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1.
Natl Sci Rev ; 9(11), 2022.
Article in English | PubMed Central | ID: covidwho-2189437

ABSTRACT

(−)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.

2.
47th IEEE International Conference on Acoustics, Speech, and Signal Processing, ICASSP 2022 ; 2022-May:9012-9016, 2022.
Article in English | Scopus | ID: covidwho-1891401

ABSTRACT

Traditional face-to-face subjective listening test has become a challenge due to the COVID-19 pandemic. We developed a remote assessment system with Tencent Meeting, a video conferencing application, to address this issue. This paper presents our work on evaluating the reliability of the remote assessment system. Two speech reception threshold (SRT) experiments were conducted to study the effects of noise suppression and maxima selection number on cochlear implant (CI) hearing. Both experiments were conducted locally and remotely, the correlations between the respective results were analyzed. Results showed that remote tests replicated the differences among testing conditions observed in local tests, but the absolute SRT values for individual conditions varied significantly between the two modes. The variations could be attributed to multiple reasons, such as online data transmission issues, audio playback devices, environmental conditions, and the training of participants. In conclusion, the relative variation of SRTs for CIs can be measured reliably, but the absolute SRT values should be carefully compared and explained according to objective and subjective experimental conditions. © 2022 IEEE

3.
Clin Infect Dis ; 75(1): e276-e288, 2022 08 24.
Article in English | MEDLINE | ID: covidwho-1709235

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions (NPIs) are recommended for COVID-19 prevention. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified. METHODS: We conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-12 November, 2021. We used conditional logistic regression to estimate adjusted odds ratios (aORs) of case status among participants who reported contact with an individual known or suspected to have been infected with SARS-CoV-2 ("high-risk exposure") ≤14 days before testing. RESULTS: 751 of 1448 cases (52%) and 255 of 1443 controls (18%) reported high-risk exposures ≤14 days before testing. Adjusted odds of case status were 3.02-fold (95% confidence interval: 1.75-5.22) higher when high-risk exposures occurred with household members (vs. other contacts), 2.10-fold (1.05-4.21) higher when exposures occurred indoors (vs. outdoors only), and 2.15-fold (1.27-3.67) higher when exposures lasted ≥3 hours (vs. shorter durations) among unvaccinated and partially-vaccinated individuals; excess risk associated with such exposures was mitigated among fully-vaccinated individuals. Cases were less likely than controls to report mask usage during high-risk exposures (aOR = 0.50 [0.29-0.85]). The adjusted odds of case status was lower for fully-vaccinated (aOR = 0.25 [0.15-0.43]) participants compared to unvaccinated participants. Benefits of mask usage were greatest among unvaccinated and partially-vaccinated participants, and in interactions involving non-household contacts or interactions occurring without physical contact. CONCLUSIONS: NPIs reduced the likelihood of SARS-CoV-2 infection following high-risk exposure. Vaccine effectiveness was substantial for partially and fully vaccinated persons.


Subject(s)
COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Case-Control Studies , Humans , SARS-CoV-2
4.
Chinese Journal of New Drugs ; 31(1):69-76, 2022.
Article in Chinese | Scopus | ID: covidwho-1661512

ABSTRACT

As of May 2021, 6 new vaccines against coronavirus disease 2019 (COVID-19) have been conditionally approved and urgently used in China, including products of 4 new inactivated vaccines, 1 new adenovirus vaccine and 1 new recombinant vaccine. All the six vaccine products have been under different stages of clinical trials in global scale, and the results of the clinical trials have demonstrated the safety of the vaccines and the efficacy against COVID-19. Focusing on the above products, this paper deeply summarizes the characteristics of different new vaccine products and the clinical trial results as the key evidence supporting the approval of the products. In addition, facing the current severe situation of COVID-19, the status and challenges regarding the research and development of new vaccines and therapeutics are analyzed. © 2022, Chinese Journal of New Drugs Co. Ltd. All right reserved.

6.
Chinese Journal of Clinical Infectious Diseases ; 13(1):9-15, 2020.
Article in Chinese | Scopus | ID: covidwho-1143641

ABSTRACT

Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province. Methods: A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Results: The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively(Z=6.722, P<0.05). Conclusions: The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy. Copyright © 2020 by the Chinese Medical Association.

7.
J Intern Med ; 289(4): 559-573, 2021 04.
Article in English | MEDLINE | ID: covidwho-1096894

ABSTRACT

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.


Subject(s)
Antibodies, Viral/blood , Antibody Formation/immunology , COVID-19 Serological Testing , COVID-19/therapy , SARS-CoV-2 , Symptom Assessment , Adult , Aged , Antibodies, Neutralizing/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19/physiopathology , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Treatment Outcome , United States
8.
Nanoscience and Nanotechnology Letters ; 12(10):1207-1214, 2020.
Article in English | Web of Science | ID: covidwho-1072852

ABSTRACT

The 2019 novel coronavirus (2019-nCoV) is extremely infectious and the human population globally is generally susceptible to it. Its spread poses a serious threat to public health. Analyzing the epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) can more fully demonstrate its characteristics and evolution, and provide effective scientific strategies for preventing and controlling the epidemic. In this study, nucleic acid detection was performed on 228 suspected COVID-19 cases in Ningbo City from January 2020 to August 2020. The RNA of the virus was extracted by the nano magnetic bead method and was detected by real-time fluorescent quantitative PCR. Patients whose test results were positive were considered as research subjects. Clinical data of the patients were collected through a medical record system and the epidemiology and characteristics of COVID-19 were analyzed. Among the 228 suspected cases, 108 patients had a positive nucleic acid test result. The 108 confirmed patients were selected as research subjects, including 9 patients with mild symptoms, 85 patients with common symptoms, and 14 patients with severe symptoms. The age range of the patients was 17-82 years. Overall, 35 patients (32.40%) had complications. The median incubation period for patients was 7.5 days. Seventy patients (64.81%) had a contact history with a diseased individual. In terms of the clinical symptoms of the patients, the following symptoms were identified: fever in 92, cough in 62, fatigue in 34, sputum expectoration in 32, dry cough in 22, sore throat in 19, diarrhea in 8, headache in 8, shortness of breath in 7, nasal congestion in 5, and muscle ache in 5 cases. The results of chest CT imaging showed that 96 patients (88.89%) exhibited bilateral or unilateral pneumonia lesions of varying degrees, manifested as bilateral or unilateral lung patches, cloudy floccules, patches with an increased density shadow. The CT images of 12 patients (11.11%) showed no obvious abnormalities, while 24 cases (22.22%) had absolute white blood cell count of <4x10(9)/L, while 1 case had one of >10x10(9)/L. The absolute neutrophil count in 10 patients (9.26%) increased (>6.3x10(9/)L). The absolute lymphocyte count in 49 patients (45.37%) decreased (<1.1x10(9)/L). The hemoglobin, hematocrit, and platelet levels of the vast majority of patients were normal, while a few were low or high. Fifty-eight patients (53.70%) had elevated C-reactive protein (>10 mg/L);14 (12.96%) had elevated D-dimer (>256 mu g/L);14 (12.96%) had high levels of alanine aminotransferase (>40 U/L);9 (8.33%) had increased aspartate aminotransferase (>40 U/L);while 32 (29.6%) had increased lactate dehydrogenase (>250 U/L). COVID-19 in Ningbo is mainly transmitted in clusters, and elderly patients are more likely to develop severe symptoms. There is no significant difference in clinical characteristics between patients with severe conditions and those with mild and common ones.

9.
Clinical Infectious Diseases ; 71(12):3232-3236, 2020.
Article in English | MEDLINE | ID: covidwho-1041905

ABSTRACT

Translation of in vitro antiviral activity to the in vivo setting is crucial to identify potentially effective dosing regimens of hydroxychloroquine. In vitro 50%/90% maximal effective concentration values for hydroxychloroquine should be compared to the in vivo free extracellular tissue concentration, which is similar to the free plasma hydroxychloroquine concentration.

10.
Nano Research ; 2020.
Article in English | Scopus | ID: covidwho-1002178

ABSTRACT

Interferon (IFN) responses are central to host defense against coronavirus and other virus infections. Manganese (Mn) is capable of inducing IFN production, but its applications are limited by nonspecific distributions and neurotoxicity. Here, we exploit chemical engineering strategy to fabricate a nanodepot of manganese (nanoMn) based on Mn2+. Compared with free Mn2+, nanoMn enhances cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo. Preferentially phagocytosed by macrophages, nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci, eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage. Besides, nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation, suggesting its potential as a vaccine adjuvant. Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese. Therefore, nanoMn offers a simple, safe, and robust nanoparticle-based strategy against coronavirus. [Figure not available: see fulltext.]. © 2020, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature.

11.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(0): E004, 2020 Feb 05.
Article in Chinese | MEDLINE | ID: covidwho-252

ABSTRACT

A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.

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