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1.
The Journal of infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1824578

ABSTRACT

Isolated reports of new-onset diabetes in patients with COVID-19 have led researchers to hypothesise that SARS-CoV-2 infects the human exocrine and endocrine pancreatic cells ex vivo and in vivo. However, existing research lacks experimental evidence indicating that SARS-CoV-2 can infect pancreatic tissue. Here, we found that cats infected with a high dose of SARS-CoV-2 exhibited hyperglycaemia. We also detected SARS-CoV-2 RNA in the pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in the islet cells. SARS-CoV-2 NP and Spike proteins were primarily detected in Glu+ cells, and most Glu+ cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that the blood glucose levels of immunised cats did not increase post-challenge. Our data indicate the cat pancreas as a SARS-CoV-2 target and suggest that the infection of Glu+ cells could contribute to the metabolic dysregulation observed in SARS-CoV-2-infected cats.

2.
Data and Information Management ; : 100005, 2022.
Article in English | ScienceDirect | ID: covidwho-1796993

ABSTRACT

To better promote information service and fight the infodemic, this paper investigated the difficulties that Chinese college students encountered in information seeking during the COVID-19 pandemic. We collected data in two stages. In the first stage in November 2020, we collected data from the Foundation of Information Science course. 54 college students who took the course completed an assignment to illustrate their information needs and difficulties during the pandemic. In the second stage in March 2021, trough convenience sampling we conducted an online survey by WenJuanXing. The participants were required to answer the same question as the question in the first stage. We collected 204 valid responses. Then, based on the search task difficulty reason scheme proposed by Liu, Kim, and Creel (2015) (denoted LKC15), we used content analysis to code the responses to analyze the difficulties that Chinese students encountered. LKC15’s difficulty reasons were classified from three aspects: user, task, and user-task interaction. The findings indicated that 14 of the 21 difficulty reasons in LKC15 were identified in this study. Moreover, we added 17 new Difficulty reasons to revise the scheme. The difficulty reasons of user-task interaction were mentioned most frequently. In terms of user-task interaction, the difficulty reasons related to document features were mentioned most frequently, followed by the search results. Finally, it provided some suggestions and discussed the directions for future study.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-313436

ABSTRACT

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312713

ABSTRACT

Background: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Methods: We generated a mouse-adapted strain SARS-CoV-2 by serial passages in the lung of BALB/c mice. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments demonstrated that two mutations in RBD significantly increased its binding affinity towards mouse ACE2. Significantly, TLR7/8 agonist Resiquimod block SARS-CoV-2 in vitro and in vivo. Findings: We adapted a wild-type SARS-CoV-2 by serial passages in the lung of BALB/c mice. The mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, The TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge, demonstrating this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies. Interpretation: We found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies, especially in determining the immunopathological consequences of any intervention. This study also verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo.Funding Statement: This research was funded by Emergency Science and Technology Project of Hubei Province(2020FCA046)and Independent Science and Technology Innovation Fund of Huazhong Agricultural University in 2020 (2662020PY002).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: The animal experiments were approved by the Research Ethics Committee, Huazhong Agricultural University, Hubei, China (HZAUMO-2020-0007). All the animal experiments were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals from the Research Ethics Committee, Huazhong Agricultural University, Hubei, China.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312623

ABSTRACT

Essential workers such as medical workers and police officers have been playing crucial roles in the fight against the COVID-19 pandemic, and are under heavy stress both physically and mentally. The goal of the present study was to develop a novel nature-based intervention to promote their well-being. A representative sample of essential workers in China was recruited for a five-day intervention program, and were randomly assigned to two groups. The experimental group watched two-minute video clips of natural scenes every day, while the control group watched urban scenes. Results indicated that after five days, the natural stimuli intervention yielded overall improvements in various indices of subjective well-being. Furthermore, analyses of nested longitudinal data confirmed that everyday nature stimuli exposure provided both immediate and cumulative restorative benefits. The proposed natural-based intervention is brief and easy-to-use, offering a cost-efficient psychological booster to promote subjective well-being of essential workers during this crisis time.

6.
J Environ Psychol ; 79: 101745, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1561223

ABSTRACT

Essential workers such as medical workers and police officers are first-line fighters during public-health crises, such as COVID-19 pandemic. Every time, they are under heavy stress both physically and mentally. The goal of the present study was to develop a novel nature-based intervention to promote their well-being. A representative sample of essential workers in China was recruited for a five-day intervention program, and were randomly assigned to two groups. The experimental group watched 2-min video clips of natural scenes every day, while the control group watched urban scenes. Results indicated that after five days, the natural stimuli intervention yielded overall improvements in various indices of subjective well-being. Furthermore, analyses of nested longitudinal data confirmed that everyday nature stimuli exposure provided both immediate and repeated restorative benefits. The proposed natural-based intervention is brief and easy-to-use, offering a cost-efficient psychological booster to promote subjective well-being of essential workers during this crisis time.

7.
IEEE J Biomed Health Inform ; 26(4): 1737-1748, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1494300

ABSTRACT

Patients experience various symptoms when they haveeither acute or chronic diseases or undergo some treatments for diseases. Symptoms are often indicators of the severity of the disease and the need for hospitalization. Symptoms are often described in free text written as clinical notes in the Electronic Health Records (EHR) and are not integrated with other clinical factors for disease prediction and healthcare outcome management. In this research, we propose a novel deep language model to extract patient-reported symptoms from clinical text. The deep language model integrates syntactic and semantic analysis for symptom extraction and identifies the actual symptoms reported by patients and conditional or negation symptoms. The deep language model can extract both complex and straightforward symptom expressions. We used a real-world clinical notes dataset to evaluate our model and demonstrated that our model achieves superior performance compared to three other state-of-the-art symptom extraction models. We extensively analyzed our model to illustrate its effectiveness by examining each component's contribution to the model. Finally, we applied our model on a COVID-19 tweets data set to extract COVID-19 symptoms. The results show that our model can identify all the symptoms suggested by the Center for Disease Control (CDC) ahead of their timeline and many rare symptoms.


Subject(s)
COVID-19 , Social Media , Electronic Health Records , Humans , Language , Natural Language Processing
8.
Bio Protoc ; 11(16): e4128, 2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1464157

ABSTRACT

Analyzing cellular structures and the relative location of molecules is essential for addressing biological questions. Super-resolution microscopy techniques that bypass the light diffraction limit have become increasingly popular to study cellular molecule dynamics in situ. However, the application of super-resolution imaging techniques to detect small RNAs (sRNAs) is limited by the choice of proper fluorophores, autofluorescence of samples, and failure to multiplex. Here, we describe an sRNA-PAINT protocol for the detection of sRNAs at nanometer resolution. The method combines the specificity of locked nucleic acid probes and the low background, precise quantitation, and multiplexable characteristics of DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT). Using this method, we successfully located sRNA targets that are important for development in maize anthers at sub-20 nm resolution and quantitated their exact copy numbers. Graphic abstract: Multiplexed sRNA-PAINT. Multiple Vetting and Analysis of RNA for In Situ Hybridization (VARNISH) probes with different docking strands (i.e., a, b, …) will be hybridized to samples. The first probe will be imaged with the a* imager. The a* imager will be washed off with buffer C, and then the sample will be imaged with b* imager. The wash and image steps can be repeated sequentially for multiplexing.

9.
JAMA ; 323(16): 1582-1589, 2020 04 28.
Article in English | MEDLINE | ID: covidwho-1453469

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. Objective: To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Design, Setting, and Participants: Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Exposures: Patients received transfusion with convalescent plasma with a SARS-CoV-2-specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Main Outcomes and Measures: Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. Results: All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2-specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. Conclusions and Relevance: In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.


Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiratory Distress Syndrome/therapy , Adult , Aged , Antibodies, Viral/blood , Antiviral Agents/therapeutic use , Blood Donors , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Critical Illness , Female , Glucocorticoids/therapeutic use , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Methylprednisolone/therapeutic use , Middle Aged , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/physiopathology , SARS-CoV-2
10.
Nat Commun ; 12(1): 5695, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1442780

ABSTRACT

The dynamics of SARS-CoV-2 RNA structure and their functional relevance are largely unknown. Here we develop a simplified SPLASH assay and comprehensively map the in vivo RNA-RNA interactome of SARS-CoV-2 genome across viral life cycle. We report canonical and alternative structures including 5'-UTR and 3'-UTR, frameshifting element (FSE) pseudoknot and genome cyclization in both cells and virions. We provide direct evidence of interactions between Transcription Regulating Sequences, which facilitate discontinuous transcription. In addition, we reveal alternative short and long distance arches around FSE. More importantly, we find that within virions, while SARS-CoV-2 genome RNA undergoes intensive compaction, genome domains remain stable but with strengthened demarcation of local domains and weakened global cyclization. Taken together, our analysis reveals the structural basis for the regulation of replication, discontinuous transcription and translational frameshifting, the alternative conformations and the maintenance of global genome organization during the whole life cycle of SARS-CoV-2, which we anticipate will help develop better antiviral strategies.


Subject(s)
Frameshifting, Ribosomal/genetics , Genome, Viral/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Animals , COVID-19/virology , Chlorocebus aethiops , Humans , RNA-Seq , Transcription, Genetic , Vero Cells , Virus Replication/genetics
12.
Nature ; 594(7862): 234-239, 2021 06.
Article in English | MEDLINE | ID: covidwho-1269388

ABSTRACT

Loss of gut microbial diversity1-6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.


Subject(s)
Bacteria/isolation & purification , Biodiversity , Biological Evolution , Feces/microbiology , Gastrointestinal Microbiome , Genome, Bacterial/genetics , Host Microbial Interactions , Anti-Bacterial Agents/administration & dosage , Bacteria/classification , Bacteria/genetics , Chronic Disease , Developed Countries , Developing Countries , Diet, Western , History, Ancient , Humans , Industrial Development/trends , Methanobrevibacter/classification , Methanobrevibacter/genetics , Methanobrevibacter/isolation & purification , Mexico , Sedentary Behavior , Southwestern United States , Species Specificity , Symbiosis
13.
Int J Med Sci ; 18(12): 2545-2550, 2021.
Article in English | MEDLINE | ID: covidwho-1248381

ABSTRACT

Objectives: The epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been researched. However, the prevalence of repositivity by real-time PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. Methods: A retrospective study was conducted involving 599 discharged patients with COVID-19 in a single medical centre. The clinical features of patients during their hospitalization and 14-day post-discharge quarantine were collected. Results: A total of 122 patients (20.4%) out of 599 patients retested positive after discharge. Specifically, 94 (15.7%) retested positive within 24 h of discharge, and another 28 patients (4.7%) were repositive on day 7 after discharge, although none showed any clinical symptomatic recurrence. Both repositives and non­repositives have similar patterns of IgG and IgM. Notably, the length of hospitalization of non-repositive patients was longer than that of 24-h repositive patients and 7-day repositive patients. In addition, the length of hospitalization of 24-h repositive patients was shorter than that of 7-day repositive patients, indicating that the length of hospitalization was also a determinant of viral shedding. Conclusion: Our study provides further information for improving the management of recovered and discharged patients, and further studies should be performed to elucidate the infectiveness of individuals with prolonged or RNA repositivity.


Subject(s)
Aftercare/statistics & numerical data , COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Adolescent , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Length of Stay/statistics & numerical data , Male , Middle Aged , Patient Discharge , RNA, Viral/isolation & purification , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Severity of Illness Index , Virus Shedding/immunology , Young Adult
14.
Transbound Emerg Dis ; 69(2): 591-597, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1241029

ABSTRACT

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis and economic losses. Although several cases of cats and dogs infected with SARS-CoV-2 have been reported during this outbreak, the prevalence of SARS-CoV-2 in dog and its transmission among other companion animals are still unknown. Here, we report an extensive serological study of SARS-CoV-2 infection in dogs in Wuhan and analyse the infection rates at different stages of the pandemic outbreak. A total of 946 dogs serum samples were collected from Wuhan, of which 36 samples were obtained prior to the pandemic outbreak. Indirect enzyme-linked immunosorbent assay (ELISA) showed that 16 sera collected during the outbreak were detected as positive through the receptor-binding domain (RBD) of SARS-CoV-2. Of these 16 sera, 10 exhibited measurable SARS-CoV-2-specific neutralizing antibodies whose titres ranged from 1/20 to 1/180. No serological cross-reactivity was detected between SARS-CoV-2 and canine coronavirus (CCV). Furthermore, with the effective control of the outbreak, a decrease in the SARS-CoV-2 seropositive dog number was observed. Our results suggest that SARS-CoV-2 has infected companion dogs during the outbreak, and that COVID-19 patient families have a higher risk of dog infection. Our findings deepen our understanding of the infection of SARS-CoV-2 in dogs and provide an important reference for prevention of COVID-19.


Subject(s)
COVID-19 , Cat Diseases , Dog Diseases , Animals , Antibodies, Viral , COVID-19/epidemiology , COVID-19/veterinary , Cats , Dog Diseases/epidemiology , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Humans , Pandemics , SARS-CoV-2
15.
EBioMedicine ; 67: 103381, 2021 May.
Article in English | MEDLINE | ID: covidwho-1228017

ABSTRACT

BACKGROUND: An ideal animal model to study SARS-coronavirus 2 (SARS-CoV-2) pathogenesis and evaluate therapies and vaccines should reproduce SARS-CoV-2 infection and recapitulate lung disease like those seen in humans. The angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, but mice are resistant to the infection because their ACE2 is incompatible with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein . METHODS: SARS-CoV-2 was passaged in BALB/c mice to obtain mouse-adapted virus strain. Complete genome deep sequencing of different generations of viruses was performed to characterize the dynamics of the adaptive mutations in SARS-CoV-2. Indirect immunofluorescence analysis and Biolayer interferometry experiments determined the binding affinity of mouse-adapted SARS-CoV-2 WBP-1 RBD to mouse ACE2 and human ACE2. Finally, we tested whether TLR7/8 agonist Resiquimod (R848) could also inhibit the replication of WBP-1 in the mouse model. FINDINGS: The mouse-adapted strain WBP-1 showed increased infectivity in BALB/c mice and led to severe interstitial pneumonia. We characterized the dynamics of the adaptive mutations in SARS-CoV-2 and demonstrated that Q493K and Q498H in RBD significantly increased its binding affinity towards mouse ACE2. Additionally, the study tentatively found that the TLR7/8 agonist Resiquimod was able to protect mice against WBP-1 challenge. Therefore, this mouse-adapted strain is a useful tool to investigate COVID-19 and develop new therapies. INTERPRETATION: We found for the first time that the Q493K and Q498H mutations in the RBD of WBP-1 enhanced its interactive affinities with mACE2. The mouse-adapted SARS-CoV-2 provides a valuable tool for the evaluation of novel antiviral and vaccine strategies. This study also tentatively verified the antiviral activity of TLR7/8 agonist Resiquimod against SARS-CoV-2 in vitro and in vivo. FUNDING: This research was funded by the National Key Research and Development Program of China (2020YFC0845600) and Emergency Science and Technology Project of Hubei Province (2020FCA046) and Robert A. Welch Foundation (C-1565).


Subject(s)
Amino Acid Substitution , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Imidazoles/administration & dosage , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/metabolism , Adaptation, Physiological , Animals , Binding Sites , COVID-19/metabolism , COVID-19/prevention & control , Caco-2 Cells , Chlorocebus aethiops , Disease Models, Animal , Female , High-Throughput Nucleotide Sequencing , Humans , Imidazoles/pharmacology , Mice , Mice, Inbred BALB C , SARS-CoV-2/genetics , Serial Passage , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Vero Cells , Virus Replication/drug effects , Whole Genome Sequencing
16.
J Virol ; 2021 Mar 10.
Article in English | MEDLINE | ID: covidwho-1127542

ABSTRACT

Age is a risk factor for coronavirus disease 2019 (COVID-19) associated morbidity and mortality in humans; hence, in this study, we compared the course of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in young and aged BALB/c mice. We found that SARS-CoV-2 isolates replicated in the respiratory tracts of 12-month-old (aged) mice and caused pathological features of pneumonia upon intranasal infection. In contrast, rapid viral clearance was observed 5 days following infection in 2-month-old (young) mice with no evidence of pathological changes in the lungs. Infection with SARS-CoV-2 elicited significantly upregulated production of cytokines, especially interleukin 6 and interferon gamma, in aged mice; whereas this response was much weaker in young mice. Subsequent challenge of infected aged BALB/c mice with SARS-CoV-2 resulted in neutralized antibody responses, a significantly reduced viral burden in the lungs, and inflammation mitigation. Deep sequencing showed a panel of mutations potentially associated with the enhanced infection in aged BALB/c mice, such as the Q498H mutations which are located at the receptor binding domain (RBD) of the spike (S) protein. We further found that the isolates can not only multiply in the respiratory tract of mice but also cause disease in aged mice. Overall, viral replication and rapid adaption in aged BALB/c mice were associated with pneumonia, confirming that the age-related susceptibility to SARS-CoV-2 in mice resembled that in humans.ImportanceAged BALB/c model are in use as a model of disease caused by SARS-CoV-2. Our research demonstrated SARS-CoV-2 can rapidly adapt in aged BALB/c mice through causing mutations at the RBD of the S protein. Moreover, SARS-CoV-2-infected aged BALB/c mice indicated that alveolar damage, interstitial pneumonia, and inflammatory immune responses were similar to the clinical manifestations of human infections. Therefore, our aged BALB/c challenge model will be useful for further understanding the pathogenesis of SARS-CoV-2 and for testing vaccines and antiviral agents.

17.
J Mol Cell Biol ; 13(3): 185-196, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1045847

ABSTRACT

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and mortality. The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2. However, whether there is a specific target of SARS-CoV-2 in the kidney remains unclear. Herein, by using in silico simulation, coimmunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labeling, and rational design of antagonist peptides, we demonstrate that kidney injury molecule-1 (KIM1), a molecule dramatically upregulated upon kidney injury, binds with the receptor-binding domain (RBD) of SARS-CoV-2 and facilitates its attachment to cell membrane, with the immunoglobulin variable Ig-like (Ig V) domain of KIM1 playing a key role in this recognition. The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2. In addition, our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV, pathogens of two severe infectious respiratory diseases. Together, these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses. We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a 'vicious cycle', and KIM1 could be further explored as a therapeutic target.


Subject(s)
COVID-19/genetics , Hepatitis A Virus Cellular Receptor 1/genetics , Receptors, Virus/genetics , SARS-CoV-2/genetics , COVID-19/pathology , COVID-19/virology , Computer Simulation , Humans , Kidney/pathology , Kidney/virology , Protein Binding/genetics , SARS-CoV-2/pathogenicity
18.
J Transl Int Med ; 9(1): 38-42, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1042396

ABSTRACT

OBJECTIVE: This study aims to explore the necessity and safety of digestive endoscopy during the epidemic of coronavirus disease 2019. METHODS: A retrospective cohort study method was used to collect patients' data from the endoscopy center of the Civil Aviation General Hospital of China from February 1 to May 31, 2020, as the observation group. The patients' data of endoscopic diagnosis and treatment during the same period in 2019 were used as a control group, to compare the differences in the number of diagnosis and treatment and the detection rate of gastrointestinal diseases in the two groups. At the same time, patients and related staff were followed up for the situation of new infection. RESULTS: During the epidemic, our endoscopy center conducted a total of 1,808 cases of endoscopic operations and 5,903 cases in the control group. The amount of endoscopic work during the epidemic period was 30.63% in the same period last year. During the epidemic, 26 patients underwent endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) treatment, 26 patients underwent ERCP, and 18 patients underwent gastrointestinal stent implantation. In the control group, 273 patients underwent EMR/ESD, 17 underwent ERCP, and 16 underwent gastrointestinal stenting. During COVID-19, compared with the same period last year, the detection rates of peptic ulcer, esophageal cancer, gastric cancer, colon cancer, and rectal cancer were significantly higher (χ 2 = 4.482, P = 0.034; χ 2 = 5.223, P = 0.006; χ 2 = 2.329, P = 0.041; χ 2 = 8.755, P = 0.003; and χ 2 = 5.136, P = 0.023). Through telephone follow-up, novel coronavirus nucleic acid detection and blood antibody detection, no patients or medical staff were infected with the novel coronavirus. CONCLUSION: During COVID-19, the number of digestive endoscopic operations decreased significantly compared with the same period last year, but the detection rate of various diseases of the digestive tract increased significantly. On the basis of strict prevention and control, orderly recovery of endoscopic work is essential.

19.
Biomed Res Int ; 2020: 3854196, 2020.
Article in English | MEDLINE | ID: covidwho-1021147

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a complex disease caused by the disturbance of genetic and environmental factors. Single-nucleotide polymorphisms (SNPs) play a vital role in the genetic dissection of complex diseases. In-depth analysis of SNP-related information could recognize disease-associated biomarkers and further uncover the genetic mechanism of complex diseases. Risk-related variants might act on the disease by affecting gene expression and gene function. Through integrating SNP disease association study and expression quantitative trait loci (eQTL) analysis, as well as functional enrichment of containing known causal genes, four risk SNPs and four corresponding susceptibility genes were identified utilizing next-generation sequencing (NGS) data of COPD. Of the four risk SNPs, one could be found in the SNPedia database that stored disease-related SNPs and has been linked to a disease in the literature. Four genes showed significant differences from the perspective of normal/disease or variant/nonvariant samples, as well as the high performance of sample classification. It is speculated that the four susceptibility genes could be used as biomarkers of COPD. Furthermore, three of our susceptibility genes have been confirmed in the literature to be associated with COPD. Among them, two genes had an impact on the significance of expression correlation of known causal genes they interact with, respectively. Overall, this research may present novel insights into the diagnosis and pathogenesis of COPD and susceptibility gene identification of other complex diseases.


Subject(s)
Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing , Pulmonary Disease, Chronic Obstructive/genetics , Quantitative Trait Loci , Algorithms , Biomarkers/metabolism , Cluster Analysis , Computational Biology , Gene Expression , Genome-Wide Association Study , Genotype , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , RNA-Seq , ROC Curve , Risk , Sensitivity and Specificity
20.
Life Sci ; 265: 118761, 2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-919593

ABSTRACT

Outbreaks and the rapid transmission of viruses, such as coronaviruses and influenza viruses, are serious threats to human health. A major challenge in combating infectious diseases caused by viruses is the lack of effective methods for prevention and treatment. Nanotechnology has provided a basis for the development of novel antiviral strategies. Owing to their large modifiable surfaces that can be functionalized with multiple molecules to realize sophisticated designs, nanomaterials have been developed as nanodrugs, nanocarriers, and nano-based vaccines to effectively induce sufficient immunologic memory. From this perspective, we introduce various nanomaterials with diverse antiviral mechanisms and summarize how nano-based antiviral agents protect against viral infection at the molecular, cellular, and organismal levels. We summarize the applications of nanomaterials for defense against emerging viruses by trapping and inactivating viruses and inhibiting viral entry and replication. We also discuss recent progress in nano-based vaccines with a focus on the mechanisms by which nanomaterials contribute to immunogenicity. We further describe how nanotechnology may improve vaccine efficacy by delivering large amounts of antigens to target immune cells and enhancing the immune response by mimicking viral structures and activating dendritic cells. Finally, we provide an overview of future prospects for nano-based antiviral agents and vaccines.


Subject(s)
Antiviral Agents/therapeutic use , Nanotechnology , Viral Vaccines/therapeutic use , Antiviral Agents/administration & dosage , Humans , Nanocapsules , Nanotechnology/methods , Viral Vaccines/administration & dosage , Virus Diseases/drug therapy , Virus Diseases/prevention & control
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