Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 101
Filter
1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1795805

ABSTRACT

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Subject(s)
COVID-19/blood , Hyperglycemia/blood , Insulin Resistance , Lipid Metabolism , Lipids/blood , SARS-CoV-2/metabolism , Adult , Aged , Biomarkers/blood , COVID-19/complications , Female , Humans , Hyperglycemia/etiology , Male , Middle Aged , Retrospective Studies
2.
Signal Transduct Target Ther ; 7(1): 114, 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1778593

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal/chemistry , Antibodies, Viral/chemistry , COVID-19 , Cryoelectron Microscopy , Humans , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331897

ABSTRACT

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

4.
J Virol ; : e0024922, 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1765081

ABSTRACT

The highly contagious and fast-spreading omicron variant of SARS-CoV-2 infects the respiratory tracts efficiently. The receptor-binding domain (RBD) of the omicron spike protein recognizes human angiotensin-converting enzyme 2 (ACE2) as its receptor and plays a critical role in the tissue tropism of SARS-CoV-2. Here, we showed that the omicron RBD (strain BA.1) binds to ACE2 more strongly than does the prototypic RBD from the original Wuhan strain. We also measured how individual omicron mutations affect ACE2 binding. We further determined the crystal structure of the omicron RBD (engineered to facilitate crystallization) complexed with ACE2 at 2.6 Å. The structure shows that omicron mutations caused significant structural rearrangements of two mutational hot spots at the RBD/ACE2 interface, elucidating how each omicron mutation affects ACE2 binding. The enhanced ACE2 binding by the omicron RBD may facilitate the omicron variant's infection of the respiratory tracts where ACE2 expression level is low. Our study provides insights into the receptor recognition and tissue tropism of the omicron variant. IMPORTANCE Despite the scarcity of the SARS-CoV-2 receptor-human angiotensin-converting enzyme 2 (ACE2)-in the respiratory tract, the omicron variant efficiently infects the respiratory tract, causing rapid and widespread infections of COVID-19. The omicron variant contains extensive mutations in the receptor-binding domain (RBD) of its spike protein that recognizes human ACE2. Here, using a combination of biochemical and X-ray crystallographic approaches, we showed that the omicron RBD binds to ACE2 with enhanced affinity and also elucidated the role of each of the omicron mutations in ACE2 binding. The enhanced ACE2 binding by the omicron RBD may contribute to the omicron variant's new viral tropism in the respiratory tract despite the low level of ACE2 expression in the tissue. These findings help us to understand tissue tropism of the omicron variant and shed light on the molecular evolution of SARS-CoV-2.

5.
Preprint in English | bioRxiv | ID: ppbiorxiv-486173

ABSTRACT

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329783

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates ( NCT05069129 ). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67;95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03;95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

7.
Nat Commun ; 13(1): 1214, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1730288

ABSTRACT

The omicron variant of SARS-CoV-2 has been spreading rapidly across the globe. The virus-surface spike protein plays a critical role in the cell entry and immune evasion of SARS-CoV-2. Here we determined the 3.0 Å cryo-EM structure of the omicron spike protein ectodomain. In contrast to the original strain of SARS-CoV-2 where the receptor-binding domain (RBD) of the spike protein takes a mixture of open ("standing up") and closed ("lying down") conformations, the omicron spike molecules are predominantly in the open conformation, with one upright RBD ready for receptor binding. The open conformation of the omicron spike is stabilized by enhanced inter-domain and inter-subunit packing, which involves new mutations in the omicron strain. Moreover, the omicron spike has undergone extensive mutations in RBD regions where known neutralizing antibodies target, allowing the omicron variant to escape immune surveillance aimed at the original viral strain. The stable open conformation of the omicron spike sheds light on the cell entry and immune evasion mechanisms of the omicron variant.


Subject(s)
COVID-19/virology , SARS-CoV-2/chemistry , SARS-CoV-2/ultrastructure , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/ultrastructure , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Cryoelectron Microscopy , Humans , Immune Evasion/genetics , Models, Molecular , Mutation , Pandemics , Protein Conformation , Protein Domains/genetics , Protein Domains/immunology , Protein Interaction Domains and Motifs/genetics , Protein Interaction Domains and Motifs/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Virus Internalization
8.
Preprint in English | medRxiv | ID: ppmedrxiv-22272062

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

9.
Cell Discov ; 8(1): 17, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1692628

ABSTRACT

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

10.
J Virol ; 96(3): e0184221, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1691423

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) is a beta coronavirus that emerged in 2012, causing severe pneumonia and renal failure. MERS-CoV encodes five accessory proteins. Some of them have been shown to interfere with host antiviral immune response. However, the roles of protein 8b in innate immunity and viral virulence was rarely studied. Here, we introduced individual MERS-CoV accessory protein genes into the genome of an attenuated murine coronavirus (Mouse hepatitis virus, MHV), respectively, and found accessory protein 8b could enhance viral replication in vivo and in vitro and increase the lethality of infected mice. RNA-seq analysis revealed that protein 8b could significantly inhibit type I interferon production (IFN-I) and innate immune response in mice infected with MHV expressing protein 8b. We also found that MERS-CoV protein 8b could initiate from multiple internal methionine sites and at least three protein variants were identified. Residues 1-23 of protein 8b was demonstrated to be responsible for increased virulence in vivo. In addition, the inhibitory effect on IFN-I of protein 8b might not contribute to its virulence enhancement as aa1-23 deletion did not affect IFN-I production in vitro and in vivo. Next, we also found that protein 8b was localized to the endoplasmic reticulum (ER)/Golgi membrane in infected cells, which was disrupted by C-terminal region aa 88-112 deletion. This study will provide new insight into the pathogenesis of MERS-CoV infection. IMPORTANCE Multiple coronaviruses (CoV) cause severe respiratory infections and become global public health threats such as SARS-CoV, MERS-CoV, and SARS-CoV-2. Each coronavirus contains different numbers of accessory proteins which show high variability among different CoVs. Accessory proteins are demonstrated to play essential roles in pathogenesis of CoVs. MERS-CoV contains 5 accessory proteins (protein 3, 4a, 4b, 5, 8b), and deletion of all four accessory proteins (protein 3, 4a, 4b, 5), significantly affects MERS-CoV replication and pathogenesis. However, whether ORF8b also regulates MERS-CoV infection is unknown. Here, we constructed mouse hepatitis virus (MHV) recombinant virus expressing MERS-CoV protein 8b and demonstrated protein 8b could significantly enhance the virulence of MHV, which is mediated by N-terminal domain of protein 8b. This study will shed light on the understanding of pathogenesis of MERS-CoV infection.


Subject(s)
Middle East Respiratory Syndrome Coronavirus/physiology , Murine hepatitis virus/physiology , Protein Interaction Domains and Motifs , Viral Regulatory and Accessory Proteins/genetics , Animals , Coronavirus Infections/immunology , Coronavirus Infections/virology , Host-Pathogen Interactions/immunology , Immunity, Innate , Mice , Mortality , Viral Regulatory and Accessory Proteins/chemistry , Viral Tropism , Virulence/genetics , Virulence Factors/genetics
11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323635

ABSTRACT

Objectives: To investigate the appetite of COVID-19 patients treated in a makeshift hospital and to evaluate the effectiveness of abdominal massage and ST-36 (Zusanli) acupressure in improving their appetite. Design: Randomized controlled trial. Methods: This study was performed between February 15 and March 2, 2020, in a sports centre makeshift hospital in Wuhan, China. The appetite of 110 COVID-19 patients was assessed using a mobile app-based Simplified Nutritional Appetite Questionnaire (SNAQ). The experimental and control groups, 55 patients each, were randomized using a prepared randomization checklist. Through video guidance and on-the-spot instruction, patients in the experimental group mastered the methods of abdominal massage and ST-36 (Zusanli) acupressure and implemented the intervention for 7 days by themselves. The appetite of the patients was assessed again after intervention. Results: : In a total of 110 participants, 43 (39.1%) patients suffered from a poor appetite. A positive correlation between poor appetite and older age as well as fever was observed ( p <0.05). In the experimental group, the SNAQ scores were significantly increased (14.07±2.46 vs 15.55±1.77, p =0.0004), and the proportion of patients with a poor appetite was markedly reduced after the intervention (41.8% vs 10.9%, p =0.0002). Compared with the control group, the rate of poor appetite in the experimental group was significantly decreased postintervention (27.3% vs 10.9%, p =0.029). Conclusion: In COVID-19 patients, a poor appetite may be correlated with older age and fever. Abdominal massage and ST-36 (Zusanli) acupressure are applicable and effective in improving the appetite of COVID-19 patients during isolation treatment. Trial registration: Chinese clinical trial registry (ChiCTR2000033261), the trial was registered retrospectively.

12.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323574

ABSTRACT

This study, using a virus-free mouse model, explores the pathogenic roles of certain antibodies specific to the spike proteins of highly pathogenic coronaviruses such as the COVID-19 and the SARS-CoV viruses. Our data showed that these pathogenic antibodies, through a mechanism of Antibody Dependent Auto-Attack (ADAA), target and bind to host vulnerable cells or tissues such as damaged lung epithelium cells, initiate a self-attack immune response, and lead to serious conditions including ARDS, cytokine release, and death. Moreover, the pathogenic antibodies also induced inflammation and hemorrhage of the kidneys, brain, and heart. Furthermore, the pathogenic antibodies can bind to unmatured fetal tissues and cause abortions, postpartum labors, still births, and neonatal deaths of pregnant mice. Novel clinical interventions, through disrupting the host-binding of these pathogenic antibodies, can be developed to fight the COVID-19 pandemic. In addition, the new concept of ADAA explored by this study may be applicable to other infectious diseases, such as the highly pathogenic influenza infections. It should be noted that the majority of anti-spike antibodies are non-pathogenic, as only 2 of 7 monoclonal antibodies tested showed significant pathogenic effects.

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321206

ABSTRACT

A novel SARS-like coronavirus (2019-nCoV) recently emerged from Wuhan, China and is quickly spreading in humans. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infection, pathogenesis, and host range. 2019-nCoV and SARS-CoV recognize the same host receptor ACE2. Here we determined the crystal structure of 2019-nCoV receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex of human ACE2.Compared with SARS-CoV, an ACE2-binding ridge in 2019-nCoV RBD takes more compact conformations, causing structural changes at the RBD/ACE2 interface. Adaptive to these structural changes, several mutations in 2019-nCoV RBD enhance ACE2- binding affinity, contributing to the high infectivity of 2019-CoV. These mutations also reveal the molecular mechanisms of the animal-to-human transmission of 2019-nCoV. Alarmingly, a single N439R mutation in 2019-nCoV RBD further enhances its ACE2- binding affinity, indicating possible future evolution of 2019-nCoV in humans. This study sheds light on the epidemiology and evolution of 2019-nCoV, and provides guidance for intervention strategies targeting receptor recognition by 2019-nCoV.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315565

ABSTRACT

Background: The emerging virus is rampaging globally. Great efforts are needed to cut down the transmission. Clinical characteristics of infected children have been described previously. No meta-analysis on this subgroup have been published. Methods: : A single-arm meta-analysis was conducted. We searched PubMed, Google Scholar, Web of Science, three preprints websites and other Chinese database for studies presenting characteristics of children confirmed with Coronavirus Disease 2019 (COVID-19) from December 1 2019 to March 28 2020. Quality Appraisal of Case Series Studies Checklist was used to assess quality and publication bias was analyzed by Egger’s test. Random-effect model was used to calculate the pooled incidence rate (IR) or mean difference (MD) with 95% confidence intervals (CI), or a fixed model instead when I 2 <50%. We conducted subgroup analysis according to geographic region. Additionally, we searched United Nations Educational Scientific and Cultural Organization to see how different countries act to the education disruption in COVID-19. Results: : 14 studies (two unpublished) with 361 pediatric patients were included. The mean age was 5.5 (95% CI: 0.344–0.765) years old. 23.4% of children were asymptomatic (95%CI: 0.112-0.377). 32.3% (95%CI: 0.163-0.503) showed normal computed tomography imaging, besides, four children were admitted in intensive care units (0, 95%CI: 0.000-0.001) and one death was reported (0, 95%CI: 0.000-0.001). Up to 191 countries have implemented nationwide school closures, affecting over 91% of the world’s students. Conclusion: Children were also susceptible to SARS-CoV-2, while critical cases or death were rare. Characterized by mild presentation, the dilemma that children may become a potential spreader in the pandemic, while strict managements like prolonged school closures, may undermine their well-beings. Thus, the public policies are facing challenge.

15.
Food Environ Virol ; 14(1): 101-104, 2022 03.
Article in English | MEDLINE | ID: covidwho-1653805

ABSTRACT

To prevent the spread of SARS-CoV-2 in cold-chain transportation in China, we developed specific cryogenic disinfectants. Carrier tests were performed against SARS-CoV-2 at - 20 °C for the four cryogenic disinfectants developed and qRT-PCR was used to test the virus RNA. Peracetic acid, chlorine disinfectants (two different concentrations), and quaternary ammonium disinfectant with their antifreeze can all inactivate SARS-CoV-2 in 5 min at - 20 °C. However, after 2-3 h of exposure, only chlorine disinfectant could destroy SARS-CoV-2 RNA. The viruses treated with peracetic acid and quaternary disinfectants showed positive Ct values even after 3 h detected with qRT-PCR. The conclusion was that the cold-chain disinfectants we tested could inactivate SARS-CoV-2 quickly and effectively, but only chlorine disinfectants could destroy nucleic acids in 3 h. Our study also illustrated that using qRT-PCR detection of viral nucleic acids to assess disinfection was inappropriate.


Subject(s)
COVID-19 , Disinfectants , COVID-19/prevention & control , Disinfectants/pharmacology , Disinfection , Humans , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2 , Temperature
17.
Genome Res ; 32(2): 228-241, 2022 02.
Article in English | MEDLINE | ID: covidwho-1642462

ABSTRACT

The pathogenesis of COVID-19 is still elusive, which impedes disease progression prediction, differential diagnosis, and targeted therapy. Plasma cell-free RNAs (cfRNAs) carry unique information from human tissue and thus could point to resourceful solutions for pathogenesis and host-pathogen interactions. Here, we performed a comparative analysis of cfRNA profiles between COVID-19 patients and healthy donors using serial plasma. Analyses of the cfRNA landscape, potential gene regulatory mechanisms, dynamic changes in tRNA pools upon infection, and microbial communities were performed. A total of 380 cfRNA molecules were up-regulated in all COVID-19 patients, of which seven could serve as potential biomarkers (AUC > 0.85) with great sensitivity and specificity. Antiviral (NFKB1A, IFITM3, and IFI27) and neutrophil activation (S100A8, CD68, and CD63)-related genes exhibited decreased expression levels during treatment in COVID-19 patients, which is in accordance with the dynamically enhanced inflammatory response in COVID-19 patients. Noncoding RNAs, including some microRNAs (let 7 family) and long noncoding RNAs (GJA9-MYCBP) targeting interleukin (IL6/IL6R), were differentially expressed between COVID-19 patients and healthy donors, which accounts for the potential core mechanism of cytokine storm syndromes; the tRNA pools change significantly between the COVID-19 and healthy group, leading to the accumulation of SARS-CoV-2 biased codons, which facilitate SARS-CoV-2 replication. Finally, several pneumonia-related microorganisms were detected in the plasma of COVID-19 patients, raising the possibility of simultaneously monitoring immune response regulation and microbial communities using cfRNA analysis. This study fills the knowledge gap in the plasma cfRNA landscape of COVID-19 patients and offers insight into the potential mechanisms of cfRNAs to explain COVID-19 pathogenesis.


Subject(s)
COVID-19 , Cell-Free Nucleic Acids , RNA/blood , COVID-19/blood , COVID-19/genetics , Cell-Free Nucleic Acids/blood , Cytokine Release Syndrome , Humans , SARS-CoV-2
19.
PLoS One ; 17(1): e0261537, 2022.
Article in English | MEDLINE | ID: covidwho-1639476

ABSTRACT

Mental health is a major public health issue that affects social development. This study aims to explore the psychological state of residents of Hainan Island and its influencing factors during the COVID-19 pandemic and to provide a scientific basis for the formulation of psychological counseling measures to be used after the pandemic. We used the nonprobability snowball sampling method to conduct an online survey from February 21 to February 28, 2020, and collected a sample of 533 respondents. Using a binary logistic regression model and network analysis, the psychological state of residents and the main factors were analyzed during the concentrated outbreak of COVID-19 (from January 20 to February 16, 2020). The study found that during the pandemic, 92.7% of the respondents were in a poor state of mind, and 54.2% experienced severe psychological stress. The mental state is spatially expressed as a pattern of "high in the middle and low in the surroundings." Second, within the four-week sample, the overall psychological tension showed an inverted U-shaped trend. Respondents feeling stressed were most common in the second week, when they accounted for 87.99% of the total. Third, individual characteristics such as gender, age, fixed expenditure, and family size significantly affect the mental state. Women, the elderly, residents with fixed expenditures, and residents with large families are at greater risk of psychological stress. Finally, external factors such as the distance between residents and the location of cases and the node degree of the pandemic transmission network have a significant impact on the psychological state. However, residents in the least developed areas of Hainan Island, which are far away from active cases and have a low node degree, are more prone to psychological pressure. The government needs to pay special attention to these groups when constructing a long-term mechanism of psychological crisis intervention and increase public health resource investment in underdeveloped areas.


Subject(s)
COVID-19/psychology , Mental Health , Stress, Psychological/psychology , Adolescent , Adult , Aged , Aged, 80 and over , China , Cross-Sectional Studies , Female , Health Surveys , Humans , Male , Middle Aged , Pandemics , Young Adult
20.
Nanoscale ; 14(4): 1054-1074, 2022 Jan 27.
Article in English | MEDLINE | ID: covidwho-1621288

ABSTRACT

COVID-19 has caused a global pandemic and millions of deaths. It is imperative to develop effective countermeasures against the causative viral agent, SARS-CoV-2 and its many variants. Vaccines and therapeutic antibodies are the most effective approaches for preventing and treating COVID-19, respectively. SARS-CoV-2 enters host cells through the activities of the virus-surface spike (S) protein. Accordingly, the S protein is a prime target for vaccines and therapeutic antibodies. Dealing with particles with dimensions on the scale of nanometers, nanotechnology has emerged as a critical tool for rapidly designing and developing safe, effective, and urgently needed vaccines and therapeutics to control the COVID-19 pandemic. For example, nanotechnology was key to the fast-track approval of two mRNA vaccines for their wide use in human populations. In this review article, we first explore the roles of nanotechnology in battling COVID-19, including protein nanoparticles (for presentation of protein vaccines), lipid nanoparticles (for formulation with mRNAs), and nanobodies (as unique therapeutic antibodies). We then summarize the currently available COVID-19 vaccines and therapeutics based on nanotechnology.


Subject(s)
Antibodies/therapeutic use , COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19/therapy , Humans , Liposomes , Nanoparticles , Nanotechnology , Pandemics
SELECTION OF CITATIONS
SEARCH DETAIL