Mechanisms for Organ Dysfunction in Covid-19 (UMODCOVID19)

Uppsala Intensive Care Study of Mechanisms for Organ Dysfunction in Covid-19

The study aims to investigate organ dysfunction and biomarkers in patients with suspected or verified COVID-19 during intensive care at Uppsala University Hospital.

Study Overview

• Status: Completed
• Conditions: COVID-19; Septic Shock; Acute Kidney Injury; Acute Respiratory Distress Syndrome; Organ Dysfunction Syndrome, Multiple; Organ Dysfunction Syndrome Sepsis

Detailed Description

Consenting patients with suspected or verified SARS-COV-2 infection, COVID-19, will undergo daily blood, urine and sputum sampling during their stay in intensive care. Data on organ dysfunction will be collected through the electronic patient journal and electronic patient data management system. The collected samples will be analysed for a panel of potential biomarkers that will be correlated to organ dysfunction and clinical outcome.

• Study Type: Observational
• Enrollment (Actual): 380

Contacts and Locations

Study Locations

• Sweden
  • Uppsala County
    • Uppsala, Uppsala County, Sweden, 75185
      • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients requiring intensive care with suspected or verified COVID19

Description

Inclusion Criteria:

• Admitted to intensive care
• suspected or verified COVID-19

Exclusion Criteria:

• Pregnancy or breastfeeding
• Under-age

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
COVID-19; Patients with suspected or verified COVID-19 admitted to intensive care at Uppsala University Hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Kidney Injury	KDIGO AKI score	During Intensive Care, an estimated average of 10 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ARDS	Acute Respiratory Distress Syndrome yes/no	During intensive care, an estimated average of 10 days.
30 day mortality	Death within 30 days of ICU admission	30 days
1 year mortality	Death within 1 year of ICU admission	1 year
Chronic Kidney Disease	Development of Chronic Kidney Disease	60 days and 1 year after ICU admission
SOFA-score	Sequential Organ Failure Score as a continuous variable	During Intensive Care, an estimated average of 10 days.
Thromboembolic events	Occurence of thrombosis and/or embolous	During intensive care
ICUAW	Intensive care acquired weakness	During intensive care or after intensive care

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Robert Frithiof, MD. PhD, Uppsala University Hospital

Publications and helpful links

General Publications

• Hultstrom M, Lipcsey M, Morrison DR, Nakanishi T, Butler-Laporte G, Chen Y, Yoshiji S, Forgetta V, Farjoun Y, Wallin E, Larsson IM, Larsson A, Marton A, Titze JM, Nihlen S, Richards JB, Frithiof R. Dehydration is associated with production of organic osmolytes and predicts physical long-term symptoms after COVID-19: a multicenter cohort study. Crit Care. 2022 Oct 21;26(1):322. doi: 10.1186/s13054-022-04203-w.
• Zhou S, Butler-Laporte G, Nakanishi T, Morrison DR, Afilalo J, Afilalo M, Laurent L, Pietzner M, Kerrison N, Zhao K, Brunet-Ratnasingham E, Henry D, Kimchi N, Afrasiabi Z, Rezk N, Bouab M, Petitjean L, Guzman C, Xue X, Tselios C, Vulesevic B, Adeleye O, Abdullah T, Almamlouk N, Chen Y, Chasse M, Durand M, Paterson C, Normark J, Frithiof R, Lipcsey M, Hultstrom M, Greenwood CMT, Zeberg H, Langenberg C, Thysell E, Pollak M, Mooser V, Forgetta V, Kaufmann DE, Richards JB. A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity. Nat Med. 2021 Apr;27(4):659-667. doi: 10.1038/s41591-021-01281-1. Epub 2021 Feb 25.
• Hultstrom M, von Seth M, Frithiof R. Hyperreninemia and low total body water may contribute to acute kidney injury in COVID-19 patients in intensive care. J Hypertens. 2020 Aug;38(8):1613-1614. doi: 10.1097/HJH.0000000000002531. No abstract available.
• Hultstrom M, Persson B, Eriksson O, Lipcsey M, Frithiof R, Nilsson B. Blood type A associates with critical COVID-19 and death in a Swedish cohort. Crit Care. 2020 Aug 12;24(1):496. doi: 10.1186/s13054-020-03223-8. No abstract available.
• Eriksson O, Hultstrom M, Persson B, Lipcsey M, Ekdahl KN, Nilsson B, Frithiof R. Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 Patients. Thromb Haemost. 2020 Dec;120(12):1720-1724. doi: 10.1055/s-0040-1715835. Epub 2020 Sep 1.
• Stattin K, Lipcsey M, Andersson H, Ponten E, Bulow Anderberg S, Gradin A, Larsson A, Lubenow N, von Seth M, Rubertsson S, Hultstrom M, Frithiof R. Inadequate prophylactic effect of low-molecular weight heparin in critically ill COVID-19 patients. J Crit Care. 2020 Dec;60:249-252. doi: 10.1016/j.jcrc.2020.08.026. Epub 2020 Sep 3.
• Frithiof R, Bergqvist A, Jarhult JD, Lipcsey M, Hultstrom M. Presence of SARS-CoV-2 in urine is rare and not associated with acute kidney injury in critically ill COVID-19 patients. Crit Care. 2020 Sep 29;24(1):587. doi: 10.1186/s13054-020-03302-w. No abstract available.
• Asif S, Frithiof R, Lipcsey M, Kristensen B, Alving K, Hultstrom M. Weak anti-SARS-CoV-2 antibody response is associated with mortality in a Swedish cohort of COVID-19 patients in critical care. Crit Care. 2020 Nov 6;24(1):639. doi: 10.1186/s13054-020-03362-y. No abstract available.
• Luther T, Bulow-Anderberg S, Larsson A, Rubertsson S, Lipcsey M, Frithiof R, Hultstrom M. COVID-19 patients in intensive care develop predominantly oliguric acute kidney injury. Acta Anaesthesiol Scand. 2021 Mar;65(3):364-372. doi: 10.1111/aas.13746. Epub 2020 Nov 28.
• Bulow Anderberg S, Luther T, Berglund M, Larsson R, Rubertsson S, Lipcsey M, Larsson A, Frithiof R, Hultstrom M. Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients. Cytokine. 2021 Feb;138:155389. doi: 10.1016/j.cyto.2020.155389. Epub 2020 Dec 14.
• Lipcsey M, Persson B, Eriksson O, Blom AM, Fromell K, Hultstrom M, Huber-Lang M, Ekdahl KN, Frithiof R, Nilsson B. The Outcome of Critically Ill COVID-19 Patients Is Linked to Thromboinflammation Dominated by the Kallikrein/Kinin System. Front Immunol. 2021 Feb 22;12:627579. doi: 10.3389/fimmu.2021.627579. eCollection 2021.
• Jarhult JD, Hultstrom M, Bergqvist A, Frithiof R, Lipcsey M. The impact of viremia on organ failure, biomarkers and mortality in a Swedish cohort of critically ill COVID-19 patients. Sci Rep. 2021 Mar 30;11(1):7163. doi: 10.1038/s41598-021-86500-y.
• Frithiof R, Rostami E, Kumlien E, Virhammar J, Fallmar D, Hultstrom M, Lipcsey M, Ashton N, Blennow K, Zetterberg H, Punga AR. Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study. Clin Neurophysiol. 2021 Jul;132(7):1733-1740. doi: 10.1016/j.clinph.2021.03.016. Epub 2021 Apr 1.
• Galien S, Hultstrom M, Lipcsey M, Stattin K, Frithiof R, Rosen J; Uppsala Intensive Care COVID-19 Research Group. Point of care ultrasound screening for deep vein thrombosis in critically ill COVID-19 patients, an observational study. Thromb J. 2021 Jun 2;19(1):38. doi: 10.1186/s12959-021-00272-z.
• Gradin A, Andersson H, Luther T, Anderberg SB, Rubertsson S, Lipcsey M, Aberg M, Larsson A, Frithiof R, Hultstrom M. Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients. Cytokine. 2021 Oct;146:155589. doi: 10.1016/j.cyto.2021.155589. Epub 2021 May 24.
• Huckriede J, Anderberg SB, Morales A, de Vries F, Hultstrom M, Bergqvist A, Ortiz-Perez JT, Sels JW, Wichapong K, Lipcsey M, van de Poll M, Larsson A, Luther T, Reutelingsperger C, de Frutos PG, Frithiof R, Nicolaes GAF. Evolution of NETosis markers and DAMPs have prognostic value in critically ill COVID-19 patients. Sci Rep. 2021 Aug 3;11(1):15701. doi: 10.1038/s41598-021-95209-x.
• Pellegrini M, Larina A, Mourtos E, Frithiof R, Lipcsey M, Hultstrom M, Segelsjo M, Hansen T, Perchiazzi G. A quantitative analysis of extension and distribution of lung injury in COVID-19: a prospective study based on chest computed tomography. Crit Care. 2021 Aug 4;25(1):276. doi: 10.1186/s13054-021-03685-4.
• Karawajczyk M, Douhan Hakansson L, Lipcsey M, Hultstrom M, Pauksens K, Frithiof R, Larsson A. High expression of neutrophil and monocyte CD64 with simultaneous lack of upregulation of adhesion receptors CD11b, CD162, CD15, CD65 on neutrophils in severe COVID-19. Ther Adv Infect Dis. 2021 Jul 31;8:20499361211034065. doi: 10.1177/20499361211034065. eCollection 2021 Jan-Dec.
• Huckriede J, de Vries F, Hultstrom M, Wichapong K, Reutelingsperger C, Lipcsey M, Garcia de Frutos P, Frithiof R, Nicolaes GAF. Histone H3 Cleavage in Severe COVID-19 ICU Patients. Front Cell Infect Microbiol. 2021 Sep 10;11:694186. doi: 10.3389/fcimb.2021.694186. eCollection 2021.
• Bulow Anderberg S, Lipcsey M, Hultstrom M, Eriksson AK, Venge P, Frithiof R, On Behalf Of The Uppsala Intensive Care Covid-Research Group. Systemic Human Neutrophil Lipocalin Associates with Severe Acute Kidney Injury in SARS-CoV-2 Pneumonia. J Clin Med. 2021 Sep 14;10(18):4144. doi: 10.3390/jcm10184144.
• Sancho Ferrando E, Hanslin K, Hultstrom M, Larsson A, Frithiof R, Lipcsey M; Uppsala Intensive Care COVID-19 Research Group. Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study. Cytokine. 2022 Jan;149:155727. doi: 10.1016/j.cyto.2021.155727. Epub 2021 Oct 5.
• Nakanishi T, Pigazzini S, Degenhardt F, Cordioli M, Butler-Laporte G, Maya-Miles D, Bujanda L, Bouysran Y, Niemi ME, Palom A, Ellinghaus D, Khan A, Martinez-Bueno M, Rolker S, Amitrano S, Roade Tato L, Fava F; FinnGen; COVID-19 Host Genetics Initiative (HGI); Spinner CD, Prati D, Bernardo D, Garcia F, Darcis G, Fernandez-Cadenas I, Holter JC, Banales JM, Frithiof R, Kiryluk K, Duga S, Asselta R, Pereira AC, Romero-Gomez M, Nafria-Jimenez B, Hov JR, Migeotte I, Renieri A, Planas AM, Ludwig KU, Buti M, Rahmouni S, Alarcon-Riquelme ME, Schulte EC, Franke A, Karlsen TH, Valenti L, Zeberg H, Richards JB, Ganna A. Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality. J Clin Invest. 2021 Dec 1;131(23):e152386. doi: 10.1172/JCI152386.
• COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021 Dec;600(7889):472-477. doi: 10.1038/s41586-021-03767-x. Epub 2021 Jul 8.
• Perchiazzi G, Larina A, Hansen T, Frithiof R, Hultstrom M, Lipcsey M, Pellegrini M. Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients. Crit Care. 2022 Oct 25;26(1):328. doi: 10.1186/s13054-022-04200-z.
• Bjarnadottir KJ, Perchiazzi G, Sidenbladh CL, Larina A, Wallin E, Larsson IM, Franzen S, Larsson AO, Sousa MLA, Segelsjo M, Hansen T, Frithiof R, Hultstrom M, Lipcsey M, Pellegrini M. Body mass index is associated with pulmonary gas and blood distribution mismatch in COVID-19 acute respiratory failure. A physiological study. Front Physiol. 2024 Jul 10;15:1399407. doi: 10.3389/fphys.2024.1399407. eCollection 2024.
• Halvorsen P, Hultstrom M, Hastbacka J, Larsson IM, Eklund R, Arnberg FK, Hokkanen L, Frithiof R, Wallin E, Orwelius L, Lipcsey M. Health-related quality of life after surviving intensive care for COVID-19: a prospective multicenter cohort study. Sci Rep. 2023 Oct 21;13(1):18035. doi: 10.1038/s41598-023-45346-2.
• Bark L, Larsson IM, Wallin E, Simren J, Zetterberg H, Lipcsey M, Frithiof R, Rostami E, Hultstrom M. Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19. Sci Rep. 2023 Aug 12;13(1):13144. doi: 10.1038/s41598-023-39698-y.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2020
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: March 13, 2020
• First Submitted That Met QC Criteria: March 18, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Lung Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Renal Insufficiency; Shock; Pathological Conditions, Signs and Symptoms; COVID-19; Respiratory Distress Syndrome; Acute Kidney Injury; Toxemia; Shock, Septic; Multiple Organ Failure
• Other Study ID Numbers: EPN 2017/043 Covid19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD may be made available upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No