Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients

Abstract

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls – HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs “CCL3 and G-CSF” and “CXCL10 and IL-6” were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.

Plasma Proteins Associated with COVID-19 Severity in Puerto Rico

“…However, in our cohort, we found decreased PDGFb, especially in mild patients compared to controls. This is consistent with a previous study that found decreased serum PDGFb levels in COVID-19 patients compared to controls [49]. A recent study found that lower levels of PDGFb in the serum of COVID-19 patients compared to healthy controls within the first 24 h of hospitalization predict mortality [50].…”

Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection

“…In a mouse model of COVID-19 infection, HA production in the lung could be triggered by IL-13 administration and reduced by blockade of IL-13 in conjunction with less HAS1 expression, suggesting that this cytokine could contribute to HA levels in COVID-19. Consistent with this, IL-13 was increased in serum samples from a cohort of 178 COVID-19 patients [159] and in a second study of 138 COVID-19 patients [160] . However, in another study of 82 patients with severe COVID-19, IL-13 was decreased [159] .…”

“…Consistent with this, IL-13 was increased in serum samples from a cohort of 178 COVID-19 patients [159] and in a second study of 138 COVID-19 patients [160] . However, in another study of 82 patients with severe COVID-19, IL-13 was decreased [159] . IL-13 was also not increased in a small study of human respiratory secretions from 22 patients [137] .…”