Dear Editor,The mechanistic pathways leading to immune dysregulation and complications driven by uncontrolled severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remain major challenges. 1,2 Hence, a detailed analysis of the proteome, metabolome and lipidome profile of coronavirus disease 2019 (COVID-19) patients showing different severity grades might shed light on the diseaseF I G U R E 1 Study design and clinical characterization of the study cohort. (A) Flowchart of the clinical strategy followed to categorize patients of the coronavirus disease-2019 (COVID-19) study cohort. (B) Incidence of comorbidities (a), COVID-19 symptoms (b), medication (c), and oxygen & intensive care (d), grouped by disease severity as mild, severe and critical patients. The size of bars (a, c) and circular (b , d) portions is proportional to the percentage of the corresponding comorbidity, symptom, medication or treatment. While patients with mild disease presented mostly anosmia, were treated with antibiotics and did not require oxygen supply, the incidence of dyspnea was significantly higher in the severe and critical groups, many of the latter requiring corticosteroids, hydroxychloroquine, lopinavir/ritonavir. Low-flow oxygen therapies were mainly necessary for severe patients, some of who required high-flow oxygen administration and, a high proportion of critical patients were intubated and required vasopressor administration or dialysis. Please note that COVID-19-related medication (b) was dispensed after blood sample collection, so that is assumed the subsequent analysis are not biased due to exposure to medication at the time of blood collectionThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
The cytokine signature present in COVID-19 could provide information on the pathogenic mechanisms of the disease and could identify possible prognostic biomarkers and possible therapeutic targets. In this longitudinal work, we studied the clinical and biochemical parameters and circulating cytokine levels of 146 patients at the time of admission for COVID-19 and 4–6 weeks later. The main objective of this study was to determine whether basal cytokines could be early prognostic biomarkers of COVID-19, and also to analyze the impact of comorbidities, such as obesity or metabolic syndrome (MS), in the cytokine profile. The levels of most inflammatory cytokines were elevated on admission in relation to the level that was reached 4–6 weeks later, except for IL-1β, which was lower on admission; these levels were irrespective of the presence of obesity or MS since the cytokine storm masks these inflammatory processes. Among the cytokines analyzed, those that correlated with a worse prognosis of COVID-19 were resistin, IL-6, IL-8, IL-15, MCP-1 and TNF-α. Specifically, resistin and IL-15 are the best early predictors of requiring invasive ventilation. Therefore, resistin and IL-15 should be included in the personalized treatment decision algorithm of patients with COVID-19.
Background: The underlying mechanisms of incomplete immune reconstitution in treated HIV-positive patients are very complex and may be multifactorial, but perturbation of chemokine secretion could play a key role in CD4 + T-cell turnover. Methods: We evaluated the circulating baseline and 48-week follow-up concentrations of SDF-1/CXCL12, fractalkine/CX3CL1, MCP-1/CCL2, MIP-a/CCL3, MIP-b/CCL4 and RANTES/CCL5, and we estimated their association with CXCL12, CX3CR1, CCR2, CCL5 and CCR5 single nucleotide polymorphisms (SNPs) to investigate multiple chemokine-chemokine receptor signatures associated with immune dysregulation preceding poor immune recovery. Findings: The circulating concentrations and gene expression patterns of SDF-1/CXCL12 (CXCL12 rs1801157) and MCP-1/CCL2 (CCR2 rs1799864_814) were associated with immune recovery status. CCR2 rs1799864_814 and CCR5 rs333_814 (D32) determine the baseline plasma RANTES and MIP-a concentrations, respectively, in participants with poor immune response. Interpretation: SDF-1/CXCL12 and MCP-1/CCL2 could be considered prognostic markers of immune failure despite suppressive antiretroviral therapy. The strong linkage disequilibrium (LD) between CCR2 rs1799864_814 and CCR5 rs1800024 indicated that the alleles of each gene are inherited together more often than would be expected by chance.
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