomarker dynamics in the first week of hospitalization were explored. Methods: Adult patients in rapid response teams in the ED were included in a prospective observational study (n = 391). Patients who received antibiotics after biomarker availability were excluded. The ED clinician (EDC) decision whether to start antibiotics was registered. Calprotectin, CRP, IL-6, and PCT were analyzed in blood samples drawn within 15 min after ED arrival and in a subgroup for 1 week. Infection likelihood was evaluated post hoc. Results: In identifying patients with infection, CRP (area under the receiver operating characteristic curve [AUC], 0.913) and IL-6 (AUC, 0.895) were superior to calprotectin (AUC, 0.777) and PCT (AUC, 0.838). The best regression model predicting infections included EDC, CRP, and IL-6. Using optimal cutoff values, CRP and IL-6 in combination reached 95% positive and 90% negative predictive values for infection. The EDC undertreated or overtreated 65 of 391 patients (17%), and CRP and IL-6 optimal cutoff values could correct this in 32 of 65 patients (49%). Longitudinal samples revealed that IL-6 peaked in the ED, whereas CRP and PCT peaked later. Conclusion: C-reactive protein and IL-6 were superior to calprotectin and PCT for recognizing infection in patients with possible sepsis in the ED. Combining these two biomarkers with different dynamics improved recognition of infection and could aid clinical management in rapid response teams in the ED.
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Christensen, Erik; Jørgensen, Marthe Jøntvedt; Nore, Kristin Grotle; Dahl, Tuva Børresdatter; Yang, Kuan & Ranheim, Trine
[Show all 16 contributors for this article]
(2021).
Critical COVID-19 is associated with distinct leukocyte phenotypes and transcriptome patterns.
Journal of Internal Medicine.
ISSN 0954-6820.
p. 1–16.
doi:
10.1111/joim.13310.
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Background Prognostic markers for disease severity and identification of therapeutic targets in COVID-19 are urgently needed. We have studied innate and adaptive immunity on protein and transcriptomic level in COVID-19 patients with different disease severity at admission and longitudinally during hospitalization. Methods Peripheral blood mononuclear cells (PBMCs) were collected at three time points from 31 patients included in the Norwegian SARS-CoV-2 cohort study and analysed by flow cytometry and RNA sequencing. Patients were grouped as either mild/moderate (n = 14), severe (n = 11) or critical (n = 6) disease in accordance with WHO guidelines and compared with patients with SARS-CoV-2-negative bacterial sepsis (n = 5) and healthy controls (n = 10). Results COVID-19 severity was characterized by decreased interleukin 7 receptor alpha chain (CD127) expression in naïve CD4 and CD8 T cells. Activation (CD25 and HLA-DR) and exhaustion (PD-1) markers on T cells were increased compared with controls, but comparable between COVID-19 severity groups. Non-classical monocytes and monocytic HLA-DR expression decreased whereas monocytic PD-L1 and CD142 expression increased with COVID-19 severity. RNA sequencing exhibited increased plasma B-cell activity in critical COVID-19 and yet predominantly reduced transcripts related to immune response pathways compared with milder disease. Conclusion Critical COVID-19 seems to be characterized by an immune profile of activated and exhausted T cells and monocytes. This immune phenotype may influence the capacity to mount an efficient T-cell immune response. Plasma B-cell activity and calprotectin were higher in critical COVID-19 while most transcripts related to immune functions were reduced, in particular affecting B cells. The potential of these cells as therapeutic targets in COVID-19 should be further explored.
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Amundsen, Erik Koldberg; Binde, Christina; Christensen, Erik Egeland; Klingenberg, Olav Inge; Kvale, Dag & Holten, Aleksander Rygh
(2021).
Prognostic Value of Nucleated RBCs for Patients
With Suspected Sepsis in the Emergency Department: A Single-Center Prospective Cohort Study.
Critical Care Explorations.
3(7),
p. 1–9.
doi:
10.1097/CCE.0000000000000490.
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Objectives: Increase of nucleated RBCs in peripheral blood has been shown to be predictive of mortality in ICU patients. The aim of this study was to explore the prognostic value of nucleated RBCs in the first blood sample taken at admission to the emergency department from patients with suspected sepsis. Design: Single-center prospective cohort study. Setting: Emergency department. Patients: One-thousand two-hundred thirty-one consecutive adult patients with suspected sepsis were included in a prospective quality register-based co-hort study. Inclusion criteria were as follows: patients received in rapid response team with blood cultures taken and immediate antibiotics given in the emergency department. Intervention: Not applicable. Measurement and main results: Nucleated RBCs, Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment, Charlson Comorbidity Index, and commonly used laboratory tests measured in the emergency department were compared with 30-day mortality. Nvaucleated RBC counts were divided into five groups, called “Nucleated RBC score,” according to nucleated RBC count levels and analyzed with logistic regression together with the Sequential Organ Failure Assessment score and Charlson Comorbidity Index. Of the 262 patients with nucleated RBCs equal to or higher than the detection limit (0.01 × 109/L), 26% died within 30 days, compared with 12% of the 969 patients with nucleated RBCs below the detection limit (p < 0.0001). Mortality was significantly higher for each increase in Nucleated RBC score, except from score 2 to 3, and was 62% in the highest group. In multivariate logistic regression, odds ratios for 30-day mortality were as follows: Nucleated RBC score: 1.33 (95% CI, 1.13–1.56), Sequential Organ Failure Assessment score: 1.32 (1.29–1.56), and Charlson Comorbidity Index: 1.17 (1.09–1.25). Conclusions: Most patients with suspected sepsis in emergency department had undetectable nucleated RBCs at admission to the emergency department. However, increased nucleated RBCs significantly predicted 30-day mortality. Nucleated RBCs may provide additional prognostic information to Sequential Organ Failure Assessment score and other laboratory tests.
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Jørgensen, Marthe Jøntvedt; Holter, Jan Cato; Christensen, Erik; Schjalm, Camilla; Tonby, Kristian & Pischke, Soeren
[Show all 22 contributors for this article]
(2020).
Increased interleukin-6 and macrophage chemoattractant protein-1 are associated with respiratory failure in COVID-19.
Scientific Reports.
10.
doi:
10.1038/s41598-020-78710-7.
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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) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2–5 and 7–10 days. RF was defined as PaO2/FiO2 ratio (P/F) < 40 kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79–0.80, p < 0.05). During hospitalization the decline was most significant for IP-10 (p < 0.001). Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.
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Døving, Mats; Christensen, Erik; Huse, Lars Peder & Vengen, Øystein
(2020).
A case of septic arthritis of the temporomandibular joint with necrotic peri-articular infection and Lemierre’s syndrome: an unusual presentation.
Oral and Maxillofacial Surgery.
ISSN 1865-1550.
doi:
10.1007/s10006-020-00921-z.
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Abstract Background Septic arthritis of the temporomandibular joint (TMJ) is rare. It usually causes isolated, locoregional symptoms related to the infected intra-articular space but may also cause fever and malaise. Case report We present a case of a 72-year-old male with septic arthritis of the TMJ complicated by extensive peri-articular necrosis, septic shock, cerebral abscess, Lemierre’s syndrome, and a pathological fracture of the mandibular condyle. Conclusion Case reports describing such a severe course of the disease are few. Moreover, this is the first report of septic arthritis of the TMJ to cause Lemierre’s syndrome.
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Christensen, Erik; Taylor, Myra; Zulu, Siphosenkosi Gift; Lillebø, Kristine; Gundersen, Svein Gunnar & Holmen, Sigve
[Show all 10 contributors for this article]
(2018).
Seasonal variations in schistosoma haematobium egg excretion in school-age girls in rural Kwazulu-Natal province, South Africa.
South African Medical Journal.
ISSN 0256-9574.
108(4),
p. 352–355.
doi:
10.7196/SAMJ.2018.v108i4.12775.
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Background. A predominant feature of Schistosoma haematobium infection is urinary egg excretion, and microscopic egg detection remains the accepted standard field diagnostic tool. Praziquantel is the drug of choice for schistosomiasis, and the World Health Organization recommends that it should be administered to all children >4 years of age living in schistosomiasis-endemic areas. The frequency of mass drug administration depends on the prevalence rate in the community. Urinary schistosome egg output has a day-to-day and hour-to-hour intrasubject variation. Therefore, it is important to assess possible seasonal variations in egg excretion to improve the planning of drug treatment. Objectives. To assess the influence of seasonality on urinary schistosome egg excretion in South Africa (SA). Methods. We performed a prospective cohort study, exploring seasonal variations of S. haematobium egg excretion in 184 girls aged 10 - 12 years from randomly selected schools in a rural area of KwaZulu-Natal Province, SA. The area has a subtropical climate characterised by a cool dry season and a hot humid season. For children, water contact is higher in the latter season. At baseline, 108 girls were examined in the hot season, and 76 in the cold season. In the next year’s cold season the untreated patients were re-investigated before treatment. Results. There was a decrease in infection in the group initially tested in the hot season compared with the group tested in the cold season at both time points when adjusted for age and water contact (adjusted odds ratio 3.61 (95% confidence interval 1.14 - 11.44); p=0.03). Conclusions. This unique study shows that schistosomiasis prevalence determined by microscopy exhibits seasonal variation, with a higher prevalence in the hot rainy season. Precise community prevalence estimations are key in decisions to treat communities. There was significantly lower egg output in the cold season, and sampling in that season may therefore underestimate the prevalence of urinary schistosomiasis. The study indicates that sampling in SA should be done in the hot season.
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Published
Jan. 28, 2019 1:06 PM
- Last modified
Jan. 29, 2019 10:28 AM
