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1.
Thromb J ; 19(1): 55, 2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1808372

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. METHODS AND ANALYSIS: We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. RESULTS: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). CONCLUSIONS: Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334352

ABSTRACT

Therapeutic efficacy of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) has been reported. However, predictive indicators of early weaning from MV in such cases have not yet been defined. Our aim was to clarify clinical utility of interleukin (IL)-6 level in ventilated patients with established ARDS. Clinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with ARDS caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation. Fifty-two patients received dexamethasone (steroid group) and the remaining 67 did not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5±0.6 vs. 16.1±1.0 days, P = 0.0005, respectively). Even when restricted to the steroid group, among the post-MV variables, the IL-6 level on day 7 was most closely correlated with the duration of MV use and showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Collectively, in intubated patients with ARDS due to SARS-CoV-2 who received dexamethasone, plasma IL-6 levels served as a predictor of early withdrawal from MV.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333057

ABSTRACT

Background Therapeutic effects of steroids on acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) have been reported. However, predictive indicators of early weaning from MV post-treatment have not yet been defined, making treating established ARDS challenging. Interleukin (IL)-6 has been associated with the pathogenesis of ARDS. Objective Our aim was to clarify clinical utility of IL-6 level in ventilated patients with established ARDS. Methods Clinical, treatment, and outcome data were evaluated in 119 invasively ventilated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated ARDS. Plasma levels of IL-6 and C-reactive protein (CRP) were measured on days 1, 4, and 7 after intubation. Results Fifty-two patients were treated with dexamethasone (steroid group), while the remaining 67 patients were not (non-steroid group). Duration of MV use was significantly shorter in the steroid group compared to non-steroid group (11.5±0.6 vs. 16.1±1.0 days, P = 0.0005, respectively) along with significantly decreased levels of IL-6 and CRP. Even when restricted to the steroid group, among variables post-MV, IL-6 level on day 7 was most closely correlated with duration of MV use (Spearman’s rank correlation coefficient [ρ] = 0.73, P < 0.0001), followed by CRP level on day 7 and the percentage change in IL-6 or CRP levels between day 1 and day 7. Moreover, among these variables, IL-6 levels on day 7 showed the highest accuracy for withdrawal from MV within 11 days (AUC: 0.88), with optimal cutoff value of 20.6 pg/mL. Consistently, the rate of MV weaning increased significantly earlier in patients with low IL-6 (≤ 20.6 pg/mL) than in those with high IL-6 (> 20.6 pg/mL) (log-rank test P < 0.0001). Conclusions In invasively ventilated patients with established ARDS due to SARS-CoV-2, plasma IL-6 levels served as a predictor of early withdrawal from MV after dexamethasone administration.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320568

ABSTRACT

The increasing requirement of mechanical ventilation (MV) due to the novel coronavirus disease (COVID-19) is still a global threat. The aim of this study is to identify markers that can easily stratify the impending use of MV in the emergency room (ER). A total of 106 patients with COVID-19 requiring oxygen support were enrolled. Fifty-nine patients were provided MV 0.5 hours (interquartile range: 0.3 to 1.4) post-admission. Clinical and laboratory data before intubation were collected. Using a multivariate logistic regression model, we identified four markers associated with the impending use of MV, including the ratio of peripheral blood oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ratio), alanine aminotransferase, blood glucose (BG), and lymphocyte counts. Among these markers, the combination of SpO 2 /FiO 2 ratio and BG, which can be measured easily and immediately, showed higher accuracy in its prediction (AUC: 0.88) compared to SpO 2 /FiO 2 ratio alone (AUC: 0.84). Moreover, even in patients without severe respiratory failure (SpO 2 /FiO 2 ratio > 300), BG (> 138 mg/dL) was predictive of MV use. Measuring BG and SpO 2 /FiO 2 ratio may be a simple and versatile new strategy to accurately identify ER patients with COVID-19 at high risk for the imminent need of MV.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318235

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microemboli or microvascular endothelial injuries. Here, we report that serum syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. Methods: and analysis : We analyzed the data of COVID-19 patients for one year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with serum SDC-1 by ELISA. Results: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group ( P =0.032, P <0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, D-dimer, ISTH score;P =0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p<0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients ( P =0.009 and P <0.0001, respectively). Conclusions: Annual changes in serum SDC-1 levels closely reflect the severity of COVID-19, therefore, serum SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317707

ABSTRACT

Background: Although some predictors of COVID-19 pneumonia severity and mortality have been identified, much of the pathophysiology of this emerging infectious disease remains unclear. We hypothesized that a patient’s cholinesterase level on admission could predict COVID-19 pneumonia severity and mortality. Methods We retrospectively collected data of 26 COVID-19 pneumonia patients from February–May 2020. Outcomes were aggravation of symptoms and in-hospital mortality. We compared receiver operating curves of cholinesterase, C-reactive protein, lymphocytes, albumin, D-dimer, and PaO 2 /FiO 2 ratio and examined prediction accuracy. Regarding the interaction between cholinesterase and other variables, each independent variable was divided into two groups using cutoff values, and interaction terms were created. Results Cholinesterase levels on admission were significantly lower in the severe group than in the mild-to-moderate group (326 vs. 218 IU/L, p = 0.006;area under the curve: 0.81;95% confidence interval 0.61–0.94). When comparing the area under the curve, cholinesterase was comparable to C-reactive protein, albumin, lymphocytes, and PaO 2 /FiO 2 ratio other than D-dimer in the prediction accuracy of severe cases and mortality. Cholinesterase levels on admission were significantly lower in the death group than in the survival group (274 vs. 187.5 IU/L, p = 0.028;area under the curve: 0.79;95% interval 0.58–0.93). Regarding the interaction between cholinesterase and established predictors, the prediction accuracy of both severity and death was higher when cholinesterase was combined with each predictor than when cholinesterase was used alone. Conclusions Cholinesterase may reflect the disease state of COVID-19 pneumonia, suggesting that a patient’s cholinesterase level on admission may be useful as a predictor of severity and prognosis.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314230

ABSTRACT

The COVID-19 is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we introduced an innovative approach utilizing data-independent acquisition (DIA) mass spectrometry to identify the serum proteins closely associated with the COVID-19 severity. We observed 23 proteins to be differentially expressed between the cohorts of critically ill COVID-19 patients with adverse and favorable prognosis. Myoglobin (MB), CHI3L1 and IGFALS were found to have a high sensitivity and specificity for their possible use as independent biomarkers to provide information on the disease prognosis. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.Funding: This work was in part supported by grants from the Japan Agency for Medical Research and Development (JP19fk0108169 to YK and JP19fk0108110/JP20he0522001 to AR).Conflict of Interest: The authors declare no competing interests.Ethical Approval: This research plan and protocol was approved by the Clinical Ethics Committee of Yokohama City University Hospital (B2002000048). This study was also performed with the approval of the Clinical Ethics Committee in each of the medical facilities. Informed consent was obtained from all patients and/or their guardians before serum samples collection.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314229

ABSTRACT

The COVID-19 pandemic is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins closely associated with the prognosis of COVID-19. We observed 27 proteins to be differentially expressed between the cohorts of severely ill COVID-19 patients with adverse and favorable prognosis. Ingenuity pathway analysis revealed that 15 out of the 27 proteins might be regulated by cytokine signalling relevant to interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF), and their differential expression was possibly implicated in the systemic inflammatory response and cardiovascular disorders. We further evaluated the practical prognosticators for the clinical prognosis of severe COVID-19 patients. Subsequent ELISA analyses further uncovered that CHI3L1 and IGFALS could be potent prognostic markers with a high sensitivity. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 patients and provide appropriate treatment based on their predicted prognosis.

10.
Sci Rep ; 11(1): 20638, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1475483

ABSTRACT

The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis.


Subject(s)
Biomarkers/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Gene Expression Profiling , Proteomics/methods , Chitinase-3-Like Protein 1/metabolism , Enzyme-Linked Immunosorbent Assay , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation , Humans , Inflammation , Interleukin-1beta/biosynthesis , Interleukin-6/biosynthesis , Prognosis , SARS-CoV-2 , Tumor Necrosis Factor-alpha/biosynthesis , Virus Diseases
11.
Thromb J ; 19(1): 55, 2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1357033

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. METHODS AND ANALYSIS: We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. RESULTS: We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). CONCLUSIONS: Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

12.
PLoS One ; 16(8): e0256022, 2021.
Article in English | MEDLINE | ID: covidwho-1352710

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality. OBJECTIVE: We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19. METHODS: Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR. RESULTS: Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/µL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively). CONCLUSIONS: Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV.


Subject(s)
COVID-19/mortality , Interleukin-6/blood , RNA, Viral/metabolism , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , Area Under Curve , COVID-19/pathology , COVID-19/virology , Female , Hospital Mortality , Humans , Male , Middle Aged , Oxygen Consumption , Prognosis , Prospective Studies , ROC Curve , Respiration, Artificial , SARS-CoV-2/isolation & purification , Viral Load
16.
Acute Med Surg ; 7(1): e536, 2020.
Article in English | MEDLINE | ID: covidwho-660193

ABSTRACT

AIM: The coronavirus disease 2019 (COVID-19) pandemic has accelerated all over the world, and global health-care systems have become overwhelmed with potentially infectious patients seeking testing and care. It is essential to set up effective and useful zoning to prevent the spread of infection to and from medical staff or other patients with effective use of standard precautions with personal protective equipment (PPE). METHODS: We repurposed a general ward into an acute care unit for severe COVID-19 patients taking into consideration airflow, the direction of movement of medical staff, and prevention of the spread of infection to medical staff and other patients. We checked the daily condition and body temperature of all medical staff for 60 days. RESULTS: There was no evidence of COVID-19 infection in any medical staff or other patients during the period thanks to effective and useful zoning with PPE. CONCLUSION: Special wards and rooms should be set up for future protection of medical staff and other patients, and prevent the explosion of COVID-19 infection with effective and useful zoning with PPE.

18.
J Infect Chemother ; 26(8): 865-869, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-245541

ABSTRACT

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Disease Outbreaks , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Aged , COVID-19 , Coronavirus Infections/complications , Diabetes Complications/complications , Female , Humans , Hypertension/complications , Japan , Male , Middle Aged , Pandemics , Patient Acuity , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Prognosis , SARS-CoV-2 , Ships
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