Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients

SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII—for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine: for the growth factors M-CSF and the soluble receptor sIL2Ra: for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R: and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine: MDC and RANTES chemokines: the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB: and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10: the sIL-1RI, sIL1RII and sTNF-RII receptors: the MCP3, IL-8, MIG and IP-10 chemokines: the M-CSF and sIL-2Ra growth factors: and the wound-healing factor FGF2 favor fatal outcomes of the disease.