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1.
Cells ; 11(5)2022 03 07.
Article in English | MEDLINE | ID: covidwho-1742341

ABSTRACT

The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Probiotics , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/physiology , Lung , Microbiota/physiology , Probiotics/therapeutic use
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321878

ABSTRACT

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan, and rapidly spread throughout China. The virus is highly infectious and can infect individuals in the community, including patients in the hospital. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. Case presentation: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in the past month in our hospital. One patient with uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases was killed by the virus, and the other three patients survived. Nearly all patients showed a decrease in lymphocytes including total CD3 + T cells, B cells, and natural killer cells after infection of the virus. Conclusion: This report suggests that the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-309351

ABSTRACT

Background: COVID-19 still become a common threat to public health.In this study, we evaluated the antiviral effects and safety of darunavir/cobicisitat (DRV/c) in patients with confirmed COVID-19. Patients and Methods: Totally 66 patients with COVID-19 infection who were admitted to Zhongnan Hospital of Wuhan University between February 3 and March 11, 2020 were collected. The patients were divided into the DRV/c group and the control group. The Primary endpoints was the time of SARS-CoV-2 nucleic acid conversion detected in respiratory specimens. Results: A total of 66 subjects with confirmed SARS-CoV-2 infection were enrolled in this study, 32 subjects were enrolled in the DRV/c group and 34 in the control group. The mean time to nucleic acid conversion (NAC) was shorter in DRV/c group. The cumulative nucleic acid conversion rate (CNACR) in the DRV/C group was higher during the first 2 weeks, but the difference was not statistically significant. The proportion of fever during hospitalization in the DRV/C group was significantly lower than that in the control group (P value 0.01). It was found that in DRV/c group NAC of patients with duration from symptom onset to admission within 3 days was significantly shorter (7.9 ± 6.7 days) than that of and above 3 days (15.9 ± 7.1 days)( P = 0.01). Conclusion: Although the combination of DRV/c and routine treatment for patients with non-severe COVID-19 can significantly reduce the proportion of fever after admission, but no significant differences were observed between the DRV/c group and the conventional therapy group, including overall time to nucleic acid conversion, safety and tolerability.

4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307723

ABSTRACT

Background: The effective treatment of COVID-19 remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence for such treatment is still lacking.Methods: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by propensity score-matched (PSM) and inverse probability of treatment weighting (IPTW) analysis.Results: Overall, 26 patients who received high-dose IVIg with standard therapy and 79 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10 and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.28 (95%CI 0.06-1.10, p=0.061) in propensity score-matched (PSM) analysis, and 0.24 (95%CI 0.06-0.99, p<0.001) in inverse probability of treatment weighting (IPTW) adjustment. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg.Conclusions: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.Funding Statement: None.Declaration of Interests: All authors declared no competing financial interests.Ethics Approval Statement: The study protocol was approved by the institutional ethics board of Peking Union Medical College Hospital (PUMCH, No. ZS-2299, Feb 6, 2020), and all participants provided written consent for participating this study.

5.
Front Immunol ; 12: 627844, 2021.
Article in English | MEDLINE | ID: covidwho-1573949

ABSTRACT

BACKGROUND: The effective treatment of coronavirus disease 2019 (COVID-19) remains unclear. We reported successful use of high-dose intravenous immunoglobulin (IVIg) in cases of severe COVID-19, but evidence from larger case series is still lacking. METHODS: A multi-center retrospective study was conducted to evaluate the effectiveness of IVIg administered within two weeks of disease onset at a total dose of 2 g/kg body weight, in addition to standard care. The primary endpoint was 28-day mortality. Efficacy of high-dose IVIg was assessed by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) analysis, and IPTW after multiple imputation (MI) analysis. RESULTS: Overall, 26 patients who received high-dose IVIg with standard therapy and 89 patients who received standard therapy only were enrolled in this study. The IVIg group was associated with a lower 28-day mortality rate and less time to normalization of inflammatory markers including IL-6, IL-10, and ferritin compared with the control. The adjusted HR of 28-day mortality in high-dose IVIg group was 0.24 (95% CI 0.06-0.99, p<0.001) in IPTW model, and 0.27 (95% CI 0.10-0.57, p=0.031) in IPTW-MI model. In subgroup analysis, patients with no comorbidities or treated in the first week of disease were associated with more benefit from high-dose IVIg. CONCLUSIONS: High-dose IVIg administered in severe COVID-19 patients within 14 days of onset was linked to reduced 28-day mortality, more prominent with those having no comorbidities or treated at earlier stage.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Immunoglobulins, Intravenous/administration & dosage , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/blood , China/epidemiology , Disease-Free Survival , Female , Ferritins/blood , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Retrospective Studies , Survival Rate
6.
Clin Infect Dis ; 73(11): e4208-e4213, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560475

ABSTRACT

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19), caused by severe adult respiratory syndrome coronavirus 2, occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 1 January to 5 February. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy of treatment after hospitalization, and the differences between groups were compared. RESULTS: Compared with patients with general COVID-19 (45.2%), those with refractory disease were older, were more likely to be male, and had more underlying comorbid conditions, a lower incidence of fever, higher maximum temperatures among patients with fever, higher incidences of shortness of breath and anorexia, more severe disease assessment at admission, higher neutrophil, aspartate aminotransferase, lactate dehydrogenase, and C-reactive protein levels, lower platelet counts and albumin levels, and higher incidences of bilateral pneumonia and pleural effusion (P < .05). Patients with refractory COVID-19 were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment, including corticosteroids, antiviral drugs, and immune enhancers (P < .05). Considering the factors of disease severity at admission, mechanical ventilation, and intensive care unit transfer, patients with refractory COVID-19 were also more likely to be male, have manifestations of anorexia on admission, and receive oxygen, expectorant, and adjunctive agents (P < .05). CONCLUSION: In nearly 50% of patients with COVID-19 obvious clinical and radiological remission was not achieved within 10 days after hospitalization. Male, anorexia, and no fever at admission was predictive of poor treatment efficacy.


Subject(s)
COVID-19 , Adult , China/epidemiology , Female , Fever , Hospitalization , Humans , Male , Retrospective Studies , SARS-CoV-2
8.
Front Immunol ; 12: 671443, 2021.
Article in English | MEDLINE | ID: covidwho-1172967

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2021.627844/full.].

9.
Epidemiol Infect ; 148: e293, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-952350

ABSTRACT

The epidemic of coronavirus disease 2019 (COVID-19) began in China and had spread rapidly to many other countries. This study aimed to identify risk factors associated with delayed negative conversion of SARS-CoV-2 in COVID-19 patients. In this retrospective single-centre study, we included 169 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from 15th January to 2nd March. The cases were divided into two groups according to the median time of SARS-CoV-2 negative conversion. The differences between groups were compared. In total, 169 patients had a median virus negative conversion time of 18 days (interquartile range: 11-25) from symptom onset. Compared with the patients with short-term negative conversion, those with long-term conversion had an older age, higher incidence of comorbidities, chief complaints of cough and chest distress/breath shortness and severer illness on admission, higher level of leucocytes, neutrophils, aspartate aminotransferase, creatine kinase and erythrocyte sedimentation rate (ESR), lower level of CD3+CD4+ lymphocytes and albumin and more likely to receive mechanical ventilation. In multivariate analysis, cough, leucocytes, neutrophils and ESR were positively correlated with delayed virus negative conversion, and CD3+CD4+ lymphocytes were negatively correlated. The integrated indicator of leucocytes, neutrophils and CD3+CD4+ lymphocytes showed a good performance in predicting the negative conversion within 2 weeks (area under ROC curve (AUC) = 0.815), 3 weeks (AUC = 0.804), 4 weeks (AUC = 0.812) and 5 weeks (AUC = 0.786). In conclusion, longer quarantine periods might be more justified for COVID-19 patients with cough, higher levels of leucocytes, neutrophils and ESR and lower levels of CD3+CD4+ lymphocytes.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , COVID-19/virology , Epidemics , Female , Humans , Male , Middle Aged , RNA, Viral/analysis , Retrospective Studies , Risk Factors , Time Factors
10.
J Infect Dis ; 221(11): 1762-1769, 2020 05 11.
Article in English | MEDLINE | ID: covidwho-688308

ABSTRACT

BACKGROUND: In December 2019, novel coronavirus (SARS-CoV-2) pneumonia (COVID-19) was reported in Wuhan and has since rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) showed clinical response, with an increase in CD8+ T cells and B cells. No significant change in any subset was detected in nonresponsive cases. In multivariate analysis, posttreatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Lymphocyte Subsets , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Pneumonia/etiology , Pneumonia/physiopathology , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , China , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Female , Flow Cytometry , Humans , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Middle Aged , Pandemics , Pneumonia/diagnosis , Pneumonia/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Prognosis , SARS-CoV-2 , Treatment Outcome
11.
Infect Dis Poverty ; 9(1): 82, 2020 Jul 02.
Article in English | MEDLINE | ID: covidwho-621510

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the outbreak of pneumonia in Wuhan. The virus is highly infectious. Patients with cancer might be susceptible to the viral infection because of the immunosuppressive state cause by therapies on tumors. CASE PRESENTATION: We present the clinical features of four cancer patients who were infected with SARS-CoV-2 in late January of 2020 in our hospital. Cases 1 and 3 were diagnosed as mild and common type of coronavirus disease 2019 (COVID-2019) and survived from the viral infection. They acquired SARS-CoV-2 infection during their staying in hospital under radiotherapy and surgery of the tumors. Cases 2 and 4 suffered from severe type of COVID-19, and Case 2 was dead owning to the advanced age, uncontrolled chronic B cell lymphocytic leukemia and many other underlying diseases. The immunosuppressive state induced by liver transplantation and anti-rejection therapy might contribute to the severity of COVID-19 in Case 4, who suffered from hepatitis B related hepatocellular carcinoma. However, Case 4 was recovered from COVID-19 after a combination therapy against virus, bacteria and fungi, and also respiratory support. Nearly all patients showed a decrease in lymphocytes including total CD3+ T cells, B cells, and natural killer cells after infection of the virus. CONCLUSIONS: The severity of COVID-19 might be influenced by immune system state and underlying diseases in cancer patients. And the treatment of SARS-CoV-2 infection in cancer patients is challenged by the immunosuppressive state of these patients under chemotherapy or surgery.


Subject(s)
Betacoronavirus , Coronavirus Infections , Neoplasms/complications , Pandemics , Pneumonia, Viral , Adult , Aged , COVID-19 , China , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Fatal Outcome , Female , Humans , Immunocompromised Host , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Neoplasms/physiopathology , Neoplasms/therapy , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Radiography, Thoracic , SARS-CoV-2
12.
J Gerontol A Biol Sci Med Sci ; 75(9): 1788-1795, 2020 09 16.
Article in English | MEDLINE | ID: covidwho-47630

ABSTRACT

BACKGROUND: In December 2019, the coronavirus disease 2019 (COVID-19) emerged in Wuhan city and spread rapidly throughout China and the world. In this study, we aimed to describe the clinical course and outcomes of older patients with COVID-19. METHODS: This is a retrospective investigation of hospitalized older patients with confirmed COVID-19 at Zhongnan Hospital of Wuhan University from January 1, 2020, to February 10, 2020. RESULTS: In total, 203 patients were diagnosed with COVID-19, with a median age of 54 years (interquartile range, 41-68; range, 20-91 years). Men accounted for 108 (53.2%) of the cases, and 55 patients (27.1%) were more than 65 years of age. Among patients who were 65 years and older, the mortality rate was 34.5% (19/55), which was significantly higher than that of the younger patients at 4.7% (7/148). Common symptoms of older patients with COVID-19 included fever (94.5%; n = 52), dry cough (69.1%; n = 38), and chest distress (63.6%; n = 35). Compared with young patients, older patients had more laboratory abnormalities and comorbidities. Through a multivariate analysis of the causes of death in older patients, we found that males, comorbidities, time from disease onset to hospitalization, abnormal kidney function, and elevated procalcitonin levels were all significantly associated with death. CONCLUSIONS: In the recent outbreak of COVID-19, our local hospital in Wuhan found that patients aged 65 and older had greater initial comorbidities, more severe symptoms, and were more likely to experience multiorgan involvement and death, as compared to younger patients.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections , Hospitalization/statistics & numerical data , Pandemics , Pneumonia, Viral , Age Factors , Aged , COVID-19 , Cause of Death , China/epidemiology , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Multiple Organ Failure/diagnosis , Multiple Organ Failure/epidemiology , Multiple Organ Failure/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Severity of Illness Index , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data
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