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1.
J Infect Dis ; 2022 Apr 20.
Article in English | MEDLINE | ID: covidwho-1873926

ABSTRACT

Isolated reports of new-onset diabetes in patients with coronavirus disease 2019 (COVID-19) have led researchers to hypothesize that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects 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 hyperglycemia. We also detected SARS-CoV-2 RNA in pancreatic tissues of these cats, and immunohistochemical staining revealed the presence of SARS-CoV-2 nucleocapsid protein (NP) in islet cells. SARS-CoV-2 NP and spike proteins were primarily detected in glucagon-positive cells, and most glucagon-positive cells expressed ACE2. Additionally, immune protection experiments conducted on cats showed that blood glucose levels of immunized cats did not increase postchallenge. Our data indicate cat pancreas as a SARS-CoV-2 target and suggest that the infection of glucagon-positive cells could contribute to the metabolic dysregulation observed in SARS-CoV-2-infected cats.

2.
Cancer Med ; 2022 May 11.
Article in English | MEDLINE | ID: covidwho-1838159

ABSTRACT

BACKGROUND: There has been a delay in the detection and treatment of lymphedema in breast cancer patients during the lockdown owing to quarantine and limited social activity. Moreover, this scenario has caused psychosocial issues in these patients. Given that there is scarce information on the prevalence and influence of lymphedema during the coronavirus disease (COVID-19) pandemic, we aimed to estimate the prevalence of lymphedema recurrence and its influencing factors among discharged breast cancer patients during the COVID-19 pandemic. METHODS: This was a multicenter, cross-sectional, hospital-based survey of discharged breast cancer patients was conducted during the COVID-19 pandemic in eight first-class hospitals in Wuhan, China. The Norman Questionnaire was used to assess lymphedema. Univariable and multivariable binary logistic regression analyses were performed to identify factors influencing moderate or severe lymphedema. Differences in living characteristics, anxiety, and depression were compared between the no/mild lymphedema group and the moderate/severe lymphedema groups. Preferences for lymphedema management during the pandemic were determined. RESULTS: Overall, 202 patients were included in this study, and 191 of them reported recurrent lymphedema (prevalence: 94.6%, 95% confidence interval [CI] 90.5% to 97.3%). Among them, 134 and 57 had mild and moderate/severe lymphedema, respectively. In 191 patients, the main symptoms were swelling (140; 69.3%) and pain (56, 27.7%). Multivariable regression showed that older age (odds ratio [OR], 1.06; 95% CI: 1.02-1.10), radical surgery (OR = 4.35, 95% CI: 1.54-12.50), and fully complete radiotherapy (OR = 2.62, 95% CI: 1.17-5.87, p = 0.019) were associated with an elevated risk of moderate/severe lymphedema. The moderate/severe lymphedema group experienced a higher rate of anxiety and depression than the no/mild lymphedema group did. Patients equally preferred treatment in the hospital and self-care at home. CONCLUSION: During the COVID-19 pandemic, high prevalence of lymphedema was observed in patients Age, radical surgery and fully completed radiotherapy were associated with increased risk of severer lymphedema. Meanwhile, the patients with severe lymphedema experienced psychological distress. While the Covid-19 pandemic was still raging, continuous efforts should be made to identify patient at risk of lymphedema and distribute feasible guidance and education for self-management in lymphedema.

3.
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.

4.
Front Pediatr ; 9: 759213, 2021.
Article in English | MEDLINE | ID: covidwho-1817994

ABSTRACT

Objective: We sought to compare the clinical characteristics of pediatric respiratory tract infection and respiratory pathogen isolations during the coronavirus disease (COVID-19) pandemic to those of cases in 2018 and 2019. Methods: Our study included all children from 28 days to 15 years old with respiratory tract infections who were admitted to the Department of Respiration, in the Children's Hospital of Soochow University, between January 2018 and December 2020. Human rhinovirus (HRV) and human metapneumovirus (hMPV) were detected by reverse transcription polymerase chain reaction (RT-PCR). Mycoplasma pneumoniae (MP) and human bocavirus (HBoV) were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR); In parallel, Mycoplasma pneumoniae was detected by enzyme-linked immunosorbent assays, and bacteria were detected by culture in blood, bronchoalveolar lavage specimen, and pleural fluid. Results: Compared to 2018 and 2019, the pathogen detection rate was significantly lower in 2020. With regard to infections caused by single pathogens, in 2020, the detection rates of MP were the lowest and those of HRV were the highest when compared to those in 2018 and 2019. Meanwhile, the positive rates of respiratory syncytial virus (RSV) and hMPV reported in 2020 were less than those recorded in 2018 but similar to those recorded in 2019. Also, the 2020 rate of adenovirus (ADV) was lower than that recorded in 2019, but similar to that recorded in 2018. There were no statistical differences in the positive rates of HBoV and PIV III over the 3 years surveyed. Infections in infants were significantly less common in 2020, but no significant difference was found among children aged 1 to 3 years. The detection rate of pathogens in children old than 5 years in 2020 was significantly lower than those recorded in the previous 2 years. Notably, the pathogen detection rates in the first and second quarters of 2020 were similar to those recorded in the previous 2 years; however, the rates were reduced in the third and fourth quarters of 2020. As for co-infections, the positive rate was at its lowest in 2020. In the previous 2 years, viral-MP was the most common type of mixed infection. By contrast, in 2020, viral-viral infections were the most common combination. Conclusion: The pathogen detection rate was significantly reduced in Suzhou City during the COVID-19 pandemic. Public interventions may help to prevent respiratory pathogen infections in children.

5.
Nat Commun ; 13(1): 2135, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1805610

ABSTRACT

Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individuals and 413 COVID-19 patients is profiled using EPIC methylation array. Epigenetic ages of each individual are determined by applying epigenetic clocks and telomere length estimator to the methylation profile of the individual. Epigenetic age acceleration is calculated and compared between groups. We observe strong correlations between the epigenetic clocks and individual's chronological age (r > 0.8, p < 0.0001). We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19. In addition, the longitudinal DNA methylation profiling analysis find that the accumulation of epigenetic aging from COVID-19 syndrome could be partly reversed at late clinic phases in some patients. In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.


Subject(s)
COVID-19 , Aging/genetics , COVID-19/complications , COVID-19/genetics , DNA Methylation , Epigenesis, Genetic , Humans , SARS-CoV-2
6.
Front Pharmacol ; 12: 790072, 2021.
Article in English | MEDLINE | ID: covidwho-1789412

ABSTRACT

Background: Acute lung injury (ALI) is characterized by dysfunction of the alveolar epithelial membrane caused by acute inflammation and tissue injury. Qingwenzhike (QWZK) prescription has been demonstrated to be effective against respiratory viral infections in clinical practices, including coronavirus disease 2019 (COVID-19) infection. So far, the chemical compositions, protective effects on ALI, and possible anti-inflammatory mechanisms remain unknown. Methods: In this study, the compositions of QWZK were determined via the linear ion trap/electrostatic field orbital trap tandem high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap MS). To test the protective effects of QWZK on ALI, an ALI model induced by lipopolysaccharide (LPS) in rats was used. The effects of QWZK on the LPS-induced ALI were evaluated by pathological changes and the number and classification of white blood cell (WBC) in bronchoalveolar lavage fluid (BALF). To investigate the possible underlying mechanisms, the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1), interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and immunoregulatory-related factors interferon-γ (IFN-γ) were detected by ELISA. Furthermore, the expression of Toll-like receptor 4 (TLR4), p-IKKα/ß, IKKα, IKKß, p-IκBα, IκBα, p-NF-κB, nuclear factor-κB (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, pro-caspase-1, apoptosis-associated speck-like protein containing CARD (ASC), and ß-actin were tested by Western blot. Results: A total of 99 compounds were identified in QWZK, including 33 flavonoids, 23 phenolic acids, 3 alkaloids, 3 coumarins, 20 triterpenoids, 5 anthraquinones, and 12 others. ALI rats induced by LPS exhibited significant increase in neutrophile, significant decrease in lymphocyte, and evidently thicker alveolar wall than control animals. QWZK reversed the changes in WBC count and alveolar wall to normal level on the model of ALI induced by LPS. ELISA results revealed that QWZK significantly reduced the overexpression of proinflammatory factors IL-6, TNF-α, MCP-1, IL-1ß, IL-18, and IFN-γ induced by LPS. Western blot results demonstrated that QWZK significantly downregulated the overexpression of TLR4, p-IKKα/ß, p-IκBα, p-NF-κB, NLRP3, cleaved caspase-1, and ASC induced by LPS, which suggested that QWZK inhibited TLR4/NF-κB signaling pathway and NLRP3 inflammasomes. Conclusions: The chemical compositions of QWZK were first identified. It was demonstrated that QWZK showed protective effects on ALI induced by LPS. The possible underlying mechanisms of QWZK on ALI induced by LPS was via inhibiting TLR4/NF-kB signaling pathway and NLRP3 inflammasome activation. This work suggested that QWZK is a potential therapeutic candidate for the treatments of ALI and pulmonary inflammation.

7.
Nucleic Acids Res ; 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1784376

ABSTRACT

WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called 'Dynamic' tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/.

8.
Pulm Circ ; 12(2): e12081, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1782687

ABSTRACT

The aim of this study is to provide evidence for the influencing factors of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus mutation by determining the impact of geographical and meteorological factors on SARS-CoV-2 transmission, and the different impacts of SARS-CoV-2 variant strains. From January 20 to March 10, 2020, we collected a number of daily confirmed new cases and meteorological factors in all cities and regions in China and Italy affected by the Alpha "variants of concern" (VOC). We also collected the daily confirmed cases of the Delta VOC infection in China and Italy from May 21 to November 30, 2021. The relationships between daily meteorological data and daily verified new cases of SARS-CoV-2 transmission were then investigated using a general additive model (GAM) with a log link function and Poisson family. The results revealed that latitude was substantially connected with daily confirmed new instances of the Alpha VOC, while there was no such correlation with Delta VOC transmission. When visibility is greater than 7 m, the propagation of the Alpha and Delta VOCs in Italy and China can be controlled. Furthermore, greater temperatures and increased wind speed reduce the transmission of the Alpha and Delta VOCs. In conclusion, geographical and meteorological factors play an important role in SARS-CoV-2 transmissibility and should be considered in virus mitigation strategies.

9.
Front Public Health ; 10: 861836, 2022.
Article in English | MEDLINE | ID: covidwho-1776094

ABSTRACT

Introduction: Health deterioration among frail older adults is a public health concern. Among the multi-dimensional factors, the neighborhood built environment is crucial for one's health. Although the relationship between the built environment and health in the general population has been thoroughly investigated, it has been ignored in the case of frail older adults, who may have difficulties in their daily basic living skills. A path analysis is constructed to model the proposed theoretical framework involving the neighborhood built environment and health among frail older adults. This study thus aims to investigate the environmental influences on health, and to validate the theoretical framework proposed for health and social services. Methods: This study used secondary data collected in Hong Kong. A sample of 969 older community dwellers aged 60 or above were frail with at least one activity of daily living. Demographic information, neighborhood built environment data, service utilization, and health conditions were collected from these participants and their caregivers. A path analysis was performed to examine the proposed theoretical framework. Results: The health condition was of general concern, including frailty and incapacities in daily activities in frail older adults. Besides psychosocial factors, service use, and caregivers' care quality, the built environment had a significant impact on the health of older adults as well. Specifically, more facilities offering services and groceries, a shorter distance to the nearest metro station, and more greenery exposure are associated with a better-expected health condition among frail older adults. Discussion: The proposed theoretical framework successfully supplements past negligence on the relationship between the built environment and the health of frail older adults. The findings further imply that policymakers should promote the usability of transit and greenery in neighborhoods and communities. In addition, service utilization should be improved to meet the basic needs of frail older adults in the communities.


Subject(s)
Built Environment , Health Status , Public Health , Aged , Cross-Sectional Studies , Hong Kong , Humans , Middle Aged
10.
Front Public Health ; 9: 722572, 2021.
Article in English | MEDLINE | ID: covidwho-1775836

ABSTRACT

Background: Diastasis rectus abdominis (DRA) is one of the common complications during pregnancy and post-partum, which has psychological and physical effects on post-partum women. Acupuncture, a worldwide alternative therapy, has attracted wide attention in preventing and treating diseases related to pregnancy and childbirth. This study aims to evaluate the efficacy of acupuncture combined with physical training in treating post-partum rectus muscle dissociation. Methods: This is a randomized, controlled trial of DRA in post-partum conducted at Hangzhou Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Chinese Medicine. The primary purpose is to evaluate the effectiveness of acupuncture and physical training on DRA in post-partum women. The study will be conducted from March 2022 to March 2023. The acupuncture group received acupuncture and physical training (n = 48), the sham acupuncture group received sham acupuncture and physical training (n = 48), and the physical training group received physical training (n = 48). These experiments perform once/day, five times a week for 2 weeks, followed up for half a year after the end of the course of treatment. Our tests perform a course of treatment, which includes a total of 10 consecutive treatments. Furthermore, the patient will be followed up for half a year after the treatment. Primary and secondary indicators, including inter recti distance (IRD), linea alba (LA) tension, the MOS item short-form health survey (SF-36), short-form McGill pain questionnaire-2 (SF-MPQ-2), body mass index (BMI), waist-to-hip ratio (WHR), leeds dyspepsia questionnaire (LDQ), menstrual distress questionnaire (MDQ), 10 items of edinburgh post-natal depression scale (EPDS-10), the modified body self-image scale (MBIS), international consultation incontinence questionnaire short-form (ICIQ-SF) and hernia-related quality-of-life survey (HerQles), which will be evaluated before and after treatment and half a year after treatment. Adverse events and side effects during each treatment will be collected and recorded. Discussion: There is evidence that acupuncture and physical training can treat DRA in post-partum. In this study, we evaluate the effectiveness of acupuncture in post-partum with DRA.


Subject(s)
Acupuncture Therapy , Diastasis, Muscle , Female , Humans , Postpartum Period , Pregnancy , Randomized Controlled Trials as Topic , Rectus Abdominis
11.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-331499

ABSTRACT

Background: Beyond its direct effects on mortality, the COVID-19 pandemic has disrupted the provision of health care services across numerous countries, giving rise to indirect but nevertheless significant impacts on public health. Methods: This study assesses how the COVID-19 pandemic has influenced health service utilization in terms of the difference between predicted and observed values with the number of COVID-19 confirmed cases, reporting the results of a time-series approach used to forecast annual and monthly health service utilization as compared with the actual results. This includes considering the number of confirmed cases, data on healthcare services and social-economic and demographic data relating to each province of China covered. The results of a multiple regression analysis are also reported to shed light on determine the relationship between the severity of pandemics and health service utilization. Findings: For the annual projections, we found a significantly negative correlation between the utilization of health services in hospitals and the number of confirmed cases, and the impact on inpatient services has been greater than that on outpatient services. With respect to the monthly analysis, as the pandemic moves from outbreak to dissemination, health care utilization is less affected. It is also found that the trough period for outpatient services has been shorter than that for inpatient services and the pandemic has had a greater impact on hospital services than on township health center services, especially during the first phase of the concentrated outbreak. At the same time, the proportion of educated persons within the population was a protective factor for the utilization of both inpatient and outpatient services. Interpretation: This study is conducted to estimate the impact of the COVID-19 pandemic and its severity on the chosen healthcare system. Given that during the COVID-19 pandemic the utilization of health services has declined significantly, there is a need to have greater regard to the potential for disruption among health services and healthcare systems in all Low-and Middle-Income Countries (LMIC).

12.
Artif Intell Rev ; 55(3): 1887-1913, 2022.
Article in English | MEDLINE | ID: covidwho-1750743

ABSTRACT

Exploring efficiency approaches to solve the problems of decision making under uncertainty is a mainstream direction. This article explores the rough approximation of the uncertainty information with Pythagorean fuzzy information on multi-granularity space over two universes combined with grey relational analysis. Based on grey relational analysis, we present a new approach to calculate the relative degree or the attribute weight with Pythagorean fuzzy set and give a new descriptions for membership degree and non-membership. Then, this paper proposes a multi-granulation rough sets combined with Pythagorean fuzzy set, including optimistic multi-granulation Pythagorean fuzzy rough set, pessimistic multi-granulation Pythagorean fuzzy rough set and variable precision Pythagorean fuzzy rough set. Several basic properties for the established models are investigated in detail. Meanwhile, we present an approach to solving the multiple-criteria group decision making problems with fuzzy information based on the proposed model. Eventually, a case study of psychological evaluation of health care workers in COVID-19 show the principle of the established model and is utilized to verify the availability. The main contributions have three aspects. The first contribution of an approach of calculating the attribute weight is presented based on Grey Relational Analysis and gives a new perspective for the Pythagorean fuzzy set. Then, this paper proposes a mutli-granulation rough set model with Pythagorean fuzzy set over two universes. Finally, we apply the proposed model to solving the psychological evaluation problems.

13.
Mol Divers ; 2022 Mar 08.
Article in English | MEDLINE | ID: covidwho-1729341

ABSTRACT

Xuanbai Chengqi Decoction (XBCQD), a classic traditional Chinese medicine, has been widely used to treat COVID-19 in China with remarkable curative effect. However, the chemical composition and potential therapeutic mechanism is still unknown. Here, we used multiple open-source databases and literature mining to select compounds and potential targets for XBCQD. The COVID-19 related targets were collected from GeneCards and NCBI gene databases. After identifying putative targets of XBCQD for the treatment of COVID-19, PPI network was constructed by STRING database. The hub targets were extracted by Cytoscape 3.7.2 and MCODE analysis was carried out to extract modules in the PPI network. R 3.6.3 was used for GO enrichment and KEGG pathway analysis. The effective compounds were obtained via network pharmacology and bioinformatics analysis. Drug-likeness analysis and ADMET assessments were performed to select core compounds. Moreover, interactions between core compounds and hub targets were investigated through molecular docking, molecular dynamic (MD) simulations and MM-PBSA calculations. As a result, we collected 638 targets from 61 compounds of XBCQD and 845 COVID-19 related targets, of which 79 were putative targets. Based on the bioinformatics analysis, 10 core compounds and 34 hub targets of XBCQD for the treatment of COVID-19 were successfully screened. The enrichment analysis of GO and KEGG indicated that XBCQD mainly exerted therapeutic effects on COVID-19 by regulating signal pathways related to viral infection and inflammatory response. Meanwhile, the results of molecular docking showed that there was a stable binding between the core compounds and hub targets. Moreover, MD simulations and MM-PBSA analyses revealed that these compounds exhibited stable conformations and interacted well with hub targets during the simulations. In conclusion, our research comprehensively explained the multi-component, multi-target, and multi-pathway intervention mechanism of XBCQD in the treatment of COVID-19, which provided evidence and new insights for further research.

15.
Bull Exp Biol Med ; 172(4): 423-429, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1696762

ABSTRACT

We studied the lung-protective effect and mechanisms of the anti-inflammatory and antioxidant effects of ultra-short-wave diathermy (USWD) in a rat model of LPS-induced acute lung injury. Histological examination of the lung tissues was performed and the levels of oxidative stress-related factors and inflammatory cytokines were measured. It was shown that the lung injury score, the lung wet-to-dry weight ratio (W/D), oxidative stress-related factors malondialdehyde and acyl-CoA synthetase long-chain family member 4 (ACSL4), and inflammatory cytokines were increased after LPS administration, while USWD treatment reduced these parameters. In addition, superoxide dismutase and glutathione peroxidase 4 were decreased in rats with LPS-induced acute lung injury, while USWD therapy up-regulated the expression of these enzymes. Thus, USWD could antagonize lung injury by inhibiting oxidative stress and inflammatory response in rats with acute lung injury. USWD can be a promising adjunctive treatment to counter oxidative stress and inflammation and a potential therapeutic candidate for the treatment of patients with this pathology.


Subject(s)
Acute Lung Injury , Diathermy , Acute Lung Injury/drug therapy , Acute Lung Injury/therapy , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/metabolism , Humans , Lipopolysaccharides/pharmacology , Lung , Oxidative Stress , Radio Waves , Rats
16.
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.

17.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325385

ABSTRACT

Background: Novel coronavirus disease 2019 (COVID-19) is a global public health emergency. Here, we developed and validated a practical model based on the data from a multi-center cohort in China for early identification and prediction of which patients will be admitted to the intensive care unit (ICU). Methods: Data of 1087 patients with laboratory-confirmed COVID-19 were collected from 49 sites between January 2 and February 28, 2020, in Sichuan and Wuhan. Patients were randomly categorized into the training and validation cohorts (7:3). The least absolute shrinkage and selection operator and logistic regression analyzes were used to develop the nomogram. The performance of the nomogram was evaluated for the C-index, calibration, discrimination, and clinical usefulness. Further, the nomogram was externally validated in a different cohort. Results: The individualized prediction nomogram included 6 predictors: age, respiratory rate, systolic blood pressure, smoking status, fever, and chronic kidney disease. The model demonstrated a high discriminative ability in the training cohort (C-index = 0.829), which was confirmed in the external validation cohort (C-index = 0.776). In addition, the calibration plots confirmed good concordance for predicting the risk of ICU admission. Decision curve analysis revealed that the prediction nomogram was clinically useful. Conclusion: We established an early prediction model incorporating clinical characteristics that could be quickly obtained on hospital admission, even in community health centers. This model can be conveniently used to predict the individual risk for ICU admission of patients with COVID-19 and optimize the use of limited resources.

18.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324771

ABSTRACT

Background: The novel coronavirus disease 2019 (Covid-19) has been a worldwide pandemic with more than 300,000 deaths. Corticosteroids have been used in some patients with severe Covid-19 in order to control the systemic inflammation or cytokine storm, however, their effects and safety have not yet been elucidated. Methods Patients with confirmed Covid-19 were retrospectively included from both the epicentre and out of the epicentre. Patients were classified into two groups according to the use of systemic corticosteroids, and the mortality and the rate of virus clearance were compared between the two groups. In addition, independent factors associated with death after corticosteroids treatment were also identified. Results A total of 775 patients were included in our final analysis, of which 238 (30.7%) patients received systemic corticosteroids treatment. Compared with patients without corticosteroids treatment, patients with corticosteroids treatment had significantly higher mortality (19.3% vs. 3.7%, P < 0.001) and lower rate of virus clearance (43.2% vs. 66.7%, P < 0.001) although along with increase of SpO 2 /FiO 2 and blood lymphocytes in patients with severe Covid-19. Corticosteroids treatment was associated with longer hospital length of stays and delayed virus clearance time. In patients with corticosteroids treatment, blood lymphocytes (odds ratio (OR) 0.792, 95% confidence interval (CI) 0.672–0.932, P = 0.005) and creatine kinase (CK) (OR 1.006, 95%CI 1.000-1.012, P = 0.038) were independent risk factors associated with death, with a sensitivity of 90.91% and 44.44% and a specificity of 70.75% and 94.05%, respectively. Conclusions In patients with Covid-19, corticosteroids treatment is associated with increased mortality and reduced rate of virus clearance.

19.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323685

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) has spread worldwide, leading to thousands of deaths. We aim to describe the epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) in Fujian province, China. Methods In this retrospective, multi-center study, we collected and analysed 165 patients of COVID-19 confirmed by real time PCR of nasopharyngeal swab specimens in five tertiary hospitals of Fujian province, China from Jan 22 to Feb 16, 2020. The final date of follow-up was February 21, 2020. Results Of the 165 hospitalized patients with COVID-19, 101 patients had relation with Wuhan within two weeks. Symptoms at illness onset mainly were fever (76.4%), cough (60%) and expectoration (38.2%). On admission, the severity of most patients were classified as mild or common and lymphopenia (33.9%), hypoxemia (15.2%), elevated and bilateral pneumonia (83.6%) was observed. Patients older than 65 years had significantly high frequency of hypertension, diabetes, severe classification, lymphopenia and hypoxemia than those younger than 65 years. Age correlated negatively with lymphocyte count and oxygenation index on admission while positively with duration from exposure to the time of negative RT-PCR. At the end of follow-up, 80 patients were discharged and one died. The median hospital stay was 17 days. Conclusions Patients with COVID-19 were mostly non-severe cases in Fujian province and older patients (>65 years) were more likely to have lymphopenia and hypoxemia, and to progress as severe cases of COVID-19 than those younger than 65.

20.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-318919

ABSTRACT

Background: To evaluate recurrence of lymphedema and its influencing factors in discharged breast cancer patients with treated lymphedema during the COVID-19 pandemic and to propose feasible improvements. Methods: A multicenter, cross-sectional, hospital-based survey of discharged breast cancer patients was conducted during the COVID-19 pandemic in eight first-class hospitals in Wuhan city, China. Norman Questionnaire was used for assessing lymphedema, and multivariable binary logistic regression was performed to risk factors of moderate or severe lymphedema. Difference in living characteristics, anxiety and depression between no or mild group and moderate or severe group were compared. Preference in management of lymphedema were collected. Results: 202 valid patients were included. 191 participants reported recurred lymphedema (prevalence: 94.6%, 95%CI 90.5% to 97.3%). 134 of them was mild and 57 were moderate/severe. In the 191 patients, the main symptom was swelling (140, 69.3%) and pain (56, 27.7%). Multivariable regression showed that age (odds ratio, 1.06, 95%CI: 1.02-1.10), radical surgery (OR=4.35, 95%CI: 1.54-12.50) and fully complete radiotherapy (OR=2.62, 95%CI: 1.17-5.87, P=0.019) was associated with the risk of moderate or severe lymphedema. No significant difference in lifestyles was observed but moderate or severe group experienced higher rate of anxiety and depression. patients preferred treatment in hospital and self-care at home equally. Conclusion: The high recurrence rate of lymphedema in breast cancer patients with during COVID-19 should draw our great attention, continuous efforts should be made to identify patient at risk of lymphedema and distribute feasible guidance and education for self-management for these patients.

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