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Diagnostic tools for severely ill COVID-19 patients

The global COVID-19 pandemic has challenged health systems worldwide, with about 5% of patients requiring admission to intensive care units (ICU). Among the main complications that include respiratory and cardiovascular diseases, an emerging body of evidence shows that endothelial dysfunction plays a central role in the pathophysiology of severe COVID-19. Read more on the relevance of novel and established biomarker assays in the management of critically ill COVID-19 patients.

Adrenomedullin and endothelial dysfunction

Two recent studies show that endotheliitis, inflammation-induced damage of vascular endothelial cells, is a hallmark of COVID-19 (Varga et al., Ackermann et al.). The resulting endothelial dysfunction plays a central role in the disease progression in severely ill COVID-19 patients. A recent publication using whole blood gene expression analysis revealed that elevated expression of adrenomedullin (ADM) is associated with higher case severity (Hupf et al.).

However, performing gene expression analysis in acute care medicine is often challenging. Unpublished data of our protein biomarker bio-ADM®, measurable within 20 minutes at the point of need, describes as well a strong correlation between high bio-ADM® blood levels and the severity as the need for organ support. Therefore, bio-ADM® can support in more accurate and objective risk stratification of COVID-19 patients upon admission.

bio-ADM® is a biomarker validated in more than 22,000 shock patients, where it was demonstrated that high bio-ADM levels independently from inflammation and comorbidities indicate distortions in the endothelial barrier function, the inner cell sheet of blood vessels. Loss of this barrier function is considered a key driver in the development of hypotension and subsequent septic shock with loss of organ perfusion in sepsis patients (Mebazaa et al.).

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D-Dimer testing to assess severity of COVID-19 patients

D-Dimer is commonly elevated in patients with COVID-19. D-dimer levels have been demonstrated to correlate with disease severity and are a reliable prognostic marker for poor outcomes in patients admitted for COVID-19 (5). According to additional data (6), D-Dimer concentrations allow to rapidly identify COVID-19 patients with a high risk of pulmonary complications and venous thromboembolism, facilitating the early initiation of effective anticoagulant therapies. D-Dimer assay is available on our point-of-care platform Nexus IB10 as a rapid test delivering results in only 20 minutes and with no sample preparation.

PCT testing to assess secondary infections in COVID-19

Procalcitonin (PCT) is an established biomarker for the diagnosis of sepsis, a condition identified as being the most frequent complication in severe COVID-19 patients as a result of bacterial superinfection (6). Additional evidence points out that "serial procalcitonin measurement may play a role for predicting evolution towards a more severe form of disease”, which was defined as needing admission to intensive care unit or use of mechanical ventilation (7). To support the monitoring of severe COVID-19 patients at the point of need, SphingoTec makes available the assay for PCT on its point-of-care platform Nexus IB10. As a rapid test, the IB10 sphingotest® PCT aids in the diagnosis of sepsis and the assessment and monitoring of sepsis severity.

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IB10 sphingotest® bio-ADM®, PCT and D-Dimer are rapid point-of-care (POC) immunoassays available on our Nexus IB10 platform.

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Reference Literature

(1) Varga et al (2020): Endothelial cell infection and endothelitis in COVID-19, DOI:https://doi.org/10.1016/S0140-6736(20)30937-5
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(2) Hupf et al (2020): RNA-expression of adrenomedullin is increased in patients with severe COVID-19, Critical Care, DOI: 10.1186/s13054-020-03246-1
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(3) Mebazaa et al (2018): Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study, Crit Care, doi: 10.1186/s13054-018-2243-2
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(4) Yao et al (2020), D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study, Journal of Intensive Care, DOI: https://doi.org/10.1186/s40560-020-00466-z
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(5) Zhou et al (2020), Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, The Lancet, DOI: doi.org/10.1016/S0140-6736(20)30566-3
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(6) Lippi et al (2020), Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis, Clinica Chimica Acta, DOI: 10.1016/j.cca.2020.03.004
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