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1.
Nat Commun ; 13(1): 322, 2022 01 14.
Article in English | MEDLINE | ID: covidwho-1625443

ABSTRACT

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0-26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out.

2.
Pediatr Pulmonol ; 57(1): 49-56, 2022 01.
Article in English | MEDLINE | ID: covidwho-1437078

ABSTRACT

OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.


Subject(s)
COVID-19 , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Adolescent , China/epidemiology , Humans , Infant , Respiratory Syncytial Virus Infections/diagnosis , Respiratory Tract Infections/diagnosis , SARS-CoV-2
3.
Signal Transduct Target Ther ; 6(1): 331, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392811

ABSTRACT

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.


Subject(s)
COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , Immunity, Innate , SARS-CoV-2/immunology , Signal Transduction/immunology , A549 Cells , COVID-19/pathology , Caco-2 Cells , HEK293 Cells , Hep G2 Cells , Humans , Interferon Type I/immunology , Phosphoproteins/immunology
4.
Pharmacol Res ; 161: 105126, 2020 11.
Article in English | MEDLINE | ID: covidwho-1318945

ABSTRACT

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Adult , Aged , COVID-19/complications , COVID-19/diagnosis , China , Disease Progression , Drugs, Chinese Herbal/administration & dosage , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Myalgia/drug therapy , Myalgia/etiology , Nausea/drug therapy , Nausea/etiology , Powders , Tablets , Treatment Outcome , Vomiting/drug therapy , Vomiting/etiology
5.
Int J Dermatol Venereol ; 2020 Mar 13.
Article in English | MEDLINE | ID: covidwho-1292185

ABSTRACT

The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.

6.
Front Immunol ; 12: 662989, 2021.
Article in English | MEDLINE | ID: covidwho-1256380

ABSTRACT

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNß and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKKϵ, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3-TANK-TBK1-IKKε complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.


Subject(s)
Interferon Type I/biosynthesis , SARS-CoV-2/immunology , Ubiquitin/metabolism , Viral Matrix Proteins/immunology , DEAD Box Protein 58/metabolism , HEK293 Cells , Humans , I-kappa B Kinase/metabolism , Interferon Regulatory Factor-3/metabolism , Interferon-Induced Helicase, IFIH1/metabolism , Proteolysis , Receptors, Immunologic/metabolism , Signal Transduction , TNF Receptor-Associated Factor 3/metabolism
7.
J Med Virol ; 93(5): 2938-2946, 2021 05.
Article in English | MEDLINE | ID: covidwho-1196525

ABSTRACT

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.


Subject(s)
Air Pollution/adverse effects , COVID-19/mortality , Inhalation Exposure/adverse effects , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/statistics & numerical data , China/epidemiology , Cities/statistics & numerical data , Humans , Inhalation Exposure/analysis , Mortality , Predictive Value of Tests , SARS-CoV-2
8.
Mathematical Problems in Engineering ; 2021, 2021.
Article in English | ProQuest Central | ID: covidwho-1133365

ABSTRACT

Small and microenterprises are most affected during the COVID-19 epidemic period. Despite the government introducing many preferential policies, financing for small and microenterprises is still difficult. Based on evolutionary game theory and Matlab r2017b software, this paper discusses the causes of financing problems from two aspects. By taking loan amount, loan interest rate, guarantee value, and intermediary business income as variables, the research shows that banks not only pay attention to the comprehensive return of small and microenterprises but also pay more attention to the coverage of loan principal and interest by the value of collateral. Relying on collateral for credit is still the main way, and the lack of collateral causes financing difficulties of small and microenterprises. Accordingly, this paper puts forward the countermeasures and suggestions to improve the guarantee compensation mechanism and innovate the financing mode.

9.
J Med Virol ; 93(5): 2938-2946, 2021 05.
Article in English | MEDLINE | ID: covidwho-1086484

ABSTRACT

Evidence in the literature suggests that air pollution exposure affects outcomes of patients with COVID-19. However, the extent of this effect requires further investigation. This study was designed to investigate the relationship between long-term exposure to air pollution and the case fatality rate (CFR) of patients with COVID-19. The data on air quality index (AQI), PM2.5, PM10, SO2 , NO2 , and O3 from 14 major cities in China in the past 5 years (2015-2020) were collected, and the CRF of COVID-19 patients in these cities was calculated. First, we investigated the correlation between CFR and long-term air quality indicators. Second, we examined the air pollutants affecting CFR and evaluated their predictive values. We found a positive correlation between the CFR and AQI (1, 3, and 5 years), PM2.5 (1, 3, and 5 years), and PM10 (1, 3, and 5 years). Further analysis indicated the more significant correlation for both AQI (3 and 5 years) and PM2.5 (1, 3, and 5 years) with CFR, and moderate predictive values for air pollution indicators such as AQI (1, 3, and 5 years) and PM2.5 (1, 3, and 5 years) for CFR. Our results indicate that long-term exposure to severe air pollution is associated with higher CFR of COVID-19 patients. Air pollutants such as PM2.5 may assist with the prediction of CFR for COVID-19 patients.


Subject(s)
Air Pollution/adverse effects , COVID-19/mortality , Inhalation Exposure/adverse effects , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/statistics & numerical data , China/epidemiology , Cities/statistics & numerical data , Humans , Inhalation Exposure/analysis , Mortality , Predictive Value of Tests , SARS-CoV-2
10.
PLoS Comput Biol ; 16(12): e1008467, 2020 12.
Article in English | MEDLINE | ID: covidwho-999796

ABSTRACT

In January 2020, a COVID-19 outbreak was detected in Sichuan Province of China. Six weeks later, the outbreak was successfully contained. The aim of this work is to characterize the epidemiology of the Sichuan outbreak and estimate the impact of interventions in limiting SARS-CoV-2 transmission. We analyzed patient records for all laboratory-confirmed cases reported in the province for the period of January 21 to March 16, 2020. To estimate the basic and daily reproduction numbers, we used a Bayesian framework. In addition, we estimated the number of cases averted by the implemented control strategies. The outbreak resulted in 539 confirmed cases, lasted less than two months, and no further local transmission was detected after February 27. The median age of local cases was 8 years older than that of imported cases. We estimated R0 at 2.4 (95% CI: 1.6-3.7). The epidemic was self-sustained for about 3 weeks before going below the epidemic threshold 3 days after the declaration of a public health emergency by Sichuan authorities. Our findings indicate that, were the control measures be adopted four weeks later, the epidemic could have lasted 49 days longer (95% CI: 31-68 days), causing 9,216 more cases (95% CI: 1,317-25,545).


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Disease Outbreaks , COVID-19/virology , China/epidemiology , Female , Humans , Male , SARS-CoV-2/isolation & purification
11.
Cell Host Microbe ; 28(1): 124-133.e4, 2020 07 08.
Article in English | MEDLINE | ID: covidwho-378130

ABSTRACT

Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections , Disease Models, Animal , Mice, Inbred C57BL , Pandemics , Pneumonia, Viral , Aging , Angiotensin-Converting Enzyme 2 , Animals , Brain/virology , COVID-19 , CRISPR-Cas Systems , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/blood , Gene Knock-In Techniques , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/pathology , Nose/virology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA, Viral/analysis , SARS-CoV-2 , Stomach/virology , Trachea/virology , Viral Load , Virus Replication
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(2): 131-138, 2020 Mar.
Article in Chinese | MEDLINE | ID: covidwho-18396

ABSTRACT

This review summarizes the ongoing researches regarding etiology, epidemiology, transmission dynamics, treatment, and prevention and control strategies of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and pandemic H1N1 virus. SARS-CoV-2 may be originated from bats, and the patients and asymptomatic carriers are the source of epidemic infection. The virus can be transmitted human-to-human through droplets and close contact, and people at all ages are susceptible to this virus. The main clinical symptoms of the patients are fever and cough, accompanied with leukocytopenia and lymphocytopenia. Effective drugs have been not yet available thus far. In terms of the prevention and control strategies, vaccine development as the primary prevention should be accelerated. Regarding the secondary prevention, ongoing efforts of the infected patients and close contacts quarantine, mask wearing promotion, regular disinfection in public places should be continued. Meanwhile, rapid detection kit for serological monitoring of the virus in general population is expected so as to achieve early detection, early diagnosis, early isolation and early treatment. In addition, public health education on this disease and prevention should be enhanced so as to mitigate panic and mobilize the public to jointly combat the epidemic.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Asymptomatic Diseases , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Cough/etiology , Early Diagnosis , Fever/etiology , Humans , Influenza A Virus, H1N1 Subtype , Leukopenia/etiology , Lymphopenia/etiology , Middle East Respiratory Syndrome Coronavirus , Pandemics/prevention & control , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , SARS Virus , SARS-CoV-2 , Secondary Prevention , Viral Vaccines
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