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2.
Metabolomics ; 18(11): 81, 2022 Oct 22.
Article in English | MEDLINE | ID: covidwho-2085518

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is strongly linked to dysregulation of various molecular, cellular, and physiological processes that change abundance of different biomolecules including metabolites that may be ultimately used as biomarkers for disease progression and severity. It is important at early stage to readily distinguish those patients that are likely to progress to moderate and severe stages. OBJECTIVES: This study aimed to investigate the utility of saliva and plasma metabolomic profiles as a potential parameter for risk stratifying COVID-19 patients. METHOD: LC-MS/MS-based untargeted metabolomics were used to profile the changes in saliva and plasma metabolomic profiles of COVID-19 patients with different severities. RESULTS: Saliva and plasma metabolites were screened in 62 COVID-19 patients and 18 non-infected controls. The COVID-19 group included 16 severe, 15 moderate, 16 mild, and 15 asymptomatic cases. Thirty-six differential metabolites were detected in COVID-19 versus control comparisons. SARS-CoV-2 induced metabolic derangement differed with infection severity. The metabolic changes were identified in saliva and plasma, however, saliva showed higher intensity of metabolic changes. Levels of saliva metabolites such as sphingosine and kynurenine were significantly different between COVID-19 infected and non-infected individuals; while linoleic acid and Alpha-ketoisovaleric acid were specifically increased in severe compared to non-severe patients. As expected, the two prognostic biomarkers of C-reactive protein and D-dimer were negatively correlated with sphingosine and 5-Aminolevulinic acid, and positively correlated with L-Tryptophan and L-Kynurenine. CONCLUSION: Saliva disease-specific and severity-specific metabolite could be employed as potential COVID-19 diagnostic and prognostic biomarkers.


Subject(s)
COVID-19 , Humans , Metabolomics , SARS-CoV-2 , Saliva/metabolism , Chromatography, Liquid , Kynurenine/metabolism , Tryptophan/metabolism , C-Reactive Protein/metabolism , Sphingosine , Linoleic Acid/metabolism , Aminolevulinic Acid/metabolism , Tandem Mass Spectrometry , Severity of Illness Index , Biomarkers
3.
Int J Environ Res Public Health ; 19(20)2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2071448

ABSTRACT

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is one of the world's most disruptive health crises. The presence of diabetes plays an important role in the severity of the infection, and a rise in newly diagnosed diabetes cases has been identified. The aim of this retrospective study was to determine the incidence of new-onset diabetes (NOD) and predictive factors with their cut-off values for patients hospitalized with COVID-19. All patients (n = 219) hospitalized for COVID-19 during three consecutive months were included. NOD was diagnosed in 26.48% of patients. The severity of the infection, hospital admission values for fasting plasma glucose, lactate dehydrogenase (LDH), PaO2/FiO2 ratio, the peak values for leucocytes, neutrophils, C-reactive protein, triglycerides, and the need for care in the intensive care unit were predictors for the occurrence of NOD in univariate analysis, while only LDH level remained a significant predictor in the multivariable analysis. In conclusion, the results of the study showed a high incidence of NOD in patients hospitalized with COVID-19 and identified LDH levels at hospital admission as a significant predictor of NOD during SARS-CoV-2 infection. However, the persistence of NOD after the COVID-19 infection is not known, therefore, the results must be interpreted with caution.


Subject(s)
COVID-19 , Diabetes Mellitus , Humans , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , C-Reactive Protein/metabolism , Blood Glucose , Diabetes Mellitus/epidemiology , L-Lactate Dehydrogenase , Triglycerides
4.
PLoS One ; 17(10): e0275745, 2022.
Article in English | MEDLINE | ID: covidwho-2065147

ABSTRACT

BACKGROUND: Although hyperinflammatory response influences the severity of coronavirus disease 2019 (COVID-19), little has been reported about the utility of tumor necrosis factor (TNF)-related biomarkers in reflecting the prognosis. We examined whether TNF receptors (TNFRs: TNFR1, TNFR2) and progranulin (PGRN) levels, in addition to interleukin 6 (IL-6) and C-reactive protein (CRP), are associated with mortality or disease severity in COVID-19 patients. METHODS: This retrospective study was conducted at Juntendo University Hospital. Eighty hospitalized patients with various severities of COVID-19 were enrolled. Furthermore, serum levels of TNF-related biomarkers were measured using enzyme-linked immunosorbent assay. RESULTS: Twenty-five patients died during hospitalization, and 55 were discharged. The median (25th and 75th percentiles) age of the study patients was 70 (61-76) years, 44 (55.0%) patients were males, and 26 (32.5%) patients had chronic kidney disease (CKD). When comparing with patients who received and did not receive treatment at the intensive care unit (ICU), the former had a higher tendency of being male and have diabetes, hypertension, and CKD; had higher levels of white blood cells, D-dimer, and lactate dehydrogenase; and had lower body mass index, estimated glomerular filtration rate, and lymphocyte counts. Significant differences were observed in TNFR, PGRN, IL-6, and CRP levels between each severity (mild-severe) group. Furthermore, the serum levels of TNFR, IL-6, and CRP, but not PGRN, in ICU patients were significantly higher than in the patients who were not admitted to the ICU. Multivariate logistic regression analysis demonstrated that high levels of TNFR2 were only associated with mortality in patients with COVID-19 even after adjustment for relevant clinical parameters. CONCLUSIONS: High TNFR2 level might be helpful for predicting mortality or disease severity in patients with COVID-19.


Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Aged , Biomarkers , C-Reactive Protein/metabolism , Female , Humans , Interleukin-6 , Lactate Dehydrogenases , Male , Progranulins , Receptors, Tumor Necrosis Factor, Type I/metabolism , Receptors, Tumor Necrosis Factor, Type II/metabolism , Retrospective Studies , Severity of Illness Index , Tumor Necrosis Factor-alpha/metabolism
5.
Biomed Pharmacother ; 156: 113783, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2060453

ABSTRACT

Pentraxin-3 (PTX3) is the prototype of the long pentraxin subfamily, an acute-phase protein consisting of a C-terminal pentraxin domain and a unique N-terminal domain. PTX3 was initially isolated from human umbilical vein endothelial cells and human FS-4 fibroblasts. It was subsequently found to be also produced by synoviocytes, chondrocytes, osteoblasts, smooth muscle cells, myeloid dendritic cells, epithelial cells, and tumor cells. Various modulatory factors, such as miRNAs, cytokines, drugs, and hypoxic conditions, could regulate the expression level of PTX3. PTX3 is essential in regulating innate immunity, inflammation, angiogenesis, and tissue remodeling. Besides, PTX3 may play dual (pro-tumor and anti-tumor) roles in oncogenesis. PTX3 is involved in the occurrence and development of many non-cancerous diseases, including COVID-19, and might be a potential biomarker indicating the prognosis, activity,and severity of diseases. In this review, we summarize and discuss the potential roles of PTX3 in the oncogenesis and pathogenesis of non-cancerous diseases and potential targeted therapies based on PTX3.


Subject(s)
COVID-19 , Endothelial Cells , Humans , Endothelial Cells/metabolism , COVID-19/drug therapy , C-Reactive Protein/genetics , C-Reactive Protein/metabolism , Inflammation/metabolism , Immunity, Innate , Carcinogenesis
6.
Medicine (Baltimore) ; 101(38): e30812, 2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2042662

ABSTRACT

There has been an epidemic of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delta variant in Jingmen, China, and the clinical and epidemiological characteristics of all patients infected with SARS-CoV-2 delta variant in an epidemic are rarely reported. All the coronavirus disease 2019 (COVID-19) patients diagnosed in Jingmen in August 2021 were enrolled in this study. Epidemiological data and clinical characteristics were analyzed. Of 58 patients (38 male and 20 female), 11 were children. The mean age was 35 years, and the median age was 39 years (range, 1-60 years; interquartile range, 28-51). The infectivity of the SARS-CoV-2 Delta variant may have increased, but pathogenicity could have decreased significantly. The vast majority of patients had either no symptoms or mild symptoms. Even though the variant virus is highly contagious, control measures have proven effective. Symptoms included fever (53%), cough (48%), headache (6%), runny nose (13%), loss of smell and taste (6%), elevated C-reactive protein (26%), increased neutrophil count (13%), decreased eosinophil count (21%), and elevated mononuclear granulocytes (26%). Thirty-eight of the 47 adults showed lymphocyte decline, but none of the children showed a significant decline, and more than half of them showed an increase. Thirty patients had no pneumonia, 27 patients had mild pneumonia, and only one patient with multiple chronic diseases had severe pneumonia. None of the 11 children had been vaccinated, 10 did not have pneumonia, and 1 had a small lung lesion. The number of new patients disappeared in 15 days after the lockdown of the city.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Adult , C-Reactive Protein/metabolism , COVID-19/epidemiology , Child , Child, Preschool , China/epidemiology , Communicable Disease Control , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Young Adult
7.
Medicine (Baltimore) ; 101(38): e30474, 2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2042654

ABSTRACT

Although some studies have reported prognostic factors for coronavirus disease 2019 (COVID-19), they were conducted before standard treatment with remdesivir and dexamethasone was implemented. This retrospective, observational study was conducted to evaluate various prognostic factors in patients with COVID-19 pneumonia receiving standard treatment with remdesivir and dexamethasone. Of 99 patients with COVID-19 pneumonia, 68 (68.7%) died within 30 days of hospitalization. The mean age was 71.3 years. Remdesivir and dexamethasone were administered to 80 (80.8%) and 84 (84.8%) patients, respectively. Early antibiotic treatment was administered to 70 patients (70.7%) within 5 days of hospitalization. Dexamethasone (79.4% vs 96.8%, P = .033) was more frequently administered in the survived group, whereas early antibiotics (60.3% vs 93.5%, P = .001) were less frequently administered. In the multivariate analysis, a high National Early Warning Score (NEWS; odds ratio [OR] 1.272), high Charlson Comorbidity Index (CCI; OR 1.441), and dyspnea (OR 4.033) were independent risk factors for 30-day mortality. There was no significant difference in age, sex, and vaccination doses between the survived and fatal groups. Lymphopenia, monocytopenia and high levels of C-reactive protein (CRP)/lactate dehydrogenase (LDH) reflected poor prognosis. NEWS, CCI, and dyspnea were predictors of 30-day mortality in patients with COVID-19 pneumonia. Early antibiotic use did not lower the 30-day mortality risk.


Subject(s)
COVID-19 , Pneumonia , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/metabolism , COVID-19/drug therapy , Dexamethasone/therapeutic use , Dyspnea , Humans , Lactate Dehydrogenases , Prognosis , Retrospective Studies , SARS-CoV-2
8.
PLoS One ; 17(9): e0274967, 2022.
Article in English | MEDLINE | ID: covidwho-2039439

ABSTRACT

BACKGROUND: The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for new variants, vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at a fast pace, the metabolic drivers of outcomes-and whether markers can be found in different biofluids-are not well understood. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. METHODS: Saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing, and COVID-19 severity was classified using clinical descriptors (respiratory rate, peripheral oxygen saturation score and C-reactive protein levels). Metabolites were extracted and analysed using high resolution liquid chromatography-mass spectrometry, and the resulting peak area matrix was analysed using multivariate techniques. RESULTS: Positive percent agreement of 1.00 between a partial least squares-discriminant analysis metabolomics model employing a panel of 6 features (5 of which were amino acids, one that could be identified by formula only) and the clinical diagnosis of COVID-19 severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, leading to an area under receiver operating characteristics curve of 1.00 for the panel of features identified. CONCLUSIONS: In this exploratory work, we found that saliva metabolomics and in particular amino acids can be capable of separating high severity COVID-19 patients from low severity COVID-19 patients. This expands the atlas of COVID-19 metabolic dysregulation and could in future offer the basis of a quick and non-invasive means of sampling patients, intended to supplement existing clinical tests, with the goal of offering timely treatment to patients with potentially poor outcomes.


Subject(s)
COVID-19 , Amino Acids/metabolism , Biomarkers/metabolism , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19 Testing , Chromatography, Liquid/methods , Humans , Mass Spectrometry/methods , Metabolomics/methods , Pandemics , Saliva/metabolism
9.
Cardiovasc Diabetol ; 21(1): 190, 2022 09 21.
Article in English | MEDLINE | ID: covidwho-2038757

ABSTRACT

BACKGROUND: Post-acute sequelae of COVID-19 (PASC), also now known as long COVID, has become a major global health and economic burden. Previously, we provided evidence that there is a significant insoluble fibrin amyloid microclot load in the circulation of individuals with long COVID, and that these microclots entrap a substantial number of inflammatory molecules, including those that might prevent clot breakdown. Scientifically, the most challenging aspect of this debilitating condition is that traditional pathology tests such as a serum CRP (C-reactive protein) may not show any significant abnormal inflammatory markers, albeit these tests measure only the soluble inflammatory molecules. Elevated, or abnormal soluble biomarkers such as IL-6, D-Dimer or fibrinogen indicate an increased risk for thrombosis or a host immune response in COVID-19. The absence of biomarkers in standard pathology tests, result in a significant amount of confusion for patients and clinicians, as patients are extremely sick or even bed-ridden but with no regular identifiable reason for their disease. Biomarkers that are currently available cannot detect the molecules present in the microclots we identified and are therefore unable to confirm their presence or the mechanisms that drive their formation. METHODS: Here we analysed the protein content of double-digested microclots of 99 long COVID patients and 29 healthy controls. The patients suffering from long COVID reported their symptoms through a questionnaire completed by themselves or their attending physician. RESULTS: Our long COVID cohort's symptoms were found to be in line with global findings, where the most prevalent symptoms were constant fatigue (74%,) cognitive impairment (71%) and depression and anxiety (30%). Our most noteworthy findings were a reduced level of plasma Kallikrein compared to our controls, an increased level of platelet factor 4 (PF4) von Willebrand factor (VWF), and a marginally increased level of α-2 antiplasmin (α-2-AP). We also found a significant presence of antibodies entrapped inside these microclots. CONCLUSION: Our results confirm the presence of pro-inflammatory molecules that may also contribute to a failed fibrinolysis phenomenon, which could possibly explain why individuals with long COVID suffer from chronic fatigue, dyspnoea, or cognitive impairment. In addition, significant platelet hyperactivation was noted. Hyperactivation will result in the granular content of platelets being shed into the circulation, including PF4. Overall, our results provide further evidence of both a failed fibrinolytic system in long COVID/PASC and the entrapment of many proteins whose presence might otherwise go unrecorded. These findings might have significant implications for individuals with pre-existing comorbidities, including cardiovascular disease and type 2 diabetes.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Thrombosis , Biomarkers , C-Reactive Protein/metabolism , COVID-19/complications , Diabetes Mellitus, Type 2/complications , Fibrin/metabolism , Fibrinogen/metabolism , Humans , Interleukin-6 , Plasma Kallikrein , Platelet Factor 4 , Proteomics , Thrombosis/diagnosis , alpha-2-Antiplasmin , von Willebrand Factor/analysis
10.
J Am Heart Assoc ; 11(19): e026571, 2022 10 04.
Article in English | MEDLINE | ID: covidwho-2038400

ABSTRACT

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.


Subject(s)
COVID-19 , Natriuretic Peptide, Brain , Biomarkers , C-Reactive Protein/metabolism , Humans , Oxygen , Peptide Fragments , Prognosis , Troponin
11.
Nutrients ; 14(18)2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-2033075

ABSTRACT

We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.


Subject(s)
COVID-19 , Aged , Body Composition/physiology , C-Reactive Protein/metabolism , Female , Humans , Intra-Abdominal Fat/metabolism , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
12.
Front Immunol ; 13: 918731, 2022.
Article in English | MEDLINE | ID: covidwho-2022708

ABSTRACT

The receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the human angiotensin-converting enzyme 2 (ACE2) receptor, which is a prerequisite for the virus to enter the cell. C-reactive protein (CRP) is an important marker of inflammation and is a putative soluble pattern recognition receptor. Clinical elevation of CRP levels in patients with COVID-19 is one of the characteristics of the disease; however, whether CRP is involved in COVID-19 pathogenesis is unknown. Here, we report that monomeric CRP (mCRP) can bind to the SARS-CoV-2 spike RBD and competitively inhibit its binding to ACE2. Furthermore, truncated mutant peptide competition assays and surface plasmon resonance binding experiments showed that the cholesterol-binding sequence (CBS, amino acids 35-47) in mCRP was critical for mediating the binding of mCRP to spike RBD. In a cell model of spike RBD and ACE2 interaction, the CBS motif effectively reduced the binding of spike RBD to ACE2 overexpressed on the cell surface. Thus, this study highlights the pattern recognition function of mCRP in innate immunity and provides a preliminary theoretical basis for the development of the CBS motif in mCRP into a functional peptide with both diagnostic significance and potential therapeutic capabilities.


Subject(s)
Angiotensin-Converting Enzyme 2 , C-Reactive Protein , COVID-19 , Spike Glycoprotein, Coronavirus , Angiotensin-Converting Enzyme 2/metabolism , C-Reactive Protein/metabolism , Cholesterol , Humans , Receptors, Virus/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism
13.
Sci Rep ; 12(1): 14732, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-2016845

ABSTRACT

Coronavirus disease 2019 (COVID-19) can be fatal in severe cases. Accordingly, predicting the severity and prognosis of the disease is valuable. This study examined the role of electrolyte imbalances in predicting the severity of COVID-19. In this cross-sectional study, 169 hospitalized patients with COVID-19 were included and categorized into three groups based on the severity of the disease (moderate, severe, and critical). Serum levels of electrolytes (calcium [Ca], phosphorus [P], sodium [Na], potassium [k], and magnesium [Mg]), inflammatory markers (D-dimer, C-reactive protein [CRP], ferritin, and lactate dehydrogenase [LDH]), and 25OHVitamin D were measured. The mean age of patients was 53 years, and 54% were male. They had moderate, severe, and critical illnesses in 22%, 47%, and 31%, respectively. CRP, D-dimer, and ferritin increased with the severity of the disease. The lower median values of Mg, Na, 25OHVitamin D, Ca, LDH, and higher median lymphocyte counts were observed in the moderate vs. the severe group (P < 0.05). These parameters have acceptable sensitivity and specificity at the suggested cut-off level to discriminate the moderate and critical cases. Serum parameters introduced in this study are appropriate for differentiating between critical and moderate cases. The electrolyte imbalance can predict critical patients.


Subject(s)
COVID-19 , C-Reactive Protein/metabolism , COVID-19/diagnosis , Cross-Sectional Studies , Electrolytes/metabolism , Female , Ferritins , Humans , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , SARS-CoV-2
14.
Rev Med Virol ; 32(6): e2390, 2022 11.
Article in English | MEDLINE | ID: covidwho-2013777

ABSTRACT

With COVID-19 still hovering around and threatening the lives of many at-risk patients, an effective, quick, and inexpensive prognostic method is required. Few studies have shown fibrinogen to albumin ratio (FAR) and C-reactive protein to albumin ratio (CAR) to be promising as prognostic markers for COVID-19 disease. However, their implications remain unclear. This meta-analysis aimed to elucidate the prognostic role of FAR and CAR in COVID-19 disease. A systematic literature search was undertaken using PubMed and Embase till April 2022. Inverse variance standardised mean difference (SMD) was calculated to report the overall effect size using random effect models. The generic inverse variance random-effects method was used to pool the area under the curve (AUC) values. All statistical analyses were performed on Revman and MedCalc Software. A total of 23 studies were included. COVID-19 non-survivors had a higher CAR on admission compared with survivors (SMD = 1.79 [1.04, 2.55]; p < 0.00001; I2  = 97%) and patients with a severe COVID-19 infection had a higher CAR on admission than non-severe patients (SMD = 1.21 [0.54, 1.89]; p = 0.0004; I2  = 97%). Similarly, higher mean FAR values on admission were significantly associated with COVID-19 mortality (SMD = 0.55 [0.32, 0.78]; p < 0.00001; I2  = 82%). However, no significant association was found between mean FAR on admission and COVID-19 severity (SMD = 0.54 [-0.09, 1.18]; p = 0.09; I2  = 91%). The pooled AUC values found that CAR had a good discriminatory-power to predict COVID-19 severity (AUC = 0.81 [0.75, 0.86]; p < 0.00001; I2  = 80%) and mortality (AUC = 0.81 [0.74, 0.87]; p < 0.00001; I2  = 86%). FAR had a fair discriminatory-power to predict COVID-19 severity (AUC = 0.73 [0.64, 0.82]; p < 0.00001; I2  = 89%). Overall, CAR was a good predictor of both severity and mortality associated with COVID-19 infection. Similarly, FAR was a satisfactory predictor of COVID-19 mortality but not severity.


Subject(s)
C-Reactive Protein , COVID-19 , Humans , C-Reactive Protein/metabolism , Prognosis , COVID-19/diagnosis , Biomarkers , Fibrinogen/analysis
15.
Bosn J Basic Med Sci ; 22(6): 1016-1024, 2022 Oct 23.
Article in English | MEDLINE | ID: covidwho-2002721

ABSTRACT

Coronavirus disease 2019 (COVID-19) is diagnosed by the evidence of the presence of multiple phenotypes, including thrombosis, inflammation, and alveolar and myocardial damage, which can cause severe illness and mortality. High-density lipoprotein cholesterol (HDL-C) has pleiotropic properties, including anti-inflammatory, anti-infectious, antithrombotic, and endothelial cell protective effects. The aim of this study was to investigate the HDL-C levels and one-year mortality after the first wave of patients with COVID-19 were hospitalized. Data from 101 patients with COVID-19 were collected for this single-center retrospective study. Lipid parameters were collected on the admission. The relationship between lipid parameters and long-term mortality was investigated. The mean age of the non-survivor group (n = 38) was 68.8 ± 14.1 years, and 55% were male. The HDL-C levels were significantly lower in the non-survivors group compared with the survivors (26.9 ± 9.5 vs 36.8 ± 12.8 mg/dl, respectively p < 0.001). Multivariate regression analysis determined that age, C-reactive protein, D-dimer, hypertension, and HDL-C as independent predictors for the development of COVID-19 mortality. HDL-C levels <30.5 mg/dl had 71% sensitivity and 68% specificity to predict one-year mortality after COVID-19. The findings of this study showed that HDL-C is a predictor of one-year mortality in Turkish patients with COVID-19. COVID-19 is associated with decreased lipid levels, and it is an indicator of the inflammatory burden and increased mortality rate. The consequences of long-term metabolic dysregulations in patients that have recovered from COVID-19 still need to be understood.


Subject(s)
COVID-19 , Pneumonia , Female , Humans , Male , Anti-Inflammatory Agents , C-Reactive Protein/metabolism , Cholesterol, HDL , Fibrinolytic Agents , Prognosis , Retrospective Studies , Adult
16.
Tohoku J Exp Med ; 258(3): 177-182, 2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2002382

ABSTRACT

Perimyocarditis is a rare and serious cardiac complication following COVID-19 vaccination. Young males are most at risk after the second dose. With the introduction of the booster (third) dose, some reports have focused on the risk of perimyocarditis after a booster dose. However, no currently available report in Japan has comprehensively described this phenomenon. A healthy 14-year-old Japanese male, who had completed a two-dose primary series of the BNT162b2 (Pfizer-BioNTech) vaccine six months prior, developed fever and chest pain within 24 hours after a homologous booster dose. He was transferred to our institute because of worsening chest pain. A multiplex PCR test showed no evidence of active viral infections, including SARS-CoV-2. Electrocardiography revealed ST-segment elevation in almost all leads, suggesting pericarditis. Echocardiography showed normal systolic function. Laboratory data demonstrated C-reactive protein levels of 8.8 mg/dL and elevated cardiac damage markers (troponin T, 1.9 ng/mL; creatine phosphokinase, 1527 U/L; MB isoenzyme, 120 U/L), suggesting myocarditis. He was diagnosed with perimyocarditis associated with the booster dose, which was confirmed by cardiac magnetic resonance imaging four days after initial symptoms. Chest pain improved spontaneously along with a resolution of electrocardiographic findings and laboratory data within several days. He was discharged eight days after admission. Perimyocarditis is less frequent after a booster dose than after primary doses. In this case, the patient with booster-dose-associated perimyocarditis showed favorable clinical course without severe sequelae. The patient's clinical course was consistent with findings on previous large-scale reports on primary-dose-associated perimyocarditis and case series on booster-dose-associated perimyocarditis.


Subject(s)
BNT162 Vaccine , COVID-19 Vaccines , Myocarditis , Adolescent , Humans , Male , BNT162 Vaccine/adverse effects , C-Reactive Protein/metabolism , Chest Pain , COVID-19/complications , COVID-19 Vaccines/adverse effects , Creatine Kinase , Isoenzymes , Japan , Myocarditis/diagnosis , Myocarditis/etiology , SARS-CoV-2 , Troponin T
17.
Cell Biochem Funct ; 40(7): 694-705, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1990431

ABSTRACT

The aim of this study was to evaluate the systemic redox state and inflammatory markers in intensive care unit (ICU) or non-ICU severe COVID-19 patients during the hospitalization period. Blood samples were collected at hospital admission (T1) (Controls and COVID-19 patients), 5-7 days after admission (T2: 5-7 days after hospital admission), and at the discharge time from the hospital (T3: 0-72 h before leaving hospital or death) to analyze systemic oxidative stress markers and inflammatory variables. The reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were analyzed in peripheral granulocytes and monocytes. THP-1 human monocytic cell line was incubated with plasma from non-ICU and ICU COVID-19 patients and cell viability and apoptosis rate were analyzed. Higher total antioxidant capacity, protein oxidation, lipid peroxidation, and IL-6 at hospital admission were identified in both non-ICU and ICU COVID-19 patients. ICU COVID-19 patients presented increased C-reactive protein, ROS levels, and protein oxidation over hospitalization period compared to non-ICU patients, despite increased antioxidant status. Granulocytes and monocytes of non-ICU and ICU COVID-19 patients presented lower MMP and higher ROS production compared to the healthy controls, with the highest values found in ICU COVID-19 group. Finally, the incubation of THP-1 cells with plasma acquired from ICU COVID-19 patients at T3 hospitalization period decreased cell viability and apoptosis rate. In conclusion, disturbance in redox state is a hallmark of severe COVID-19 and is associated with cell damage and death.


Subject(s)
COVID-19 , Antioxidants/metabolism , C-Reactive Protein/metabolism , Humans , Interleukin-6/metabolism , Oxidation-Reduction , Reactive Oxygen Species/metabolism , SARS-CoV-2
18.
Front Immunol ; 13: 964179, 2022.
Article in English | MEDLINE | ID: covidwho-1987498

ABSTRACT

Abnormal inflammatory mediator concentrations during SARS-CoV-2 infection may represent disease severity. We aimed to assess plasma inflammatory mediator concentrations in patients with SARS-CoV-2 in Addis Ababa, Ethiopia. In this study, 260 adults: 126 hospitalized patients with confirmed COVID-19 sorted into severity groups: severe (n=68) and mild or moderate (n=58), and 134 healthy controls were enrolled. We quantified 39 plasma inflammatory mediators using multiplex ELISA. Spearman rank correlation and Mann-Whitney U test were used to identify mechanistically coupled inflammatory mediators and compare disease severity. Compared to healthy controls, patients with COVID-19 had significantly higher levels of interleukins 1α, 2, 6, 7, 8, 10 and 15, C-reactive protein (CRP), serum amyloid A (SAA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), IFN-γ-inducible protein-10 (IP-10, CXCL10), macrophage inflammatory protein-1 alpha (MIP-1α, CCL3), eotaxin-3 (CCL26), interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and fms-like tyrosine kinase 1 (Flt-1). Patients with severe COVID-19 had higher IL-10 and lower macrophage-derived chemokine (MDC, CCL22) compared to the mild or moderate group (P<0.05). In the receiver operating characteristic curve, SAA, IL-6 and CRP showed strong sensitivity and specificity in predicting the severity and prognosis of COVID-19. Greater age and higher CRP had a significant association with disease severity (P<0.05). Our findings reveal that CRP, SAA, VCAM-1, CXCL10, CCL22 and IL-10 levels are promising biomarkers for COVID-19 disease severity, suggesting that plasma inflammatory mediators could be used as warning indicators of COVID-19 severity, aid in COVID-19 prognosis and treatment.


Subject(s)
COVID-19 , Inflammation Mediators , Adult , C-Reactive Protein/metabolism , Ethiopia , Female , Humans , Interleukin-10 , Placenta Growth Factor , SARS-CoV-2 , Serum Amyloid A Protein/analysis , Vascular Cell Adhesion Molecule-1
19.
PLoS One ; 17(5): e0269005, 2022.
Article in English | MEDLINE | ID: covidwho-1923703

ABSTRACT

BACKGROUND: Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing. OBJECTIVE: We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections. MATERIALS AND METHODS: Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days. RESULTS: Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850-0.948]; AUC for CRP 0.922 [95%CI 0.879-0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694-0.894]; AUC for CRP 0.807 [95%CI 0.721-0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls. CONCLUSION: In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.


Subject(s)
COVID-19 , Pneumonia, Bacterial , Respiratory Tract Infections , Biomarkers , C-Reactive Protein/metabolism , COVID-19/diagnosis , Humans , Interleukin-6 , Pneumonia, Bacterial/diagnosis , Prospective Studies
20.
PLoS One ; 17(5): e0266652, 2022.
Article in English | MEDLINE | ID: covidwho-1910582

ABSTRACT

OBJECTIVES: Procalcitonin (PCT) is an acute-phase reactant with concentrations ≥0.5 µg/L indicative of possible bacterial infection in patients with SARS-CoV-2 infection (COVID-19). Some with severe COVID-19 develop cytokine storm secondary to virally driven hyper-inflammation. However, increased pro-inflammatory cytokines are also seen in bacterial sepsis. This study aimed to assess the clinical utility of a cytokine panel in the assessment of COVID-19 with bacterial superinfections along with PCT and C-reactive protein (CRP). METHODS: The retrospective analysis included serum cytokines (interleukins; IL-1ß, IL-6, IL-8 and tumour necrosis factor (TNFα)) measured using Ella™ (Bio-Techne, Oxford, UK) and PCT measured by Roche Cobas (Burgess Hill, UK) in patients admitted with COVID-19 between March 2020 and January 2021. Patients enrolled into COVID-19 clinical trials, treated with Remdesivir/IL-6 inhibitors were excluded. The cytokine data was compared between intensive care unit (ICU) patients, age matched non-ICU patients and healthy volunteers as well as ICU patients with high and normal PCT (≥0.5 vs. <0.5 µg/L). RESULTS: Cytokine concentrations and CRP were higher in COVID-19 patients (76; ICU & non-ICU) vs. healthy controls (n = 24), all p<0.0001. IL-6, IL-8, TNFα and were higher in ICU patients (n = 46) vs. non-ICU patients (n = 30) despite similar CRP. Among 46 ICU patients, the high PCT group (n = 26) had higher TNFα (p<0.01) and longer ICU stay (mean 47 vs. 25 days, p<0.05). There was no difference in CRP and blood/respiratory culture results between the groups. CONCLUSIONS: Pro-inflammatory cytokines and PCT were higher in COVID-19 patients requiring ICU admission vs. non-ICU admissions despite no difference in CRP. Furthermore, TNFα was higher in those with high PCT and requiring longer ICU admission despite no difference in CRP or rate of bacterial superinfection.


Subject(s)
COVID-19 , Procalcitonin , C-Reactive Protein/metabolism , Calcitonin , Calcitonin Gene-Related Peptide , Critical Care , Cytokines , Humans , Intensive Care Units , Interleukin-6 , Interleukin-8 , Retrospective Studies , SARS-CoV-2 , Tumor Necrosis Factor-alpha
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