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2.
EClinicalMedicine ; 25: 100478, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1047557

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.

3.
Am J Chin Med ; 48(7): 1523-1538, 2020.
Article in English | MEDLINE | ID: covidwho-910318

ABSTRACT

This study aimed to investigate the efficacy of Traditional Chinese Medicine (TCM) decoction with different intervention timepoints in the treatment of coronavirus disease 2019 (COVID-19) patients. We retrospectively collected the medical records and evaluated the outcomes of COVID-19 patients that received TCM decoction treatment at different timepoints. A total of 234 COVID-19 patients were included in this study. Patients who received TCM decoction therapy within 3 days or 7 days after admission could achieve shorter hospitalization days and disease periods compared to those who received TCM decoction [Formula: see text] 7 days after admission (all [Formula: see text]). Patients who received TCM decoction therapy within 3 days had significantly fewer days to negative SARS-CoV-2 from nasopharyngeal/oral swab and days to negative SARS-CoV-2 from urine/stool/blood samples compared to those received TCM decoction [Formula: see text] days after admission (all [Formula: see text]). Patients who received TCM decoction therapy on the 3rd to 7th day after admission had a faster achievement of negative SARS-CoV-2 from urine/stool/blood samples compared to those who received TCM decoction [Formula: see text] days after admission ([Formula: see text]). Logistic models revealed that more days from TCM decoction to admission [Formula: see text] days might be a risk factor for long hospitalization days, disease period, and slower negative-conversion of SARS-CoV-2 (all [Formula: see text]). Conclusively, our results suggest that TCM decoction therapy should be considered at the early stage of COVID-19 patients.

4.
Open Forum Infect Dis ; 7(9): ofaa286, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-665998

ABSTRACT

Background: The course of disease in mild and moderate COVID-19 has many implications for mobile patients, such as the risk of spread of the infection, precautions taken, and investigations targeted at preventing transmission. Methods: Three hundred thirty-one adults were hospitalized from January 21 to February 22, 2020, and classified as severe (10%) or critical (4.8%) cases; 1.5% died. Two hundred eighty-two (85.2%) mild or moderate cases were admitted to regular wards. Epidemiological, demographic, clinical, chest computed tomography (CT) scan, laboratory, treatment, and outcome data from patient records were analyzed retrospectively. Results: Patients were symptomatic for 9.82±5.75 (1-37) days. Pulmonary involvement was demonstrated on a chest CT scan in 97.9% of cases. It took 16.81±8.54 (3-49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09±7.82 (1-44) days. Subsequently, 131 patients were discharged. One hundred sixty-nine remained in the hospital; these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24±7.57 (2-47) days; the time interval from the first symptom to discharge was 21.37±7.85 (3-52) days. Conclusions: With an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients.

5.
Science ; 369(6504): 650-655, 2020 08 07.
Article in English | MEDLINE | ID: covidwho-610891

ABSTRACT

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Adult , Animals , Antibodies, Monoclonal/blood , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/metabolism , Antibodies, Viral/blood , Antibodies, Viral/chemistry , Antibodies, Viral/metabolism , Antibody Affinity , Antibody Specificity , Antigens, Viral/immunology , B-Lymphocytes/immunology , Chlorocebus aethiops , Coronavirus Infections/therapy , Cryoelectron Microscopy , Enzyme-Linked Immunosorbent Assay , Genes, Immunoglobulin Heavy Chain , Humans , Immunologic Memory , Middle Aged , Mutation , Nucleocapsid Proteins/immunology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Phosphoproteins , Pneumonia, Viral/therapy , Protein Domains , Protein Interaction Domains and Motifs/immunology , Receptors, Virus/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Young Adult
6.
Open Forum Infect Dis ; 7(7): ofaa241, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-608812

ABSTRACT

Background: We aimed to evaluate the antiviral activity and safety of darunavir/cobicistat (DRV/c) in treating COVID-19 patients. Methods: In this single-center, randomized, and open-label trial, mild patients with polymerase chain reaction (PCR)-confirmed COVID-19 were enrolled in Shanghai, China. Participants were randomized to receive DRV/c for 5 days on the top of interferon alpha 2b inhaling or interferon alpha 2b inhaling alone. The primary end point was the virological clearance rate of oropharyngeal swabs at day 7 after randomization in the intention-to-treat population (clinicaltrials.gov: NCT04252274). Results: From January 30, 2020, to February 6, 2020, a total of 30 patients were enrolled, of whom 18 (60%) were male, aged 47.2 ±â€…2.8 years; 63.3% (19/30) of the participants had fever, and 46.7% (14/30) had cough at enrollment. The participants were randomized (range) at 4 (2-5) days after onset of symptoms. The proportion of negative PCR results at day 7 was 46.7% (7/15) and 60.0% (9/15) in the DRV/c and control groups (P = .72), respectively. The viral clearance rate at day 3 was 20% (3/15) in both study groups, while the number increased to 26.7% (4/15) in the DRV/c group and remained 20% (3/15) in the control group at day 5. Fourteen days after randomization, 1 participant in the DRV/c group progressed to critical illness and discontinued DRV/c, while all the patients in the control group were stable (P = 1.0). The frequencies of adverse events in the 2 groups were comparable. Conclusions: Five days of DRV/c did not increase the proportion of negative conversion vs standard of care alone, although it was well tolerated.

8.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 2020.
Article | WHO COVID | ID: covidwho-242643

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19) METHODS: We prospectively enrolled 30 treatment-naive patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center The patients were randomized 11 to HCQ group and the control group Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517) RESULTS: One patient in HCQ group developed to severe during the treatment On day 7, nucleic acid of throat swabs was negative in 13 (86 7%) cases in the HCQ group and 14 (93 3%) cases in the control group (P>0 05) The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1 27, P>0 05] The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day] Radiological progression was shown on CT images in 5 cases (33 3%) of the HCQ group and 7 cases (46 7%) of the control group, and all patients showed improvement in follow-up examinations Four cases (26 7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0 05) CONCLUSIONS: The prognosis of COVID-19 moderate patients is good Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19 Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size

9.
J Vet Sci ; 21(1): e12, 2020 Jan.
Article in English | MEDLINE | ID: covidwho-124741

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus that causes diarrhea in piglets. However, the biological characteristics of PDCoV are unclear. In this study, the hemagglutination (HA) abilities of two PDCoV strains (CH-01 and HNZK-04) were investigated. Our results showed that PDCoV has the ability to agglutinate rabbit erythrocytes after virion pretreatment with trypsin or neuraminidase. Additionally, the HA assay results showed a significant positive correlation with the infectious viral titer. Our results suggest that assessing the HA activity of PDCoV may be a useful diagnostic method for investigating and surveilling PDCoV infections.


Subject(s)
Coronavirus Infections/veterinary , Coronavirus/physiology , Hemagglutination , Swine Diseases/immunology , Animals , Coronavirus Infections/immunology , Coronavirus Infections/virology , Diarrhea/immunology , Diarrhea/veterinary , Diarrhea/virology , Erythrocytes/immunology , Neuraminidase/administration & dosage , Rabbits , Swine , Swine Diseases/virology , Trypsin/administration & dosage , Virion/drug effects
10.
Science ; 367(6485): 1444-1448, 2020 03 27.
Article in English | MEDLINE | ID: covidwho-17388

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.


Subject(s)
Amino Acid Transport Systems, Neutral/ultrastructure , Peptidyl-Dipeptidase A/ultrastructure , Receptors, Virus/ultrastructure , Spike Glycoprotein, Coronavirus/ultrastructure , Amino Acid Sequence , Betacoronavirus , Coronavirus Infections , Cryoelectron Microscopy , Humans , Models, Molecular , Pandemics , Pneumonia, Viral , Protein Binding , Protein Domains , Protein Multimerization , SARS Virus , Sequence Alignment
11.
Chinese Journal of Organ Transplantation ; (12): E006-E006, 2020.
Article in Chinese | WPRIM (Western Pacific) | ID: covidwho-6561

ABSTRACT

Objective@#To analyze the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease (COVID-19) .@*Method@#The clinical diagnosis and treatment of one relative renal transplant recipient after the occurrence of COVID-19 were analyzed retrospectively, including the course of onset, clinical manifestations, blood routine test, renal function, lung CT scan, nucleic acid detection, outpatient and inpatient therapies and outcomes.@*Result@#The case was diagnosed as COVID-19 (severe type) with influenza A virus infection. The clinical symptoms were gradually relieved and the lung lesions were absorbed through the treatment of reduce and stop taking immunosuppressant, antiviral therapy of abidol/oseltamivir, prevention of bacterial infection, hormone anti-inflammatory, oxygen inhalation, nutritional support and adequate rest.@*Conclusion@#This case present typical characteristics of COVID-19 in epidemiological investigation, clinical manifestation, examination, pulmonary imaging and etiology. After comprehensive treatment including reduce and stop immunosuppressive therapy, clinical cure was achieved. The long-term effect of COVID-19 on this immunosuppressive patient remains follow-up.

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