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1.
BMC Pulm Med ; 22(1): 1, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1608729

ABSTRACT

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.


Subject(s)
COVID-19/classification , COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Body Temperature , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lymphocyte Count , Male , Middle Aged , Mucin-1/blood , Neutrophils , Predictive Value of Tests , Prognosis , Pyrazines/therapeutic use , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies , SARS-CoV-2 , Steroids/therapeutic use
2.
Ann Med ; 53(1): 257-266, 2021 12.
Article in English | MEDLINE | ID: covidwho-1574445

ABSTRACT

OBJECTIVES: To appraise effective predictors for COVID-19 mortality in a retrospective cohort study. METHODS: A total of 1270 COVID-19 patients, including 984 admitted in Sino French New City Branch (training and internal validation sets randomly split at 7:3 ratio) and 286 admitted in Optical Valley Branch (external validation set) of Wuhan Tongji hospital, were included in this study. Forty-eight clinical and laboratory features were screened with LASSO method. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed death risk prediction model with simple-tree XGBoost model. Performances of models were evaluated by AUC, prediction accuracy, precision, and F1 scores. RESULTS: Six features, including disease severity, age, levels of high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), ferritin, and interleukin-10 (IL-10), were selected as predictors for COVID-19 mortality. Simple-tree XGBoost model conducted by these features can predict death risk accurately with >90% precision and >85% sensitivity, as well as F1 scores >0.90 in training and validation sets. CONCLUSION: We proposed the disease severity, age, serum levels of hs-CRP, LDH, ferritin, and IL-10 as significant predictors for death risk of COVID-19, which may help to identify the high-risk COVID-19 cases. KEY MESSAGES A machine learning method is used to build death risk model for COVID-19 patients. Disease severity, age, hs-CRP, LDH, ferritin, and IL-10 are death risk factors. These findings may help to identify the high-risk COVID-19 cases.


Subject(s)
COVID-19/mortality , Clinical Decision Rules , Hospitalization , Machine Learning , Adult , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/physiopathology , Cardiovascular Diseases/epidemiology , China/epidemiology , Cohort Studies , Comorbidity , Diabetes Mellitus/epidemiology , Female , Ferritins/metabolism , Humans , Hypertension/epidemiology , Interleukin-10/metabolism , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Prognosis , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
3.
Tohoku J Exp Med ; 255(4): 315-323, 2021.
Article in English | MEDLINE | ID: covidwho-1574510

ABSTRACT

The third wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing damage all over the world, especially in Pakistan and India. Although vaccines are available and preventive measures are being taken, but SARS-CoV-2 is unstoppable. Currently, there are around 841,636 positive cases in Pakistan and 18,429 deaths, whereas, in India, both are high. From April 8th to 12th, 2021, nasopharyngeal swabs of 190 patients were submitted to PRL (PACP) lab for the SARS-CoV-2 testing, and blood samples were collected at the Mayo Hospital lab for ferritin, D-dimers, lactate dehydrogenase (LDH), and C-reactive protein (CRP) testing. This study observed that coronavirus disease 2019 (COVID-19) was more likely in individuals aged 51-60 than 61-70. In addition, our study found that COVID-19 patients exhibited a statistically significant increase in levels of ferritin, D-dimers, LDH, and CRP. In addition, this study found that COVID-19 patients had significantly higher levels of ferritin, D-dimers, LDH, and CRP. Our study revealed that SARS-CoV-2 relapsed. Furthermore, we concluded that these biochemical parameters are useful indicators for severity of COVID-19.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/diagnosis , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , L-Lactate Dehydrogenase/blood , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19 Testing , Humans , Middle Aged , Pakistan/epidemiology , Pandemics , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
4.
Dis Markers ; 2021: 6304189, 2021.
Article in English | MEDLINE | ID: covidwho-1553755

ABSTRACT

Background: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. Methods: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (n = 465) were divided into stable (n = 409) and progressive (n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. Results: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. Conclusion: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/diagnosis , Coronary Disease/diagnosis , Hypertension/diagnosis , Pulmonary Disease, Chronic Obstructive/diagnosis , SARS-CoV-2/pathogenicity , Serum Albumin, Human/metabolism , Aged , Area Under Curve , Biomarkers/blood , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , China/epidemiology , Comorbidity , Coronary Disease/epidemiology , Coronary Disease/mortality , Coronary Disease/virology , Disease Progression , Early Diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Length of Stay/statistics & numerical data , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Neutrophils/pathology , Neutrophils/virology , Prognosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/virology , ROC Curve , Retrospective Studies , SARS-CoV-2/growth & development , Severity of Illness Index , Survival Analysis
5.
Lab Med ; 52(5): 493-498, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1526169

ABSTRACT

OBJECTIVE: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19. METHODS: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated. RESULTS: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001). CONCLUSION: We found that MR-proADM could represent a prognostic biomarker of COVID-19.


Subject(s)
Adrenomedullin/blood , COVID-19/diagnosis , Hypertension/diagnosis , Lung Diseases/diagnosis , Protein Precursors/blood , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/mortality , COVID-19/virology , Comorbidity , Female , Humans , Hypertension/blood , Hypertension/mortality , Hypertension/virology , Interleukin-6/blood , Lung Diseases/blood , Lung Diseases/mortality , Lung Diseases/virology , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis , Triage/methods
6.
Front Immunol ; 12: 741061, 2021.
Article in English | MEDLINE | ID: covidwho-1506190

ABSTRACT

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, challenging both the medical and scientific community for the development of novel vaccines and a greater understanding of the effects of the SARS-CoV-2 virus. COVID-19 has been associated with a pronounced and out-of-control inflammatory response. Studies have sought to understand the effects of inflammatory response markers to prognosticate the disease. Herein, we aimed to review the evidence of 11 groups of systemic inflammatory markers for risk-stratifying patients and prognosticating outcomes related to COVID-19. Numerous studies have demonstrated the effectiveness of neutrophil to lymphocyte ratio (NLR) in prognosticating patient outcomes, including but not limited to severe disease, hospitalization, intensive care unit (ICU) admission, intubation, and death. A few markers outperformed NLR in predicting outcomes, including 1) systemic immune-inflammation index (SII), 2) prognostic nutritional index (PNI), 3) C-reactive protein (CRP) to albumin ratio (CAR) and high-sensitivity CAR (hsCAR), and 4) CRP to prealbumin ratio (CPAR) and high-sensitivity CPAR (hsCPAR). However, there are a limited number of studies comparing NLR with these markers, and such conclusions require larger validation studies. Overall, the evidence suggests that most of the studied markers are able to predict COVID-19 prognosis, however NLR seems to be the most robust marker.


Subject(s)
COVID-19/diagnosis , Inflammation/diagnosis , Lymphocytes/immunology , Neutrophils/immunology , SARS-CoV-2/physiology , Biomarkers , C-Reactive Protein/metabolism , Disease Progression , Humans , Prognosis , Severity of Illness Index
7.
Eur Cytokine Netw ; 32(1): 8-14, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1477642

ABSTRACT

Cytokine release syndrome is a serious complication of the new coronavirus infection (COVID-19). The aim of the study was to assess effectiveness and safety of the IL-17 antagonist nekatimab for its treatment. The retrospective study included COVID-19 patients with C-reactive protein levels >60 mg/L. Patients received either netakimab (group NET), IL-6 antagonist tocilizumab (group TOC) or no anti-cytokine treatment (group CON). Forty-four patients were enrolled in the NET group, 27 patients in the TOC group, and 47 patients in the CON group. Mortality was lower in the NET group than in TOC and CON groups (2.3% vs. 14.8% and 31.9%; p = 0.018 and p < 0.001). NET group patients required intensive care unit admission (6.8% vs. 25.9% and 46.3%; p = 0.025 and p < 0.001) and mechanical ventilation (4.6% vs. 22.2% and 31.9%; p = 0.022 and p = 0.002) less frequently than patients of the TOC and CON groups. After 7-10 days of anti-cytokine drug administration, a reduction in lung lesion volume (p = 0.016) and an increase in the proportion of patients who did not need oxygen support (p = 0.005) or stayed in prone position (p = 0.044) was observed in the NET group only group; C-reactive protein levels were the same in the TOC and NET groups (p = 0.136) and lower in the CON group (p < 0.001 and p = 0.005). IL-6 levels decreased in the NET group (p = 0.005) and did not change in the TOC group (p = 0.953). There was no difference in the incidence of side effects between groups. The IL-17 antagonist netakimab is effective and safe in the treatment of cytokine release syndrome in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Interleukin-17/antagonists & inhibitors , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/virology , Case-Control Studies , Humans , Interleukin-17/metabolism , Interleukin-6/blood , Lung/pathology , Lung/virology , SARS-CoV-2/physiology , Treatment Outcome
8.
Mol Med ; 27(1): 129, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1477255

ABSTRACT

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.


Subject(s)
COVID-19/diagnosis , Chemokine CXCL10/blood , Coronary Artery Disease/diagnosis , Diabetes Mellitus/diagnosis , Hypertension/diagnosis , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/immunology , COVID-19/mortality , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/immunology , Coronary Artery Disease/mortality , Creatine/blood , Diabetes Mellitus/blood , Diabetes Mellitus/immunology , Diabetes Mellitus/mortality , Female , Hospitalization , Humans , Hypertension/blood , Hypertension/immunology , Hypertension/mortality , Immunity, Humoral , Immunity, Innate , Inflammation , Intensive Care Units , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lymphocytes/immunology , Lymphocytes/pathology , Male , Middle Aged , Neutrophils/immunology , Neutrophils/pathology , Prognosis , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
9.
S Afr Med J ; 111(10): 950-956, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1478411

ABSTRACT

BACKGROUND: The phenomenon of silent hypoxaemia has been described in patients with COVID-19 pneumonia, which is characterised by low oxygen saturation levels of <90% in those who appear clinically well and do not show signs of significant respiratory distress. OBJECTIVES: To assess the impact on clinical outcomes for high-risk COVID-19 patients using a pulse oximeter to monitor oxygen saturation levels in a home setting. METHODS: We performed a retrospective cohort analysis using data from a large South African insurance administrator. Patients were categorised as high risk, based on age and specific underlying clinical conditions, or from predictive models derived from medical scheme administrative claims data. The impact of pulse oximetry home monitoring on COVID-19 clinical outcomes was investigated by the use of Cox proportional hazard models. RESULTS: Between 2 March 2020 and 31 October 2020, of 38 660 patients analysed, 8 115 were in the intervention group. The 60-day mortality rate for the evaluated high-risk population was 1.35%. After adjusting for age and comorbidity differences, the intervention group was found to have an adjusted hazard ratio of 0.52 (p<0.0001). No statistical significance was found between the intervened and control groups for admission to hospital, admission to intensive care unit (ICU) and use of mechanical ventilation. The intervention group had a lower median C-reactive protein (CRP) level on admission (p=0.03). After adjustment for admission CRP levels, elevated CRP was associated with an increased mortality (p<0.0001), while the statistical significance in mortality between the intervention and the control group was lost. CONCLUSIONS: High-risk COVID-19 patients who used a pulse oximeter to monitor oxygen saturation levels had significantly lower mortality rates compared with other high-risk patients. The mortality benefit may be explained by earlier presentation to hospital, as suggested by lower initial CRP levels.


Subject(s)
COVID-19/physiopathology , Hospitalization/statistics & numerical data , Oximetry/methods , Adult , C-Reactive Protein/metabolism , COVID-19/mortality , Cohort Studies , Female , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Severity of Illness Index , South Africa
10.
Clin Microbiol Infect ; 26(10): 1380-1385, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1439953

ABSTRACT

OBJECTIVES: The aim was to determine the clinical characteristics of COVID-19 patients because the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multicentre, cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into three groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second-generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes and duration of viral shedding were analysed. RESULTS: A total of 171 patients were enrolled, with 83, 44 and 44 patients in the first-, second-, and third-generation, respectively. Compared with the first and second generations, third-generation patients were older (61.3 vs. 48.3 and 44.0 years, p < 0.001) and had more coexisting conditions (56.8% vs. 36.1% and 27.3%, p 0.013). At 7 ± 1 days from illness onset, third-generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8 × 109/L, p 0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8 mg/L, p 0.018) and D-dimer (1066 vs. 412.5 and 549 µg/L, p 0.002) and more lesions involving the pulmonary lobes (lobes ≥5, 81.8% vs. 53.0% and 34.1%, p < 0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, p < 0.001), critical illness (38.6% vs. 10.8% and 6.8%, p < 0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, p 0.002) were higher than in the other two groups. DISCUSSION: Third-generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness than first- and second-generation patients.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Adult , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , China/epidemiology , Comorbidity , Contact Tracing , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Diabetes Mellitus/blood , Diabetes Mellitus/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypertension/blood , Hypertension/physiopathology , Interleukin-6/blood , Intubation, Intratracheal , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/physiopathology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Travel/statistics & numerical data , Virus Shedding
11.
Aging (Albany NY) ; 13(18): 21903-21913, 2021 09 22.
Article in English | MEDLINE | ID: covidwho-1436455

ABSTRACT

The mortality rate of young female COVID-19 patients is reported to be lower than that of young males but no significant difference in mortality was found between female and male COVID-19 patients aged over 65 years, and the underlying mechanism is unknown. We retrospectively analyzed clinical characteristics and outcomes of severely ill pre- and post-menopausal COVID-19 patients and compared with age-matched males. Of the 459 patients included, 141 aged ≤55, among whom 19 died (16 males vs. 3 females, p<0.005). While for patients >55 years (n=318), 115 died (47 females vs. 68 males, p=0.149). In patients ≤55 years old, the levels of NLR, median LDH, median c-reactive protein and procalcitonin were significantly higher while the median lymphocyte count and LCR were lower in male than in female (all p<0.0001). In patients over 55, these biochemical parameters were far away from related normal/reference values in the vast majority of these patients in both genders which were in contrast to that seen in the young group. It is concluded that the mortality of severely ill pre-menopausal but not post-menopausal COVID-19 female patients is lower than age-matched male. Our findings support the notion that estrogen plays a beneficial role in combating COVID-19.


Subject(s)
COVID-19/mortality , Estrogens/metabolism , Menopause , Severity of Illness Index , Adult , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/metabolism , Female , Gender Identity , Humans , Lymphocyte Count , Male , Middle Aged , Neutrophils/metabolism , Postmenopause , Premenopause , Procalcitonin/blood , Retrospective Studies , SARS-CoV-2 , Sex Factors
13.
Respir Investig ; 59(6): 804-809, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401819

ABSTRACT

BACKGROUND: This study aimed to examine risk factors associated with critical coronavirus disease 19 (COVID-19) and to establish a risk predictive model for Japanese patients. METHODS: We retrospectively assessed adult Japanese patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center, Tokyo, Japan between February 1, 2020 and March 10, 2021. The patients were divided into critical and non-critical groups based on their condition during the clinical courses. Univariate and multivariate logistic regression analyses were performed to investigate the relationship between clinical characteristics and critical illness. Based on the results, we established a predictive model for the development of critical COVID-19. RESULTS: In total, 300 patients were enrolled in this study. Among them, 86 were included in the critical group. Analyses revealed that age ≥65 y, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL were independently associated with the development of critical COVID-19. Next, a predictive model for the development of critical COVID-19 was created, and this included the following variables: age ≥65 y, male sex, diabetes, hemodialysis, need for O2 supplementation upon diagnosis, and an initial serum C-reactive protein level of ≥6.5 mg/dL. The area under the receiver operating characteristic curve of the model was 0.86 (95% confidence interval, 0.81-0.90). Using a cutoff score of 12, the positive and negative predictive values of 74.0% and 80.4% were obtained, respectively. CONCLUSIONS: Upon diagnosis, the predictive model can be used to identify adult Japanese patients with COVID-19 who will require intensive treatment.


Subject(s)
COVID-19 , Critical Illness/epidemiology , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Female , Humans , Japan/epidemiology , Male , Predictive Value of Tests , Prognosis , Renal Dialysis , Retrospective Studies , Risk Factors , SARS-CoV-2
14.
Clin Pharmacol Ther ; 110(5): 1358-1367, 2021 11.
Article in English | MEDLINE | ID: covidwho-1384149

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a severe acute respiratory syndrome with an underlying inflammatory state. We have previously demonstrated that acute inflammation modulates cytochromes P450 (CYPs) activity in an isoform-specific manner. We therefore hypothesized that COVID-19 might also impact CYP activity, and thus aimed to evaluate the impact of acute inflammation in the context of SARS-CoV-2 infection on the six main human CYPs activity. This prospective observational study was conducted in 28 patients hospitalized at the Geneva University Hospitals (Switzerland) with a diagnosis of moderate to severe COVID-19. They received the Geneva phenotyping cocktail orally during the first 72 hours of hospitalization and after 3 months. Capillary blood samples were collected 2 hours after cocktail administration to assess the metabolic ratios (MRs) of CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A. C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were also measured in blood. CYP1A2, CYP2C19, and CYP3A MRs decreased by 52.6% (P = 0.0001), 74.7% (P = 0.0006), and 22.8% (P = 0.045), respectively, in patients with COVID-19. CYP2B6 and CYP2C9 MRs increased by 101.1% (P = 0.009) and 55.8% (P = 0.0006), respectively. CYP2D6 MR variation did not reach statistical significance (P = 0.072). As expected, COVID-19 was a good acute inflammation model as mean serum levels of CRP, IL-6, and TNF-α were significantly (P < 0.001) higher during SARS-CoV-2 infection. CYP activity are modulated in an isoform-specific manner by SARS-CoV-2 infection. The pharmacokinetics of CYP substrates, whether used to treat the disease or as the usual treatment of patients, could be therefore clinically impacted.


Subject(s)
COVID-19/enzymology , Cytochrome P-450 Enzyme System/metabolism , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , COVID-19/blood , Cytochrome P-450 Enzyme System/genetics , Female , Genetic Variation , Humans , Interleukin-6/blood , Linear Models , Male , Middle Aged , Models, Theoretical , Prospective Studies , Tumor Necrosis Factor-alpha/blood
15.
BMJ Open Respir Res ; 7(1)2020 11.
Article in English | MEDLINE | ID: covidwho-1388517

ABSTRACT

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is the major cause of mortality in patients with SARS-CoV-2 pneumonia. It appears that development of 'cytokine storm' in patients with SARS-CoV-2 pneumonia precipitates progression to ARDS. However, severity scores on admission do not predict severity or mortality in patients with SARS-CoV-2 pneumonia. Our objective was to determine whether patients with SARS-CoV-2 ARDS are clinically distinct, therefore requiring alternative management strategies, compared with other patients with ARDS. We report a single-centre retrospective study comparing the characteristics and outcomes of patients with ARDS with and without SARS-CoV-2. METHODS: Two intensive care unit (ICU) cohorts of patients at the Queen Elizabeth Hospital Birmingham were analysed: SARS-CoV-2 patients admitted between 11 March and 21 April 2020 and all patients with community-acquired pneumonia (CAP) from bacterial or viral infection who developed ARDS between 1 January 2017 and 1 November 2019. All data were routinely collected on the hospital's electronic patient records. RESULTS: A greater proportion of SARS-CoV-2 patients were from an Asian ethnic group (p=0.002). SARS-CoV-2 patients had lower circulating leucocytes, neutrophils and monocytes (p<0.0001), but higher CRP (p=0.016) on ICU admission. SARS-CoV-2 patients required a longer duration of mechanical ventilation (p=0.01), but had lower vasopressor requirements (p=0.016). DISCUSSION: The clinical syndromes and respiratory mechanics of SARS-CoV-2 and CAP-ARDS are broadly similar. However, SARS-CoV-2 patients initially have a lower requirement for vasopressor support, fewer circulating leukocytes and require prolonged ventilation support. Further studies are required to determine whether the dysregulated inflammation observed in SARS-CoV-2 ARDS may contribute to the increased duration of respiratory failure.


Subject(s)
COVID-19/complications , Critical Care/methods , Patient Outcome Assessment , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/etiology , C-Reactive Protein/metabolism , Cohort Studies , Female , Humans , Leukocytes/metabolism , Male , Middle Aged , Monocytes/metabolism , Neutrophils/metabolism , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/therapy , Respiratory Mechanics , Retrospective Studies , SARS-CoV-2 , Time , United Kingdom , Vasoconstrictor Agents/therapeutic use
16.
Biomark Med ; 15(13): 1167-1175, 2021 09.
Article in English | MEDLINE | ID: covidwho-1379920

ABSTRACT

Aim: To investigate whether C-reactive protein/albumin ratio (CAR) has an association with new onset atrial fibrillation (NOAF) in SARS-CoV-2. Materials & methods: This study included 782 patients with SARS-CoV-2 infection, who were hospitalized in Turkey. The end point of the study was an occurrence of NOAF. Results: NOAF was identified in 41 patients (5.2%). Subjects who developed NOAF had a higher CAR compared with those who did not develop NOAF (p < 0.001). In the multivariate logistic regression analysis the CAR (odds ratio = 2.879; 95% CI: 1.063-7.793; p = 0.037) was an independent predictor of NOAF. Conclusion: A high level of CAR in blood samples is associated with an increased risk of developing NOAF in SARS-CoV-2.


Subject(s)
Albumins/metabolism , Atrial Fibrillation/metabolism , C-Reactive Protein/metabolism , COVID-19/complications , Aged , Atrial Fibrillation/complications , COVID-19/virology , Female , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification , Turkey
17.
Front Immunol ; 12: 720363, 2021.
Article in English | MEDLINE | ID: covidwho-1376702

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Humans , Inflammation/blood , Influenza A Virus, H1N1 Subtype , Influenza, Human/blood , Influenza, Human/complications , Stroke/blood , Virus Diseases
18.
Stroke ; 52(11): e706-e709, 2021 11.
Article in English | MEDLINE | ID: covidwho-1371922
19.
Front Immunol ; 12: 708101, 2021.
Article in English | MEDLINE | ID: covidwho-1365543

ABSTRACT

Background: Plasma levels of C-reactive protein (CRP), induced by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) triggering COVID-19, can rise surprisingly high. The increase of the CRP concentration as well as a certain threshold concentration of CRP are indicative of clinical deterioration to artificial ventilation. In COVID-19, virus-induced lung injury and the subsequent massive onset of inflammation often drives pulmonary fibrosis. Fibrosis of the lung usually proceeds as sequela to a severe course of COVID-19 and its consequences only show months later. CRP-mediated complement- and macrophage activation is suspected to be the main driver of pulmonary fibrosis and subsequent organ failure in COVID-19. Recently, CRP apheresis was introduced to selectively remove CRP from human blood plasma. Case Report: A 53-year-old, SARS-CoV-2 positive, male patient with the risk factor diabetes type 2 was referred with dyspnea, fever and fulminant increase of CRP. The patient's lungs already showed a pattern enhancement as an early sign of incipient pneumonia. The oxygen saturation of the blood was ≤ 89%. CRP apheresis using the selective CRP adsorber (PentraSorb® CRP) was started immediately. CRP apheresis was performed via peripheral venous access on 4 successive days. CRP concentrations before CRP apheresis ranged from 47 to 133 mg/l. The removal of CRP was very effective with up to 79% depletion within one apheresis session and 1.2 to 2.14 plasma volumes were processed in each session. No apheresis-associated side effects were observed. It was at no point necessary to transfer the patient to the Intensive Care Unit or to intubate him due to respiratory failure. 10 days after the first positive SARS-CoV-2 test, CRP levels stayed below 20 mg/l and the patient no longer exhibited fever. Fourteen days after the first positive SARS-CoV-2 test, the lungs showed no sign of pneumonia on X-ray. Conclusion: This is the first report on CRP apheresis in an early COVID-19 patient with fulminant CRP increase. Despite a poor prognosis due to his diabetes and biomarker profile, the patient was not ventilated, and the onset of pneumonia was reverted.


Subject(s)
Blood Component Removal/methods , C-Reactive Protein/metabolism , COVID-19/therapy , Respiratory Insufficiency/prevention & control , C-Reactive Protein/analysis , C-Reactive Protein/immunology , COVID-19/blood , COVID-19/complications , COVID-19/immunology , Humans , Lung/diagnostic imaging , Lung/immunology , Male , Middle Aged , Respiratory Insufficiency/immunology , Respiratory Insufficiency/pathology , Respiratory Insufficiency/virology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Treatment Outcome
20.
J Med Virol ; 93(9): 5438-5445, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363683

ABSTRACT

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.


Subject(s)
COVID-19/blood , COVID-19/immunology , Pregnancy Trimesters/blood , SARS-CoV-2/pathogenicity , Selenium/blood , Adult , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/virology , Case-Control Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hematocrit , Hemoglobins/metabolism , Humans , Interleukin-6/blood , Lymphocytes/immunology , Lymphocytes/virology , Monocytes/immunology , Monocytes/virology , Neutrophils/immunology , Neutrophils/virology , Pregnancy , Pregnancy Trimesters/immunology , Severity of Illness Index
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