Today, severely affected COVID-19 patients receive standard of care at intensive care unit (ICU), but clinical trials are still ongoing for new treatments, aiming at preventing long-term sequelae.


Based on the pathophysiology of SARS-CoV-2 on its ACE2-receptor, the angiotensin pathway is activated and circulating biomarkers of interest can be measured. Here, a diagnostic test accuracy study is presented, to classify COVID-19 patients in severe versus mild cases with the intention of guiding treatment decisions, to prevent pulmonary fibrosis.


Plasma samples have been collected from COVID-19 patients with ARDS at ICU (N=17), and compared with asymptomatic COVID-19 (N=7) and healthy controls (N=10) using non-parametrical statistics. The biological markers angiotensin-(1-7) (Ang-(1-7)), transforming growth factor beta (TGF-?), ferritin and C-reactive protein (CRP) were measured. Cut-off for a composite index was obtained through ROC.


COVID-19 patients with insufficient Ang-(1-7), are eligible for substitution therapy and novel expensive therapies beside standard of care, while the subpopulation of high Ang-(1-7) is analyzed with a composite index test including TGF-?, ferritin and CRP. A cut-off of 34 in the composite index, differentiates asymptomatic COVID-19 from severe COVID-19 at ICU having acute respiratory distress syndrome (SENS=100%, SPEC=80%, AUC=0.933, LR=5) and evolving to pulmonary fibrosis (PPV=97%).


A theranostic approach is proposed with objective biomarker measurement, to guide therapeutic decisions in COVID-19 (e.g. Ang-(1-7) substitution therapy and anti-fibrotics). This could probably diminish sequels like post-ARDS pulmonary fibrosis.