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1.
Front Immunol ; 13: 836232, 2022.
Article in English | MEDLINE | ID: covidwho-1775668

ABSTRACT

The continuous emergence of SARS-coronavirus 2 (SARS-CoV-2) variants, especially the variants of concern (VOC), exacerbated the impact of the coronavirus disease 2019 (COVID-19) pandemic. As the key of viral entry into host cells, the spike (S) protein is the major target of therapeutic monoclonal antibodies (mAbs) and polyclonal antibodies elicited by infection or vaccination. However, the mutations of S protein in variants may change the infectivity and antigenicity of SARS-CoV-2, leading to the immune escape from those neutralizing antibodies. To characterize the mutations of S protein in newly emerging variants, the proteolytic property and binding affinity with receptor were assessed, and the vesicular stomatitis virus (VSV)-based pseudovirus system was used to assess the infectivity and immune escape. We found that some SARS-CoV-2 variants have changed significantly in viral infectivity; especially, B.1.617.2 is more likely to infect less susceptible cells than D614G, and the virus infection process can be completed in a shorter time. In addition, neutralizing mAbs and vaccinated sera partially or completely failed to inhibit host cell entry mediated by the S protein of certain SARS-CoV-2 variants. However, SARS-CoV-2 variant S protein-mediated viral infection can still be blocked by protease inhibitors and endocytosis inhibitors. This work provides a deeper understanding of the rise and evolution of SARS-CoV-2 variants and their immune evasion.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal , Antibodies, Neutralizing , Humans , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325010

ABSTRACT

Background: Since December 2019, COVID-19 has rapidly swept the world. It is particularly important to understand the dynamic changes of the whole disease course of non-severe patients from the onset to the follow-up after discharge. Methods: : On February 1, 2020, 18 cases of non-severe COVID-19 appeared in a hospital in Beijing. All patients were SARS-CoV-2 RNA positive by RT-PCR for pharyngeal swabs. We recorded the clinical information and viral dynamics of these patients from the onset of the disease to 2 months after discharge. According to the severity of lung consolidation, 18 patients were divided into two groups (mild pulmonary consolidation group [imaging score ≤10];severe pulmonary consolidation group [imaging score >10]). Results: : Eighteen patients (median age 43) were included, including 14 females. Fever (11/18) and cough (8/18) were the most common symptoms. The duration of SARS-CoV-2 RNA positive in mild pulmonary consolidation group was significantly longer than severe pulmonary consolidation group (the median time was 30 days and 13 days, respectively, P= 0.0031). Two months after discharge, almost all patients were followed up for IgM antibody disappearance and IgG antibody production. Conclusion: In non-severe COVID-19 patients, the positive duration of the SARS-CoV-2 RNA in patients with mild pulmonary consolidation was longer than the severe pulmonary consolidation. However, it is necessary for a large sample to verify our conclusions.

4.
Front Cell Infect Microbiol ; 11: 813645, 2021.
Article in English | MEDLINE | ID: covidwho-1581376

ABSTRACT

[This corrects the article DOI: 10.3389/fcimb.2021.720357.].

5.
Int Immunopharmacol ; 102: 108383, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1521087

ABSTRACT

BACKGROUNDS: To date, the effects of SARS-CoV-2 vaccines on people living with HIV (PLWH) were mainly focused on messenger RNA (mRNA) and adenovirus vector-based vaccines, and little is known about the effects of inactivated virus-based vaccine. This study was designed to determine the effects of inactivated SARS-CoV-2 vaccines on PLWH. METHODS: Twenty-four HIV-positive individuals and 24 healthy donors (HD) were respectively recruited from Malipo Country People's Hospital and community in Kunming city. Enumeration of lymphocyte and CD4+CD45RO+ memory T cells were evaluated by flow cytometry. Competitive ELISA was used to measure the level of Anti-SARS-CoV-2 neutralization antibody. Spearman or Pearson correlation analysis was used to analyze the relationship between laboratory indicators and neutralization antibodies in PLWH. T-cell responses (Th1, Th2, Th17, Treg) and intracellular expression of cytokines (IL-2 and TNF-α) in CD4 or CD8 were induced by spike protein in SARS-CoV-2 (SARS-2-S) and further measured by intracellular staining. RESULTS: CD4, B cells, CD4+CD45RO+ memory T cells in peripheral blood of PLWH are dramatically decreased in comparison with HD. Importantly, PLWH display comparable neutralizing antibody positive rate to HD after inoculation with inactivated SARS-CoV-2 vaccine. However, PLWH showed weaker responses to vaccines exhibited by lower levels of neutralizing antibodies. Correlation analysis shows that this is possibly caused by low number of CD4 and B cells. Furthermore, SARS-2-S-induced Th2 and Th17 responses are also decreased in PLWH, while no influences on Treg and other cytokines (IL-2, TNF-α and IFN-γ) observed. CONCLUSIONS: PLWH and HD have comparable neutralizing antibodies positive rates, but PLWH display weaker responses to inactivated SARS-CoV-2 vaccines in magnitude, which suggests that a booster dose or dose adjustment are required for HIV-infected individuals, especially for those with lower counts of CD4 T and B cells.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , HIV Infections/immunology , Vaccines, Inactivated/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Female , HIV Infections/blood , HIV Infections/complications , Healthy Volunteers , Humans , Immunogenicity, Vaccine , Male , Middle Aged , SARS-CoV-2/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Vaccines, Inactivated/administration & dosage
6.
Front Cell Infect Microbiol ; 11: 720357, 2021.
Article in English | MEDLINE | ID: covidwho-1497025

ABSTRACT

SARS-coronavirus 2 (SARS-CoV-2), pathogen of coronavirus disease 2019 (COVID-19), is constantly evolving to adapt to the host and evade antiviral immunity. The newly emerging variants N501Y.V1 (B.1.1.7) and N501Y.V2 (B.1.351), first reported in the United Kingdom and South Africa respectively, raised concerns due to the unusually rapid global spread. The mutations in spike (S) protein may contribute to the rapid spread of these variants. Here, with a vesicular stomatitis virus (VSV)-based pseudotype system, we demonstrated that the pseudovirus bearing N501Y.V2 S protein has higher infection efficiency than pseudovirus with wildtype (WT) and D614G S protein. Moreover, pseudovirus with N501Y.V1 or N501Y.V2 S protein has better thermal stability than WT and D614G, suggesting these mutations of variants may increase the stability of SARS-CoV-2 S protein and virion. However, the pseudovirus bearing N501Y.V1 or N501Y.V2 S protein has similar sensitivity to inhibitors of protease and endocytosis with WT and D614G. These findings could be of value in preventing the spread of virus and developing drugs for emerging SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Humans , Mutation , Spike Glycoprotein, Coronavirus/genetics
7.
Int Immunopharmacol ; 97: 107702, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1198831

ABSTRACT

BACKGROUND: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. METHODS: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. RESULTS: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting. CONCLUSION: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.


Subject(s)
Amides/administration & dosage , Antiviral Agents/administration & dosage , COVID-19/drug therapy , Pyrazines/administration & dosage , Reinfection/drug therapy , Administration, Oral , Adult , Aged , Amides/adverse effects , Antiviral Agents/adverse effects , COVID-19/blood , Female , Humans , Lymphocyte Subsets/drug effects , Male , Middle Aged , Patient Discharge , Pyrazines/adverse effects , RNA, Viral/analysis , RNA, Viral/drug effects , Reinfection/blood , SARS-CoV-2/drug effects , Treatment Outcome
8.
J Med Virol ; 93(3): 1378-1386, 2021 03.
Article in English | MEDLINE | ID: covidwho-1196511

ABSTRACT

Since December 2019, coronavirus disease (COVID-19) has rapidly swept the world. So far, more than 30 million people have been infected and nearly one million have died. Although the world is still in the stage of COVID-19 pandemic, the treatment of new cases and critically ill patients is the focus of the current work. However, COVID-19 patients lead to pulmonary fibrosis, such a serious threat to the prognosis of complications were also worthy of our attention. First of all, we proposed the possible mechanism of pulmonary fibrosis caused by SARS-CoV-2, based on the published data of COVID-19 ((i) Direct evidence: pulmonary fibrosis was found in autopsy and pulmonary puncture pathology. (ii) Indirect evidence: increased levels of fibrosis-related cytokines[transforming growth factor [TGF]- ß, tumor necrosis factor [TNF]- α, interleukin [IL]-6, etc] in peripheral blood of severe patients.) What is more, we summarized the role of three fibrosis-related signaling pathways (TGF- ß signal pathway, WNT signal pathway and YAP/TAZ signal pathway) in pulmonary fibrosis. Finally, we suggested the therapeutic value of two drugs (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis in COVID-19-induced pulmonary fibrosis.


Subject(s)
COVID-19/complications , Indoles/therapeutic use , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/metabolism , COVID-19/pathology , Humans , Lung/pathology , Patient Discharge , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Severity of Illness Index , Signal Transduction
9.
Medicine (Baltimore) ; 99(52): e23800, 2020 Dec 24.
Article in English | MEDLINE | ID: covidwho-1084731

ABSTRACT

ABSTRACT: Since December 2019, an outbreak of COVID-19 sweeping the world. Understanding the clinical and SARS-CoV-2 dynamic changes of mild and ordinary patients of COVID-19, so as to provide basis for the prevention and control of COVID-19.On February 1st, 2020, 16 SARS-CoV-2 RNA positive patients diagnosed in the same site in Beijing. The patients symptoms, signs, medication, and SARS-CoV-2 results were recorded.Of the 16 patients, 12 were female. Although they were infected at the same time in the same workplace, their clinical processes were very different and can be roughly divided into three different types: persistent sputum positive, persistent stool positive and persistent both positive. In 7 patients with mild clinical manifestations, the median days of SARS-CoV-2 RNA negative conversion in sputum samples were significantly later than those with obvious lung injury (27 days [range: 18 to 36]; 17 days, [range 6 to 25], P = .021). The negative conversion of SARS-CoV-2 RNA in stool was significant later than in sputum.There were various clinical manifestations after SARS-CoV-2 infection, even if they were infected by the same source of infection in the same place. The presence of SARS-CoV-2 virus RNA in stool samples was longer than that in respiratory tract.


Subject(s)
COVID-19/epidemiology , Disease Outbreaks , Occupational Exposure , Pneumonia, Viral/epidemiology , Workplace , Adult , COVID-19 Testing , China/epidemiology , Feces/virology , Female , Humans , Male , Pneumonia, Viral/virology , RNA, Viral/analysis , SARS-CoV-2 , Sputum/virology
10.
Biomed Pharmacother ; 133: 110825, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1002354

ABSTRACT

BACKGROUND: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, tocilizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. METHODS: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14-day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). RESULTS: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08-6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62-16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39-4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. CONCLUSION: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflammation of COVID-19 patients and inhibit the deterioration of the disease.


Subject(s)
Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Pyrazines/therapeutic use , SARS-CoV-2/drug effects , Adult , Aged , Aged, 80 and over , Amides/administration & dosage , Amides/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/diagnostic imaging , COVID-19/pathology , COVID-19/therapy , Drug Therapy, Combination , Female , Humans , Interleukin-6/blood , Kaplan-Meier Estimate , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Models, Immunological , Pyrazines/administration & dosage , Pyrazines/adverse effects , Receptors, Interleukin-6/antagonists & inhibitors , Respiration, Artificial/statistics & numerical data , Sample Size , Treatment Outcome
11.
J Med Virol ; 93(3): 1378-1386, 2021 03.
Article in English | MEDLINE | ID: covidwho-891893

ABSTRACT

Since December 2019, coronavirus disease (COVID-19) has rapidly swept the world. So far, more than 30 million people have been infected and nearly one million have died. Although the world is still in the stage of COVID-19 pandemic, the treatment of new cases and critically ill patients is the focus of the current work. However, COVID-19 patients lead to pulmonary fibrosis, such a serious threat to the prognosis of complications were also worthy of our attention. First of all, we proposed the possible mechanism of pulmonary fibrosis caused by SARS-CoV-2, based on the published data of COVID-19 ((i) Direct evidence: pulmonary fibrosis was found in autopsy and pulmonary puncture pathology. (ii) Indirect evidence: increased levels of fibrosis-related cytokines[transforming growth factor [TGF]- ß, tumor necrosis factor [TNF]- α, interleukin [IL]-6, etc] in peripheral blood of severe patients.) What is more, we summarized the role of three fibrosis-related signaling pathways (TGF- ß signal pathway, WNT signal pathway and YAP/TAZ signal pathway) in pulmonary fibrosis. Finally, we suggested the therapeutic value of two drugs (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis in COVID-19-induced pulmonary fibrosis.


Subject(s)
COVID-19/complications , Indoles/therapeutic use , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/metabolism , COVID-19/pathology , Humans , Lung/pathology , Patient Discharge , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Severity of Illness Index , Signal Transduction
12.
Trials ; 21(1): 495, 2020 Jun 08.
Article in English | MEDLINE | ID: covidwho-574504

ABSTRACT

OBJECTIVES: Patients with severe COVID-19 often suffer from significant pulmonary fibrosis. Although the pathogenesis of pulmonary fibrosis has not been fully explained, the signal pathways and cytokines involved are very similar to hepatic fibrosis. This has been successfully treated with the Anluohuaxian Pill, a proprietary Chinese medicine composed of a variety of Chinese herbal medicines. The aim of this study is to evaluate the efficacy and safety of Anluohuaxian in the treatment of pulmonary fibrosis in patients with severe COVID-19. TRIAL DESIGN: This is a prospective, multicenter, open, randomized controlled trial. The distribution ratio was 2:1, 500 cases in the experimental group and 250 cases in the control group. PARTICIPANTS: Minimum Age: 18 Years Maximum Age: 80 Years Sex: All Gender Based: No Accepts Healthy Volunteers: No Inclusion Criteria: 1.Confirmed COVID-19, and the nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs is negative twice after the treatment (sampling interval is at least 24 hours);2.Negative nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs during screening visits;3.High-resolution CT of the lung (HRCT) indicates pulmonary fibrosis (thickness of lobular septum, honeycomb-like changes, with or without bronchial / pleural distraction);4.Voluntarily participate in research and sign informed consent. EXCLUSION CRITERIA: 1.Combined with severe heart, lung (diagnosed with interstitial lung disease, bronchial asthma, chronic obstructive pulmonary disease, etc.), liver and kidney disease or with endocrine, rheumatic, neurologic, malignant and other systemic diseases;2.Have been diagnosed with connective tissue disease;3.Pregnant or lactating women;4.History of mental disorders, substance abuse or dependence;5.Have used other anti-pulmonary fibrosis drugs in the past 14 days, such as nintedanib, pirfenidone, penicillamine, colchicine, tumor necrosis factor alpha blocker, imatinib, glucocorticoid hormones, morphomycodyl esters, azathioprine, cyclophosphamide, interferon-γ, and traditional Chinese medicine;6.Researchers consider it inappropriate to participate in research;7.Participating in other clinical research. This mutli-centre RCT will be undertaken in 9 trial centres: The Second People's Hospital of Fuyang, Ezhou Central Hospital, Huoshenshan Hospital of Wuhan, Jinyintan Hospital of Wuhan, Tongji Hospital of Huazhong University of Science and Technology, West Hospital Union Hospital Huazhong University of Science and Technology, Wuhan Pulmonary Hospital, Zhongnan Hospital of Wuhan University, Wenzhou Medical University Affiliated First Hospital. INTERVENTION AND COMPARATOR: The research drug is Anluohuaxian Pill, which is provided by Senlong Pharmaceutical Co., Ltd. The basic therapeutic drugs for COVID-19 involved in the study include antiviral drugs. Brands can be selected according to the treatment routines of each research center to facilitate the improvement of treatment compliance. MAIN OUTCOMES: Primary Outcome Measure: 1.Changes in high-resolution computer tomography of the lung Changes in ground-glass shadows, interstitial or air nodules found on high-resolution computer tomography [Time Frame: 3 months] 2.Change in 6-minute walking distance [Time Frame: 3 months] RANDOMISATION: In this study, the central randomization system (IWRS, an interactive network response system based on network) is used to randomise the groups. The subjects who met the entry criteria were randomly divided into the experimental group and the control group according to the proportion of 2:1. In this study, the block randomized grouping method is used, and the block length is 6. The random grouping program is set up by statistical and computer professionals in the randomization process. BLINDING (MASKING): This is an open label trial. Trial participants, investigators, care givers, outcome assessors, and date analysts are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 750 patients are expected to be enrolled and the cases are allocated according to the ratio of 2 (Anluohuaxian combined with regular treatment group):1 (regular treatment group). TRIAL STATUS: Protocol version number 3.0, 10th April 2020. The recruitment has not yet started. Actual Study Start Date: April 1, 2020 Estimated Primary Completion Date: June 1, 2020 Estimated Study Completion Date: December 1, 2020 TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04334265. Registered on 3 April 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Drugs, Chinese Herbal/adverse effects , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Multicenter Studies as Topic , Outcome Assessment, Health Care , Pandemics , Prospective Studies , SARS-CoV-2 , Walking , Young Adult
13.
Trials ; 21(1): 488, 2020 Jun 05.
Article in English | MEDLINE | ID: covidwho-534074

ABSTRACT

OBJECTIVES: A variety of possible mechanisms can make the nucleic acid test of patients who meet the discharge conditions positive again, including reinfection, reactivation of the original virus, lack of strict discharge criteria, new infection, and so on. Different reasons will correspond to different prevention and control measures. We will enroll patients who are discharged after treatment, whose nucleic acid test has changed from negative to positive during the screening visit, regardless of the severity of the symptoms, to investigate the mechanism, clinical outcome and therapeutic efficacy with Favipiravir patients with Corona virus Disease 2019. Favipiravir is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase, it has been used for treatment of some life-threatening infections such as Ebola virus, Lassa virus and rabies. Its therapeutic efficacy has been proven in these diseases. TRIAL DESIGN: This is a multi-center, two arm, open label, parallel group, randomized controlled trial. PARTICIPANTS: Eligibility criteria: Inclusion criteria: 1.Adults 18 to 80 years, male or female.2.After the first diagnosis and treatment of COVID-19, the nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs, has been negative for two consecutive times (sampling time interval of at least 24 hours), in accordance with the COVID-19's diagnosis and treatment Plan (7th Edition), discharged.3.During screening visit (follow-up after discharge), The nucleic acid test of COVID-19 is positive in any one of the following samples: sputum, throat swabs, blood, feces or other specimens. Regardless of whether or not they had symptoms and the severity of symptoms.4.Volunteer to participate in the research and sign the Informed Consent Form. EXCLUSION CRITERIA: 1.Allergic to Favipiravjr;2.Pregnant or lactating women3.Uncontrolled diseases of the blood and cardiovascular system, liver or kidney.4.History of mental disorders, drug abuse or dependence;5.Researchers consider it inappropriate for adults to participate;6.Participating in other clinical studies. Loss to Follow up: Cases that do not complete the clinical trial program will be regarded as lost to follow up. Including the withdrawal of patients by themselves (such as poor compliance, etc.), or the withdrawal of patients ordered by the researcher (those who need other drugs which affect the judgment of the curative effect, and those who need to stop taking drugs for severe adverse events) Study setting: The participating hospitals are some of the designated hospitals that have been or may be admitting patients who meet the eligibility criteria, mainly in Hubei, Shenzhen, Anhui and Beijing. Participants will be recruited from these 15 hospitals: Wuhan Pulmonary Hospital, Hubei; Jinyintan Hospital of Wuhan, Hubei; Ezhou Central Hospital, Hubei; The Second People's Hospital of Fuyang, Anhui; The First Affiliated Hospital of USTC, Anhui; Beijing Youan Hospital, Beijing; Capital Medical University Beijing Institute of Hepatology, Beijing; Ezhou Hospital of Traditional Chinese Medicine, Hubei; Zhongnan Hospital of Wuhan University, Hubei; The Fifth Hospital of ShiJiazhuang, Hebei; Jinan Infectious Diseases Hospital, Shandong; Public Health Clinical Center of Chengdu, Sichuan; Wuxi No.5 People's Hospital, Jiangsu; The Third People's Hospital of Shenzhen, Guangdong; The First Affiliated Hospital of Bengfu Medical College, AnHui. INTERVENTION AND COMPARATOR: Favipiravir group (experimental): Favipiravir 1600mg each dose, twice a day on the 1st day; 600mg each dose, twice a day from the 2nd to the 7th day, Oral administration, the maximum number of days taken will be no more than 14 days plus routine treatment for COVID-19. Regular treatment group (control): Treatments other than Antiviral drugs can be given. Routine treatment for patients with the corona virus will be administered, this includes oxygen therapy, drugs that reduced phlegm and relieve cough, including thymosin, proprietary Chinese medicine, etc. MAIN OUTCOMES: Primary Outcome Measures: Viral nucleic acid test negative [Time Frame: 5 months]: Subjects who tested negative for nucleic acid from sputum or nasopharyngeal swabs for two consecutive times (sampling time interval of at least 24 hours). SECONDARY OUTCOME MEASURES: Clinical cure [Time Frame: 5 months]: 1.Body temperature returned to normal for more than 3 days;2.Lung image improved.3.Clinical manifestation improved;4.The viral nucleic acid test of respiratory specimens was negative for two consecutive times (sampling time interval of at least 24 hours). RANDOMIZATION: The central randomization system (Interactive Web Response Management System), will be used to randomly divide the subjects into the experimental group and the control group according to the ratio of 2:1. In this study, block randomization will be used, in blocks of 6. BLINDING (MASKING): This is an open label trial. Trial participants, investigators, care givers, outcome assessors, and date analysts are not blinded to group assignment. NUMBERS TO BE RANDOMISED: 210 patients are expected to be enrolled and allocated according to the ratio of 2 (Favipiravir group, n=140): 1(regular treatment group, n=70). TRIAL STATUS: Protocol version number 3.0, 10th April 2020 First Patient, first visit 17th March 2020; recruitment end date anticipated June 1, 2020. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04333589, April 3, 2020. Registered April 3, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Pyrazines/therapeutic use , RNA, Viral/analysis , Randomized Controlled Trials as Topic , Adolescent , Adult , Aged , Aged, 80 and over , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome , Young Adult
14.
Int J Antimicrob Agents ; 55(5): 105954, 2020 May.
Article in English | MEDLINE | ID: covidwho-17680

ABSTRACT

Since December 2019, a viral pneumonia, named coronavirus disease 2019 (COVID-19), from Wuhan, China, has swept the world. Although the case fatality rate is not high, the number of people infected is large and there is still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. Therefore, treatment of the cytokine storm has become an important part of rescuing severe COVID-19 patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome. If it is possible to block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe COVID-19 patients. Tocilizumab is an IL-6 receptor (IL-6R) blocker that can effectively block the IL-6 signal transduction pathway and thus is likely to become an effective drug for patients with severe COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/etiology , Pneumonia, Viral/drug therapy , Receptors, Interleukin-6/antagonists & inhibitors , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , SARS-CoV-2 , Severity of Illness Index
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