Publications
-
-
-
Wickstrøm, Kristin; Holten, Aleksander Rygh; Prebensen, Christian Haugland; Luque, Alvaro Kohn; Vitelli, Valeria & Amundsen, Erik Koldberg
(2025).
Sysmex Cell Population Data for Diagnosing Infection in Patients With Suspected Sepsis in the Emergency Department.
International Journal of Laboratory Hematology (IJLH).
ISSN 1751-5521.
48(1),
p. 71–80.
doi:
10.1111/ijlh.70008.
Full text in Research Archive
Show summary
Objectives: Early diagnosis of suspected sepsis is crucial to improve patient survival. Cell population (CP) data, a set of leuco-cyte research parameters from hematology instruments, has a potential as markers for infection. The aim of this study was toinvestigate the diagnostic accuracy for infection of CP variables from Sysmex XN instruments in patients with suspected sepsisin the emergency department (ED).
Methods: Adult patients with suspected sepsis in the ED were included. CP variables, C-reactive protein (CRP), and post hocassessments of infection were recorded. Logistic regression and machine learning methods were used to develop multivariablemodels, which were evaluated by area under the receiver operating curve (AUC) and calibration plots.
Results: The development cohort and the validation cohort consisted of 600 and 656 patients, respectively. Univariate analysesrevealed that complexity in monocytes (MO-X); AUC of 0.78 (0.74, 0.82), reactivity intensity of neutrophils (NEUT-RI); 0.72 (0.67,0.76), and CRP 0.87 (0.84, 0.90) had the highest diagnostic accuracy for infection. A final multivariable model (the optimal model)using Multilayer perceptron (MLP), including MO-X, NEUT-RI, monocyte size (MO-Z), and neutrophil size (NE-FSC), had anAUC of 0.86 (0.85, 0.87) in the development cohort and 0.78 (0.74, 0.82) in the validation cohort with reasonable calibration.Including CRP in this model further improved accuracy and calibration.
Conclusions: Sysmex CP variables may help diagnose infections in the ED. However, the lack of well-described calibration pro-cedures and quality assurance for non-IVD approved CP variables is an impediment to clinical implementation
-
Alirezaylavasani, Amin; Skeie, Linda Gail; Egner, Ingrid Marie; Chopra, Adity; Dahl, Tuva Børresdatter & Prebensen, Christian Haugland
[Show all 16 contributors for this article]
(2024).
Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections.
npj Vaccines.
9(1),
p. 1–15.
doi:
10.1038/s41541-024-00972-3.
Full text in Research Archive
Show summary
The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm3). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.
-
-
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.
Full text in Research Archive
Show summary
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.
-
Prebensen, Christian Haugland; Lefol, Yohan Pierre; Myhre, Peder Langeland; Lüders, Torben; Jonassen, Christine M & Blomfeldt, Anita
[Show all 9 contributors for this article]
(2023).
Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19.
Scientific Reports.
13(1).
doi:
10.1038/s41598-023-37606-y.
Full text in Research Archive
Show summary
Abstract A maladaptive inflammatory response has been implicated in the pathogenesis of severe COVID-19. This study aimed to characterize the temporal dynamics of this response and investigate whether severe disease is associated with distinct gene expression patterns. We performed microarray analysis of serial whole blood RNA samples from 17 patients with severe COVID-19, 15 patients with moderate disease and 11 healthy controls. All study subjects were unvaccinated. We assessed whole blood gene expression patterns by differential gene expression analysis, gene set enrichment, two clustering methods and estimated relative leukocyte abundance using CIBERSORT. Neutrophils, platelets, cytokine signaling, and the coagulation system were activated in COVID-19, and this broad immune activation was more pronounced in severe vs. moderate disease. We observed two different trajectories of neutrophil-associated genes, indicating the emergence of a more immature neutrophil phenotype over time. Interferon-associated genes were strongly enriched in early COVID-19 before falling markedly, with modest severity-associated differences in trajectory. In conclusion, COVID-19 necessitating hospitalization is associated with a broad inflammatory response, which is more pronounced in severe disease. Our data suggest a progressively more immature circulating neutrophil phenotype over time. Interferon signaling is enriched in COVID-19 but does not seem to drive severe disease.
-
Lefol, Yohan Pierre; Korfage, Tom; Mjelle, Robin; Prebensen, Christian Haugland; Lüders, Torben & Müller, Bruno
[Show all 13 contributors for this article]
(2023).
TiSA: TimeSeriesAnalysis - A pipeline for the analysis of longitudinal transcriptomics data.
NAR Genomics and Bioinformatics.
5(1).
doi:
10.1093/nargab/lqad020.
Full text in Research Archive
Show summary
Improved transcriptomic sequencing technologies now make it possible to perform longitudinal experiments, thus generating a large amount of data. Currently, there are no dedicated or comprehensive methods for the analysis of these experiments. In this article, we describe our TimeSeries Analysis pipeline (TiSA) which combines differential gene expression, clustering based on recursive thresholding, and a functional enrichment analysis. Differential gene expression is performed for both the temporal and conditional axes. Clustering is performed on the identified differentially expressed genes, with each cluster being evaluated using a functional enrichment analysis. We show that TiSA can be used to analyse longitudinal transcriptomic data from both microarrays and RNA-seq, as well as small, large, and/or datasets with missing data points. The tested datasets ranged in complexity, some originating from cell lines while another was from a longitudinal experiment of severity in COVID-19 patients. We have also included custom figures to aid with the biological interpretation of the data, these plots include Principal Component Analyses, Multi Dimensional Scaling plots, functional enrichment dotplots, trajectory plots, and complex heatmaps showing the broad overview of results. To date, TiSA is the first pipeline to provide an easy solution to the analysis of longitudinal transcriptomics experiments.
-
Garcia-Gallo, Esteban; Merson, Laura; Kennon, Kalynn; Kelly, Sadie; Citarella, Barbara Wanjiru & Fryer, Daniel Vidali
[Show all 1,775 contributors for this article]
(2022).
ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.
Scientific Data.
9(1).
doi:
10.1038/s41597-022-01534-9.
Full text in Research Archive
Show summary
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 Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.
-
Bouziotis, Jason; Arvanitakis, Marianna; Preiser, Jean-Charles; Abbas, Ali; Abdukahil, Sheryl Ann & Abdulkadir, Nurul Najmee
[Show all 50 contributors for this article]
(2022).
Association of body mass index with COVID-19 related in-hospital death.
Clinical Nutrition.
ISSN 0261-5614.
41(12),
p. 2924–2926.
doi:
10.1016/j.clnu.2022.01.017.
Full text in Research Archive
Show summary
Background: Patients with extreme body mass indices (BMI) could have an increased risk of death while hospitalized for COVID-19.<p> <p>Methods: The database of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) was used to assess the time to in-hospital death with competing-risks regression by sex and between the categories of BMI. <p>Results: Data from 12,137 patients (age 60.0 ± 16.2 years, 59% males, BMI 29.4 ± 6.9 kg/m<sup>2</sup> ) of 48 countries were available. By univariate analysis, underweight patients had a higher risk of mortality than the other patients (sub-hazard ratio (SHR) 1.75 [1.44e2.14]). Mortality was lower in normal (SHR 0.69 [0.58e0.85]), overweight (SHR 0.53 [0.43e0.65]) and obese (SHR 0.55 [0.44e0.67]) than in underweight patients. Multivariable analysis (adjusted for age, chronic pulmonary disease, malignant neoplasia, type 2 diabetes) confirmed that in-hospital mortality of underweight patients was higher than overweight patients (females: SHR 0.63 [0.45e0.88] and males: 0.69 [0.51e0.94]). <p>Conclusion: Even though these findings do not imply changes in the medical care of hospitalized patients, they support the use of BMI category for the stratification of patients enrolled in interventional studies where mortality is recorded as an outcome.
-
-
-
-
Myhre, Peder Langeland; Heck, Siri Lagethon; Skranes, Julia Brox; Prebensen, Christian Haugland; Jonassen, Christine M & Berge, Trygve
[Show all 15 contributors for this article]
(2021).
Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity.
American Heart Journal.
ISSN 0002-8703.
242,
p. 61–70.
doi:
10.1016/j.ahj.2021.08.001.
Full text in Research Archive
Show summary
Background Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. Methods Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. Results Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. Conclusions CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. Trial Registration COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232
-
Myhre, Peder L.; Prebensen, Christian; Jonassen, Christine Monceyron; Berdal, Jan Erik & Omland, Torbjørn
(2021).
Sars-cov-2 viremia is associated with inflammatory, but not cardiovascular biomarkers, in patients hospitalized for covid-19.
Journal of the American Heart Association (JAHA).
10(9),
p. 1–5.
doi:
10.1161/JAHA.120.019756.
Full text in Research Archive
Show summary
Background COVID‐19 may present with a variety of cardiovascular manifestations, and elevations of biomarkers reflecting myocardial injury and stress are prevalent. SARS‐CoV‐2 has been found in cardiac tissue, and myocardial dysfunction post‐COVID‐19 may occur. However, the association between SARS‐CoV‐2 RNA in plasma and cardiovascular biomarkers remains unknown. Methods and Results COVID MECH (COVID‐19 Mechanisms) was a prospective, observational study enrolling consecutive, hospitalized patients with laboratory‐confirmed infection with SARS‐CoV‐2 and symptoms of COVID‐19. Biobank plasma samples used to measure SARS‐CoV‐2 RNA and cardiovascular and inflammatory biomarkers were collected in 123 patients at baseline, and in 96 patients (78%) at day 3. Patients were aged 60±15 (mean ± SD) years, 71 (58%) were men, 68 (55%) were White, and 31 (25%) received mechanical ventilation during hospitalization. SARS‐CoV‐2 RNA was detected in plasma from 48 (39%) patients at baseline. Patients with viremia were more frequently men, had more diabetes mellitus, and lower oxygen saturation. Patients with viremia had higher concentrations of interleukin‐6, C‐reactive protein, procalcitonin, and ferritin (all <0.001), but comparable levels of cTnT (cardiac troponin T; P=0.09), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; P=0.27) and D‐dimer (P=0.67) to patients without viremia. SARS‐CoV‐2 RNA was present in plasma at either baseline or day 3 in 50 (52%) patients, and these patients experienced increase from baseline to day 3 in NT‐proBNP and D‐dimer concentrations, while there was no change in cTnT. Conclusions SARS‐CoV‐2 viremia was associated with increased concentrations of inflammatory, but not cardiovascular biomarkers. NT‐proBNP and D‐dimer, but not cTnT, increased from baseline to day 3 in patients with viremia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04314232.
-
Omland, Torbjørn; Prebensen, Christian Haugland; Jonassen, Christine M; Svensson, My Hanna Sofia; Berdal, Jan-Erik & Seljeflot, Ingebjørg
[Show all 7 contributors for this article]
(2021).
Soluble ST2 concentrations associate with in-hospital mortality and need for mechanical ventilation in unselected patients with COVID-19.
Open heart.
8(2),
p. 1–7.
doi:
10.1136/openhrt-2021-001884.
Full text in Research Archive
Show summary
Objective Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. Methods We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. Results Concentrations of sST2 at baseline was median 48 (IQR 37–67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36–59) ng/mL; ICU 67 (39–104) ng/mL and non-survivors 107 (72–116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . Conclusions sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19.
-
Prebensen, Christian; Myhre, Peder Langeland; Jonassen, Christine M; Rangberg, Anbjørg; Blomfeldt, Anita & Svensson, My Hanna Sofia
[Show all 8 contributors for this article]
(2020).
Severe Acute Respiratory Syndrome Coronavirus 2 RNA in Plasma Is Associated with Intensive Care Unit Admission and Mortality in Patients Hospitalized with Coronavirus Disease 2019.
Clinical Infectious Diseases.
ISSN 1058-4838.
73(3).
doi:
10.1093/cid/ciaa1338.
Full text in Research Archive
-
-
-
Søvik, Signe; Bådstøløkken, Per Martin; Sørensen, Vibecke; Myhre, Peder Langeland; Prebensen, Christian & Omland, Torbjørn
[Show all 7 contributors for this article]
(2020).
A single‐centre, prospective cohort study of COVID‐19 patients admitted to ICU for mechanical ventilatory support.
Acta Anaesthesiologica Scandinavica.
ISSN 0001-5172.
doi:
10.1111/aas.13726.
Full text in Research Archive
Show summary
Background Mortality rates in COVID‐19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID‐19 patients from a resource‐rich, publicly financed healthcare system. Methods Prospective study from a tertiary hospital. Consecutive SARS‐CoV‐2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High‐dose dalteparin was adjusted by D‐dimer. Demographics, treatments and high‐resolution physiological variables were collected. Outcomes were 30‐day and hospital mortality. Data are medians (quartiles). Results Of the 1484 persons in the hospital catchment area testing positive for SARS‐CoV‐2, 201 (13.5%) were hospitalized. Thirty‐eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53‐70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8‐23). D‐dimer peaked at 3.8 mg/L (2.1‐5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000‐15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved. Conclusion In a prospective cohort study of mechanically ventilated COVID‐19 patients treated in a resource‐rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.
-
Prebensen, Christian; Trøseid, Marius; Ueland, Thor; Dahm, Anders Erik A; Sandset, Per Morten & Aaberge, Ingeborg Sundsvalen
[Show all 10 contributors for this article]
(2017).
Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial.
PLOS ONE.
12(5).
doi:
10.1371/journal.pone.0176527.
Full text in Research Archive
Show summary
Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART)-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL. Patients in each of the two study groups were randomized to receive 90 mg qd of the cyclooxygenase-2 inhibitor etoricoxib for six months, two weeks or to a control arm, respectively. T cell activation status, HIV Gag-specific T cell responses and plasma inflammatory markers, tryptophan metabolism and thrombin generation were analyzed at baseline and after four months. In addition, patients received tetanus toxoid, conjugated pneumococcal and seasonal influenza vaccines, to which IgG responses were determined after four weeks. In ART-naïve patients, etoricoxib reduced the density of the activation marker CD38 in multiple CD8+ T cell subsets, improved Gag-specific T cell responses, and reduced in vitro plasma thrombin generation, while no effects were seen on plasma markers of inflammation or tryptophan metabolism. No significant immunological effects of etoricoxib were observed in ART-treated patients. Patients receiving long-term etoricoxib treatment had poorer tetanus toxoid and conjugated pneumococcal vaccine responses than those receiving short-course etoricoxib. Cyclooxygenase-2 inhibitors may attenuate harmful immune activation in HIV-infected patients without access to ART.
-
Prebensen, Christian; Lind, Andreas; Dyrhol-Riise, Anne Ma & Kvale, Dag
(2016).
Regulation of Gag- and Env-specific CD+ T cell responses in ART-naïve HIV-infected patients: Potential implications for individualized immunotherapy.
PLOS ONE.
11(4).
doi:
10.1371/journal.pone.0153849.
Full text in Research Archive
Show summary
Strategies to develop a functional cure for HIV infection will likely require boosting of effector T cell responses to eliminate reactivated, latently infected cells. We have recently explored an assay for assessing antigen-specific regulation of T cell proliferation, which was related to clinical progression in untreated patients and to vaccine efficacy in two trials of therapeutic Gag-based vaccines. We here expand the same assay to further investigate regulation mediated by various inhibitory pathways. Peripheral blood mononuclear cells from 26 asymptomatic HIV-infected, antiretroviral therapy-naïve patients were stimulated with Gag and Env overlapping peptide panels for 5 days. Monoclonal antibodies (mAbs) blocking inhibitory mediators interleukin (IL) 10, transforming growth factor (TGF) β, programmed death ligand (PD–L) 1 and herpes virus entry mediator (HVEM) were added to parallel cultures. Functional T cell regulation (FTR) was defined as the difference in proliferation between stimulated cultures with and without blocking mAbs. FTR was detected in 54% of patients. Blockade of IL-10/PD-L1 and IL10/TGF-β detected all cases with Gag- and Env-associated FTR, respectively. In accordance with previous findings, isolated Env FTR was associated with higher plasma HIV RNA and lower CD4 counts, while patients with both Gag and Env FTR also had higher Gag- and Env-specific proliferative CD8+ T cell responses. There was no association between FTR and frequencies of activated regulatory T cells. In conclusion, we observed substantial heterogeneity in FTR between patients, inhibitory pathways and HIV antigens. FTR may help to individualize immunomodulation and warrants further assessment in clinical immunotherapy trials.
-
View all works in NVA
-
-
Prebensen, Christian Haugland; Lefol, Yohan Pierre; Myhre, Peder Langeland; Lüders, Torben; Jonassen, Christine M & Blomfeldt, Anita
[Show all 9 contributors for this article]
(2023).
Author Correction: Longitudinal whole blood transcriptomic analysis characterizes neutrophil activation and interferon signaling in moderate and severe COVID-19 (Scientific Reports, (2023), 13, 1, (10368), 10.1038/s41598-023-37606-y).
Scientific Reports.
13(1).
doi:
10.1038/s41598-023-39872-2.
Full text in Research Archive
-
Wickstrøm, Kristin; Amundsen, Erik Koldberg; Vitelli, Valeria & Prebensen, Christian Haugland
(2026).
Supervised and unsupervised modeling on routine clinical and laboratory variables for diagnosis, prognosis and subgrouping of infectious diseases.
Universitetet i Oslo.
ISSN 9788234807787.
Full text in Research Archive
Show summary
In this thesis we used supervised and unsupervised models on patients with infectious diseases, with a focus on laboratory variables from patients admitted to the emergency department (ED). These models are used for diagnosis, prognosis, and subgrouping of patients.
In the first part of the thesis, we evaluated four published supervised models for prediction of outcomes in COVID‑19 patients. Using cohorts from Oslo and London, we found that all models performed worse and with greater variability than in their original studies. Recalibration improved performance and the results highlight the importance of validating prediction models across different populations.
Next, we developed a supervised model to predict infection using Sysmex cell population (CP) data from patients with suspected sepsis. These research parameters are produced by hematology instruments when analyzing white blood cells and reflect the cells morphology and degree of activation. Among the parameters, monocyte complexity (MO‑X) and neutrophil fluorescence activity (NEUT‑RI) showed the strongest individual predictive value. Using LASSO and backward selection, we created a four‑variable model that performed slightly below C‑reactive protein (CRP) alone. The multilayer perceptron model demonstrated the best calibration, particularly when CRP was added. Further standardization and external validation are required before clinical use.
Finally, we explored unsupervised clustering to identify subgroups of sepsis patients. Unlike the SENECA study, which reported four phenotypes, our analyses did not reproduce these subgroups. A large multicenter replication study with cohorts from Oslo, Karolinska, and Oxford also failed to reproduce the SENECA subgroups, suggesting that these phenotypes may not generalize across populations. In the Oslo cohort, seven clusters were more stable and clinically distinct. Further validation of the seven clusters should be conducted.
View all works in NVA
Published
Apr. 7, 2020 11:36 AM
- Last modified
Apr. 1, 2026 10:28 AM
