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1.
Environmental Research ; 221:115282, 2023.
Article in English | ScienceDirect | ID: covidwho-2178501

ABSTRACT

To inhibit the COVID-19 (Coronavirus disease 2019) outbreak, unprecedented nationwide lockdowns were implemented in China in early 2020, resulting in a marked reduction of anthropogenic emissions. However, reasons for the insignificant improvement in air quality in megacities of northeast China, including Shenyang, Changchun, Jilin, Harbin, and Daqing, were scarcely reported. We assessed the influences of meteorological conditions and changes in emissions on air quality in the five megacities during the COVID-19 lockdown (February 2020) using the WRF-CMAQ model. Modeling results indicated that meteorology contributed a 14.7% increment in Air Quality Index (AQI) averaged over the five megacities, thus, the local unfavorable meteorology was one of the causes to yield little improved air quality. In terms of emission changes, the increase in residential emissions (+15%) accompanied by declining industry emissions (−15%) and transportation (−90%) emissions resulted in a slight AQI decrease of 3.1%, demonstrating the decrease in emissions associated with the lockdown were largely offset by the increment in residential emissions. Also, residential emissions contributed 42.3% to PM2.5 concentration on average based on the Integrated Source Apportionment tool. These results demonstrated the key role residential emissions played in determining air quality. The findings of this study provide a scenario that helps make appropriate emission mitigation measures for improving air quality in this part of China.

2.
Multiple sclerosis and related disorders ; 2022.
Article in English | EuropePMC | ID: covidwho-2168916

ABSTRACT

Objective To assess safety data of the inactivated COVID-19 vaccines in a real-world sample of people with autoimmune encephalitis (pwAE). Methods A cross-sectional study was performed between 1 March and 30 April 2022. We invited pwAE from our previous ONE-WC (Outcome of Autoimmune Encephalitis Study in Western China) registration study database, to attend neurological clinics, at West China Hospital to participate in a face-to-face survey using a custom-designed questionnaire for this study. The ONE-WC study began in October 2011 and prospectively enrolled pwAE from four large comprehensive neurological centers in Sichuan province, China. Results Of the 387 pwAE, 240 (62.0%) completed the questionnaire. Half the 240 participants (121, 50.4%) reported receiving at least one dose of COVID-19 vaccine, which in all but two patients received inactivated COVID-19 vaccine. Among vaccinated pwAE, the median age was 35 years (range 15-69) and 57.8% of them were women. The most frequent reasons that unvaccinated individuals reported for not receiving the COVID-19 vaccine were concern about vaccine-induced relapse of AE (50.4%) and advice from a physician to delay vaccination (21.0%). Small proportions of vaccinated individuals reported adverse events after the first dose (11.5%) or the second dose (10.2%), and none of the adverse events was serious. Across the entire sample, one individual reported relapsing within 30 days after the first dose and three individuals reported relapsing more than 120 days after the first dose. Conclusions This real-world survey indicates an overall favorable safety profile of the inactivated COVID-19 vaccine for pwAE.

3.
Multiple Sclerosis and Related Disorders ; 70:104495, 2023.
Article in English | ScienceDirect | ID: covidwho-2165726

ABSTRACT

Objective To assess safety data of the inactivated COVID-19 vaccines in a real-world sample of people with autoimmune encephalitis (pwAE). Methods A cross-sectional study was performed between 1 March and 30 April 2022. We invited pwAE from our previous ONE-WC (Outcome of Autoimmune Encephalitis Study in Western China) registration study database, to attend neurological clinics, at West China Hospital to participate in a face-to-face survey using a custom-designed questionnaire for this study. The ONE-WC study began in October 2011 and prospectively enrolled pwAE from four large comprehensive neurological centers in Sichuan province, China. Results Of the 387 pwAE, 240 (62.0%) completed the questionnaire. Half the 240 participants (121, 50.4%) reported receiving at least one dose of COVID-19 vaccine, which in all but two patients received inactivated COVID-19 vaccine. Among vaccinated pwAE, the median age was 35 years (range 15-69) and 57.8% of them were women. The most frequent reasons that unvaccinated individuals reported for not receiving the COVID-19 vaccine were concern about vaccine-induced relapse of AE (50.4%) and advice from a physician to delay vaccination (21.0%). Small proportions of vaccinated individuals reported adverse events after the first dose (11.5%) or the second dose (10.2%), and none of the adverse events was serious. Across the entire sample, one individual reported relapsing within 30 days after the first dose and three individuals reported relapsing more than 120 days after the first dose. Conclusions This real-world survey indicates an overall favorable safety profile of the inactivated COVID-19 vaccine for pwAE.

5.
Front Immunol ; 13: 975848, 2022.
Article in English | MEDLINE | ID: covidwho-2142004

ABSTRACT

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with a high mortality rate. In clinical practice, we have noted that many critically ill or critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. In addition, it has been demonstrated that severe COVID-19 has some pathological similarities with sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted and neutrophil dysfunction. Considering the parallels between COVID-19 and non-SARS-CoV-2 induced sepsis (hereafter referred to as sepsis), the aim of this study was to analyze the underlying molecular mechanisms between these two diseases by bioinformatics and a systems biology approach, providing new insights into the pathogenesis of COVID-19 and the development of new treatments. Specifically, the gene expression profiles of COVID-19 and sepsis patients were obtained from the Gene Expression Omnibus (GEO) database and compared to extract common differentially expressed genes (DEGs). Subsequently, common DEGs were used to investigate the genetic links between COVID-19 and sepsis. Based on enrichment analysis of common DEGs, many pathways closely related to inflammatory response were observed, such as Cytokine-cytokine receptor interaction pathway and NF-kappa B signaling pathway. In addition, protein-protein interaction networks and gene regulatory networks of common DEGs were constructed, and the analysis results showed that ITGAM may be a potential key biomarker base on regulatory analysis. Furthermore, a disease diagnostic model and risk prediction nomogram for COVID-19 were constructed using machine learning methods. Finally, potential therapeutic agents, including progesterone and emetine, were screened through drug-protein interaction networks and molecular docking simulations. We hope to provide new strategies for future research and treatment related to COVID-19 by elucidating the pathogenesis and genetic mechanisms between COVID-19 and sepsis.


Subject(s)
COVID-19 , Sepsis , Biomarkers , Computational Biology/methods , Critical Illness , Cytokines/genetics , Emetine , Gene Expression Profiling/methods , Humans , Molecular Docking Simulation , NF-kappa B/genetics , Progesterone , Receptors, Cytokine/genetics , SARS-CoV-2 , Sepsis/genetics , Sepsis/metabolism
6.
Commun Biol ; 5(1): 1179, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2133651

ABSTRACT

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.


Subject(s)
COVID-19 , Coronavirus 229E, Human , Humans , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2 , Antigens, Viral , Epitopes , Antibodies, Neutralizing
7.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.12.19.517879

ABSTRACT

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has presented numerous challenges to global health. The vaccines, including lipid-based nanoparticle mRNA, inactivated virus and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and are immensely helpful against the epidemic. Here, we first present an oral mRNA vaccine based on bovine milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor binding domain (RBD) as an immunogen. The results indicated that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptide in 293 cells in vitro and stimulated neutralizing antibodies against RBD in mice. These results indicated that bovine milk-derived exosome-based mRNA vaccine could serve as a new strategy for preventing SARS-CoV-2 infection. Meanwhile, it also can work as a new oral delivery system for mRNA. Keywords: bovine milk-derived exosomes; SARS-CoV-2; receptor binding domain; mRNA; oral vaccines; neutralizing antibody

8.
Nature Machine Intelligence ; 4(11):964-976, 2022.
Article in English | Web of Science | ID: covidwho-2121932

ABSTRACT

The effects of novel antibodies are hard to predict owing to the complex interactions between antibodies and antigens. Zhang and colleagues use a graph-based method to learn a dynamic representation that allows for predictions of neutralization activity and demonstrate the method by recommending probable antibodies for human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, influenza and dengue. Most natural and synthetic antibodies are 'unseen'. That is, the demonstration of their neutralization effects with any antigen requires laborious and costly wet-lab experiments. The existing methods that learn antibody representations from known antibody-antigen interactions are unsuitable for unseen antibodies owing to the absence of interaction instances. The DeepAAI method proposed herein learns unseen antibody representations by constructing two adaptive relation graphs among antibodies and antigens and applying Laplacian smoothing between unseen and seen antibodies' representations. Rather than using static protein descriptors, DeepAAI learns representations and relation graphs 'dynamically', optimized towards the downstream tasks of neutralization prediction and 50% inhibition concentration estimation. The performance of DeepAAI is demonstrated on human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, influenza and dengue. Moreover, the relation graphs have rich interpretability. The antibody relation graph implies similarity in antibody neutralization reactions, and the antigen relation graph indicates the relation among a virus's different variants. We accordingly recommend probable broad-spectrum antibodies against new variants of these viruses.

9.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2331958.v1

ABSTRACT

Background Cytokine release syndrome (CRS) is a life-threatening complication of chimeric antigen receptor T cell (CAR-T) therapy. Macrophages/ monocytes are mediators of CRS. Tripterygium glycosides is an immunomodulator which could inhibit macrophages/ monocytes in animal models.Methods Two patients with relapsed and refractory hematological malignancies developed CRS after receiving CAR-T therapy. They received short-term tripterygium glycosides orally.Results Both patients showed rapid mitigation of fever with evidently decrease in elevated inflammatory cytokines within 72 hours. The patients' monocytes diminished remarkably, while CAR-T cells were neglectably affected. Treatment of 30 ng/mL triptolide in ex vivo cultured patients' blood for 24 hours selectively deplete over half of monocytes. Single cell RNA sequencing suggested selective depletion of CD14+CD16+ monocytes with decreased pro-inflammatory cytokines.Conclusions The low-cost and orally available tripterygium glycosides could be a promising alternative for CAR-T induced CRS, as well as other diseases complicated with CRS, e.g., coronavirus disease 2019.

11.
Comput Struct Biotechnol J ; 20: 5713-5728, 2022.
Article in English | MEDLINE | ID: covidwho-2068856

ABSTRACT

Since COVID-19 emerged in 2019, significant levels of suffering and disruption have been caused on a global scale. Although vaccines have become widely used, the virus has shown its potential for evading immunities or acquiring other novel characteristics. Whether current drug treatments are still effective for people infected with Omicron remains unclear. Due to the long development cycles and high expense requirements of de novo drug development, many researchers have turned to consider drug repositioning in the search to find effective treatments for COVID-19. Here, we review such drug repositioning and combination efforts towards providing better handling. For potential drugs under consideration, aspects of both structure and function require attention, with specific categories of sequence, expression, structure, and interaction, the key parameters for investigation. For different data types, we show the corresponding differing drug repositioning methods that have been exploited. As incorporating drug combinations can increase therapeutic efficacy and reduce toxicity, we also review computational strategies to reveal drug combination potential. Taken together, we found that graph theory and neural network were the most used strategy with high potential towards drug repositioning for COVID-19. Integrating different levels of data may further improve the success rate of drug repositioning.

12.
Eur J Radiol Open ; 9: 100438, 2022.
Article in English | MEDLINE | ID: covidwho-2061087

ABSTRACT

Objectives: When diagnosing Coronavirus disease 2019(COVID-19), radiologists cannot make an accurate judgments because the image characteristics of COVID-19 and other pneumonia are similar. As machine learning advances, artificial intelligence(AI) models show promise in diagnosing COVID-19 and other pneumonias. We performed a systematic review and meta-analysis to assess the diagnostic accuracy and methodological quality of the models. Methods: We searched PubMed, Cochrane Library, Web of Science, and Embase, preprints from medRxiv and bioRxiv to locate studies published before December 2021, with no language restrictions. And a quality assessment (QUADAS-2), Radiomics Quality Score (RQS) tools and CLAIM checklist were used to assess the quality of each study. We used random-effects models to calculate pooled sensitivity and specificity, I2 values to assess heterogeneity, and Deeks' test to assess publication bias. Results: We screened 32 studies from the 2001 retrieved articles for inclusion in the meta-analysis. We included 6737 participants in the test or validation group. The meta-analysis revealed that AI models based on chest imaging distinguishes COVID-19 from other pneumonias: pooled area under the curve (AUC) 0.96 (95 % CI, 0.94-0.98), sensitivity 0.92 (95 % CI, 0.88-0.94), pooled specificity 0.91 (95 % CI, 0.87-0.93). The average RQS score of 13 studies using radiomics was 7.8, accounting for 22 % of the total score. The 19 studies using deep learning methods had an average CLAIM score of 20, slightly less than half (48.24 %) the ideal score of 42.00. Conclusions: The AI model for chest imaging could well diagnose COVID-19 and other pneumonias. However, it has not been implemented as a clinical decision-making tool. Future researchers should pay more attention to the quality of research methodology and further improve the generalizability of the developed predictive models.

13.
J Med Virol ; 2022 Sep 25.
Article in English | MEDLINE | ID: covidwho-2059520

ABSTRACT

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with high transmission rates and striking immune evasion have posed a serious challenge to the application of current first-generation SARS-CoV-2 vaccines. Other sarbecoviruses, such as SARS-CoV and SARS-related coronaviruses (SARSr-CoVs), have the potential to cause outbreaks in the future. These facts call for the development of variant-proof SARS-CoV-2, pan-sarbecovirus or pan-ß-CoV vaccines. Several novel vaccine platforms have been used to develop vaccines with broad-spectrum neutralizing antibody responses and protective immunity to combat the current SARS-CoV-2 and its variants, other sarbecoviruses, as well as other ß-CoVs, in the future. In this review, we discussed the major target antigens and protective efficacy of current SARS-CoV-2 vaccines and summarized recent advances in broad-spectrum vaccines against sarbecoviruses and ß-CoVs.

14.
Viruses ; 14(9)2022 09 16.
Article in English | MEDLINE | ID: covidwho-2043975

ABSTRACT

Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine ß-lactoglobulin (3HP-ß-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human papillomavirus (HPV) infections. Here, we show its efficacy in potently inhibiting infection by divergent influenza A and B viruses. Mechanistic studies suggest that 3HP-ß-LG binds, possibly through its negatively charged residues, to the receptor-binding domain in the hemagglutinin 1 (HA1) subunit in the HA of the influenza virus, thus inhibiting the attachment of the HA to sialic acid on host cells. The intranasal administration of 3HP-ß-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-ß-LG is highly stable when stored at 50 °C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-ß-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks.


Subject(s)
COVID-19 , HIV Fusion Inhibitors , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Animals , Antibodies, Viral , Cattle , Disease Outbreaks , Hemagglutinin Glycoproteins, Influenza Virus , Hemagglutinins , Humans , Influenza A Virus, H3N2 Subtype , Lactoglobulins/pharmacology , Mice , N-Acetylneuraminic Acid , Orthomyxoviridae Infections/prevention & control , SARS-CoV-2
15.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2034149

ABSTRACT

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with a high mortality rate. In clinical practice, we have noted that many critically ill or critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. In addition, it has been demonstrated that severe COVID-19 has some pathological similarities with sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted and neutrophil dysfunction. Considering the parallels between COVID-19 and non-SARS-CoV-2 induced sepsis (hereafter referred to as sepsis), the aim of this study was to analyze the underlying molecular mechanisms between these two diseases by bioinformatics and a systems biology approach, providing new insights into the pathogenesis of COVID-19 and the development of new treatments. Specifically, the gene expression profiles of COVID-19 and sepsis patients were obtained from the Gene Expression Omnibus (GEO) database and compared to extract common differentially expressed genes (DEGs). Subsequently, common DEGs were used to investigate the genetic links between COVID-19 and sepsis. Based on enrichment analysis of common DEGs, many pathways closely related to inflammatory response were observed, such as Cytokine-cytokine receptor interaction pathway and NF-kappa B signaling pathway. In addition, protein-protein interaction networks and gene regulatory networks of common DEGs were constructed, and the analysis results showed that ITGAM may be a potential key biomarker base on regulatory analysis. Furthermore, a disease diagnostic model and risk prediction nomogram for COVID-19 were constructed using machine learning methods. Finally, potential therapeutic agents, including progesterone and emetine, were screened through drug-protein interaction networks and molecular docking simulations. We hope to provide new strategies for future research and treatment related to COVID-19 by elucidating the pathogenesis and genetic mechanisms between COVID-19 and sepsis.

16.
J Med Virol ; 2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-2027382

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the currently ongoing coronavirus disease 2019 (COVID-19) pandemic, has posed a serious threat to global public health. Recently, several SARS-CoV-2 variants of concern (VOCs) have emerged and caused numerous cases of reinfection in convalescent COVID-19 patients, as well as breakthrough infections in vaccinated individuals. This calls for the development of broad-spectrum antiviral drugs to combat SARS-CoV-2 and its VOCs. Pan-coronavirus fusion inhibitors, targeting the conserved heptad repeat 1 (HR1) in spike protein S2 subunit, can broadly and potently inhibit infection of SARS-CoV-2 and its variants, as well as other human coronaviruses. In this review, we summarized the most recent development of pan-coronavirus fusion inhibitors, such as EK1, EK1C4, and EKL1C, and highlighted their potential application in combating current COVID-19 infection and reinfection, as well as future emerging coronavirus infectious diseases.

17.
J Appl Toxicol ; 42(10): 1688-1700, 2022 10.
Article in English | MEDLINE | ID: covidwho-2013548

ABSTRACT

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.


Subject(s)
COVID-19 , Water Pollutants, Chemical , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , COVID-19/drug therapy , Ecosystem , Embryo, Nonmammalian , Hepatocyte Nuclear Factor 1-beta/metabolism , Hepatocyte Nuclear Factor 1-beta/pharmacology , Larva , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/toxicity , Zebrafish , Zebrafish Proteins/metabolism
18.
Cell Discov ; 8(1): 88, 2022 Sep 08.
Article in English | MEDLINE | ID: covidwho-2008268

ABSTRACT

The receptor-binding domain (RBD) in S1 subunit and heptad repeat 1 (HR1) domain in S2 subunit of SARS-CoV-2 spike (S) protein are the targets of neutralizing antibodies (nAbs) and pan-coronavirus (CoV) fusion inhibitory peptides, respectively. However, neither nAb- nor peptide-based drugs can be used orally. In this study, we screened a one-bead-two-compound (OBTC) cyclic γ-AApeptide library against SARS-CoV-2 S protein and identified a hit: S-20 with potent membrane fusion inhibitory activity, but moderate selectivity index (SI). After modification, one derivative, S-20-1, exhibited improved fusion inhibitory activity and SI (>1000). S-20-1 could effectively inhibit infection by pseudotyped and authentic SARS-CoV-2 and pseudotyped variants of concern (VOCs), including B.1.617.2 (Delta) and B.1.1.529 (Omicron), as well as MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-229E, and HCoV-NL63. It could also inhibit infection of a pseudotyped SARS-related coronavirus WIV1 (SARSr-CoV-WIV1) from bats. Intranasal application of S-20-1 to mice before or after challenge with HCoV-OC43 or SARS-CoV-2 provided significant protection from infection. Importantly, S-20-1 was highly resistant to proteolytic degradation, had long half-life, and possessed favorable oral bioavailability. Mechanistic studies suggest that S-20-1 binds with high affinity to RBD in S1 and HR1 domain in S2 of SARS-CoV-2 S protein. Thus, with its pan-CoV fusion and entry inhibitory activity by targeting two sites in S protein, desirable half-life, and promising oral bioavailability, S-20-1 is a potential candidate for further development as a novel therapeutic and prophylactic drug against infection by SARS-CoV-2 and its variants, as well as future emerging and reemerging CoVs.

19.
European journal of radiology open ; 9:100438-100438, 2022.
Article in English | EuropePMC | ID: covidwho-1998887

ABSTRACT

Objectives When diagnosing Coronavirus disease 2019(COVID‐19), radiologists cannot make an accurate judgments because the image characteristics of COVID‐19 and other pneumonia are similar. As machine learning advances, artificial intelligence(AI) models show promise in diagnosing COVID-19 and other pneumonias. We performed a systematic review and meta-analysis to assess the diagnostic accuracy and methodological quality of the models. Methods We searched PubMed, Cochrane Library, Web of Science, and Embase, preprints from medRxiv and bioRxiv to locate studies published before December 2021, with no language restrictions. And a quality assessment (QUADAS-2), Radiomics Quality Score (RQS) tools and CLAIM checklist were used to assess the quality of each study. We used random-effects models to calculate pooled sensitivity and specificity, I2 values to assess heterogeneity, and Deeks' test to assess publication bias. Results We screened 32 studies from the 2001 retrieved articles for inclusion in the meta-analysis. We included 6737 participants in the test or validation group. The meta-analysis revealed that AI models based on chest imaging distinguishes COVID-19 from other pneumonias: pooled area under the curve (AUC) 0.96 (95 % CI, 0.94–0.98), sensitivity 0.92 (95 % CI, 0.88–0.94), pooled specificity 0.91 (95 % CI, 0.87–0.93). The average RQS score of 13 studies using radiomics was 7.8, accounting for 22 % of the total score. The 19 studies using deep learning methods had an average CLAIM score of 20, slightly less than half (48.24 %) the ideal score of 42.00. Conclusions The AI model for chest imaging could well diagnose COVID-19 and other pneumonias. However, it has not been implemented as a clinical decision-making tool. Future researchers should pay more attention to the quality of research methodology and further improve the generalizability of the developed predictive models.

20.
Clin Infect Dis ; 2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1985050

ABSTRACT

BACKGROUND: Early antiviral therapy was effective in the treatment of COVID-19. We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients. METHODS: We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200mg loading on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point was the time to complete alleviation of symptoms (NEWS2 = 0). RESULTS: Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom-onset was 3 days. The median age was 65 years and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary-endpoint, the combination-group was significantly quicker to NEWS2 = 0 (4 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upon follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), was the most significant independent factor associated with NEWS2 = 0 on day 4. CONCLUSIONS: Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.

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