Systemic and cerebrospinal fluid immune mediators coordinate a dichotomic microenvironment in parturients with acute or convalescent phases of COVID-19

The present study intended to characterize the profile of soluble immune mediators in serum samples and in the cerebrospinal fluid (CSF) microenvironment from parturients with acute and convalescent COVID-19 as compared to healthy controls (HC), during the circulation of B.1.1.28 and B.1.1.33 SARS-CoV-2 strains, which were identified during the initial spread of COVID-19 in Brazil. Data demonstrated increased levels of immune mediators in serum at acute infection with a clear waning during convalescent COVID-19. Conversely, a progressive increase of immune mediators was observed in CSF from acute infection towards convalescent COVID19. Immune mediator signatures and integrative correlation circuits further confirmed these findings and supported the existence of dichotomic microenvironments in the serum and CSF compartments. While a waning of correlations involving pro-inflammatory cytokines with increased connectivity of regulatory cytokines was observed in serum samples from acute towards convalescent COVID-19, an increasing frequency of correlations mediated by pro-inflammatory cytokines with decreased connectivity of regulatory cytokine was the hallmark of CSF. Correlations analysis identified a set of molecules associated with the dichotomic crosstalk between serum and CSF compartments, including chemokines (CXCL8, CCL5, CXCL10) and regulatory cytokines (IL-4 and IL-9). These immune biomarkers may represent potential targets for therapeutic strategies in parturients with COVID19. Together, these findings demonstrated the existence of a divergent landscape of soluble immune mediators in serum and CSF, emphasizing the relevance of understanding the systemic and compartmentalized immune response elicited by SARS-CoV-2 infection during pregnancy.