Aleksander Rygh Holten

• Anthon, Carl Thomas; Pène, Frédéric; Perner, Anders; Azoulay, Elie; Puxty, Kathryn & Van De Louw, Andry [Show all 47 contributors for this article] (2024). Platelet transfusions in adult ICU patients with thrombocytopenia: A sub-study of the PLOT-ICU inception cohort study. Acta Anaesthesiologica Scandinavica. ISSN 0001-5172. doi: 10.1111/aas.14467.
• Barratt-Due, Andreas; Pettersen, Kristin; Dahl, Tuva Børresdatter; Holter, Jan Cato; Grønli, Renathe Henriksen & Dyrhol-Riise, Anne Ma [Show all 20 contributors for this article] (2024). Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients. Journal of Internal Medicine. ISSN 0954-6820. doi: 10.1111/joim.13783.
• Ueland, Thor; Michelsen, Annika Elisabet; Tveita, Anders; Kåsine, Trine; Dahl, Tuva Børresdatter & Finbråten, Ane-Kristine [Show all 16 contributors for this article] (2023). Coagulopathy and adverse outcomes in hospitalized patients with COVID-19: results from the NOR-Solidarity trial. Research and Practice in Thrombosis and Haemostasis (RPTH). ISSN 2475-0379. 8(1). doi: 10.1016/j.rpth.2023.102289. Full text in Research Archive
• Murphy, Sarah Louise Mikalsen; Halvorsen, Bente; Holter, Jan Cato; Huse, Camilla; Tveita, Anders & Trøseid, Marius [Show all 24 contributors for this article] (2023). Circulating markers of extracellular matrix remodelling in severe COVID-19 patients. Journal of Internal Medicine. ISSN 0954-6820. 294(6), p. 784–797. doi: 10.1111/joim.13725. Full text in Research Archive
• Anthon, Carl Thomas; Pène, Frédéric; Perner, Anders; Azoulay, Elie; Puxty, Kathryn & Van De Louw, Andry [Show all 55 contributors for this article] (2023). Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU). Intensive Care Medicine. ISSN 0342-4642. 49(11), p. 1327–1338. doi: 10.1007/s00134-023-07225-2. Full text in Research Archive
• Trøseid, Marius; Holter, Jan Cato; Holm, Kristian; Vestad, Beate; Sazonova, Taisiia & Granerud, Beathe Kiland [Show all 17 contributors for this article] (2023). Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19. Critical Care. ISSN 1364-8535. 27(1). doi: 10.1186/s13054-023-04356-2. Full text in Research Archive
• 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. ISSN 2639-8028. 5(2). doi: 10.1097/CCE.0000000000000865. Full text in Research Archive
• Trøseid, Marius; Arribas, José R.; Assoumou, Lambert; Holten, Aleksander Rygh; Poissy, Julien & Terzić, Vida [Show all 56 contributors for this article] (2023). Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial. Critical Care. ISSN 1364-8535. 27, p. 1–15. doi: 10.1186/s13054-022-04205-8. Full text in Research Archive
• Pan, Hongchao; Peto, Richard; Karim, Quarraisha Abdool; Alejandria, Marissa M.; Henao-Restrepo, Ana-Maria & Hernández-García, César [Show all 51 contributors for this article] (2022). Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. The Lancet. ISSN 0140-6736. 399(10339), p. 1941–1953. doi: 10.1016/S0140-6736(22)00519-0. Full text in Research Archive Show summary

  Background The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date. Methods Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948. Findings Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82–1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89–1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76–0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46–1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76–0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77–1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75–0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings. Interpretation Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).

• Wainstein, Marina; MacDonald, Samual; Fryer, Daniel; Young, Kyle; Balan, Valeria & Begum, Husna [Show all 50 contributors for this article] (2022). Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study using the ISARIC–WHO clinical characterisation protocol. PLoS Medicine. ISSN 1549-1277. 19(4). doi: 10.1371/journal.pmed.1003969.
• Reyes, Luis Felipe; Murthy, Srinivas; Garcia-Gallo, Esteban; Merson, Laura; Ibáñez-Prada, Elsa D. & Rello, Jordi [Show all 51 contributors for this article] (2022). Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study. Critical Care. ISSN 1364-8535. 26(1). doi: 10.1186/s13054-022-04155-1.
• Cho, Sung-Min; White, Nicole; Premraj, Lavienraj; Battaglini, Denise; Fanning, Jonathon & Suen, Jacky [Show all 50 contributors for this article] (2022). Neurological manifestations of COVID-19 in adults and children. Brain. ISSN 0006-8950. doi: 10.1093/brain/awac332.
• Gonçalves, Bronner P.; Hall, Matthew; Jassat, Waasila; Balan, Valeria; Murthy, Srinivas & Kartsonaki, Christiana [Show all 50 contributors for this article] (2022). An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients. eLIFE. ISSN 2050-084X. 11. doi: 10.7554/eLife.80556.
• 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. Full text in Research Archive
• 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. ISSN 2052-4463. 9(1). doi: 10.1038/s41597-022-01534-9. Full text in Research Archive
• Tveita, Anders Aune; Murphy, Sarah Louise Mikalsen; Holter, Jan Cato; Kildal, Anders Benjamin; Michelsen, Annika Elisabet & Lerum, Tøri Vigeland [Show all 28 contributors for this article] (2022). High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19. Journal of Infectious Diseases. ISSN 0022-1899. 226(12), p. 2150–2160. doi: 10.1093/infdis/jiac313. Full text in Research Archive
• Trøseid, Marius; Dahl, Tuva Børresdatter; Holter, Jan Cato; Kildal, Anders Benjamin; Murphy, Sarah Louise Mikalsen & Yang, Kuan [Show all 28 contributors for this article] (2022). Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies. Journal of Internal Medicine. ISSN 0954-6820. 292(5), p. 816–828. doi: 10.1111/joim.13549. Full text in Research Archive
• Degenhardt, Frauke; Ellinghaus, David; Juzenas, Simonas; Lerga-Jaso, Jon; Wendorff, Mareike & Maya-Miles, Douglas [Show all 51 contributors for this article] (2022). Detailed stratified GWAS analysis for severe COVID-19 in four European populations. Human Molecular Genetics. ISSN 0964-6906. 31(23), p. 3945–3966. doi: 10.1093/hmg/ddac158. Full text in Research Archive Show summary

  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 genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ∼0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

• 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
• Hammer, Quirin; Dunst, Josefine; Christ, Wanda; Picarazzi, Francesca; Wendorff, Mareike & Momayyezi, Pouria [Show all 51 contributors for this article] (2022). SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells. Cell reports. ISSN 2211-1247. 38(10). doi: 10.1016/j.celrep.2022.110503. Full text in Research Archive Show summary

  Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.

• Abdukahil, Sheryl Ann; Abe, Ryuzo; Abel, Laurent; Absil, Lara; Acker, Andrew & Adachi, Shingo [Show all 50 contributors for this article] (2021). COVID‐19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study. Infection. ISSN 0300-8126. 49, p. 889–905. doi: 10.1007/s15010-021-01599-5. Full text in Research Archive
• Abdukahil, Sheryl Ann; Abe, Ryuzo; Abel, Laurent; Absil, Lara; Acharya, Subhash & Acker, Andrew [Show all 50 contributors for this article] (2021). Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: An observational cohort. eLIFE. ISSN 2050-084X. 10:e70970, p. 1–30. doi: 10.7554/eLife.70970. Full text in Research Archive
• Reyes, Luis Felipe; Murthy, Srinivas; Garcia-Gallo, Esteban; Irvine, Mike; Merson, Laura & Martin-Loeches, Ignacio [Show all 50 contributors for this article] (2021). Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the ISARIC WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study. European Respiratory Journal Open Research (ERJ Open Research). ISSN 2312-0541. 8(1). doi: 10.1183/23120541.00552-2021. Full text in Research Archive
• Kåsine, Trine; Riise, Anne Margarita Dyrhol; Barratt-Due, Andreas; Kildal, Anders Benjamin; Olsen, Inge Christoffer & Nezvalova-Henriksen, Katerina [Show all 39 contributors for this article] (2021). Neutrophil count predicts outcome in hospitalized COVID-19 patients. Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 291(2), p. 241–243. doi: 10.1111/joim.13377. Show summary

  Despite numerous studies on SARS-CoV-2-induced inflammation, we still lack markers for rapid disease progression with admission to intensive care unit (ICU) or respiratory failure(RF). Few studies have evaluated the prognostic value of routine diagnostic repertoire available at most hospitals. The NOR-Solidarity trial is an independent add-on study to the WHO Solidarity trial, evaluating hydroxychloroquine (HCQ)and remdesivir compared to standard of care in hospitalized COVID-19 patients [1]. We explored whether standard biomarkers in peripheral blood could give information on ICU admission and RFin hospitalized COVID-19 patients.

• Aarskog, Nikolai Ravn; Aass, Hans Christian Dalsbotten; Holter, Jan Cato; Rostrup, Morten & Holten, Aleksander Rygh (2021). Interleukin-6 in Critical Coronavirus Disease 2019, a Driver of Lung Inflammation of Systemic Origin? Critical Care Explorations. ISSN 2639-8028. 3(10). doi: 10.1097/cce.0000000000000542. Full text in Research Archive
• Niemi, Mari E.K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark & Ganna, Andrea [Show all 84 contributors for this article] (2021). Mapping the human genetic architecture of COVID-19. Nature. ISSN 0028-0836. 600(7889), p. 472–477. doi: 10.1038/s41586-021-03767-x. Full text in Research Archive Show summary

  The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

• 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. ISSN 2639-8028. 3(7), p. 1–9. doi: 10.1097/CCE.0000000000000490. Full text in Research Archive
• Wickstrøm, Kristin Elisabeth; Vitelli, Valeria; Carr, Ewan; Holten, Aleksander R.; Bendayan, Rebecca & Reiner, Andrew Henry [Show all 15 contributors for this article] (2021). Regional performance variation in external validation of four prediction models for severity of COVID-19 at hospital admission: An observational multi-centre cohort study. PLOS ONE. ISSN 1932-6203. 16(8), p. 1–13. doi: 10.1371/journal.pone.0255748. Full text in Research Archive
• Barratt-Due, Andreas; Olsen, Inge Christoffer; Nezvalova-Henriksen, Katerina; Kåsine, Trine; Lund-Johansen, Fridtjof & Hoel, Hedda Benedicte [Show all 43 contributors for this article] (2021). Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Annals of Internal Medicine. ISSN 0003-4819. 174(9), p. 1261–1269. doi: 10.7326/M21-0653. Full text in Research Archive Show summary

  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-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). Setting: 23 hospitals in Norway. Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. Limitation: The trial had no placebo group. Conclusion: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.

• Ueland, Thor; Dyrhol-Riise, Anne Ma; Woll, Bjørn Martin; Holten, Aleksander Rygh; Pettersen, Frank O. & Lind, Andreas [Show all 10 contributors for this article] (2021). Increased inflammatory markers reflecting fibrogenesis are independently associated with cardiac involvement in hospitalized COVID-19 patients. Journal of Infection. ISSN 0163-4453. 82(5), p. 186–230. doi: 10.1016/j.jinf.2021.01.017.
• 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. Full text in Research Archive
• Carr, Ewan; Bendayan, Rebecca; Bean, Daniel; Stammers, Matt; Wang, Wenjuan & Zhang, Huayu [Show all 48 contributors for this article] (2021). Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study. BMC Medicine. ISSN 1741-7015. 19(23), p. 1–16. doi: 10.1186/s12916-020-01893-3. Full text in Research Archive Show summary

  Background The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. Methods Training cohorts comprised 1276 patients admitted to King’s College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy’s and St Thomas’ Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. Results A baseline model of ‘NEWS2 + age’ had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. Conclusions NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.

• Holten, Aleksander Rygh; Nore, Kristin Grotle; Tveiten, Caroline Emilie Van Woensel Ko; Olasveengen, Theresa M. & Tonby, Kristian (2020). Predicting severe COVID-19 in the Emergency Department. Resuscitation Plus. ISSN 2666-5204. 4. doi: 10.1016/j.resplu.2020.100042.
• 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. ISSN 2045-2322. 10. doi: 10.1038/s41598-020-78710-7. Full text in Research Archive
• Ueland, Thor; Heggelund, Lars; Lind, Andreas; Holten, Aleksander Rygh; Tonby, Kristian & Michelsen, Annika [Show all 26 contributors for this article] (2020). Elevated plasma sTIM-3 levels in patients with severe COVID-19. Journal of Allergy and Clinical Immunology. ISSN 0091-6749. 147(1), p. 92–98. doi: 10.1016/j.jaci.2020.09.007. Full text in Research Archive
• Holter, Jan Cato; Pischke, Soeren; de Boer, Eline; Lind, Andreas; Jenum, Synne & Holten, Aleksander Rygh [Show all 32 contributors for this article] (2020). Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients . Proceedings of the National Academy of Sciences of the United States of America. ISSN 0027-8424. 117(40), p. 25018–25025. doi: 10.1073/pnas.2010540117. Full text in Research Archive
• Gundem, Trine; Olasveengen, Theresa M.; Hovda, Knut Erik; Gaustad, Knut; Schøndorf, Christina Luise & Rostrup, Morten [Show all 11 contributors for this article] (2020). Ventilasjonsstotte for hypoksemiske intensivpasienter med covid-19. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 140(11), p. 1–10. doi: 10.4045/tidsskr.20.0445. Full text in Research Archive
• Trydal, Elisabet; Martinsen, Anders B.; Beisland, Frode; Jacobsen, Dag & Holten, Aleksander Rygh (2019). Strukturert mottak av sepsispasienter og oppstart av antibiotika. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 139(9), p. 811–816. doi: 10.4045/tidsskr.18.0216. Show summary

  BAKGRUNN Akuttmottaket ved Oslo universitetssykehus, Ullevål, innførte i 2017 en egen prosedyre for mottak av pasienter med mistenkt sepsis. Et strukturert sepsismottak skulle utløses hos disse pasientene, spesielt hvis minst to av tre kriterier i skåringsverktøyet Quick Sequential Organ Failure Assessment (qSOFA) var oppfylt. Vi ønsket å undersøke om tiltaket var hensiktsmessig for å oppfylle nasjonale anbefalinger om oppstart av antibiotika innen én time ved behandling av sepsis. MATERIALE OG METODE Voksne pasienter med mistenkt sepsis som ble tatt imot i strukturerte teammottak i perioden 15.5.–15.11.2017 ble inkludert. Det ble gjort en retrospektiv vurdering av om de inkluderte faktisk hadde hatt sepsis eller ikke. RESULTATER Det ble gitt antibiotika mot mistenkt sepsis i 216 strukturerte pasientmottak (172 sepsismottak og 44 medisinske teammottak). 175 (81 %) av pasientene fikk antibiotika innen den første timen i akuttmottaket. Mediantid fra ankomst til antibiotika ble igangsatt var 35 minutter. Bruk av qSOFA-skår alene fanget opp 80 (71 %) av de 112 pasientene som i ettertid ble klassifisert til å ha sepsis. FORTOLKNING Etter innføring av strukturert mottak av pasienter med mistenkt sepsis ble antibiotikabehandling i stor grad gitt innen én time.

• Holten, Aleksander Talgøy; Morland, Cecilie; Nordengen, Kaja & Gundersen, Vidar (2008). Vesicular Release of L- and D-Aspartate from Hippocampal Nerve Terminals: Immunogold Evidence. Open Neuroscience Journal. ISSN 1874-0820. 2, p. 51–58. doi: 10.2174/1874082000802010051.
• Holten, Aleksander Talgøy; Danbolt, Niels Christian; Keiko, S & Gundersen, Vidar (2008). Low-affinity excitatory amino acid uptake in hippocampal astrocytes: A possible role of Na+/dicarboxylate cotransporters. Glia. ISSN 0894-1491. 56, p. 990–997. doi: 10.1002/glia.20672.
• Holten, Aleksander Talgøy & Gundersen, Vidar (2008). Glutamine as a precursor for transmitter glutamate, aspartate and GABA in the cerebellum: a role for phosphate-activated glutaminase. Journal of Neurochemistry. ISSN 0022-3042. 104. doi: 10.1111/j.1471-4159.2007.05065.x.
• Gundersen, Vidar; Holten, Aleksander Talgøy & Storm-Mathisen, Jon (2004). GABAergic synapses in hippocampus exocytose aspartate on to NMDA receptors: quantitative immunogold evidence for co-transmission. Molecular and Cellular Neuroscience. ISSN 1044-7431. 26(1), p. 156–165.

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• Anthon, Carl Thomas; Pène, Frédéric; Perner, Anders; Azoulay, Elie; Puxty, Kathryn & Van De Louw, Andry [Show all 121 contributors for this article] (2023). Correction: Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU) (Intensive Care Medicine, (2023), 49, 11, (1327-1338), 10.1007/s00134-023-07225-2). Intensive Care Medicine. ISSN 0342-4642. doi: 10.1007/s00134-023-07291-6.
• Holten, Aleksander Rygh & Skrede, Steinar (2023). Tidlig antibiotikabehandling til de rett pasientene. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 143(2). doi: 10.4045/tidsskr.22.0702.
• Quiles-Jiménez, Ana M T; Sousa, Mirta; Huse, Camilla; Dyrhol-Riise, Anne Ma; Holter, Jan Cato & Christensen, Erik Egeland [Show all 12 contributors for this article] (2023). Severely ill COVID-19 patients have altered circulating levels of proteins controlling the epitranscriptome. Journal of Infection. ISSN 0163-4453. doi: 10.1016/j.jinf.2023.03.002.
• Gregersen, Ida; Ueland, Thor; Holter, Jan Cato; Olsen, Maria Belland; Michelsen, Annika Elisabet & Murphy, Sarah L [Show all 22 contributors for this article] (2022). CXCL16 associates with adverse outcome and cardiac involvement in hospitalized patients with Covid-19. Journal of Infection. ISSN 0163-4453. 85(6), p. 735–738. doi: 10.1016/j.jinf.2022.09.029.
• Gundem, Trine; Olasveengen, Theresa M.; Schøndorf, Christina Luise; Hovda, Knut Erik; Rostrup, Morten & Frøyshov, Sten [Show all 11 contributors for this article] (2020). T.M. Gundem og medarbeidere svarer. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 140(12), p. 1–2. doi: 10.4045/tidsskr.20.0650. Full text in Research Archive
• Kolberg, Espen Skarstein; Wickstrøm, Kristin; Tonby, Kristian; Dyrhol-Riise, Anne Ma; Holten, Aleksander Rygh & Amundsen, Erik Koldberg (2020). Serum ACE as a prognostic biomarker in COVID-19: A Case series. APMIS - Journal of Pathologiy, Microbiology and Immunology. ISSN 0903-4641. p. 1–2. doi: 10.1111/apm.13108. Full text in Research Archive
• Ueland, Thor; Holter, Jan Cato; Holten, Aleksander Rygh; Muller, Karl Erik; Lind, A. & Bekken, Gry Klouman [Show all 10 contributors for this article] (2020). Distinct and early increase in circulating MMP-9 in COVID-19 patients with respiratory failure: MMP-9 and respiratory failure in COVID-19. Journal of Infection. ISSN 0163-4453. 81(3), p. e41–e43. doi: 10.1016/j.jinf.2020.06.061.
• Holten, Aleksander Talgøy (2013). Dobbel pylorus. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 133(6), p. 645–645. doi: 10.4045/tidsskr.13.0033.

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