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

Abstract

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.

Fraction of plasma exomeres and low-density lipoprotein cholesterol as a predictor of fatal outcome of COVID-19

“…It should be noting that proinflammatory cytokines induced by viral infection may modulate lipid metabolism [ 21 ]. Our study found increased secretion of pro-inflammatory cytokines such as CCL20/MIP3ɑ, IL-10, IL-15, IL-27 in non-survivors than in controls that is consistent with previously published data (Supplementary materials) [ 22 ]. Also, our finding is that increased expression levels of LDL receptors genes ( LDLR , CD36 , STAB1 ) were found in non-survivors and survivors compared to controls at time to admission to the ICU.…”

The role of cholesterol metabolism in predicting clinical outcome of patients with severe COVID-19

“…CCL20/MIP3ɑ mainly elicits its effector function via CCR6 receptor binding; interestingly enough, we previously noted a negative correlation between CCR6 ex-pressing CD8+ cells and IL-27 [31]. However, secretion of IL-15 and IL-27 was increased in non-survivors compared to both survived patients and controls that is consistent with previously published data [32]. It is interesting to note that IL-15 and IL-27 are early cytokines, and this change in their concentration indicates the activation of the innate immune response when the virus is recognized by the epithelial or dendritic cells of the body, followed by the induction of the innate defense of body and induction of inflammation processes [31,[33][34].…”

“…It is interesting to note that IL-15 and IL-27 are early cytokines, and this change in their concentration indicates the activation of the innate immune response when the virus is recognized by the epithelial or dendritic cells of the body, followed by the induction of the innate defense of body and induction of inflammation processes [31,33–34]. In accordance with our and previous data, IL-15, IL-27 were previously associated with the severity and fatal outcome of COVID-19 [32, 35–38]. Additionally, we revealed the negative correlation between concentration of these cytokines and key lipid parameters (TC, LDL, HDL), in particular, LDL cholesterol level, and this correlation was more pronounced after 7 days in the patient subgroup with fatal outcome.…”

Vitamin D and SARS‐CoV‐2

“…Among others, severe COVID-19 patients present with elevated circulating levels of IL-6, TNFα, IL-1β, IFNγ and others, 38 and the levels are often correlated with COVID-19 severity. [50][51][52][53][54] Some patients develop a cytokine release syndrome and even a cytokine storm, which can be fatal as it can result in an acute respiratory distress syndrome (ARDS) and multiple organ dysfunction (MOD). 55 Taken together, the current knowledge indicates that a successful immune response (leading to fast elimination of the virus and a full recovery) relies on an efficient and wellcoordinated immune response involving all parts of the immune system.…”