%0 Journal Article
%T Biomarkers of early SARS-CoV-2 infection before the onset of respiratory symptoms.
%A Teng O
%A Quek AML
%A Nguyen TM
%A Wang S
%A Ng IXQ
%A Fragata L
%A Mohd-Abu-Bucker FB
%A Tambyah PA
%A Seet RCS
%J Clin Microbiol Infect
%V 30
%N 4
%D 2024 Apr 29
%M 38160754
%F 13.31
%R 10.1016/j.cmi.2023.12.024
%X <B>OBJECTIVE: </B>Currently, limited data exist regarding the pathological changes occurring during the incubation phase of SARS-CoV-2 infection. We utilized proteomic analysis to explore changes in the circulatory host response in individuals with SARS-CoV-2 infection before the onset of symptoms.<BR><B>METHODS: </B>Participants were individuals from a randomized clinical trial of prophylaxis for COVID-19 in a workers' dormitory. Proteomic signatures of blood samples collected within 7 days before symptom onset (incubation group) were compared with those collected >21 days (non-incubation group) to derive candidate biomarkers of incubation. Candidate biomarkers were assessed by comparing levels in the incubation group with both infected individuals (positive controls) and non-infected individuals (negative controls).<BR><B>RESULTS: </B>The study included men (mean age 34.2 years and standard deviation 7.1) who were divided into three groups: an incubation group consisting of 44 men, and two control groups-positive (n = 56) and negative (n = 67) controls. Through proteomic analysis, we identified 49 proteins that, upon pathway analyses, indicated an upregulation of the renin-angiotensin and innate immune systems during the virus incubation period. Biomarker analyses revealed increased concentrations of plasma angiotensin II (mean 731 vs. 139 pg/mL), angiotensin (1-7) (302 vs. 9 pg/mL), CXCL10 (423 vs. 85 pg/mL), CXCL11 (82.7 vs. 32.1 pg/mL), interferon-gamma (0.49 vs. 0.20 pg/mL), legumain (914 vs. 743 pg/mL), galectin-9 (1443 vs. 836 pg/mL), and tumour necrosis factor (20.3 vs. 17.0 pg/mL) during virus incubation compared with non-infected controls (all p < 0.05). Plasma angiotensin (1-7) exhibited a significant increase before the onset of symptoms when compared with uninfected controls (area under the curve 0.99, sensitivity 0.97, and specificity 0.99).<BR><B>CONCLUSIONS: </B>Angiotensin (1-7) could play a crucial role in the progression of symptomatic COVID-19 infection, and its assessment could help identify individuals who would benefit from enhanced monitoring and early antiviral intervention.