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1.
PLoS One ; 17(3): e0264178, 2022.
Article in English | MEDLINE | ID: covidwho-1731596

ABSTRACT

Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March-June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91-0·98) and increased survival alone by 6% (HR 0·95; CI 0·90-0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease.


Subject(s)
COVID-19/pathology , Monoamine Oxidase/blood , Adult , Aged , COVID-19/mortality , COVID-19/virology , Endothelium/metabolism , Endothelium/pathology , Female , Hospitalization , Humans , Intensive Care Units , Interleukin-6/blood , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index
3.
Biomark Med ; 16(5): 317-330, 2022 04.
Article in English | MEDLINE | ID: covidwho-1703144

ABSTRACT

Aim: To investigate the serum circulating DPP4 activity in patients with COVID-19 disease. Materials & methods: Serum samples from 102 hospitalized COVID-19 patients and 43 post-COVID-19 plasma donors and 39 SARS-CoV-2 naive controls and their medical data were used. Circulating DPP4 activities according to different COVID-19 disease peak severity (WHO) groups at sampling and at peak were assessed. Results: A significant decrease (p < 0.0001) in serum DPP4 activity was found in study groups of higher disease severity. When the circulating DPP4 activity was assessed as a prognostic marker, the logistic regression (p = 0.0023) indicated that the enzyme activity is a predictor of mortality (median 9.5 days before death) with receiver operating characteristic area under the curves of 73.33% (p[area = 0.5] < 0.0001) as single predictor and 83.45% (p[area = 0.5] < 0.0001) in combination with age among hospitalized patients with COVID-19. Conclusion: Decreased circulating DPP4 activity is associated with severe COVID-19 disease and is a strong prognostic biomarker of mortality.


Subject(s)
Biomarkers/blood , COVID-19/blood , Dipeptidyl Peptidase 4/blood , Inpatients/statistics & numerical data , Adult , Aged , Biomarkers/metabolism , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/therapy , Dipeptidyl Peptidase 4/metabolism , Female , Humans , Interleukin-6/blood , Interleukin-6/metabolism , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2/physiology , Severity of Illness Index
4.
PLoS One ; 17(2): e0262911, 2022.
Article in English | MEDLINE | ID: covidwho-1700320

ABSTRACT

BACKGROUND: COVID-19 pandemic resulted in about 165 million infections and 3.4 million deaths all over the world across 15 months. The most severe clinical presentation of COVID-19 diseases is interstitial pneumonia. METHODS: In this paper we describe clinical outcomes based on radiological features as well as the pattern of haematochemical parameters and IgG/IgM antibodies in 75 patients hospitalized due to COVID-related interstitial pneumonia not requiring intensive care assistance. Each patient underwent routine laboratory tests, including inflammatory markers and coagulation profile at baseline. Computed Tomography (CT) was performed at baseline and after 3 months to assess the persistence of radiological sequelae. A Generalized Linear Model (GLM) was used to test for each patient the association between individual haematochemical parameters at the time of hospital admission and the subsequent radiological features after three months. The presence of IgG antibodies was quantitatively determined in 70 patients at the time of hospital admission and after 3 months. A subgroup of 49 and 21 patients underwent additional dosage of IgG after 6 and 12 months, respectively. IgM serological antibodies were available for 17 patients at baseline and 61 at T3, with additional follow-up for 51 and 20 subjects after 6 and 12 months, respectively. RESULTS: Only 28 out of 75 patients discharged from the hospital were totally healed after 3 months, while 47 patients (62.7%) still presented radiological sequelae. According to the GLM model, specific haematochemical baseline parameters-such as IL-6, GPT, platelets and eosinophil count-showed a statistically significant association with the presence of radiological sequelae at month 3 highlighting an OR = 0.5, thus meaning that subjects completely healed after 3 months presented half levels of IL-6 at baseline compared to patients with sequelae. In general, IgG serum levels were always higher than IgM at the time of hospitalization (75% at T0; n = 12 out of 16 patients with data available in both visits), after 3 months (72.1%; n = 44 out of 61 pts.), after 6 months (56.8%; 25 out of 44 pts.), and one year after hospitalization (60%; 12 out of 20 pts.). Overall, IgG and IgM serum levels presented a statistically significant decreasing trend from the baseline to month 3, 6 and 12. One patient presented an increase in IgM between baseline and month 3 but negative PCR test for SARS-COV2 on throat swab. CONCLUSIONS: As supported by our findings on 75 patients, COVID-related interstitial pneumonia triggers early IgG levels (higher than IgM) that gradually decrease over 12 months. Mid-term sequelae are still detectable at lung Computed Tomography after 3 months from the hospital admission. Occasionally, it is possible to observe increase of IgM levels in presence of low concentrations of IgG and negative PCR ELISA tests for SARS-COV2 RNA. Baseline levels of IL-6 could be proposed as predictor of radiological mid/long-term sequelae after COVID-related interstitial pneumonia.


Subject(s)
Antibodies, Viral/blood , COVID-19 , Hospitalization , Immunoglobulin G/blood , Immunoglobulin M/blood , Interleukin-6/blood , SARS-CoV-2/metabolism , Tomography, X-Ray Computed , Adult , COVID-19/blood , COVID-19/drug therapy , COVID-19/therapy , Female , Follow-Up Studies , Humans , Male
5.
J Leukoc Biol ; 111(1): 269-281, 2022 01.
Article in English | MEDLINE | ID: covidwho-1591653

ABSTRACT

The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID-19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID-19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID-19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL-6 and IL-10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL-6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927-1.000, P < 0.0001). In addition, the preoperative IL-6 concentration of 77.38 pg/ml was the optimal cutoff value (sensitivity: 84.6%, specificity: 100%). Using multivariate logistic regression analysis and ROC curves, IL-6 > 106.44 pg/ml and CD8+ T cell counts <150 cells/µl were found to be associated with mortality. Measuring the immune parameters and defining a risk threshold can segregate patients who develop a severe disease from those with a mild pathology. The identification of these parameters may help clinicians to predict the outcome of the patients with high risk of unfavorable progress of the disease.


Subject(s)
COVID-19/blood , COVID-19/mortality , Interleukin-6/blood , Severity of Illness Index , Africa, Northern , Aged , Biomarkers/blood , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Cytokines/metabolism , Female , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Middle Aged , Multivariate Analysis , Prognosis , Treatment Outcome
6.
PLoS One ; 16(12): e0261529, 2021.
Article in English | MEDLINE | ID: covidwho-1599654

ABSTRACT

BACKGROUND: Risk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management. METHODS: We conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease. FINDINGS: We identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 µg/L, fibrin degradation products >5 µg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease. INTERPRETATION: We have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Hospitalization , SARS-CoV-2 , Severity of Illness Index , Adolescent , Adult , Age Factors , C-Reactive Protein/analysis , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospitals , Humans , India/epidemiology , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Procalcitonin/blood , Risk Factors , Young Adult
7.
Front Public Health ; 9: 778340, 2021.
Article in English | MEDLINE | ID: covidwho-1595542

ABSTRACT

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide, and the WHO declared it a pandemic on March 11, 2020. Clinical characteristics and epidemiology features of patients infected with SARS-CoV-2 have been explored in the previous study. However, little is known about the combinative association of liver dysfunction and abnormal interleukins (ILs) in severe patients with COVID-19. This study was designed to estimate whether liver dysfunction and abnormal ILs could predict the severity of COVID-19. This study integrated liver function data and ILs data in patients with COVID-19 and found that liver injury and two ILs, interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6), were closely related to the prognosis of patients with COVID-19. This study may give more exact information to clinicians about the prognosis of patients with COVID-19. In addition, this correlational study between liver disorder and ILs may provide a new vision to diagnosis and treatment in patients.


Subject(s)
COVID-19 , Interleukin-6 , Liver/pathology , Receptors, Interleukin-2/blood , COVID-19/diagnosis , Humans , Interleukin-6/blood , Pandemics
8.
Dis Markers ; 2021: 7686374, 2021.
Article in English | MEDLINE | ID: covidwho-1595046

ABSTRACT

Objective: S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are indicators of global transmethylation and may play an important role as markers of severity of COVID-19. Methods: The levels of plasma SAM and SAH were determined in patients admitted with COVID-19 (n = 56, mean age = 61). Lung injury was identified by computed tomography (CT) in accordance with the CT0-4 classification. Results: SAM was found to be a potential marker of lung damage risk in COVID-19 patients (SAM > 80 nM; CT3,4 vs. CT 0-2: relative ratio (RR) was 3.0; p = 0.0029). SAM/SAH > 6.0 was also found to be a marker of lung injury (CT2-4 vs. CT0,1: RR = 3.47, p = 0.0004). There was a negative association between SAM and glutathione level (ρ = -0.343, p = 0.011). Interleukin-6 (IL-6) levels were associated with SAM (ρ = 0.44, p = 0.01) and SAH (ρ = 0.534, p = 0.001) levels. Conclusions: A high SAM level and high methylation index are associated with the risk of lung injury in patients with COVID-19. The association of SAM with IL-6 and glutathione indicates an important role of transmethylation in the development of cytokine imbalance and oxidative stress in patients with COVID-19.


Subject(s)
COVID-19/complications , Lung Injury/blood , S-Adenosylhomocysteine/blood , S-Adenosylmethionine/blood , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Atherosclerosis/epidemiology , Biomarkers , COVID-19/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Female , Glutathione/blood , Humans , Hypertension/epidemiology , Interleukin-6/blood , Lung Injury/diagnostic imaging , Lung Injury/etiology , Male , Methylation , Middle Aged , Military Personnel , Risk , Tomography, X-Ray Computed , Young Adult
9.
Iran J Immunol ; 18(4): 331-337, 2021 12.
Article in English | MEDLINE | ID: covidwho-1594484

ABSTRACT

BACKGROUND: According to the World Health Organization, Mexico presents one of the highest mortality rates due to coronavirus disease 2019 (COVID-19). The "cytokine storm" phenomenon has been proposed as a pathological hallmark of severe COVID-19. OBJECTIVE: To determine the association of serum cytokine levels with COVID-19 severity. METHODS: We studied the cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and the IFN-γ serum levels through flow cytometry in 56 COVID-19 patients (24 critical and 32 non-critical) from Northwest Mexico. RESULTS: We observed a significant increase in the IL-6 and the IL-10 levels in the sera of critical patients. These cytokines were also associated with mechanical ventilation necessity and death, IL-6 showing AUC values above 0.7 for both variables; and correlated with Na+, creatinine, and platelet levels. On the other hand, no association was found between IL-2, IL-4, TNF-α, and IFN-γ with tested variables. CONCLUSION: Our results corroborate previous observations regarding IL-6 and IL-10 involvement in the severity of COVID-19.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Interleukin-10/metabolism , Interleukin-6/metabolism , COVID-19/pathology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Female , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Mexico , Patient Acuity
10.
Cytokine ; 150: 155790, 2022 02.
Article in English | MEDLINE | ID: covidwho-1587975

ABSTRACT

BACKGROUND: Several immune mediators (IM) including cytokines, chemokines, and their receptors have been suggested to play a role in COVID-19 pathophysiology and severity. AIM: To determine if early IM profiles are predictive of clinical outcome and which of the IMs tested possess the most clinical utility. METHODS: A custom bead-based multiplex assay was used to measure IM concentrations in a cohort of SARS-CoV-2 PCR positive patients (n = 326) with varying disease severities as determined by hospitalization status, length of hospital stay, and survival. Patient groups were compared, and clinical utility was assessed. Correlation plots were constructed to determine if significant relationships exist between the IMs in the setting of COVID-19. RESULTS: In PCR positive SARS-CoV-2 patients, IL-6 was the best predictor of the need for hospitalization and length of stay. Additionally, MCP-1 and sIL-2Rα were moderate predictors of the need for hospitalization. Hospitalized PCR positive SARS-CoV-2 patients displayed a notable correlation between sIL-2Rα and IL-18 (Spearman's ρ = 0.48, P=<0.0001). CONCLUSIONS: IM profiles between non-hospitalized and hospitalized patients were distinct. IL-6 was the best predictor of COVID-19 severity among all the IMs tested.


Subject(s)
COVID-19/immunology , Cytokines/physiology , Hospitalization , Receptors, Cytokine/physiology , SARS-CoV-2 , Adult , Area Under Curve , Biomarkers , C-Reactive Protein/analysis , COVID-19/physiopathology , COVID-19/therapy , Chemokines/blood , Chemokines/physiology , Cytokines/blood , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Interleukin-6/blood , Length of Stay/statistics & numerical data , Male , Middle Aged , Prognosis , ROC Curve , Receptors, Chemokine/physiology , Respiration, Artificial/statistics & numerical data , Severity of Illness Index , Treatment Outcome
11.
Front Immunol ; 12: 627844, 2021.
Article in English | MEDLINE | ID: covidwho-1573949

ABSTRACT

BACKGROUND: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. METHODS: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. RESULTS: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. CONCLUSIONS: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Immunoglobulins, Intravenous/administration & dosage , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , China/epidemiology , Disease-Free Survival , Female , Ferritins/blood , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Survival Rate
12.
Ann Med ; 53(1): 410-412, 2021 12.
Article in English | MEDLINE | ID: covidwho-1573909

ABSTRACT

OBJECTIVE: Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. METHODS: We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. RESULTS: Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. CONCLUSIONS: IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Interleukin-6/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Male , Middle Aged , Severity of Illness Index , Young Adult
13.
Viruses ; 13(12)2021 12 15.
Article in English | MEDLINE | ID: covidwho-1572672

ABSTRACT

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.


Subject(s)
Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , Leukocytes/metabolism , Matrix Metalloproteinase 8/metabolism , Severity of Illness Index , Triggering Receptor Expressed on Myeloid Cells-1/blood , Adolescent , Adult , Aged , Aged, 80 and over , Brazil , Female , Humans , Inflammation , Interleukin-10/blood , Interleukin-6/blood , Interleukin-8/blood , Leukocyte Count , Male , Middle Aged , Neutrophils/metabolism , Prospective Studies , SARS-CoV-2 , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Young Adult
14.
Viruses ; 13(12)2021 12 10.
Article in English | MEDLINE | ID: covidwho-1572659

ABSTRACT

Large variability in COVID-19 clinical progression urges the need to find the most relevant biomarkers to predict patients' outcomes. We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. One hundred and twenty-seven tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into five groups according to severity. Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. The levels of interleukin (IL)-6 and monocyte chemoattractant protein 1 (MCP-1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients. Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in COVID-19-positive patients.


Subject(s)
Biomarkers/blood , COVID-19 , Iron/blood , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Chemokine CCL2/blood , Cohort Studies , Cytokines/blood , Female , Ferritins , Hepcidins , Humans , Inflammation , Interleukin-6/blood , Male , Middle Aged , Portugal , SARS-CoV-2
15.
PLoS One ; 16(12): e0261432, 2021.
Article in English | MEDLINE | ID: covidwho-1571995

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is the ongoing pandemic with multitude of manifestations and association of ABO blood group in South-East Asian population needs to be explored. METHODS: It was a retrospective study of patients with COVID-19. Blood group A, B, O, and AB were identified in every participant, irrespective of their RH type and allotted groups 1, 2,3, and 4, respectively. Correlation between blood group and lab parameters was presented as histogram distributed among the four groups. Multivariate regression and logistic regression were used for inferential statistics. RESULTS: The cohort included 1067 patients: 521 (48.8%) participants had blood group O as the prevalent blood type. Overall, 10.6% COVID-19-related mortality was observed at our center. Mortality was 13.9% in blood group A, 9.5% in group B, 10% in group C, and 10.2% in AB blood group (p = 0.412). IL-6 was elevated in blood group A (median [IQR]: 23.6 [17.5,43.8]), Procalcitonin in blood group B (median [IQR]: 0.54 [0.3,0.7]), D-dimers and CRP in group AB (median [IQR]: 21.5 [9,34]; 24 [9,49], respectively). Regarding severity of COVID-19 disease, no statistical difference was seen between the blood groups. Alteration of the acute phase reactants was not positively associated with any specific blood type. CONCLUSION: In conclusion, this investigation did not show significant association of blood groups with severity and of COVID-19 disease and COVID-19-associated mortality.


Subject(s)
ABO Blood-Group System , COVID-19/blood , COVID-19/mortality , Adult , Aged , Humans , Interleukin-6/blood , Middle Aged , Multivariate Analysis , Patient Acuity , Procalcitonin/blood , Retrospective Studies
16.
J Clin Lab Anal ; 36(1): e24182, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1568117

ABSTRACT

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine associated with various diseases, including coronavirus disease (COVID-19). Although IL-6 levels can be assessed using serum samples, use of the AFIAS (Boditech Med Inc.) automated immunoassay analyzer enables quick and simple measurement of IL-6 levels in both serum and whole blood specimens. This study aimed to assess the correlation between IL-6 measurements obtained from the AFIAS IL-6 assay and Elecsys IL-6 assay (Roche Diagnostics). Additionally, utilization of the AFIAS IL-6 assay was evaluated. METHODS: The IL-6 levels from 113 serum samples quantified using two assay systems were evaluated for their degree of correlation. Meanwhile, the linearity, analytical sensitivity, and precision/reproducibility of the AFIAS IL-6 assay were also assessed. RESULTS: Quantification of IL-6 with the AFIAS IL-6 and Elecsys IL-6 assays showed excellent agreement (kappa 0.802) and were found to be correlated (y = -0.2781 + 1.068x; 95% confidence interval: 1.007-1.124). AFIAS IL-6 showed good analytical performances. IL-6 levels were significantly higher in deceased patients compared to those with non-complicated disease and those who were intubated (p = 0.002 and p < 0.0001, respectively). Finally, IL-6 levels more accurately predicted poor prognosis in patients, than did C-reactive protein (area under the curve, 0.716 vs. 0.634). CONCLUSION: The overall analytical performance of the AFIAS assay was comparable to that of the Elecsys IL-6 assay. In light of the ongoing COVID-19 pandemic, the AFIAS may be an attractive tool for measuring IL-6 levels.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Interleukin-6/blood , SARS-CoV-2/immunology , C-Reactive Protein/analysis , Diagnostic Tests, Routine/methods , Female , Humans , Immunoassay/methods , Male , Middle Aged , Sensitivity and Specificity
17.
J Cell Mol Med ; 26(2): 274-286, 2022 01.
Article in English | MEDLINE | ID: covidwho-1566302

ABSTRACT

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.


Subject(s)
COVID-19/blood , Cardiovascular Diseases/blood , Cardiovascular System/metabolism , SARS-CoV-2/pathogenicity , Biomarkers/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/immunology , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/immunology , Cardiovascular System/pathology , Cardiovascular System/virology , Chemokine CCL2/blood , Creatine Kinase, MB Form/blood , Fibrin Fibrinogen Degradation Products/metabolism , Homocysteine/blood , Humans , Interferon-gamma/blood , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , Troponin I/blood , Troponin T/blood , Tumor Necrosis Factor-alpha/blood
18.
Signal Transduct Target Ther ; 6(1): 418, 2021 12 10.
Article in English | MEDLINE | ID: covidwho-1565706

ABSTRACT

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.


Subject(s)
Antibodies, Viral/blood , Blood Proteins/metabolism , COVID-19/diagnosis , Cytokine Release Syndrome/diagnosis , Endothelium, Vascular/virology , Lymphopenia/diagnosis , SARS-CoV-2/pathogenicity , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Chemokine CXCL10/blood , Chemokine CXCL9/blood , Cluster Analysis , Convalescence , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Disease Progression , Endothelium, Vascular/immunology , Granulocytes/immunology , Granulocytes/virology , Hematopoietic Cell Growth Factors/blood , Hepatocyte Growth Factor/blood , Humans , Intensive Care Units , Interleukin-12 Subunit p40/blood , Interleukin-6/blood , Interleukin-8/blood , Killer Cells, Natural/immunology , Killer Cells, Natural/virology , Lectins, C-Type/blood , Lymphopenia/immunology , Lymphopenia/mortality , Lymphopenia/virology , Plasma Cells/immunology , Plasma Cells/virology , Survival Analysis , T-Lymphocytes/immunology , T-Lymphocytes/virology
19.
J Clin Lab Anal ; 36(1): e24162, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1555764

ABSTRACT

OBJECTIVE: Most patients infected with the novel coronavirus (SARS-CoV-2), as the causative agent of COVID-19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID-19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity. METHODS: In this prospective cross-sectional study, 50 patients with COVID-19 and 20 patients without COVID-19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non-severe and severe. Differences in the serum levels of C-reactive protein (CRP), IL-6, and TNF-α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed. RESULTS: Out of the 50 patients with COVID-19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID-19 patients in terms of gender and age. Blood tests of COVID-19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL-6, TNF-α, and CRP between the severe and non-severe groups, which were higher in the severe group. Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL-6 (r = 0.74), LYM with NEU (r = -0.97), and ESR with TNF-α (r = 0.7). CONCLUSION: The findings of this study, as the first study in Iran, suggest that the levels of IL-6, TNF-α, ESR, and CRP could be used to predict the severity of COVID-19 disease.


Subject(s)
Biomarkers/blood , COVID-19/etiology , Inflammation/blood , Adult , Aged , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/blood , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Inflammation/virology , Interleukin-6/blood , Lymphocyte Count , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Tumor Necrosis Factor-alpha/blood , Young Adult
20.
Front Immunol ; 12: 745515, 2021.
Article in English | MEDLINE | ID: covidwho-1551502

ABSTRACT

Objective: A critical role in coronavirus disease 2019 (COVID-19) pathogenesis is played by immune dysregulation that leads to a generalized uncontrolled multisystem inflammatory response, caused by overproduction of proinflammatory cytokines, known as "a cytokine storm" (CS), strongly associated with a severe course of disease. The aim of this study is to identify prognostic biomarkers for CS development in COVID-19 patients and integrate them into a prognostic score for CS-associated risk applicable to routine clinical practice. Materials and Methods: The authors performed a review of 458 medical records from COVID-19 patients (241 men and 217 women aged 60.0 ± 10.0) who received treatment in the St. Petersburg State Budgetary Institution of Healthcare City Hospital 40 (City Hospital 40, St. Petersburg), from Apr. 18, 2020 to Nov. 21, 2020. The patients were split in two groups: one group included 100 patients with moderate disease symptoms; the other group included 358 patients with progressive moderately severe, severe, and extremely severe disease. The National Early Warning Score (NEWS) score was used alongside with clinical assessment, chest computed tomographic (CT) scans, electrocardiography (ECG), and lab tests, like ferritin, C-reactive protein (CRP), interleukin (IL)-6, lactate dehydrogenase (LDH), and D-dimer. Results: The basic risk factors for cytokine storms in COVID-19 patients are male gender, age over 40 years, positive test result for replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, absolute lymphocyte count, dynamics in the NEWS score, as well as LDH, D-dimer, ferritin, and IL-6 levels. These clinical and instrumental findings can be also used as laboratory biomarkers for diagnosis and dynamic monitoring of cytokine storms. The suggested prognostic scale (including the NEWS score dynamics; serum IL-6 greater than 23 pg/ml; serum CRP 50 mg/L or greater; absolute lymphocyte count less than 0.72 × 109/L; positive test result for replicative coronavirus (SARS-CoV-2) RNA; age 40 years and over) is a useful tool to identify patients at a high risk for cytokine storm, requiring an early onset of anti-inflammatory therapy.


Subject(s)
COVID-19/pathology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/pathology , Cytokines/blood , Severity of Illness Index , Adult , Age Factors , Aged , Biomarkers/analysis , C-Reactive Protein/analysis , COVID-19/drug therapy , Cytokines/metabolism , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Lymphocyte Count , Male , Middle Aged , Prognosis , Risk Factors , SARS-CoV-2/immunology
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