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Biomarkers and the management of COVID-19 patients

 

In need of treatments next to vaccinations

The COVID-19 pandemic is still a serious burden on the healthcare system worldwide, despite the availability of vaccines. For moderately to severely ill patients, the treatment options are limited, and very little innovation has found its way into the clinical practice (1).

A personalized approach in managing COVID-19

The University Medical Center Hamburg-Eppendorf (UKE) in Hamburg, Germany is leading one of the first precision medicine, biomarker-guided trials in moderately to severely ill COVID-19 patients (2). In the planned trial, two innovative biomarkers will guide the application of a potential new drug candidate. The first-in class humanized-monoclonal antibody Adrecizumab was already investigated in a phase II clinical trial in septic shock (3). COVID-19 and sepsis have a common disease mechanism that leads to vascular leakage and organ dysfunction (3,4). The treatment with Adrecizumab aims to reduce vascular leakage, improve organ function and reduce mortality.   

Biomarkers aid in personalized decision making

In critical care settings, one of the main causes of organ failure and subsequent mortality is loss of endothelial function, which is associated with leakage of blood vessels. Endothelial dysfunction is a hallmark of sepsis, and recent evidence have shown that it also plays a central role in the pathophysiology of COVID-19 (4). The endothelial function is modulated by the hormone Adrenomedullin, measurable using the biomarker bioactive Adrenomedullin 1-52 (bio-ADM*) (5). Published data have shown that elevated levels of bio-ADM indicate disease severity and predict the need for extracorporeal organ assistance in COVID-19 patients (6).

The drug candidate Adrecizumab targets Adrenomedullin to restore the compromised endothelial barrier function (3). In this novel precision medicine approach, the biomarker bio-ADM allows the early identification of patients suffering from endothelial dysfunction for treatment with Adrecizumab. At the same time, the biomarker dipeptidyl peptidase 3 (DPP3*) is used to exclude patients with an additional underlying disease mechanism leading to cardiac depression and requiring different therapeutic options (5).

Endothelial dysfunction leads to vascular leakage and is a consequence of critical diseases such as COVID-19 and sepsis. The biomarker bio-ADM allows the assessment of endothelial function. 

Point of care testing for rapid results


The multicenter study plans to enroll more than 200 hospitalized patients with moderate to severe COVID-19 disease for randomized treatment with either Adrecizumab or placebo on top of current standard of care. The biomarker measurements are performed using SphingoTec’s rapid point of care platform.

Read the press release


*Disclaimer

Sphingotest® penKid®, sphingotest® bio-ADM®, sphingotest® DPP3 are offered for in vitro diagnostics. “penKid”, “bio-ADM” and “DPP3” represent the analytes Proenkephalin A 119-159, bioactive Adrenomedullin 1-52, and Dipeptidyl Peptidase 3, respectively.

Reference Literature

(1)    https://www.global-sepsis-alliance.org.

(2)    https://clinicaltrials.gov/ct2/show/NCT05156671

(3)    Laterre PF, et al. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med. 2021 Nov;47(11):1284-1294. doi: 10.1007/s00134-021-06537-5. 

(4)    Varga et al. Endothelial cell infection and endothelitis in COVID-19. The Lancet, 2020, DOI: doi.org/10.1016/S0140-6736(20)30937-5 

(5)    van Lier et al 2020, Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3, J. Intern. Med., DOI: doi.org/10.1111/joim.13220

(6)    Simon T-P et al. Prognostic Value of Bioactive Adrenomedullin in Critically Ill Patients with COVID-19 in Germany: An Observational Cohort Study. Journal of Clinical Medicine. 2021, 10, 1667. doi.org/10.3390/jcm10081667