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1.
Front Mol Biosci ; 9: 985571, 2022.
Article in English | MEDLINE | ID: covidwho-2022801

ABSTRACT

Ferroptosis is an iron-dependent mode of cell death characterized by intracellular lipid peroxide accumulation and a redox reaction imbalance. Compared with other modes of cell death, ferroptosis has specific biological and morphological features. The iron-dependent lipid peroxidation accumulation is manifested explicitly in the abnormal metabolism of intracellular lipid oxides catalyzed by excessive iron ions with the production of many reactive oxygen species and over-oxidization of polyunsaturated fatty acids. Recent studies have shown that various diseases, which include intestinal diseases and cancer, are associated with ferroptosis, but few studies are related to airway inflammatory diseases. This review provides a comprehensive analysis of the primary damage mechanisms of ferroptosis and summarizes the relationship between ferroptosis and airway inflammatory diseases. In addition to common acute and chronic airway inflammatory diseases, we also focus on the progress of research on COVID-19 in relation to ferroptosis. New therapeutic approaches and current issues to be addressed in the treatment of inflammatory airway diseases using ferroptosis are further proposed.

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312697

ABSTRACT

Background: The severe acute respiratory syndrome coronavirus-2 outbreak was identified in China in December 2019 and spread worldwide, reaching the pandemic levels. However, a specific, effective and proven therapy for the patients with coronavirus disease 2019 (COVID-19) remains elusive. We aim to compare the efficacy and the safety of three antiviral monotherapies (chloroquine phosphate, arbidol (Umifenovir) or lopinavir/ritonavir) in non-severe, hospitalised COVID-19 patients. Methods: : We retrospectively analysed the hospitalised, laboratory-confirmed COVID-19 patients, treated with antiviral monotherapies at Huizhou Municipal Central Hospital between Jan 19 and Mar 16, 2020. Demographic and clinical data were extracted from electronic medical records. The primary outcome of the study was the viral shedding interval. Results: : Twenty-seven patients with COVID-19 were included in the study with 10 receiving chloroquine phosphate, 11 receiving arbidol and 6 receiving lopinavir/ritonavir. Baseline demographics and clinical data were similar between groups. The median viral shedding interval in the lopinavir/ritonavir group was 13.0 days (95% CI: 12.2-23.8), while significantly shorter in the chloroquine group at 5.0 days (95% CI: 0.4-9.6) (p=0.003). A reduced median interval was also observed in the arbidol group, with 8.0 days (95%CI: 4.9-11.1) (p=0.008). Moreover, the hospitalisation duration was shorter in the chloroquine (9.3 ± 1.8 days, p<0.001) and arbidol groups (11.7 ± 3.7 days, p<0.001), and the hospitalisation costs were significantly reduced in the chloroquine (USD 1327 ± 566, p=0.001) and arbidol groups (USD 1167 ± 434, p<0.001), when compared with the lopinavir/ritonavir group (hospitalisation length and costs: 19.7 ± 4.4 days and USD 3806 ± 2262, respectively). Conclusions: : Chloroquine and arbidol could not only shorten the viral shedding interval but also decreased the hospitalisation duration and hospitalisation expenses. Trial registration: The ethics committee of the Huizhou Municipal Central Hospital approved this study, and the trial was registered with www.chictr.org.cn (ChiCTR2000030931).

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295314

ABSTRACT

Background: The benefits of baricitinib, which is a Janus kinase inhibitor, in coronavirus disease-2019 (COVID-19) are inadequately defined. We performed a systematic review and meta-analysis of randomised, controlled trials and observational studies of baricitinib to determine its clinical efficacy and adverse events in patients with COVID-19.Methods: Major databases were searched from 2019 to 2021 inclusive. The primary outcome was the coefficient of mortality. We also compared increasing different doses of baricitinib, intensive care unit admission, the requirement for mechanical ventilation, the oxygenation index, and adverse events between baricitinib treatment and placebo or other treatments.Findings: Twelve studies of 3564 patients were included and assessed qualitatively (Jadad and Newcastle–Ottawa Scale scores). Baricitinib effectively improved the mortality rate (relative risk of mortality = 0.56;95% confidence interval: 0.46–0.69;P < 0.00001;I2 = 2%), and this result was unchanged by subgroup analysis. Baricitinib also improved intensive care unit admission, the requirement for invasive mechanical ventilation, and the oxygenation index. Data from these studies also showed that baricitinib slightly reduced the risk of adverse events. With regard to the choice of the drug dosage of baricitinib, the high-dose group appeared to have additional benefits for clinical efficacy.Interpretation: Our study shows that baricitinib may be a promising, safe, and effective anti-severe acute respiratory syndrome-coronavirus-2 drug candidate, with the advantages of a low cost, easy production, and convenient storage.Funding Information: We gratefully acknowledge the financial supports by the Basic research program of Guangzhou (202102010224), Clinical Transformation program of the first affiliated hospital of Guangzhou medical university (ZH201802, ZH201914), High-level university program of Guangzhou medical university (2017(160)) and Opening Project of State Key Laboratory of Respiratory Disease (SKLRD-0P-202115).Declaration of Interests: The authors have no potential conflict of interest to disclose.

4.
J Med Virol ; 94(4): 1523-1534, 2022 04.
Article in English | MEDLINE | ID: covidwho-1540137

ABSTRACT

The benefits of baricitinib in coronavirus disease-2019 are inadequately defined. We performed a systematic review and meta-analysis of studies of baricitinib to determine its clinical efficacy and adverse events in patients with COVID-19. Databases were searched from their inception to September 5, 2021. The primary outcome was the coefficient of mortality. We also compared secondary indicators and adverse events between baricitinib treatment and placebo or other treatments. Twelve studies of 3564 patients were included and assessed qualitatively (modified Jadad and Newcastle-Ottawa Scale scores). Baricitinib effectively improved the mortality rate (relative risk of mortality = 0.56; 95% confidence interval: 0.46-0.69; p < 0.001; I2 = 2%), and this result was unchanged by subgroup analysis. Baricitinib improved intensive care unit admission, the requirement for invasive mechanical ventilation, and improved the oxygenation index. Data from these studies also showed that baricitinib slightly reduced the risk of adverse events. Regarding the choice of the drug dosage of baricitinib, the high-dose group appeared to have additional benefits for clinical efficacy. Our study shows that baricitinib may be a promising, safe, and effective anti-severe acute respiratory syndrome-coronavirus-2 drug candidate, with the advantages of low cost, easy production, and convenient storage.


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Azetidines/administration & dosage , COVID-19/mortality , Dose-Response Relationship, Drug , Humans , Purines/administration & dosage , Pyrazoles/administration & dosage , SARS-CoV-2 , Sulfonamides/administration & dosage , Treatment Outcome
5.
Int J Biol Sci ; 17(6): 1565-1573, 2021.
Article in English | MEDLINE | ID: covidwho-1206427

ABSTRACT

Dysregulated immune response and abnormal repairment could cause secondary pulmonary fibrosis of varying severity in COVID-19, especially for the elders. The Krebs Von den Lungen-6 (KL-6) as a sensitive marker reflects the degree of fibrosis and this study will focus on analyzing the evaluative efficacy and predictive role of KL-6 in COVID-19 secondary pulmonary fibrosis. The study lasted more than three months and included total 289 COVID-19 patients who were divided into moderate (n=226) and severe groups (n=63) according to the severity of illness. Clinical information such as inflammation indicators, radiological results and lung function tests were collected. The time points of nucleic acid test were also recorded. Furthermore, based on Chest radiology detection, it was identified that 80 (27.7%) patients developed reversible pulmonary fibrosis and 34 (11.8%) patients developed irreversible pulmonary fibrosis. Receiver operating characteristic (ROC) curve analysis shows that KL-6 could diagnose the severity of COVID-19 (AUC=0.862) and predict the occurrence of pulmonary fibrosis (AUC = 0.741) and irreversible pulmonary fibrosis (AUC=0.872). Importantly, the cross-correlation analysis demonstrates that KL-6 rises earlier than the development of lung radiology fibrosis, thus also illuminating the predictive function of KL-6. We set specific values (505U/mL and 674U/mL) for KL-6 in order to assess the risk of pulmonary fibrosis after SARS-CoV-2 infection. The survival curves for days in hospital show that the higher the KL-6 levels, the longer the hospital stay (P<0.0001). In conclusion, KL-6 could be used as an important predictor to evaluate the secondary pulmonary fibrosis degree for COVID-19.


Subject(s)
COVID-19/complications , Mucin-1/metabolism , Pulmonary Fibrosis/complications , Adult , Aged , COVID-19/virology , Female , Humans , Male , Middle Aged , Pulmonary Fibrosis/therapy , Risk Factors , SARS-CoV-2/isolation & purification
6.
J Med Virol ; 93(3): 1443-1448, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196454

ABSTRACT

Our study intended to longitudinally explore the prediction effect of immunoglobulin A (IgA) on pulmonary exudation progression in COVID-19 patients. The serum IgA was tested with chemiluminescence method. Autoregressive moving average model was used to extrapolate the IgA levels before hospital admission. The positive rate of IgA and IgG in our cohort was 97% and 79.0%, respectively. In this study, the IgA levels peaks within 10-15 days after admission, while the IgG levels peaks at admission. We found that the time difference between their peaks was about 10 days. Viral RNA detection results showed that the positive rate in sputum and feces were the highest. Blood gas analysis showed that deterioration of hypoxia with the enlargement of pulmonary exudation area. And alveolar-arterial oxygen difference and oxygenation index were correlated with IgA and IgG. The results of biopsy showed that the epithelium of lung was exfoliated and the mucosa was edematous. In severe COVID-19 patients, the combination of IgA and IgG can predict the progress of pulmonary lesions and is closely related to hypoxemia and both also play an important defense role in invasion and destruction of bronchial and alveolar epithelium by SARS-CoV-2.


Subject(s)
COVID-19/pathology , COVID-19/virology , Immunoglobulin A/blood , Immunoglobulin G/blood , Sputum/virology , Aged , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , Antibodies, Viral/blood , Bronchi/metabolism , Bronchi/virology , COVID-19/blood , COVID-19/metabolism , Female , Humans , Hypoxia/blood , Hypoxia/metabolism , Male , Middle Aged , Mucous Membrane/metabolism , Mucous Membrane/virology , Oxygen/metabolism , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/virology , RNA, Viral/genetics , SARS-CoV-2/genetics
7.
ERJ Open Res ; 7(1)2021 Jan.
Article in English | MEDLINE | ID: covidwho-1076123

ABSTRACT

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients may suffer persistent systemic inflammation and multiple organ failure, leading to a poor prognosis. RESEARCH QUESTION: To examine the relevance of the novel inflammatory factor heparin-binding protein (HBP) in critically ill COVID-19 patients, and evaluate the correlation of the biomarker with disease progression. STUDY DESIGN AND METHODS: 18 critically ill COVID-19 patients who suffered from respiratory failure and sepsis, including 12 cases who experienced a rapidly deteriorating clinical condition and six cases without deterioration, were investigated. They were compared with 15 age- and sex- matched COVID-19-negative patients with respiratory failure. Clinical data were collected and HBP levels were investigated. RESULTS: HBP was significantly increased in critically ill COVID-19 patients following disease aggravation and tracked with disease progression. HBP elevation preceded the clinical manifestations for up to 5 days and was closely correlated with patients' pulmonary ventilation and perfusion status. INTERPRETATION: HBP levels are associated with COVID-19 disease progression in critically ill patients. As a potential mediator of disease aggravation and multiple organ injuries that are triggered by continuing inflammation and oxygen deficits, HBP warrants further study as a disease biomarker and potential therapeutic target.

8.
Biosci Trends ; 14(4): 290-296, 2020 Sep 21.
Article in English | MEDLINE | ID: covidwho-609824

ABSTRACT

This study aimed to determine the clinical significance of Krebs von den Lungen-6 (KL-6) in patients with COVID-19, so as to find a marker with high sensitivity, specificity and easy detection to evaluate the lung injury and inflammation of COVID-19. Sixty-three COVID-19 patients and 43 non-COVID-19 patients with similar clinical phenotypes and/or imaging findings were enrolled to test the levels of KL-6 using chemiluminescent immunoassay. In addition, the blood gas, imaging and lymphocyte factors tests were collected from all participants. The data was finally analyzed using multivariate statistical analysis. The results showed KL-6 levels in COVID-19 patients were higher than those in non-COVID-19 patients (P < 0.001). Moreover, the KL-6 levels in severe and critically severe patients were significantly upregulated compared with patients with mild and common type (P < 0.05). Meanwhile, the imaging evaluation showed a significant correlation between KL-6 and pulmonary lesion area (P < 0.05). KL-6 was also found to be significantly correlated with oxygenation index and oxygen partial pressure difference of alveolar artery (PA-aDO2) (Both P < 0.01). In conclusion, KL-6 could be an indicator to evaluate the progression of COVID-19, which is parallel to the level of lung injury and inflammation in patients. Moreover, it can also reflect the pulmonary ventilation function.


Subject(s)
Coronavirus Infections/blood , Lung/diagnostic imaging , Mucin-1/blood , Pneumonia, Viral/blood , Adult , Aged , Betacoronavirus , Blood Gas Analysis , COVID-19 , Case-Control Studies , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/immunology , SARS-CoV-2
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