Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 31
Filter
1.
Cell ; 185(8): 1389-1401.e18, 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1788017

ABSTRACT

The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies have been limited by the continuous emergence of viral variants and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on the Omicron variant receptor-binding domain recognized by broadly neutralizing antibodies. Furthermore, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant receptor-binding domain as revealed by cryo-EM structures. We demonstrated that this bispecific antibody can be effectively delivered to lung via inhalation administration and exhibits exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. Importantly, this study also deciphered an uncommon and highly conserved cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.


Subject(s)
COVID-19 Vaccines , Single-Domain Antibodies , Administration, Inhalation , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , COVID-19 Vaccines/administration & dosage , Disease Models, Animal , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
2.
Signal Transduct Target Ther ; 7(1): 91, 2022 03 18.
Article in English | MEDLINE | ID: covidwho-1751707

ABSTRACT

Currently, there is no effective drugs for treating clinically COVID-19 except dexamethasone. We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid (HA). As the inhibitor of HA synthesis, hymecromone is an approved prescription drug used for treating biliary spasm. Here, we aimed to investigate the relation between HA and COVID-19, and evaluate the therapeutic effects of hymecromone on COVID-19. Firstly, HA was closely relevant to clinical parameters, including lymphocytes (n = 158; r = -0.50; P < 0.0001), C-reactive protein (n = 156; r = 0.55; P < 0.0001), D-dimer (n = 154; r = 0.38; P < 0.0001), and fibrinogen (n = 152; r = 0.37; P < 0.0001), as well as the mass (n = 78; r = 0.43; P < 0.0001) and volume (n = 78; r = 0.41; P = 0.0002) of ground-glass opacity, the mass (n = 78; r = 0.48; P < 0.0001) and volume (n = 78; r = 0.47; P < 0.0001) of consolidation in patient with low level of hyaluronan (HA < 48.43 ng/mL). Furthermore, hyaluronan could directly cause mouse pulmonary lesions. Besides, hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression. Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P < 0.0001). In addition, lymphocytes recovered more quickly in hymecromone-treated patients (n = 8) than control group (n = 5) (P < 0.05). These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.


Subject(s)
COVID-19 , Hyaluronic Acid , Animals , COVID-19/drug therapy , Humans , Hymecromone/metabolism , Hymecromone/pharmacology , Mice , Prescriptions , SARS-CoV-2
4.
EBioMedicine ; 76: 103861, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1734342

ABSTRACT

BACKGROUND: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. METHODS: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. FINDINGS: Five short sequences (24-27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. INTERPRETATION: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. FUNDING: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).


Subject(s)
Gene Regulatory Networks/genetics , Genome, Human , Hyaluronic Acid/metabolism , RNA, Viral/genetics , SARS-CoV-2/genetics , Antagomirs/metabolism , Argonaute Proteins/genetics , Base Sequence , COVID-19/pathology , COVID-19/virology , Cell Line , Disease Progression , Enhancer Elements, Genetic/genetics , Humans , Hyaluronan Synthases/genetics , Hyaluronan Synthases/metabolism , Hyaluronic Acid/blood , MicroRNAs/genetics , RNA, Viral/chemistry , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Up-Regulation
5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324114

ABSTRACT

Background: The impact of corticosteroid therapy on outcomes of patients with Coronavirus disease-2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. Methods In this single-centre retrospective observational study, patients with ARDS caused by COVID-19 between 24 December 2019 and 24 February 2020 were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. Results A total of 382 patients including 226 (59.2%) patients who received systemic corticosteroids and 156 (40.8%) patients with standard treatment were analyzed. The maximum dose of corticosteroids was 80.0 (IQR 40.0–80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0–12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days (HR, 0.48;95% CI, 0.25, 0.93;p  = 0.0285). The association remained significantly after adjusting for age, sex, Sequential Organ Failure Assessment score at hospital admission, propensity score of corticosteroid treatment, and comorbidities (HR: 0.51;CI: 0.27, 0.99;p  = 0.0471). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. Conclusion In this clinical practice setting, low-to-moderate dose corticosteroid treatment was associated with reduced risk of death in COVID-19 patients who developed ARDS.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308258

ABSTRACT

Background: Hospitalized patients with COVID-19 appeared high risk of venous thromboembolism (VTE), which exhibited the predictor of mortality in non-COVID-19 patients. Objectives: We aimed to investigate the association between risk of VTE with 30-day mortality in COVID-19 patients. Methods: : In this retrospective cohort study, 1030 consecutive hospitalized patients with COVID-19 were recruited in two hospitals of Wuhan, China. We collected baseline data on demographics, SOFA parameters, and VTE risk assessment models (RAMs) including Padua Prediction Score (PPS), IMPROVE and Caprini RAM. The primary outcome of the study was 30-day mortality. Results: : Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk defined by PPS. Similar findings were also observed for risk of VTE defined by IMPROVE and Caprini score. Progressive increases in VTE risk also were associated with higher SOFA score. Our findings showed that the presence of high risk of VTE was independently associated with 30-day mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19, 37.37, 20.60 for PPS, IMPROVE and Caprini RAM, respectively ( P < 0.001 for all comparisons). Predictive accuracy of PPS (AUC, 0.900), IMPROVE (AUC, 0.917) or Caprini RAM (AUC, 0.861) as the risk of 30-day mortality was markedly well. Conclusions: : The presence of high risk of VTE identifies a group of patients with COVID-19 at higher risk for 30-day mortality. Furthermore, there is higher accuracy of VTE RAMs to predict 30-day mortality in these patients.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308257

ABSTRACT

Background: Hospitalized patients with COVID-19 appeared high risk of venous thromboembolism (VTE) defined by some risk assessment models (RAMs), which exhibited the predictor of mortality in patients with non-COVID-19. We aimed to investigate the association between risk of VTE with 30-day mortality in COVID-19 patients.Methods: In this retrospective cohort study, 1030 consecutive hospitalized patients, between January 26, 2020 and March 29, 2020, aged 14–98 years with a confirmed diagnosis of COVID-19-related pneumonia were recruited from Jinyintan Hospital and Union Hosptial, Wuhan, China. We collected baseline data on demographics, SOFA parameters, and VTE RAMs including Padua Prediction Score (PPS), IMPROVE RAM and Caprini RAM. The primary outcome of the study was 30-day mortality. The secondary outcome was the length of stay in hospital. Findings: Thirty-day mortality increased progressively from 2% in patients at low risk of VTE to 63% in those at high risk of VTE defined by PPS ≥ 4. Similar findings were also observed for risk of VTE defined by IMPROVE score ³ 2 and Caprini score ³ 5. Progressive increases in VTE risk also were associated with higher SOFA score. Our findings showed that the presence of high risk of VTE was independently associated with 30-day mortality regardless of adjusted gender, smoking status and some comorbidities with hazard ratios of 29.19 (95% CI 15.76 - 54.05), 37.37 (95% CI 18.43 - 75.78), 20.60 (95% CI 11.41 - 37.19) for PPS, IMPROVE RAM and Caprini RAM, respectively (P < 0.001 for all comparisons). Predictive accuracy of PPS (AUC, 0.900;95% CI 0.881 - 0.919), IMPROVE RAM (AUC, 0.917;95% CI 0.898 - 0.936) or Caprini RAM (AUC, 0.861;95% CI 0.840 - 0.882) as the risk of 30-day mortality was markedly well.Interpretation: The presence of high risk of VTE identifies a group of patients with COVID-19 at higher risk for 30-day mortality. Furthermore, there is higher accuracy of VTE RAMs to predict 30-day mortality in COVID-19 hospitalized patients.Funding Statement: This study is funded by the National Nature Science Foundation of China (81870062 to Jinjun Jiang, 81900038 to Shujing Chen).Declaration of Interests: The authors have no conflict of interest to disclose.Ethics Approval Statement: The study was approved by Jinyintan Hospital Ethics Committee (KY2020-06.01) and Union Hospital Ethics Committee (2020-0039). Written informed consent was waived by the Ethics Commission.

10.
Signal Transduct Target Ther ; 6(1): 378, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1500450

ABSTRACT

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , COVID-19 , SARS-CoV-2/chemistry , Single-Chain Antibodies/chemistry , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , Crystallography, X-Ray , Epitopes/chemistry , Epitopes/immunology , Humans , Mice , SARS-CoV-2/immunology , Single-Chain Antibodies/immunology , Single-Chain Antibodies/therapeutic use
12.
Int J Infect Dis ; 108: 543-549, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1409633

ABSTRACT

OBJECTIVES: To investigate the association of risk of venous thromboembolism with 30-day mortality in COVID-19 patients. METHODS: A total of 1030 COVID-19 patients were retrospectively collected, with baseline data on demographics, sequential organ failure assessment (SOFA) score, and VTE risk assessment models (RAMs), including Padua prediction score (PPS), International Medical Prevention Registry (IMPROVE), and Caprini. RESULTS: Thirty-day mortality increased progressively from 2% in patients at low VTE risk to 63% in those at high risk defined by PPS. Similar findings were observed in IMPROVE and Caprini scores. Progressive increases in VTE risk were also associated with higher SOFA score. High risk of VTE was independently associated with mortality regardless of adjusted gender, smoking status and some comorbidities, with hazard ratios of 29.19, 37.37 and 20.60 for PPS, IMPROVE and Caprini RAM, respectively (P < 0.001 for all comparisons). The predictive accuracy of PPS (area under curve (AUC) 0.900), IMPROVE (AUC 0.917), or Caprini (AUC 0.861) RAM for risk of hospitalized mortality was unexpectedly strong. CONCLUSIONS: We established that the presence of a high risk of VTE identifies a group of COVID-19 patients at higher risk for mortality. Furthermore, there is a high accuracy of VTE RAMs to predict mortality in these patients.


Subject(s)
COVID-19 , Venous Thromboembolism , Humans , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/epidemiology
13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(7): 774-778, 2021 Jul.
Article in Chinese | MEDLINE | ID: covidwho-1367940

ABSTRACT

OBJECTIVE: To evaluate the effect of Xuebijing injection on the improvement of pneumonia severity index (PSI) and prognosis in patients with severe coronavirus disease 2019 (COVID-19). METHODS: A multicenter prospective cohort study was designed. Adult patients with COVID-19 admitted to the intensive care unit (ICU) of 28 designated COVID-19 hospitals in 15 provinces and cities of China from January to March 2020 were enrolled. All patients were treated according to the standard treatment plan of COVID-19 issued by the National Health Commission of the People's Republic of China. They were divided into Xuebijing group and standard treatment group according to whether they received Xuebijing injection or not. In the standard treatment group, routine medical care measures such as antiviral, respiratory support, circulatory support and symptomatic treatment were taken. In the Xuebijing group, on the basis of standard treatment, Xuebijing was used within 12 hours of admission to the ICU, 100 mL each time, twice daily. The minimum duration of Xuebijing administration was 1 day. The improvement rate of PSI risk rating on the 8th day and clinical outcome on the 28th day were recorded. RESULTS: A total of 276 COVID-19 patients were screened continuously, and the data of 144 severe patients who met PSI risk rating III-V were analyzed. Seventy-two cases were involved each in standard treatment group and Xuebijing group. The average age of the standard treatment group and Xuebijing group were (65.7±7.9) years old and (63.5±10.9) years old, and male accounted for 75.0% (54/72) and 70.8% (51/72), respectively. There were no significant differences in general conditions, comorbidities, PSI risk rating and score, sequential organ failure assessment (SOFA) score, oxygenation index (PaO2/FiO2), respiratory support mode and other baseline indicators between the two groups. Compared with the standard treatment group, the improvement rate of PSI risk rating in Xuebijing group on the 8th day after admission was significantly improved [56.9% (41/72) vs. 20.8% (15/72), between-group difference and 95% confidence interval (95%CI) was 36.1% (21.3% to 50.9%), P < 0.01], PSI score, SOFA score and PaO2/FiO2 were significantly improved [PSI score: 83.7±34.8 vs. 108.2±25.6, between-group difference (95%CI) was -24.5 (-34.9 to -14.1); SOFA score: 2.0 (1.0, 4.0) vs. 7.0 (4.0, 10.0), between-group difference (95%CI) was -3.5 (-5.0 to -2.0); PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 289.4±111.6 vs. 188.5±98.1, between-group difference (95%CI) was 100.9 (65.3 to 136.5); all P < 0.01]. The 28-day discharge rate of Xuebijing group was 44.5% higher than that of standard treatment group [66.7% (48/72) vs. 22.2% (16/72), P < 0.01], and the 28-day survival rate was 9.8% [91.7% (66/72) vs. 81.9% (59/72), P < 0.01]. There was no significant difference in the combination of antiviral drugs, antibiotics, anticoagulants and vasopressor drugs between the two groups. There was no significant difference in the incidence of adverse events between the Xuebijing group and standard treatment group [41.7% (30/72) vs. 43.1% (31/72), P > 0.05], and no serious adverse events and adverse reactions of Xuebijing were reported. CONCLUSIONS: Standard treatment combined with Xuebijing injection can significantly improve the PSI risk score and clinical prognosis of patients with severe COVID-19 without increasing drug safety risk.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Adult , Aged , Drugs, Chinese Herbal/therapeutic use , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2
14.
Crit Care ; 24(1): 643, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-1067255

ABSTRACT

BACKGROUND: The impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. METHODS: In this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. RESULTS: A total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0-3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0-80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0-12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. CONCLUSION: In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Propensity Score , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/mortality , Aged , COVID-19 , Cohort Studies , Dexamethasone/administration & dosage , Female , Hospitalization/trends , Humans , Male , Methylprednisolone/administration & dosage , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2 , Survival Rate/trends
15.
SciFinder; 2020.
Preprint | SciFinder | ID: ppcovidwho-4908

ABSTRACT

A review. Strengthen supportive treatment, active oxygen therapy and respiratory support (ventilator-assisted ventilation and extracorporeal membrane oxygenation) are important means for the treatment of severe and critical COVID-19 patients based on the National Health Commission Department and the State Administration of Traditional Chinese Medicine issued the "New Coronavirus Infection Pneumonia Diagnosis and Treatment Program (Trial Version 5)" and "New Coronavirus Pneumonia Severe, Critical and Severe Case Diagnosis and Treatment Program (Trial Version 2)". When conventional treatment cannot prevent the progression of COVID-19, it is recommended to use small doses of short-term glucocorticoids, but no evidence Academic basis;the therapeutic effect of Xuebijing injection on severe COVID-19 patients needs to be confirmed. Strictly adhere to the principle of scientific rescue, and do a good job in the treatment of critical and critical illnesses in isolation and wards, isolation wards, and isolation intensive care units The protection of medical personnel of COVID-19 patients is very important.

16.
BMJ Open Diabetes Res Care ; 8(2)2020 11.
Article in English | MEDLINE | ID: covidwho-936897

ABSTRACT

INTRODUCTION: To investigate the risk factors for the death in patients with COVID-19 with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We retrospectively enrolled inpatients with COVID-19 from Wuhan Jinyintan Hospital (Wuhan, China) between December 25, 2019, and March 3, 2020. The epidemiological and clinical data were compared between non-T2DM and T2DM or between survivors and non-survivors. Univariable and multivariable Cox regression analyses were used to explore the effect of T2DM and complications on in-hospital death. RESULTS: A total of 1105 inpatients with COVID-19, 967 subjects with without T2DM (n=522 male, 54.0%) and 138 subjects with pre-existing T2DM (n=82 male, 59.4%) were included for baseline characteristics analyses. The complications were also markedly increased in patients with pre-existing T2DM, including acute respiratory distress syndrome (ARDS) (48.6% vs 32.3%, p<0.001), acute cardiac injury (ACI) (36.2% vs 16.7%, p<0.001), acute kidney injury (AKI) (24.8% vs 9.5%, p<0.001), coagulopathy (24.8% vs 11.1%, p<0.001), and hypoproteinemia (21.2% vs 9.4%, p<0.001). The in-hospital mortality was significantly higher in patients with pre-existing T2DM compared with those without T2DM (35.3% vs 17.4%, p<0.001). Moreover, in hospitalized patients with COVID-19 with T2DM, ARDS and coagulopathy were the main causes of mortality, with an HR of 7.96 (95% CI 2.25 to 28.24, p=0.001) for ARDS and an HR of 2.37 (95% CI 1.08 to 5.21, p=0.032) for coagulopathy. This was different from inpatients with COVID-19 without T2DM, in whom ARDS and cardiac injury were the main causes of mortality, with an HR of 12.18 (95% CI 5.74 to 25.89, p<0.001) for ARDS and an HR of 4.42 (95% CI 2.73 to 7.15, p<0.001) for cardiac injury. CONCLUSIONS: Coagulopathy was a major extrapulmonary risk factor for death in inpatients with COVID-19 with T2DM rather than ACI and AKI, which were well associated with mortality in inpatients with COVID-19 without T2DM.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Diabetes Mellitus, Type 2/complications , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/mortality , Hospital Mortality , SARS-CoV-2/genetics , Acute Kidney Injury/complications , Acute Kidney Injury/mortality , Adult , Aged , COVID-19/virology , China/epidemiology , Female , Follow-Up Studies , Heart Injuries/complications , Heart Injuries/mortality , Hospitalization , Humans , Male , Middle Aged , Respiratory Distress Syndrome/complications , Retrospective Studies , Risk Factors
17.
Clin Respir J ; 15(3): 293-309, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-916058

ABSTRACT

INTRODUCTION: COVID-19 has spread rapidly worldwide and has been declared a pandemic. OBJECTIVES: To delineate clinical features of COVID-19 patients with different severities and prognoses and clarify the risk factors for disease progression and death at an early stage. METHODS: Medical history, laboratory findings, treatment and outcome data from 214 hospitalised patients with COVID-19 pneumonia admitted to Eastern Campus of Renmin Hospital, Wuhan University in China were collected from 30 January 2020 to 20 February 2020, and risk factors associated with clinical deterioration and death were analysed. The final date of follow-up was 21 March 2020. RESULTS: Age, comorbidities, higher neutrophil cell counts, lower lymphocyte counts and subsets, impairment of liver, renal, heart, coagulation systems, systematic inflammation and clinical scores at admission were significantly associated with disease severity. Ten (16.1%) moderate and 45 (47.9%) severe patients experienced deterioration after admission, and median time from illness onset to clinical deterioration was 14.7 (IQR 11.3-18.5) and 14.5 days (IQR 11.8-20.0), respectively. Multivariate analysis showed increased Hazards Ratio of disease progression associated with older age, lymphocyte count <1.1 × 109/L, blood urea nitrogen (BUN)> 9.5 mmol/L, lactate dehydrogenase >250 U/L and procalcitonin >0.1 ng/mL at admission. These factors were also associated with the risk of death except for BUN. Prediction models in terms of nomogram for clinical deterioration and death were established to illustrate the probability. CONCLUSIONS: These findings provide insights for early detection and management of patients at risk of disease progression or even death, especially older patients and those with comorbidities.


Subject(s)
COVID-19/diagnosis , Hospitalization/trends , Pandemics , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , China/epidemiology , Disease Progression , Female , Hospital Mortality/trends , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends
18.
Signal Transduct Target Ther ; 5(1): 256, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-899906

ABSTRACT

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is spreading globally and poses a huge threat to human health. Besides common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2 (ACE2) and there is increasing evidence of a possible fecal-oral transmission route. In addition, there exist multiple abnormalities in liver enzymes. COVID-19-related liver injury may be due to drug-induced liver injury, systemic inflammatory reaction, and hypoxia-ischemia reperfusion injury. The direct toxic attack of SARS-CoV-2 on the liver is still questionable. This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.


Subject(s)
Chemical and Drug Induced Liver Injury/epidemiology , Coronavirus Infections/epidemiology , Gastrointestinal Diseases/epidemiology , Liver Diseases/epidemiology , Pneumonia, Viral/epidemiology , Angiotensin-Converting Enzyme 2 , COVID-19 , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/virology , Coronavirus Infections/genetics , Coronavirus Infections/pathology , Coronavirus Infections/virology , Feces/virology , Gastrointestinal Diseases/complications , Gastrointestinal Diseases/genetics , Gastrointestinal Diseases/virology , Gastrointestinal Tract/injuries , Gastrointestinal Tract/pathology , Gastrointestinal Tract/virology , Humans , Liver/physiopathology , Liver/virology , Liver Diseases/genetics , Liver Diseases/pathology , Liver Diseases/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology
19.
Ann Biomed Eng ; 48(12): 3003-3013, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-880328

ABSTRACT

In patients with critically ill COVID-19 pneumonia, lower airways are filled with plenty of highly viscous exudates or mucus, leading to airway occlusion. The estimation of airway opening pressures and effective mucus clearance are therefore two issues that clinicians are most concerned about during mechanical ventilation. In this study we retrospectively analyzed respiratory data from 24 critically ill patients with COVID-19 who received invasive mechanical ventilation and recruitment maneuver at Jinyintan Hospital in Wuhan, China. Among 24 patients, the mean inspiratory plateau pressure was 52.4 ± 4.4 cmH2O (mean ± [SD]). Particularly, the capnograms presented an upward slope during the expiratory plateau, indicting the existence of airway obstruction. A computational model of airway opening was subsequently introduced to investigate possible fluid dynamic mechanisms for the extraordinarily high inspiratory plateau pressures among these patients. Our simulation results showed that the predicted airway opening pressures could be as high as 40-50 cmH2O and the suction pressure could exceed 20 kPa as the surface tension and viscosity of secretion simulants markedly increased, likely causing the closures of the distal airways. We concluded that, in some critically ill patients with COVID-19, limiting plateau pressure to 30 cmH2O may not guarantee the opening of airways due to the presence of highly viscous lower airway secretions, not to mention spontaneous inspiratory efforts. Active airway humidification and effective expectorant drugs are therefore strongly recommended during airway management.


Subject(s)
COVID-19/physiopathology , Computer Simulation , Lung/physiopathology , Models, Biological , Pulmonary Gas Exchange , Respiratory Mechanics , SARS-CoV-2 , Adult , Aged , Air Pressure , COVID-19/therapy , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies
20.
J Transl Int Med ; 8(3): 115-118, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-874403
SELECTION OF CITATIONS
SEARCH DETAIL