suPAR is predictive of outcome in viral and respiratory disease By Jesper Eugen-Olsen, PhD ([email protected]) – March 13, 2020. suPAR is a marker of chronic , and patients with high suPAR have a chronically activated , that is not capable of fighting disease. suPAR is elevated in elderly with comorbidities and capture the most fragile patients. In acute medical patients in general, suPAR is a strong marker of 30-day readmission and mortality1,2. suPAR has been investigated in several viral , including HIV, HCV, Crimean-Congo hemorrhagic fever and hantavirus. In all cases, suPAR is associated with clinical severity and mortality 3-6. Perhaps because, in patients with chronic inflammation, virus has an easier time evading, settling and replicating.

Furthermore, patients with respiratory diseases (e.g. pneumonia 7 or COPD 8) have elevated suPAR and those with the highest level of suPAR have increased 30-day mortality. It is therefore expected that a virus that causes respiratory distress syndrome will have a more severe impact on patients with elevated suPAR.

COVID-19 is also likely to elevate the suPAR level. In a paper from Wuhan, 15/52 (29%) of patients suffering from severe COVID-19 developed acute kidney injury 9, which may be induced by the increase in suPAR 10.

With regard to COVID-19, it is therefore likely that suPAR can triage whether patients will have a mild or a severe outcome of the infection.

This may aid in selecting which patients that could be sent home (low suPAR, mild outcome of infection) and which patients that should be admitted to the hospital for care (elevated suPAR, high risk of mortality) (figure 1).

Figure 1: Presumed course of SARS-CoV-2 infection according to baseline suPAR

References cited:

1. Rasmussen LJ et al, Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort study. Emerg Med J. 2016 Nov;33(11):769-775.

2. Rasmussen LJH et al, Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study. Crit Care Med. 2018 Dec;46(12):1961-1968.

3. Hoenigl M et al, Soluble Urokinase Plasminogen Activator Receptor Is Predictive of Non-AIDS Events During Antiretroviral Therapy-mediated Viral Suppression.Clin Infect Dis. 2019 Aug 1;69(4):676-686

4. Oliveira I et al, Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study. BMJ Open. 2012 Nov 14;2(6).

5. Yilmaz G et al, The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol. 2011 Mar;50(3):209-11.

6. Outinen TK et al, Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection. PLoS One. 2013 Aug 21;8(8):e71335.

7. Çitlenbik H et al, Levels of Soluble Urokinase Plasminogen Activator Receptor in Pediatric Lower Respiratory Tract Infections. Pediatr Allergy Immunol Pulmonol. 2019 Sep 1;32(3):121-127

8. Gumus A et al, Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD. Int J Chron Obstruct Pulmon Dis. 2015 Feb 13;10:357-65.

9. Yang X et al, Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020 Feb 24. pii: S2213-2600(20)30079-5.

10. Hayek SS et al, Soluble and Acute Kidney Injury. N Engl J Med. 2020 Jan 30;382(5):416-426