Clinical trial NCT04316884: Mechanisms for Organ Dysfunction in Covid-19
Official title: Uppsala Intensive Care Study of Mechanisms for Organ Dysfunction in Covid-19
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: COVID-19
Organ Dysfunction Syndrome Sepsis
Organ Dysfunction Syndrome, Multiple
Septic Shock
Acute Kidney Injury
Acute Respiratory Distress Syndrome
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2020-03-20
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients requiring intensive care with suspected or verified COVID19

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

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Pregnancy or breastfeeding
* Under-age

Primary outcomes:
measure: Acute Kidney Injury
timeFrame: During Intensive Care, an estimated average of 10 days.
Secondary outcomes:
measure: ARDS
timeFrame: During intensive care, an estimated average of 10 days.
measure: 30 day mortality
timeFrame: 30 days
measure: 1 year mortality
timeFrame: 1 year
measure: Chronic Kidney Disease
timeFrame: 60 days and 1 year after ICU admission
measure: SOFA-score
timeFrame: During Intensive Care, an estimated average of 10 days.
measure: Thromboembolic events
timeFrame: During intensive care
measure: ICUAW
timeFrame: During intensive care or after intensive care
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Uppsala University Hospital
name: Robert Frithiof, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.