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1.
Chinese Journal of Digestive Endoscopy ; 38(3):195-199, 2021.
Article in Chinese | EMBASE | ID: covidwho-20245314
2.
ACM International Conference Proceeding Series ; : 73-79, 2022.
Article in English | Scopus | ID: covidwho-20245310

ABSTRACT

Aiming at the severe form of new coronavirus epidemic prevention and control, a target detection algorithm is proposed to detect whether masks are worn in public places. The Ghostnet and SElayer modules with fewer design parameters replace the BottleneckCSP part in the original Yolov5s network, which reduces the computational complexity of the model and improves the detection accuracy. The bounding box regression loss function DIOU is optimized, the DGIOU loss function is used for bounding box regression, and the center coordinate distance between the two bounding boxes is considered to achieve a better convergence effect. In the feature pyramid, the depthwise separable convolution DW is used to replace the ordinary convolution, which further reduces the amount of parameters and reduces the loss of feature information caused by multiple convolutions. The experimental results show that compared with the yolov5s algorithm, the proposed method improves the mAP by 4.6% and the detection rate by 10.7 frame/s in the mask wearing detection. Compared with other mainstream algorithms, the improved yolov5s algorithm has better generalization ability and practicability. © 2022 ACM.

3.
Social and Personality Psychology Compass ; 2023.
Article in English | Web of Science | ID: covidwho-20245309

ABSTRACT

Cultures responded to the COVID-19 pandemic differently. We investigated cultural differences in mental health during the pandemic. We found regional differences in people's reports of anxiety in China over two years from 2020 to 2021 (N = 1186). People in areas with a history of rice farming reported more anxiety than people in wheat-farming areas. Next, we explored more proximal mechanisms that could help link the distal, historical factor of rice farming to people's modern experience of anxiety. Rice areas scored higher on collectivism and tight social norms than wheat areas, and collectivism, rather than norm tightness, mediated the rice-anxiety relationship. These findings advance our understanding of the distal sources of cultural differences, the proximal mechanisms, and mental health problems during the pandemics.

4.
Progress in Geography ; 42(2):328-340, 2023.
Article in Chinese | Scopus | ID: covidwho-20245301

ABSTRACT

In order to analyze the impact of COVID-19 prevention and control measures on the hotspots of residential burglary, the data of crimes that occurred during the First Level Response period of Major Public Health Emergencies in Beijing in 2020 and the same period in 2019 were collected, and the changes of hotspots during the two periods were compared by using kernel density estimation and predictive accuracy index. Consequently, the environmental features such as street network, point of interest (POI) diversity, crime locations, and repeat victimization in significantly varied hotspot areas were investigated. The results show that: 1) After the outbreak of the pandemic, the occurrence of residential burglary in the core urban areas of Beijing dropped significantly, and daily occurrence of crimes during the First Level Response period in 2020 decreased by 66.8% compared with the same days in 2019. 2) The eight major hotspots that existed in 2019 apparently declined during the corresponding days in 2020, five of them basically disappeared, and three hotspots weakened. 3) The declined hotspots were generally clustered around traffic hubs, areas with high diversity of POIs, clustered crimes, and repeat victimizations. 4) Home isolation and social restriction strategies implemented during the First Level Response period reduced the opportunities of offenders, and the real-name inspection adopted in public places increased the exposure risk of offenders, which are the main reasons for the hotspots decline during the pandemic. This work has some implications for crime prevention and police resources optimization during the pandemic. © 2023, Editorial office of PROGRESS IN GEOGRAPHY. All rights reserved.

5.
Academic Journal of Naval Medical University ; 43(11):1234-1239, 2022.
Article in Chinese | EMBASE | ID: covidwho-20245300

ABSTRACT

The coronavirus disease 2019 (COVID-19) has become a global pandemic. It is urgent to find treatments to control the infection and improve symptoms. Homologous modeling and clinical analyses suggest that histamine receptor antagonists have broad prospects in the treatment of COVID-19. This article introduces the research progress of histamine H1 receptor antagonist combined with azithromycin, histamine H2 receptor antagonist famotidine alone or combined with aspirin, and histamine H1 and H2 receptor antagonists used in combination in the treatment of COVID-19. Finally, the possible mechanism of histamine receptor antagonists in the treatment of COVID-19 was introduced and the application prospect of histamine receptor antagonists in the treatment of COVID-19 was analyzed.Copyright © 2022, Second Military Medical University Press. All rights reserved.

6.
Clinical Immunology ; Conference: 2023 Clinical Immunology Society Annual Meeting: Immune Deficiency and Dysregulation North American Conference. St. Louis United States. 250(Supplement) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-20243104

ABSTRACT

Genotypic definition of monogenic inborn errors of immunity (IEIs) continues to accelerate with broader access to next generation sequencing, underscoring this aggregated group of disorders as a major health burden impacting both civilian and military populations. At an estimated prevalence of 1 in 1200 individuals, IEIs affect ~8,000 patients within the Military Health System (MHS). Despite access to targeted gene/exome panels at military treatment facilities, most affected patients never receive a definitive genetic diagnosis that would significantly improve clinical care. To address this gap, we established the first registry of IEI patients within the MHS with the goal of identifying known and novel pathogenic genetic defects to increase diagnosis rates and enhance clinical care. Using the registry, a research protocol was opened in July 2022. Since July we have enrolled 75 IEI patients encompassing a breadth of phenotypes including severe and recurrent infections, bone marrow failure, autoimmunity/autoinflammation, atopic disease, and malignancy. Enrolled patients provide blood and bone marrow samples for whole genome, ultra-deep targeted panel and comprehensive transcriptome sequencing, plus cryopreservation of peripheral blood mononuclear cells for future functional studies. We are also implementing and developing analytical methods for identifying and interrogating non-coding and structural variants. Suspected pathogenic variants are adjudicated by a clinical molecular geneticist using state-of-the-art analysis pipelines. These analyses subsequently inform in vitro experiments to validate causative mutations using cell reporter systems and primary patient cells. Clinical variant validation and return of genetic results are planned with genetic counseling provided. As a proof of principle, this integrated genetic evaluation pipeline revealed a novel, candidate TLR7 nonsense variant in two adolescent brothers who both endured critical COVID-19 pneumonia, requiring mechanical ventilation and extracorporeal membrane oxygenation. Our protocol is therefore poised to greatly enrich clinical genetics resources available in the MHS for IEI patients, contributing to better diagnosis rates, informed family counseling, and targeted treatments that collectively improve the health and readiness of the military community. Moreover, our efforts should yield new mechanistic insights on immune pathogenesis for a broad variety of known and novel IEIs.Copyright © 2023 Elsevier Inc.

8.
Asian Pacific Journal of Tropical Medicine ; 16(4):176-186, 2023.
Article in English | EMBASE | ID: covidwho-20237012

ABSTRACT

Objective: To examine COVID-19 vaccine uptake and its determinants among teenagers and their parents in Zhejiang, China. Method(s): An online cross-sectional study was conducted among parents of teenagers in Zhejiang, China from May 1 to 31, 2022. Data were interpreted via univariate and multivariate analyses using the statistical package for the social sciences (SPSS) program. Result(s): A total of 11115 (96.11%) participants and 11449 (99.00%) of their children in Zhejiang, China had been vaccinated against COVID-19. Children whose parents did not receive COVID-19 vaccination were 19 times (aOR 18.96, 95%CI 12.36-29.08) more likely to be unvaccinated than their counterparts. In addition, children with no previous influenza vaccination, those whose parents doubted the COVID-19 vaccine's safety or effectiveness, were 6.11 times (aOR 6.11, 95%CI 2.80-13.34), 8.27 times (aOR 8.27, 95%CI 5.33-12.83), and 2.69 times (aOR 2.69, 95%CI 1.11-6.50) more likely to be unvaccinated than their counterparts, respectively. COVID-19 vaccine uptake varied between different sociodemographic groups. However, the odds of receiving the COVID-19 vaccine decreased as age and education level increased. The main refusal reasons claimed by participants were that they had medical conditions that may not qualify them for vaccination (53.78%), followed by safety concerns about the vaccine (13.56%), not knowing where to get vaccinated (6.44%), and concerns about fertility issues (5.56%). Conclusion(s): Despite a highly encouraging level of COVID-19 vaccine uptake in Zhejiang, China, the elderly and highly educated people had lower COVID-19 vaccine uptake. It is suggested that tailored health education strategies should be taken to increase the COVID-19 vaccine uptake in such groups. Furthermore, with vaccination rates at such a high level, the pandemic is still ongoing, and public confidence in vaccines may decline. Thus, sufficient evidence-based information regarding COVID-19 vaccines should be provided to the public. Copyright © 2023 Asian Pacific Journal of Tropical Medicine.

9.
Social and Personality Psychology Compass ; 2023.
Article in English | Web of Science | ID: covidwho-20230940

ABSTRACT

The outbreak of the COVID-19 pandemic brought unrelenting waves of xenophobia against people representing vulnerable populations, among them those identified as Asians or more specifically as Chinese. Although previous studies have found that some discriminatory actions against overseas Chinese were closely related to mask use during the pandemic, there is not much evidence that explicates what might be the social-cultural triggers or impact of self-other mask discrepancy. The current study aims to examine how a mask use gap impacts perceived discrimination and anxiety during the first outbreak of COVID-19, and how perceived discrimination mediates the mask gap-anxiety relationship. This was operationalized by developing a new "mask gap" variable to capture the incongruent mask use norms between Chines and others around them in the host country. Data were collected from a cross-sectional sample of Chinese (n = 745) residing in 21 countries from March to May 2020 during the first wave of the pandemic. Results showed the newly explicated "mask gap" variable was associated with a higher level of anxiety. In addition, perceived discrimination mediated the mask gap-anxiety relationship. These findings advance both theoretical and practical understandings of how incongruent social norms impact discrimination and mental health during health threat events like the COVID-19 pandemic. The results also suggest important implications for both societal responses and the mental health of sojourners or immigrants during pandemics.

10.
Asian Pacific Journal of Tropical Medicine ; 16(4):176-186, 2023.
Article in English | Web of Science | ID: covidwho-20230774

ABSTRACT

Objective: To examine COVID-19 vaccine uptake and its determinants among teenagers and their parents in Zhejiang, China. Methods: An online cross-sectional study was conducted among parents of teenagers in Zhejiang, China from May 1 to 31, 2022. Data were interpreted via univariate and multivariate analyses using the statistical package for the social sciences (SPSS) program. Results: A total of 11115 (96.11%) participants and 11449 (99.00%) of their children in Zhejiang, China had been vaccinated against COVID-19. Children whose parents did not receive COVID-19 vaccination were 19 times (aOR 18.96, 95%CI 12.36-29.08) more likely to be unvaccinated than their counterparts. In addition, children with no previous influenza vaccination, those whose parents doubted the COVID-19 vaccine's safety or effectiveness, were 6.11 times (aOR 6.11, 95%CI 2.80-13.34), 8.27 times (aOR 8.27, 95%CI 5.33-12.83), and 2.69 times (aOR 2.69, 95%CI 1.11-6.50) more likely to be unvaccinated than their counterparts, respectively. COVID-19 vaccine uptake varied between different sociodemographic groups. However, the odds of receiving the COVID-19 vaccine decreased as age and education level increased. The main refusal reasons claimed by participants were that they had medical conditions that may not qualify them for vaccination (53.78%), followed by safety concerns about the vaccine (13.56%), not knowing where to get vaccinated (6.44%), and concerns about fertility issues (5.56%). Conclusions: Despite a highly encouraging level of COVID-19 vaccine uptake in Zhejiang, China, the elderly and highly educated people had lower COVID-19 vaccine uptake. It is suggested that tailored health education strategies should be taken to increase the COVID-19 vaccine uptake in such groups. Furthermore, with vaccination rates at such a high level, the pandemic is still ongoing, and public confidence in vaccines may decline. Thus, sufficient evidence-based information regarding COVID-19 vaccines should be provided to the public.

11.
Chinese Traditional and Herbal Drugs ; 54(4):1201-1207, 2023.
Article in Chinese | EMBASE | ID: covidwho-2324524

ABSTRACT

Objective To explore the clinical effect and safety of Suhexiang Pills () in the treatment of patients infected with SARS-CoV-2. Methods A total of 192 patients infected with SARS-CoV-2 admitted to 17 hospitals including Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University from December 2022 to January 2023 were randomly divided into control group and treatment group, with 89 patients in the treatment group and 103 in the control group. The patients in control group received basic treatment according to the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 10). The patients in treatment group were oral administered with Suhexiang Pills on the basis of the control group, one pill each time, twice day. The patients in two groups were treated for 5 d. The clinical efficacy of the two groups after treatment was compared. The differences in scores of headache, chest pain, limb pain and inflammatory indexes before and after treatment were compared. Results After treatment, the total clinical effective rate of the treatment group was 95.51%, which was significantly higher than that of the control group (81.55%, P < 0.05). After treatment, headache, chest pain and limb pain scores were significantly decreased in both groups (P < 0.05), the headache score of the treatment group was significantly lower than that of the control group from the first day of treatment (P < 0.05), the chest pain score of the treatment group was significantly lower than that of the control group on the fifth day of treatment (P < 0.05), the limb pain score of the treatment group was significantly lower than that of the control group from the third day of treatment (P < 0.05). After treatment, the levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6) in the two groups were decreased significantly (P < 0.05) and the levels of CRP and IL-6 in the treatment group were significantly lower than those of the control group (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups. Conclusion Suhexiang Pills have a certain effect on headache, chest pain and limb pain, inhibiting the inflammatory response in patients infected with SARS-CoV-2, with good safety.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

12.
Academic Journal of Naval Medical University ; 43(11):1234-1239, 2022.
Article in Chinese | EMBASE | ID: covidwho-2327382

ABSTRACT

[ ] The coronavirus disease 2019 (COVID-19) has become a global pandemic. It is urgent to find treatments to control the infection and improve symptoms. Homologous modeling and clinical analyses suggest that histamine receptor antagonists have broad prospects in the treatment of COVID-19. This article introduces the research progress of histamine H1 receptor antagonist combined with azithromycin, histamine H2 receptor antagonist famotidine alone or combined with aspirin, and histamine H1 and H2 receptor antagonists used in combination in the treatment of COVID-19. Finally, the possible mechanism of histamine receptor antagonists in the treatment of COVID-19 was introduced and the application prospect of histamine receptor antagonists in the treatment of COVID-19 was analyzed.Copyright © 2022, Second Military Medical University Press. All rights reserved.

13.
ACM Transactions on Management Information Systems ; 13(1), 2021.
Article in English | Scopus | ID: covidwho-2326987

ABSTRACT

(Aim) COVID-19 has caused more than 2.28 million deaths till 4/Feb/2021 while it is still spreading across the world. This study proposed a novel artificial intelligence model to diagnose COVID-19 based on chest CT images. (Methods) First, the two-dimensional fractional Fourier entropy was used to extract features. Second, a custom deep stacked sparse autoencoder (DSSAE) model was created to serve as the classifier. Third, an improved multiple-way data augmentation was proposed to resist overfitting. (Results) Our DSSAE model obtains a micro-averaged F1 score of 92.32% in handling a four-class problem (COVID-19, community-acquired pneumonia, secondary pulmonary tuberculosis, and healthy control). (Conclusion) Our method outperforms 10 state-of-the-art approaches. © 2021 Copyright held by the owner/author(s). Publication rights licensed to ACM.

14.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(5): 728-731, 2023 May 06.
Article in Chinese | MEDLINE | ID: covidwho-2325811

ABSTRACT

An epidemiological investigation was conducted on a cluster epidemic of COVID-19 in the vaccinated population in Beijing in 2022, and serum samples were collected from 21 infected cases and 61 close contacts (including 20 cases with positive nucleic acid in the isolation observation period). The results of antibody detection showed that the IgM antibody of two infected persons was positive, and the IgG antibody positive rates of patients who were converted, not converted to positive and infected persons were 36.84% (7/19), 63.41% (26/41) and 71.43% (15/21), respectively. About 98.78% of patients had been vaccinated with the SARS-CoV-2 inactivated vaccine. The positive rate of IgG antibody in patients immunized with three doses of vaccine was 86.00% (43/50), which was higher than that in patients with one or two doses [16.12% (5/31)]. The antibody level of M (Q1, Q3) in patients immunized with three doses was 4.255 (2.303, 7.0375), which was higher than that in patients with one or two doses [0.500 (0.500, 0.500)] (all P values<0.001). The antibody level of patients who were vaccinated less than three months [7.335 (1.909, 7.858)] was higher than that of patients vaccinated more than three months after the last vaccination [2.125 (0.500, 4.418)] (P=0.007). The positive rate and level of IgG antibody in patients who were converted to positive after three doses were 77.78% (7/9) and 4.207 (2.216, 7.099), respectively, which were higher than those in patients who were converted after one or two doses [0 and 0.500 (0.500, 0.500)] (all P values<0.05).


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Disease Outbreaks , COVID-19 Vaccines , Immunoglobulin G , Antibodies, Viral
15.
2022 Asia Communications and Photonics Conference, ACP 2022 and International Conference on Information Photonics and Optical Communications, IPOC 2022 ; 2022-November:2025-2028, 2022.
Article in English | Scopus | ID: covidwho-2320959

ABSTRACT

The emergence of the Covid-19 pandemic has drawn great attention to vulnerable people affected by major diseases. Among them, Alzheimer's disease (AD) is the most prevalent disease. However, a long-standing challenge is to achieve early diagnosis of AD by detecting biomarkers such as amyloid beta (Aβ42), thus avoiding the labor of specialized hospital personnel and the high cost of imaging examinations using positron emission tomography. In this paper, we report a straightforward approach to realize a non-invasive lab-around fiber (LaF) optical sensor for AD biomarker detection, which is based on a tilted fiber Bragg grating (TFBG) combined with a nanoscale metallic thin film. We successfully demonstrated the detection of Aβ42 in complex biological matrices with a detection limit of 5 pg/mL. Therefore, our TFBG-SPR biosensor platform enables large-scale early disease screening and has great potential for clinical applications in early AD diagnosis. © 2022 IEEE.

16.
Medical Journal of Peking Union Medical College Hospital ; 12(5):755-760, 2021.
Article in Chinese | EMBASE | ID: covidwho-2320863

ABSTRACT

With the development of technology, doctors can diagnose and treat many diseases through telemedicine. At present, teleophthalmology is mainly used in screening and diagnosing some ocular diseases, monitoring chronic ocular diseases, as well as teleconsultation. With the increasing demand and application of teleophthalmology, some problems will gradually become prominent, such as insufficient equipment and staff, medical risks, patient acceptance and satisfaction, network security, privacy, and covering of medical insurance. The global pandemic of COViD-19 has unexpectedly brought telemedicine to the forefront of ophthalmic services, and may continue to change the way of ophthalmic diagnosis and treatment. With the development of artificial intelligence technology, the expansion of 5G communication network coverage, the standardized training of primary medical staff, and the introduction of relevant laws and regulations, teleophthalmology will become more improved, universal, and widely applied, so as to provide patients with sustainable medical services of higher quality.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

17.
34th IEEE International Conference on Tools with Artificial Intelligence, ICTAI 2022 ; 2022-October:1002-1006, 2022.
Article in English | Scopus | ID: covidwho-2319639

ABSTRACT

Since the beginning of the COVID-19 pandemic, remote conferencing and school-teaching have become important tools. The previous applications aim to save the commuting cost with real-time interactions. However, our application is going to lower the production and reproduction costs when preparing the communication materials. This paper proposes a system called Pre-Avatar, generating a presentation video with a talking face of a target speaker with 1 front-face photo and a 3-minute voice recording. Technically, the system consists of three main modules, user experience interface (UEI), talking face module and few-shot text-to-speech (TTS) module. The system firstly clones the target speaker's voice, and then generates the speech, and finally generate an avatar with appropriate lip and head movements. Under any scenario, users only need to replace slides with different notes to generate another new video. The demo has been released here11https://pre-avatar.github.io/ and will be published as free software for use. © 2022 IEEE.

18.
Chinese Journal of Experimental Traditional Medical Formulae ; 28(11):125-131, 2022.
Article in Chinese | EMBASE | ID: covidwho-2315759

ABSTRACT

Objective:To observe the efficacy and safety of Fuzheng Huayu tabletsFHTfor treating pulmonary inflammation in patients with coronavirus disease 2019COVID-19. Method(s):A total of 704 cases were lost to follow-up, and 66 cases were finally completedCOVID-19 patients were recruited from February 1 to April 15 in 2020. They were assigned to a control group35 patientsand a FHT group31 patients. The patients in the control group received routine treatment alone and those in the FHT group received FHT in addition to routine treatment. The primary outcome was the ratio of patients showing improvement in chest computed tomographic manifestations after 14 days. The secondary outcome measures included remission rate or progression rate of critical illness,clinical remission rate of respiratory symptoms,routine blood examination, C-reactive proteinCPRlevel,procalcitoninPCTlevel,and blood oxygen saturationSPO2 . The safety was assessed based on liver and kidney functions and adverse events. Result(s): After the 14-day treatment,the ratio of patients showing improvement in the FHT group100%was higher than that in the control group 77.1%chi2 =8.063,P<0.01. The ratio of disease stages after treatment showed no significant difference between two groups. In the FHT group,the symptoms including cough,dyspnea,and fatigue were alleviated after treatmentP<0.01. In the control group,the symptoms including fever,cough,and dyspnea were alleviatedP<0.01,while the fatigue was not relieved after treatment. No significant difference was observed in the clinical symptoms between the two groups after treatment. After treatment,the FHT group showed decreased white blood cellWBCcount and neutrophil-to-lymphocyte ratioNLRP<0.01,elevated plateletPLTlevelP<0.05,lowered CRP levelP<0.05,and no significant difference in lymphocyte LYM,hemoglobinHb,SPO2 or PCT level. The control group showed decreased NLRP<0.05and WBC countP<0.01,elevated PCT levelP<0.05,and no significant change in LYM,Hb,PLT,SPO2 or CRP level after treatment. Furthermore,the FHT group had higher PLT level than the control groupP<0.05after treatment,and other indicators had no significant differences between the two groups. The liver and kidney functions had no significant difference between the two groups after treatment. Conclusion(s): FHT can safely promote the absorption of acute pulmonary inflammation in COVID-19 patients.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

19.
Topics in Antiviral Medicine ; 31(2):193, 2023.
Article in English | EMBASE | ID: covidwho-2313499

ABSTRACT

Background: Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. Post-acute sequelae of SARS-COV-2 infection (PASC) is associated with cognitive impairment (CI) with unclear pathogenesis though blood brain barrier (BBB) impairment and excitotoxic injury appear significant. We hypothesized that PASC CI patients would have brain inflammation and BBB disruption using advanced MR imaging. Method(s): In this prospective longitudinal study, 14 patients with PASC CI (mild and non-hospitalised) were enrolled (mean age of 45;10 F and 4 M) and 10 sex and age matched healthy controls. 13 had a follow up MR at 9-12 months (mean 10 months). All participants underwent DCE perfusion (an index of BBB integrity with Ktrans as the measurement), Diffusion Tensor Imaging (DTI) and single voxel MR spectroscopy (MRS) of the frontal cortex/white matter and the brainstem in addition to brain anatomical MRI. Between group analyses were used to determine which MRI outcomes were significantly different from controls in patients with PASC CI. Result(s): The PASCI CI group showed significantly increased (ie BBB impairment) Ktrans, and increased region (Frontal white matter and Brain Stem)-specific areas in the brain (p=< 0.005), reduction in NAA (ie neuronal injury) and mild reduction of Glx (ie excitotoxicity) in the frontal white matter and brain stem (p=0.004), and reduction in white matter integrity (increased diffusivity -greater radial and mean diffusivity). Increased Ktrans was correlated with increased both radial and mean diffusivity (r=0.9) in all tested brain regions. Ktrans significantly improved in the follow up MR (p= 002596 Z=-2.794872) with no difference between subjects and controls indicating BBB normalisation (p= 0.442418, z= -0.144841). White matter integrity also improved especially in the fractional anisotropy values in the executive networks (p=< 0.00045). MRS showed significant improvement in the NAA in the frontal white matter but Glx remain high as compared to the controls (p=0.0006). Conclusion(s): PASC CI was characterised by reversible diffuse BBB impairment, neuronal/axonal and excitotoxic injury. BBB impairment was associated with white matter disruption. These are suggestive biomarkers for the presence, severity and prognosis of PASC CI. Such biomarkers could underpin appropriate trial design and timing of intervention.

20.
Topics in Antiviral Medicine ; 31(2):213-214, 2023.
Article in English | EMBASE | ID: covidwho-2313407

ABSTRACT

Background: SARS-CoV-2 evolution has contributed to successive waves of infections and severely compromised the efficacy of available SARS-CoV-2 monoclonal antibodies. Decaying vaccine-induced immunity, vaccine hesitancy, and limited vaccine protection in older and immunocompromised populations further compromises vaccine efficacy at the population level. Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease due to COVID-19. An orally bioavailable RDV analog could facilitate earlier widespread administration to non-hospitalized COVID-19 patients. Method(s): We synthesized monoalkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. We evaluated the in vivo efficacy of our lead compound, 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (V2043), in an oral treatment model of murine SARS-CoV-2 infection. We then synthesized numerous phospholipid analogs of RVn and determined which modifications enhanced in vitro antiviral activity and selectivity. The most effective compounds against SARS-CoV-2 were then evaluated for antiviral activity against other RNA viruses. Result(s): Oral treatment of SARS-CoV-2 infected BALB/c mice with V2043 (60 mg/kg once daily for 5 days, starting 12 hrs after infection) reduced lung viral load by more than 100-fold versus vehicle at day 2 and to below the LOD at day 5. V2043 inhibited previous and contemporary SARS-CoV-2 Variants of concern to a similar degree, as measured by the half maximal effective concentration (EC50) in a human lung epithelial cell line (Calu-3). Evaluation of multiple RVn analogs with hydrophobic esters at the sn-2 of glycerol revealed that in vitro antiviral activity was improved by the introduction of a 3-fluoro-4-methoxysubstituted benzyl or a 3-or 4-cyano-substituted benzyl. These compounds showed a 2-to 6-fold improvement in antiviral activity compared to analogs having an unsubstituted benzyl, such as V2043, and were more active than RDV. These compounds also showed enhanced antiviral activity against multiple contemporary and emerging RNA viruses. Conclusion(s): Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections and as preparation for future outbreaks of pandemic RNA viruses.

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