Abnormal Upregulation of Cardiovascular Disease Biomarker PLA2G7 Induced by Proinflammatory Macrophages in COVID-19 patients

LI, Y.; JIANG, Y.; ZHANG, Y.; LI, N.; YIN, Q.; LIU, L.; LV, X.; LIU, Y.; LI, A.; FANG, B.; LI, J.; YE, H.; YANG, G.; CUI, X.; QU, Y.; LI, C.; LI, D.; WANG, S.; GAI, Z.; ZHAN, F.; LIANG, M.

BACKGROUND. Coronavirus disease 2019 (COVID-19) triggers distinct patterns of pneumonia progression with multiorgan disease, calling for cell- and/or tissue-type specific host injury markers. METHODS. An integrated hypothesis-free single biomarker analysis framework was performed on nasal swabs (n=484) from patients with COVID-19 in GSE152075. The origin of candidate biomarker was assessed in single-cell RNA data (GSE145926). The candidate biomarker was validated in a cross-sectional cohort (n=564) at both nucletide and protein levels. RESULTS. Phospholipase A2 group VII (PLA2G7) was identified as a candidate biomarker in COVID-19. PLA2G7 was predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, PLA2G7 was found in patients with COVID-19 and pneumonia, especially in severe pneumonia, rather than patients suffered mild H1N1 influenza infection. The positive rates of PLA2G7 ranging from 29.37% to 100.00% were positively correlated with not only viral loads in patients with COVID-19 but also severity of pneumonia in non COVID-19 patients. Although Ct values of PLA2G7 in severe pneumonia was siginificantly lower than that in moderate pneumonia (P=7.2e-11), no differences were observed in moderate pneumonia with COVID-19 between severe pneumonia without COVID-19 (P=0.81). Serum protein levels of PLA2G7, also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), were further found to be elevated and beyond the upper limit of normal in patients with COVID-19, especially among the re-positive patients. CONCLUSIONS. We firstly identified and validated PLA2G7, a biomarker for cardiovascular diseases (CVDs), was abnormally enhanced in COVID-19 patients at both nucletide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in COVID-19 patients. PLA2G7 could be a hallmark of COVID-19 for monitoring disease progress and therapeutic response.