Early core signature of soluble factors in mild to moderate SARSCOV-2 infection

ABSTRACT

Background: Understanding the kinetics of early immune responses to SARSCoV-2 infection is critical to identify potentials biomarkers of disease outcome. A myriad of soluble mediators including, pro-inflammatory, immune-suppressors and growth factors, play a relevant role in the disease progression. However, to date, limited data is available about the role of soluble factors and most studies focus only in severe cases with limited follow-up. Here, we studied with high resolution the kinetics of soluble mediators in mild to moderate cases of SARSCoV-2 infection 1-90 days from symptom onset (DfSO). Methods: We selected individuals from the ProHEpiC-19 cohort study that included mainly healthcare workers with a PCR+ and mild or moderate disease within 1-14 DfSO. IgG and IgM levels were determined by ELISA. We selected plasma samples (n=30) in the range of 1-90 DfSO, and performed a Luminex multiplex assay including 45 soluble human factors. Results: We identified a core signature including 19 highly correlated soluble factors at 1-14 DfSO, based on clustering analysis. The core signature contained three sub-clusters #1 (RANTES, IL13, TGFa, PDGF-AB, PDGF-AA, EGF, MIP1b, CD40L and GROb), #2 (G-CSF, PDL1-B7, Fractalkine, IL8, IFNg, Granzyme B and IL10) and #3 (IL7, IL6, and VEGF). We found major changes in #2 and #3 cluster composition between 1-14 and 30-45 DfSO, due to the loss of PDL1-B7, Fractalkine, IL8, IL7, IL6, and VEGF association. Moreover, by 60-75 DfSO, the soluble factor association in #2 and #3 disappeared from the core signature. In addition, we observed a negative correlation between IgG and IgM levels with IL4 production at 1-14 DfSO (IgG ρ =-0.82, p=0.012;IgM ρ=-0.83, p=0.011). Similarly, a negative correlation was observed between Igs and Mip3a at 30-45 DfSO (IgG ρ=-0.78, p=0.023;IgM ρ =-0.81, p=0.022). Conclusion: We delineated a core signature of soluble factors in mild to moderate SARS-CoV-2 infection, including growth factors, chemokines and pro-inflammatory cytokines. The longitudinal follow-up of this signature revealed significant changes during the 1-90 DfSO. This information can provide new insights for the definition of biomarkers for patient stratification in mild or moderate SARS-Cov-2 infection. Further data is needed to understand the association between IL4 and Mip3a with low Igs levels.