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1.
Front Endocrinol (Lausanne) ; 12: 727419, 2021.
Article in English | MEDLINE | ID: covidwho-1444039

ABSTRACT

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.


Subject(s)
COVID-19/blood , Cholesterol, HDL/blood , Diabetes Mellitus/blood , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , China , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Female , Humans , Kaplan-Meier Estimate , Leukocytes/cytology , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Severity of Illness Index
2.
PLoS One ; 16(6): e0253894, 2021.
Article in English | MEDLINE | ID: covidwho-1286873

ABSTRACT

OBJECTIVE: To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. METHODS: A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. DATA SYNTHESIS: The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. CONCLUSIONS: This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/pathology , Cytokine Release Syndrome/diagnosis , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Cytokine Release Syndrome/etiology , Ferritins/blood , Humans , Interleukin-6/blood , Leukocytes/cytology , Leukocytes/metabolism , SARS-CoV-2/isolation & purification , Severity of Illness Index
3.
Viruses ; 13(5)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1224260

ABSTRACT

The role of the adaptive microenvironment components in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection is widely researched, but remains unclear. Studying the common dynamics of adaptive immune response changes can help understand the pathogenesis of coronavirus disease 2019 (COVID-19), especially in critical patients. The aim of the present study was to determine the cytokines concentration and leukocyte subpopulations profiles in the severe COVID-19 (n = 23) and critical (n = 18) COVID-19 group distinguished by the computed tomography (CT) severity score. We observed lower percentage of lymphocyte subpopulation, higher neutrophils to lymphocytes ratio (NLR) and higher IL-6 concentration in critical COVID-19 group than in severe group. CT severity score was negative correlated with proportion of lymphocytes, lymphocytes T, CD4+ cells, Treg cells and NK cells and positive correlated with neutrophils, NLR, and IL-6. In critical group more correlations between cytokines and lymphocytes were observed, mainly between TNF-α, IL-1ß and lymphocyte subpopulations. The collective assessment of the cytokine profile, leukocyte subpopulations and the CT severity score can help to characterize and differentiate patient in advanced COVID-19 than the study of single parameters. We have shown that the interconnection of elements of the adaptive microenvironment can play an important role in critical COVID-19 cases.


Subject(s)
COVID-19/immunology , Cytokines/analysis , Leukocytes/cytology , Adult , Aged , COVID-19/metabolism , Cytokines/immunology , Female , Humans , Interleukin-1beta/immunology , Killer Cells, Natural/immunology , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Neutrophils/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index , T-Lymphocytes, Regulatory/immunology , Tomography, X-Ray Computed , Tumor Necrosis Factor-alpha/immunology
5.
PLoS Pathog ; 16(11): e1009034, 2020 11.
Article in English | MEDLINE | ID: covidwho-950851

ABSTRACT

The interferon-induced tetratricopeptide repeat protein (Ifit2) protects mice from lethal neurotropic viruses. Neurotropic coronavirus MHV-RSA59 infection of Ifit2-/- mice caused pronounced morbidity and mortality accompanied by rampant virus replication and spread throughout the brain. In spite of the higher virus load, induction of many cytokines and chemokines in the brains of infected Ifit2-/- mice were similar to that in wild-type mice. In contrast, infected Ifit2-/- mice revealed significantly impaired microglial activation as well as reduced recruitment of NK1.1 T cells and CD4 T cells to the brain, possibly contributing to the lack of viral clearance. These two deficiencies were associated with a lower level of microglial expression of CX3CR1, the receptor of the CX3CL1 (Fractalkine) chemokine, which plays a critical role in both microglial activation and leukocyte recruitment. The above results uncovered a new potential role of an interferon-induced protein in immune protection.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Cell Movement/immunology , Coronavirus Infections/virology , Leukocytes/virology , Murine hepatitis virus/pathogenicity , RNA-Binding Proteins/metabolism , Virus Replication/immunology , Animals , Apoptosis Regulatory Proteins/deficiency , Coronavirus Infections/immunology , Cytokines/metabolism , Interferons/metabolism , Leukocytes/cytology , Leukocytes/metabolism , Mice, Inbred C57BL , Microglia/metabolism , Murine hepatitis virus/metabolism
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