SMRUTI NAIR
HENRY DANIELL
| SMRUTI NAIR | HENRY DANIELL |
Smruti Nair, Henry Daniell
Department of Basic and Translational Sciences, University of Pennsylvania, School of Dental Medicine
Introduction
After two years of this pandemic, there are no tests to end the quarantine as PCR uses amplification and doesn’t distinguish infectious from non-infectious viral particles, vital in monitoring transmission. Several COVID-19 symptoms are associated with RAS dysregulation and SARS-CoV-2 enters human cells via ACE2 receptors. Therefore, we investigate the association between the triad – sACE2 activity, concentration, and Ang (1-7) levels and a potential role of soluble ACE2 (sACE2) activity as a metabolic biomarker for COVID -19 disease severity and recovery.
Methods
We analyzed sACE2 enzymatic activity in the plasma (n=59), saliva (n=21) samples of 80 hospitalized COVID-19 patients and healthy volunteers. All COVID-19 patients were confirmed to be PCR positive for SARS-CoV-2, while all controls negative for SARS-CoV-2 antibody on serology testing. Samples for the plasma analyses were collected from individuals hospitalized with COVID-19 within the University of Pennsylvania Health System. ACE2/Ang (1-7) concentration in plasma samples was analyzed in a cohort of 16 patients (Ronald G. Collman-IRB#823392; Krzysztof Laudanski-#842613). Restoration of sACE2 activity were also analyzed in plasma samples (n=45) of early hospitalized COVID-19 patients (Katherine J. Bar-NCT04397757) undergoing convalescent plasma (CCP) therapy.
Results
Soluble ACE2 activity was reduced in COVID-19 plasma as compared to healthy controls (4.86 ±1.15 to 46.49±6.43 mU/mg enzyme activity units; p-value < 0.0001). ACE2 activity was also substantially reduced in the saliva of COVID-19 patients than healthy controls (70.51±22.75.vs 126.8±27.71 mU/mg enzyme activity units; p value = 0.0065). Lows sACE2 activity at early hospitalization was restored during disease recovery, that was statistically higher than matched controls in CCP administered patients (6.707 ± 1.080 vs 13.79 ± 1.528 mU/mg enzyme activity units; p value < 0.0021). A positive correlation was observed between ACE2 activity and Ang (1-7) concentration in COVID-19 and control samples (r2=0.39; p value=0.0073) but not ACE2 concentration.
Conclusion
Significant reduction in sACE2 activity was observed in COVID-19 plasma and saliva. Reduced plasma sACE2 activity correlated strongly with low Ang (1-7) levels compared to healthy volunteers. Early hospitalized patients treated with convalescent plasma therapy recovered with sACE2 enzyme activity levels almost reaching levels of healthy controls especially in patients with compromised RAS pathway.