Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 34
Filter
1.
Acta Pharmacol Sin ; 2020 Jul 31.
Article in English | MEDLINE | ID: covidwho-691161

ABSTRACT

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

2.
EClinicalMedicine ; 2020.
Article | WHO COVID | ID: covidwho-689222

ABSTRACT

BackgroundThe outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health New and effective intervention strategies are urgently needed to combat the disease

3.
EClinicalMedicine ; 2020.
Article | WHO COVID | ID: covidwho-684336

ABSTRACT

Background The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health New and effective intervention strategies are urgently needed to combat the disease Methods We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol Patients were assigned in a 1:2 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2, every 48 h for three consecutive dosages, in addition to standard treatment (experimental group), or standard treatment alone (control group) The end point was the time to discharge from the hospital This study is registered with chictr org cn, ChiCTR2000030262 Findings A total of thirty-three eligible COVID-19 patients were enrolled from February 1, 2020 to April 6, 2020, eleven were assigned to the IFN-κ plus TFF2 group, and twenty-two to the control group Safety and efficacy were evaluated for both groups No treatment-associated severe adverse effects (SAE) were observed in the group treated with aerosol inhalation of IFN-κ plus TFF2, and no significant differences in the safety evaluations were observed between experimental and control groups CT imaging was performed in all patients with the median improvement time of 5 0 days (IQR 3 0–9 0) in the experimental group versus 8 5 days (IQR 3 0–17 0) in the control group (p<0 05) In addition, the experimental group had a significant shorten median time in cough relief (4 5 days [IQR 2 0–7 0]) than the control group did (10 0 days [IQR 6 0–21 0])(p<0 005), in viral RNA reversion of 6 0 days (IQR 2 0–13 0) in the experimental group vs 9 5 days (IQR 3 0–23 0) in the control group (p < 0 05), and in the median hospitalization stays of 12 0 days (IQR 7 0–20 0) in the experimental group vs 15 0 days (IQR 10 0–25 0) in the control group (p<0 001), respectively Interpretation Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization These data support to explore a scale-up trial with IFN-κ plus TFF2 Funding National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission

4.
Medicine ; 99(30):e21335, 2020.
Article | WHO COVID | ID: covidwho-683201

ABSTRACT

Rationale: Since the end of December 2019, the outbreak of coronavirus disease 2019 (COVID-19) epidemic has occurred and spread rapidly throughout China At present, China's epidemic situation has been basically controlled, but the number of cases worldwide is increasing day by day On March 11, the WHO officially announced that the COVID-19 had become a global pandemic However, there are currently limited data on pregnant women with COVID-19 pneumonia and their infants In this paper, a case of a pregnant woman infected with COVID-19 pneumonia is reported Patient concerns: We report a clinically confirmed COVID-19 pregnant woman The patient was tested negative 4 times in nucleic acid test, but immunoglobulin G was positive and immunoglobulin M was negative before delivery, suggesting a previous infection Diagnoses: The pregnant woman underwent a computed tomography scan of both lungs at 29 + 2 weeks of pregnancy, and scattered stiffness and frosted glass shadows of both lungs were observed According to the diagnostic criteria for COVID-19 pneumonia in the “New Coronavirus Prevention and Control Plan Fifth Edition” of the National Health Commission of China, she was diagnosed as a clinically confirmed case Interventions: The pregnant women received nebulized inhalation and oral cephalosporin treatment in a community hospital and was discharged after the symptoms disappeared After that, she was isolated at home Outcomes: The pregnant woman gave birth to a healthy baby after being cured from COVID-19 infection The nucleic acid test of the neonatal pharyngeal swab was negative, and the neonatal serum test showed positive for immunoglobulin G and negative for immunoglobulin M Lessons subsections: The findings of this case report are useful for understanding the possible clinical features of COVID-19 infection in pregnant women, the duration of the antibody, and passive immunity of the fetus

5.
Clinical & Translational Immunology ; 9(7):e1160-e1160, 2020.
Article | WHO COVID | ID: covidwho-679726

ABSTRACT

Abstract Objectives A wide range of duration of viral RNA shedding in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been observed We aimed to investigate factors associated with prolonged and intermittent viral RNA shedding in a retrospective cohort of symptomatic COVID-19 patients Methods Demographic, clinical and laboratory data from hospitalised COVID-19 patients from a single centre with two consecutive negative respiratory reverse transcription-polymerase chain reaction (RT-PCR) results were extracted from electronic medical records Kaplan?Meier survival curve analysis was used to assess the effect of clinical characteristics on the duration and pattern of shedding Plasma levels of immune mediators were measured using Luminex multiplex microbead-based immunoassay Results There were 201 symptomatic patients included Median age was 49 years (interquartile range 16?61), and 52 2% were male Median RNA shedding was 14 days (IQR 9?18) Intermittent shedding was observed in 77 (38 3%) We did not identify any factor associated with prolonged or intermittent viral RNA shedding Duration of shedding was inversely correlated with plasma levels of T-cell cytokines IL-1? and IL-17A at the initial phase of infection, and patients had lower levels of pro-inflammatory cytokines during intermittent shedding Conclusions Less active T-cell responses at the initial phase of infection were associated with prolonged viral RNA shedding, suggesting that early immune responses are beneficial to control viral load and prevent viral RNA shedding Intermittent shedding is common and may explain re-detection of viral RNA in recovered patients

6.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3013-3019, 2020 Jul.
Article in Chinese | MEDLINE | ID: covidwho-679283

ABSTRACT

The epidemic situation of coronavirus disease 2019(COVID-19) is developing rapidly in the world, and the influence is serious. In this study, the prescription of Mongolian medicine to prevent new type of COVID-19 was investigated. Based on the second edition and the third edition of COVID-19 Mongolian Medicine Prevention and Treatment Guidance Program issued by the Inner Mongolia Autonomous Region Health Commission, using Excel 2007, SPSS Modeler 18, SPSS Statistics 25, Cytoscape 3.7.1 statistical software as a tool, the association rules analysis and cluster analysis of Mongolian medicine included in the standard were carried out. Among the 45 prophylactic prescriptions included in the standard, a total of 34 high-frequency drugs using frequency ≥5 were used, of which Carthami Flos(21 times, 4.46%), Chebulae Fructus(20 times, 4.26%), Moschus(13 times, 2.77%), Myristicae Semen(12 times, 2.55%), Santali Albi Lignum(12 times, 2.55%), and Bovis Calculus(12 times, 2.55%) were the most common. The main drugs for the prevention of COVID-19 were Liang(13 times, 38.23%), Wen(9 times, 26.47%), the flavor was Ku(20 times, 34.48%), Xin(13 times, 22.41%), Gan(11 times, 18.97%), the most used drugs treating hot evil(99 times, 32.46%), treatment of "Heyi" drugs(51 times, 16.72%), treatment of "Badagan" drugs(40 times, 13.11%), treatment of "sticky" drugs(37 times, 12.13%), and a cough, eliminating phlegm and antiasthmatic(31 times, 10.16%), the association rule analysis found that the highest association intensity of the drug pair combination of 11. Clustering analysis using the cluster analysis of inter-group join method found a total of 8 categories. In this study, 45 prescriptions of Mongolian medicine for the prevention of COVID-19 were collec-ted and further analyzed, hoping to provide new ideas for clinical diagnosis and treatment.

7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(6): 671-676, 2020 Jun.
Article in Chinese | MEDLINE | ID: covidwho-655213

ABSTRACT

OBJECTIVE: To analyze the research hotspot and frontier of severe coronavirus disease 2019 (COVID-19) in China and abroad. METHODS: The CiteSpace software was used to visually analyze the relevant research of severe COVID-19 published by CNKI and Web of Science databases from January 30th to April 20th in 2020. The analysis content included the author of the literature, the publishing institutions, and high-frequency keywords. RESULTS: There were 389 Chinese literatures and 59 English literatures included. Analysis using CiteSpace software showed that there were four large teams in China currently concerning about the research on severe COVID-19. The co-authoring of each team was relatively close, but the teams were lack of cooperation. The main issuing institutions were affiliated hospitals of colleges and universities, but colleges and enterprises had less participation. The authors of English-language publications mainly had five research teams, some of whom had co-authored relationships. The country with the most enormous volume of English-language publications was China, followed by the United States and Canada. The Chinese keyword co-occurrence, clustering and highlighted words analysis showed that the main research areas of severe COVID-19 included clinical features, traditional Chinese medicine treatment, medical imaging, integrated traditional Chinese and Western medicine treatment and so on; nucleic acid detection, clinical features and diagnosis, plague theory and etiology mechanism, traditional Chinese medicine and integrated Chinese and Western medicine treatment, severe COVID-19 combined with diabetes and prognosis research will become future research trends; keyword cluster analysis showed that severe COVID-19, combined chronic underlying diseases, CT imaging characteristics will also become new trends in the field of research. Co-occurrence analysis of keywords in English literatures showed that the main research areas of severe COVID-19 included the names of novel coronavirus, pandemic diseases, infectious diseases, medical supplies distribution, and indicators related to myocardial damage. CONCLUSIONS: Researchers in China and abroad have different concerns about severe COVID-19. Domestic research focuses on the diagnosis and treatment of severe cases, while foreign countries attach importance to epidemic response and prevention.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , China , Humans , United States
8.
J Clin Invest ; 2020 Jul 07.
Article in English | MEDLINE | ID: covidwho-635481

ABSTRACT

The SARS-CoV-2 is the causative agent for COVID-19 pneumonia. Little is known about the kinetics, tissue distribution, cross-reactivity and neutralization antibody response in COVID-19 patients. Two groups of RT-PCR confirmed COVID-19 patients were enrolled in this study, including 12 severe patients in ICUs who needed mechanical ventilation and 11 mild patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severe patients had viral shedding in a variety of tissues for 20~40 days post onset of disease (8/12, 66.7%); while the majority of mild patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA after 10 days post-onset (9/11, 81.8%). Mild patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in COVID-19 patients but not in MERS patients. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from COVID-19 patients, but not convalescent SARS and MERS patients inhibited SARS-CoV-2 entry. Anti-SARS-CoV-2 S and N IgG level exhibited moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in human after SARS-CoV-2 infection.

10.
Eur Respir J ; 55(6)2020 06.
Article in English | MEDLINE | ID: covidwho-622479

ABSTRACT

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.


Subject(s)
Coronavirus Infections/mortality , Hospitalization , Pneumonia, Viral/mortality , Adult , Aged , Betacoronavirus , Cardiovascular Diseases/epidemiology , China , Cohort Studies , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Cough/etiology , Diabetes Mellitus/epidemiology , Disease Outbreaks , Dyspnea/etiology , Fatigue/etiology , Female , Fever/etiology , Geography , Humans , Hypertension/epidemiology , Intensive Care Units/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pharyngitis/etiology , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Prognosis , Proportional Hazards Models , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Time Factors , Time-to-Treatment/statistics & numerical data , Tomography, X-Ray Computed
11.
Front. Pharmacol. ; (11)20200525.
Article in English | ELSEVIER | ID: covidwho-613298

ABSTRACT

Background: Development of a core outcome set (COS) for clinical trials for COVID-19 is urgent because of the pandemic wreaking havoc worldwide and the heterogeneity of outcomes in clinical trials. Methods: A preliminary list of outcomes was developed after a systematic review of protocols of clinical trials for COVID-19. Then, two rounds of the Delphi survey were conducted. Stakeholders were traditional Chinese medicine (TCM) experts, Western medicine (WM) experts, nurses, and the public. Patients with confirmed COVID-19 were also invited to participate in a questionnaire written in understandable language. Then different stakeholders participated in a consensus meeting by video conference to vote. Results: Ninety-seven eligible study protocols were identified from 160 clinical trials. Seventy-six outcomes were identified from TCM clinical trials and 126 outcomes were identified from WM clinical trials. Finally, 145 outcomes were included in the first round of the Delphi survey. Then, a COS for clinical trials of TCM and WM was developed. The COS included clinical outcomes (recovery/improvement/progression/death), etiology (SARS-CoV-2 nucleic-acid tests, viral load), inflammatory factor (C-reactive protein), vital signs (temperature, respiration), blood and lymphatic-system parameters (lymphocytes, virus antibody), respiratory outcomes (pulmonary imaging, blood oxygen saturation, PaO2/FiO2 ratio, arterial blood gas analysis, mechanical ventilation, oxygen intake, pneumonia severity index), clinical efficacy (prevalence of preventing patients with mild-to-moderate disease progressing to severe disease), and symptoms (clinical symptom score). Outcomes were recommended according to different types of disease. Outcome measurement instruments/definitions were also recommended. Conclusion: Though there are some limitations for the research, such as insufficient patients and the public involvement, and the unbalanced stakeholders' region, the COS for COVID-19 may improve consistency of outcome reporting in clinical trials. It also should be updated with research progression.

12.
Vaccine ; 38(35): 5653-5658, 2020 07 31.
Article in English | MEDLINE | ID: covidwho-612504

ABSTRACT

The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in <20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Coronavirus Infections/immunology , Immunoglobulin Fc Fragments/chemistry , Macaca/immunology , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Animals , CHO Cells , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Cricetulus , Female , HEK293 Cells , Humans , Immunization, Passive , Immunoglobulin Fc Fragments/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Mice , Pandemics , Rabbits
13.
J Microbiol Immunol Infect ; 2020 Jun 20.
Article in English | MEDLINE | ID: covidwho-609097

ABSTRACT

Coronavirus Disease-19 (COVID-19) has been in a global pandemic currently and relating symptoms were reported variously around the world. We reported a previously healthy man of COVID-19 presenting with anosmia as the obvious symptom with relevant radiological findings on brain magnetic resonance imaging.

14.
Clin Infect Dis ; 2020 Jun 17.
Article in English | MEDLINE | ID: covidwho-601198
15.
Ann. Transl. Med. ; 10(8)20200501.
Article in English | ELSEVIER | ID: covidwho-594420

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide from Wuhan. An easy-to-use index capable of the early identification of inpatients who are at risk of becoming critically ill is urgently needed in clinical practice. Hence, the aim of this study was to explore an easy-to-use nomogram and a model to triage patients into risk categories to determine the likelihood of developing a critical illness. Methods: A retrospective cohort study was conducted. We extracted data from 84 patients with laboratory-confirmed COVID-19 from one designated hospital. The primary endpoint was the development of severe/critical illness within 7 days after admission. Predictive factors of this endpoint were selected by LASSO Cox regression model. A nomogram was developed based on selected variables. The predictive performance of the derived nomogram was evaluated by calibration curves and decision curves. Additionally, the predictive performances of individual and combined variables under study were evaluated by receiver operating characteristic curves. The developed model was also tested in a separate validation set with 71 laboratory-confirmed COVID-19 patients. Results: None of the 84 inpatients were lost to follow-up in this retrospective study. The primary endpoint occurred in 23 inpatients (27.4%). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were selected as the final prognostic factors. A nomogram was developed based on the NLR and CRP. The calibration curve and decision curve indicated that the constructed nomogram model was clinically useful. The AUCs for the NLR, CRP and Combined Index in both training set and validation sets were 0.685 (95% CI: 0.574-0.783), 0.764 (95% CI: 0.659-0.850), 0.804 (95% CI: 0.702-0.883), and 0.881 (95% CI: 0.782-0.946), respectively. Conclusions: Our results demonstrated that the nomogram and Combined Index calculated from the NLR and CRP are potential and reliable predictors of COVID-19 prognosis and can triage patients at the time of admission.

16.
J Sports Med Phys Fitness ; 2020 Jun 25.
Article in English | MEDLINE | ID: covidwho-619601
18.
J Med Virol ; 2020 May 29.
Article in English | MEDLINE | ID: covidwho-436660

ABSTRACT

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID-19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with SARS-CoV-2, including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest CT. All laboratory examination were measured within first 24 hours after admission, and chest CT were performed before admission. 56 (65.9%) patients had a history of exposure to Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID-2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (p=0.003) and coronary heart disease (p=0.017). All severe and critical patients infected with SARS-CoV-2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (p<0.001). Severe and critical patients showed higher WBC count (p=0.006), NEU count (p=0.001), NEU% (p=0.002), PCT (p=0.011), CRP (p=0.003), PT (p=0.035), D-dimer (p=0.025), AST (p=0.006), and lower LYM count (p=0.019), LYM% (p=0.001), ALB (p<0.001). Logistic regression analysis showed NEU count is a independent risk factor for deterioration, with the threshold of 6.5×109 ·L-1 . We concluded that the laboratory independent risk factor for the progression of COVID-19 pneumonia is NEU count. In addition, COVID-19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease. This article is protected by copyright. All rights reserved.

19.
Clin Infect Dis ; 2020 May 22.
Article in English | MEDLINE | ID: covidwho-351568

ABSTRACT

BACKGROUND: We previously reported that lymphocytopenia and T cell exhaustion is notable in acute COVID19 patients, especially in aged and severe cases. Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and mechanism of Tα1 supplement to COVID-19 are still unclear. METHODS: We retrospectively reviewed the clinical outcomes of 76 severe cases with COVID-19 admitted into two hospitals in Wuhan from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients was measured by T cell receptor excision circles (TREC). The levels of T cell exhaustion markers PD-1 and Tim-3 on CD8+ T cells were detected by flow cytometry. RESULTS: Compared with untreated group, Tα1 treatment significantly reduces mortality of severe COVID-19 patients (11.11% vs. 30.00%, p=0.044). Tα1 timely enhances blood T cell numbers in COVID-19 patients with severe lymphocytopenia (the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/µL or 650/µL, respectively). Under such conditions, Tα1 also successfully restores CD8+ and CD4+ T cell numbers in aged patients. Meanwhile, Tα1 reduces PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients in comparison with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells are roughly parallel to the rise of TRECs. CONCLUSIONS: Tα1 supplement significantly reduce mortality of severe COVID-19 patients. COVID-19 patients with the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/µL or 650/µL, respectively, gain more benefits from Tα1. Tα1 reverses T cell exhaustion and recovers immune reconstitution through promoting thymus output during SARS-CoV-2 infection.

20.
Clin Infect Dis ; 2020 May 22.
Article in English | MEDLINE | ID: covidwho-343498

ABSTRACT

BACKGROUND: We previously reported that lymphocytopenia and T cell exhaustion is notable in acute COVID19 patients, especially in aged and severe cases. Thymosin alpha 1 (Tα1) had been used in the treatment of viral infections as an immune response modifier for many years. However, clinical benefits and mechanism of Tα1 supplement to COVID-19 are still unclear. METHODS: We retrospectively reviewed the clinical outcomes of 76 severe cases with COVID-19 admitted into two hospitals in Wuhan from December 2019 to March 2020. The thymus output in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients was measured by T cell receptor excision circles (TREC). The levels of T cell exhaustion markers PD-1 and Tim-3 on CD8+ T cells were detected by flow cytometry. RESULTS: Compared with untreated group, Tα1 treatment significantly reduces mortality of severe COVID-19 patients (11.11% vs. 30.00%, p=0.044). Tα1 timely enhances blood T cell numbers in COVID-19 patients with severe lymphocytopenia (the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/µL or 650/µL, respectively). Under such conditions, Tα1 also successfully restores CD8+ and CD4+ T cell numbers in aged patients. Meanwhile, Tα1 reduces PD-1 and Tim-3 expression on CD8+ T cells from severe COVID-19 patients in comparison with untreated cases. It is of note that restoration of lymphocytopenia and acute exhaustion of T cells are roughly parallel to the rise of TRECs. CONCLUSIONS: Tα1 supplement significantly reduce mortality of severe COVID-19 patients. COVID-19 patients with the counts of CD8+ T cells or CD4+ T cells in circulation lower than 400/µL or 650/µL, respectively, gain more benefits from Tα1. Tα1 reverses T cell exhaustion and recovers immune reconstitution through promoting thymus output during SARS-CoV-2 infection.

SELECTION OF CITATIONS
SEARCH DETAIL