Baseline immune signatures are associated with prospective COVID-19 infection and clinical outcomes in healthcare workers: Evidence from a cohort study in Brazil

The present study intended to characterize the profile of serum immune mediators in healthcare professionals at the pandemic onset, aiming to identify baseline immunological patterns associated with prospective COVID-19 diagnosis. A total of 386 participants with negative COVID-19 diagnosis were enrolled in a 19-month follow-up observational study. Quantitative analysis of immune mediators (chemokines, pro-inflammatory & regulatory cytokines and growth factors) was carried out by high-throughput multiplex array. All participants were SARS-CoV-2-negative at baseline, and immune mediators were measured prior to any documented COVID-19 diagnosis. Participants were categorized according to prospective diagnosis of COVID-19 COVID-19 (-) and COVID-19 (+), time elapsed prior COVID-19 (+) diagnosis, disease outcome and age ranges. Data demonstrated that participants with prospective COVID-19 (+) diagnosis presented higher levels of immune mediators as compared to COVID-19 (-). The higher the baseline levels of immune mediators, the shorter the elapsed time prior COVID-19 (+) diagnosis. GM-CSF, IL-5, VEGF, IL-13, CCL11 and IL-10 presented higher increment magnitude in COVID-19 (+) over the COVID (-) counterpart. Signatures profiles further confirmed these findings. Symptomatic or severe disease outcomes, as well as persistent symptom duration were associated with distinct profiles of immune mediators. Networks with higher correlation numbers were observed in COVID-19 (+), particularly in short-time prior prospective diagnosis, symptomatic mild disease and with short symptom duration. Multivariate and decision tree analysis demonstrated that GM-CSF, CCL11, CXCL10 and TNF-α effectively distinguished COVID-19 (+) individuals and pointed out that G-CSF was consistently associated with severe disease and prolonged symptom duration. These findings demonstrate that baseline serum immune mediator profiles are associated with prospective COVID-19 diagnosis and clinical outcomes, as identified through non-linear modeling.