Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 61
Filter
2.
Front Nutr ; 9: 870370, 2022.
Article in English | MEDLINE | ID: covidwho-1834490

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has led to 4,255,892 deaths worldwide. Although COVID-19 vaccines are available, mutant forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have reduced the effectiveness of vaccines. Patients with cancer are more vulnerable to COVID-19 than patients without cancer. Identification of new drugs to treat COVID-19 could reduce mortality rate, and traditional Chinese Medicine(TCM) has shown potential in COVID-19 treatment. In this study, we focused on lung adenocarcinoma (LUAD) patients with COVID-19. We aimed to investigate the use of curcumol, a TCM, to treat LUAD patients with COVID-19, using network pharmacology and systematic bioinformatics analysis. The results showed that LUAD and patients with COVID-19 share a cluster of common deregulated targets. The network pharmacology analysis identified seven core targets (namely, AURKA, CDK1, CCNB1, CCNB2, CCNE1, CCNE2, and TTK) of curcumol in patients with COVID-19 and LUAD. Clinicopathological analysis of these targets demonstrated that the expression of these targets is associated with poor patient survival rates. The bioinformatics analysis further highlighted the involvement of this target cluster in DNA damage response, chromosome stability, and pathogenesis of LUAD. More importantly, these targets influence cell-signaling associated with the Warburg effect, which supports SARS-CoV-2 replication and inflammatory response. Comparative transcriptomic analysis on in vitro LUAD cell further validated the effect of curcumol for treating LUAD through the control of cell cycle and DNA damage response. This study supports the earlier findings that curcumol is a potential treatment for patients with LUAD and COVID-19.

3.
Open Forum Infect Dis ; 9(5): ofac142, 2022 May.
Article in English | MEDLINE | ID: covidwho-1788525

ABSTRACT

Background: Population-based seroprevalence studies offer comprehensive characterization of coronavirus disease 2019 (COVID-19) spread, but barriers exist and marginalized populations may not be captured. We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence among decedents in Maryland over 6 months in 2020. Methods: Data were collected on decedents undergoing forensic postmortem examination in Maryland from 24 May through 30 November 2020 from whom a blood specimen could be collected. Those with available blood specimens were tested with the CoronaCHEK lateral flow antibody assay. We assessed monthly seroprevalence compared to the statewide estimated number of cases and proportion of positive test results (testing positivity). We used Poisson regression with robust variance to estimate adjusted prevalence ratios (aPRs) with 95% confidence intervals (CIs) for associations of demographic characteristics, homelessness, and manner of death with SARS-CoV-2 antibodies. Results: Among 1906 decedents, 305 (16%) were positive for SARS-CoV-2 antibodies. Monthly seroprevalence increased from 11% to 22% over time and was consistently higher than state-level estimates of testing positivity. Hispanic ethnicity was associated with 2- to 3.2-fold higher seropositivity (P < .05) irrespective of sex. Deaths due to motor vehicle crash were associated with 62% increased seropositivity (aPR, 1.62 [95% CI, 1.15-2.28]) vs natural manner of death. Though seroprevalence was lower in decedents of illicit drug overdose vs nonoverdose in early months, this shifted, and seroprevalence was comparable by November 2020. Conclusions: Decedents undergoing forensic postmortem examination, especially those dying due to motor vehicle trauma, may be a sentinel population for COVID-19 spread in the general population and merits exploration in other states/regions.

4.
Open forum infectious diseases ; 9(5), 2022.
Article in English | EuropePMC | ID: covidwho-1781870

ABSTRACT

Background Population-based seroprevalence studies offer comprehensive characterization of coronavirus disease 2019 (COVID-19) spread, but barriers exist and marginalized populations may not be captured. We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence among decedents in Maryland over 6 months in 2020. Methods Data were collected on decedents undergoing forensic postmortem examination in Maryland from 24 May through 30 November 2020 from whom a blood specimen could be collected. Those with available blood specimens were tested with the CoronaCHEK lateral flow antibody assay. We assessed monthly seroprevalence compared to the statewide estimated number of cases and proportion of positive test results (testing positivity). We used Poisson regression with robust variance to estimate adjusted prevalence ratios (aPRs) with 95% confidence intervals (CIs) for associations of demographic characteristics, homelessness, and manner of death with SARS-CoV-2 antibodies. Results Among 1906 decedents, 305 (16%) were positive for SARS-CoV-2 antibodies. Monthly seroprevalence increased from 11% to 22% over time and was consistently higher than state-level estimates of testing positivity. Hispanic ethnicity was associated with 2- to 3.2-fold higher seropositivity (P < .05) irrespective of sex. Deaths due to motor vehicle crash were associated with 62% increased seropositivity (aPR, 1.62 [95% CI, 1.15–2.28]) vs natural manner of death. Though seroprevalence was lower in decedents of illicit drug overdose vs nonoverdose in early months, this shifted, and seroprevalence was comparable by November 2020. Conclusions Decedents undergoing forensic postmortem examination, especially those dying due to motor vehicle trauma, may be a sentinel population for COVID-19 spread in the general population and merits exploration in other states/regions. SARS-CoV-2 antibody seroprevalence was 16% among Maryland decedents undergoing forensic postmortem examination (May–November 2020). Hispanic ethnicity and motor vehicle deaths were associated with seropositivity. Estimates in decedents exemplify feasible/real-time data for disease spread and potential sentinel surveillance meriting exploration.

5.
Huan Jing Ke Xue ; 43(4): 1747-1755, 2022 Apr 08.
Article in Chinese | MEDLINE | ID: covidwho-1776689

ABSTRACT

Volatile organic compounds (VOCs) are the key precursors of the ozone (O3) formation processes in the troposphere and are important control objects for the coordinated governance of O3 and PM2.5. The Spring Festival of 2020 was affected by the novel coronavirus (COVID-19) pneumonia epidemic:companies stopped work and production, and traffic was restricted, providing scientific experimentation opportunities for pollutant emission reduction research. This study analyzed the variety of the composition, chemical reaction activity, and sources of VOCs in the Pearl River Delta during the Spring Festival and the epidemic control period, using real-time online monitoring data of VOCs obtained at four sites(Guangzhou, Dongguan, Zhongshan, and Duanfen)in the Pearl River Delta from January 1, 2020 to February 29, 2020. The results showed that during the Spring Festival and the epidemic control period, the average of φ (VOCs) in the Pearl River Delta was 15.89×10-9, and the maximum hourly average concentration was 45.43×10-9, values that were 44% and 60% lower, respectively, than those before the Spring Festival holiday. Among the VOCs component concentration decreases, the aromatic hydrocarbon component decreased the most, and the decrease in the urban area of the Pearl River Delta (74%) was significantly greater than that in the suburban area (56%). As a result, the contribution rate of aromatic hydrocarbons to the total VOCs was reduced to less than 10%. The analysis of the·OH reaction activity of VOCs(L·OH)and ozone formation potential(OFP)showed that the L·OH and OFP of VOCs decreased significantly in the Pearl River Delta during the Spring Festival and the epidemic control period. Compared with those before the Spring Festival holiday, the total L·OH and total OFP decreased by an average of 60% and 63% in the urban area of the Pearl River Delta, respectively. Additionally, the atmospheric oxidation had also been significantly reduced, which showed a 28% decrease in ρ(Ox). The ratio of toluene/benzene showed that the influence of industrial sources had almost disappeared during the Spring Festival and the epidemic control period, and the total points of the representative components of industrial-related solvent-use sources such as toluene, ethylbenzene, and m/p-xylene dropped by 72% to 91%. The results of this study suggest that solvent-use sources and vehicle exhaust emission sources are the current sources of VOCs that need to be paid attention to in the prevention and control of O3 pollution in the Pearl River Delta region, and the impact of petrochemical sources cannot be ignored in the work of further reducing the background concentration of O3.


Subject(s)
Air Pollutants , COVID-19 , Ozone , Volatile Organic Compounds , Air Pollutants/analysis , COVID-19/epidemiology , COVID-19/prevention & control , China/epidemiology , Environmental Monitoring/methods , Holidays , Humans , Ozone/analysis , Solvents/analysis , Toluene/analysis , Vehicle Emissions/analysis , Volatile Organic Compounds/analysis
6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331690

ABSTRACT

The unprecedented coronavirus disease (COVID-19) epidemic has created a worldwide public health emergency, and there is an urgent need to develop an effective antiviral drug to control this severe infectious disease. Here, we found that the E, or M membrane proteins of coronavirus could be targeted by a 28-residue antibody mimetic by fusing two antibody Fab complementarity-determining regions (VHCDR1 and VLCDR3) through a cognate framework region (VHFR2) of the antibodies which recognize the coronavirus E or M proteins. We constructed a fusion protein, pheromonicin-covid-19 (PMC-covid-19), by linking colicin Ia, a bactericidal molecule produced by E.coli which kills target cells by forming a voltage-dependent channel in target lipid bilayers, to that antibody mimetic. The E, or M protein/antibody mimetic interaction initiated the formation of irreversible PMC-covid-19 channel in the covid-19 envelope and infected host cell membrane resulting in leakage of cellular contents. PMC-covid-19 demonstrates broad-spectrum protective efficacy against tested variants of coronavirus severe acute respiratory syndrome (p<0.01-0.0001). PMC-covid-19 significantly altered outcomes of in vivo fatal covid-19 challenge infection without evident toxicity, making it an appropriate candidate for further clinical evaluation.

7.
R Soc Open Sci ; 8(12): 211606, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1758981

ABSTRACT

Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses gives that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells can lead to more significant inflammation, proposing an explanation for the monotonic increase of COVID-19 mortality with age and higher mortality for males. We propose that T cells play a crucial role in the immunity against COVID-19, which provides a new direction-improvement of T cell number for advancing current prevention and treatment.

8.
Curr Top Med Chem ; 22(2): 83-94, 2022.
Article in English | MEDLINE | ID: covidwho-1725177

ABSTRACT

As a traditional Chinese medicine (TCM), Shuang-Huang-Lian (SHL) has been widely used for treating infectious diseases of the respiratory tract such as encephalitis, pneumonia, and asthma. During the past few decades, considerable research has focused on pharmacological action, pharmacokinetic interaction with antibiotics, and clinical applications of SHL. A huge and more recent body of pharmacokinetic studies support the combination of SHL and antibiotics have different effects such as antagonism and synergism. SHL has been one of the best-selling TCM products. However, there is no systematic review of SHL preparations, ranging from protection against respiratory tract infections to interaction with antibiotics. Since their important significance in clinical therapy, the pharmacodynamics, pharmacokinetics, and interactions with antibiotics of SHL were reviewed and discussed. In addition, this review attempts to explore the possible potential mechanism of SHL preparations in the prevention and treatment of COVID-19. We are concerned about the effects of SHL against viruses and bacteria, as well as its interactions with antibiotics in an attempt to provide a new strategy for expanding the clinical research and medication of SHL preparations.


Subject(s)
COVID-19 , Drugs, Chinese Herbal , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drugs, Chinese Herbal/pharmacology , Humans , Medicine, Chinese Traditional , SARS-CoV-2
9.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-325847

ABSTRACT

In this work, we propose a bi-directional long short-term memory (BiLSTM) network based COVID-19 detection method using breath/speech/cough signals. By using the acoustic signals to train the network, respectively, we can build individual models for three tasks, whose parameters are averaged to obtain an average model, which is then used as the initialization for the BiLSTM model training of each task. This initialization method can significantly improve the performance on the three tasks, which surpasses the official baseline results. Besides, we also utilize a public pre-trained model wav2vec2.0 and pre-train it using the official DiCOVA datasets. This wav2vec2.0 model is utilized to extract high-level features of the sound as the model input to replace conventional mel-frequency cepstral coefficients (MFCC) features. Experimental results reveal that using high-level features together with MFCC features can improve the performance. To further improve the performance, we also deploy some preprocessing techniques like silent segment removal, amplitude normalization and time-frequency mask. The proposed detection model is evaluated on the DiCOVA dataset and results show that our method achieves an area under curve (AUC) score of 88.44% on blind test in the fusion track.

10.
Adv Sci (Weinh) ; 9(11): e2105378, 2022 04.
Article in English | MEDLINE | ID: covidwho-1680239

ABSTRACT

The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.


Subject(s)
COVID-19 , Nanoparticles , Animals , Broadly Neutralizing Antibodies , COVID-19/prevention & control , Macaca mulatta/metabolism , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Conjugate
11.
Front Public Health ; 9: 812737, 2021.
Article in English | MEDLINE | ID: covidwho-1662638

ABSTRACT

Background: In China, sickness presenteeism, job burnout, and fatigue are common among nurses during the COVID-19 pandemic. We propose the prevalence of sickness presenteeism can adversely affect nurses' physical and mental health, negatively impact their work productivity and quality, and pose a threat to patients' safety. Therefore, this study examines the mechanism of productivity loss caused by sickness presenteeism, fatigue, and job burnout. Objectives: To investigate the serial-multiple mediating effect of job burnout and fatigue in the relationship between sickness presenteeism and productivity loss among nurses. Methods: A multicenter cross-sectional survey was undertaken by administering an online questionnaire from December 2020 to May 2021. Stratified cluster sampling was used to include 3,491 nurses from 14 hospitals in Shandong Province, China. Variables were measured using the Sickness Presenteeism Questionnaire, Stanford Presenteeism Scale, Chalder Fatigue Scale, and Maslach Burnout Inventory. Data analyses were carried out using descriptive statistics, one-way analysis of variance, independent-samples t-test, Pearson correlation analysis, hierarchical regression, and bootstrapping method. Results: From the 3,491 nurses who volunteered in this online survey, only 2,968 valid questionnaires were returned. Sickness presenteeism exhibited a prevalence of 70.6% during the COVID-19 pandemic. The average score of health-related productivity loss was 15.05 ± 4.52, fatigue was 8.48 ± 3.40, and job burnout was 39.14 ± 19.64. Sickness presenteeism was positively associated with fatigue and job burnout while job burnout was positively associated with nurse fatigue. Sickness presenteeism, fatigue, and job burnout were also positively correlated with health-related productivity loss. Statistically significant paths via the single mediation of fatigue and job burnout were established. A statistically significant serial-multiple mediating effect of fatigue and job burnout on the association between sickness presenteeism and productivity loss accounted for 35.12% of the total effect size. Conclusions: There was a high incidence of sickness presenteeism and job burnout among Chinese nurses. High-frequency sickness presenteeism may result in increased productivity loss through the two mediating effects of fatigue and job burnout. Sickness presenteeism may increase fatigue, promote job burnout, and result in increased productivity loss among Chinese nurses during the COVID-19 pandemic.


Subject(s)
Burnout, Professional , COVID-19 , Burnout, Professional/epidemiology , Cross-Sectional Studies , Fatigue/epidemiology , Fatigue/etiology , Humans , Pandemics , Presenteeism , SARS-CoV-2
12.
mBio ; : e0290621, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1649374

ABSTRACT

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global health emergency. While most human disease is mild to moderate, some infections lead to a severe disease characterized by acute respiratory distress, hypoxia, anosmia, ageusia, and, in some instances, neurological involvement. Small-animal models reproducing severe disease, including neurological sequela, are needed to characterize the pathophysiological mechanism(s) of disease and to identify medical countermeasures. Transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2) viral receptor under the control of the K18 promoter develop severe and lethal respiratory disease subsequent to SARS-CoV-2 intranasal challenge when high viral doses are used. Here, we report on SARS-CoV-2 infection of hamsters engineered to express the hACE2 receptor under the control of the K18 promoter. K18-hACE2 hamsters infected with a relatively low dose of 100 or 1,000 PFU of SARS-CoV-2 developed a severe and lethal disease, with most animals succumbing by day 5 postinfection. Hamsters developed severe lesions and inflammation within the upper and lower respiratory system, including infection of the nasal cavities causing marked destruction of the olfactory epithelium as well as severe bronchopneumonia that extended deep into the alveoli. Additionally, SARS-CoV-2 infection spread to the central nervous system (CNS), including the brain stem and spinal cord. Wild-type (WT) hamsters naturally support SARS-CoV-2 infection, with the primary lesions present in the respiratory tract and nasal cavity. Overall, infection in the K18-hACE2 hamsters is more extensive than that in WT hamsters, with more CNS involvement and a lethal outcome. These findings demonstrate the K18-hACE2 hamster model will be valuable for studying SARS-CoV-2. IMPORTANCE The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-CoV-2 disease is mild, some people develop severe, life-threatening disease. Small-animal models mimicking the severe aspects of human disease are needed to more clearly understand the pathophysiological processes driving this progression. Here, we studied SARS-CoV-2 infection in hamsters engineered to express the human angiotensin-converting enzyme 2 viral receptor under the control of the K18 promoter. SARS-CoV-2 produces a severe and lethal infection in transgenic hamsters that mirrors the most severe aspects of COVID-19 in humans, including respiratory and neurological injury. In contrast to other animal systems, hamsters manifest disease with levels of input virus more consistent with natural human infection. This system will be useful for the study of SARS-CoV-2 disease and the development of drugs targeting this virus.

13.
Nature ; 603(7902): 687-692, 2022 03.
Article in English | MEDLINE | ID: covidwho-1641974

ABSTRACT

The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.


Subject(s)
COVID-19/pathology , COVID-19/virology , Disease Models, Animal , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cricetinae , Female , Humans , Lung/pathology , Lung/virology , Male , Mesocricetus , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Viral Load
14.
J Virol Methods ; 301: 114441, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1634654

ABSTRACT

The aim of this study was to estimate the PCR results for SARS-CoV-2 testing in 32 participating laboratories in a localized small-scale external quality assessment (EQA) scheme. EQA samples were distributed to the participants and detected immediately on the day of delivery. Qualitative results were submitted to the EQA provider, including negative or positive results along with cycle threshold (Ct) values for different target genes. Although the variability of Ct values differed among the laboratories in the EQA, a total of 32 (100 %) participants reported correct qualitative results. The study showed that the mean loads of N or E gene were higher than those of ORF1ab in SARS-CoV-2 RNA samples. Regardless of the analyzed gene target, the mean Ct values for weak positive and positive samples varied by fewer than 1.74 and 1.91 cycles, respectively. Less than 12 % of reported Ct values for ORF1ab and N genes deviated by more than ±4 cycles (maximum: -9.92 cycles), while none deviated by more than ±4 cycles for the E gene. The current EQA program can provide a robust practical basis for follow-up planning to conduct evaluations for SARS-CoV-2 PCR testing and other novel emerging pathogens in the future.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Humans , Laboratories , Polymerase Chain Reaction , RNA, Viral/analysis , RNA, Viral/genetics
15.
Signal Transduct Target Ther ; 7(1): 7, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1606287

ABSTRACT

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.


Subject(s)
AIDS Vaccines/immunology , B-Cell Activating Factor/immunology , COVID-19 Vaccines/immunology , Cytidine Deaminase/immunology , HIV-1/immunology , Nanoparticles , SARS-CoV-2/immunology , Signal Transduction/immunology , Ubiquitin Thiolesterase/immunology , Ubiquitination/immunology , AIDS Vaccines/genetics , Animals , B-Cell Activating Factor/genetics , COVID-19 Vaccines/genetics , Cytidine Deaminase/genetics , HEK293 Cells , HIV-1/genetics , Humans , Mice , Mice, Knockout , SARS-CoV-2/genetics , Signal Transduction/genetics , Ubiquitin Thiolesterase/genetics
16.
Front Public Health ; 9: 785518, 2021.
Article in English | MEDLINE | ID: covidwho-1581105

ABSTRACT

Background: Nurses have a high incidence of shift work sleep disorder, which places their health and patient safety in danger. Thus, exploring the factors associated with shift work sleep disorder in nurses is of great significance in improving their sleep health, nursing personnel staffing, and scheduling during the COVID-19 pandemic. Objectives: The purpose of this study was to investigate the incidence of shift work sleep disorder during the COVID-19 pandemic and explore the factors associated with shift work sleep disorder in Chinese nurses. Methods: This was a multicenter cross-sectional study using an online survey. Stratified cluster sampling was used to include 4,275 nurses from 14 hospitals in Shandong, China from December 2020 to June 2021. Stepwise multivariate logistic regression analysis and random forest were used to identify the factors associated with shift work sleep disorder. Results: The prevalence of shift work sleep disorder in the sampled shift nurses was 48.5% during the COVID-19 pandemic. Physical fatigue, psychological stress, shift work more than 6 months per year, busyness during night shift, working more than 40 h per week, working more than four night shifts per month, sleeping more than 8 h before night shift, using sleep medication, irregular meals, and high-intensity physical activity were associated with increased odds of shift work sleep disorder. Good social support, good work-family balance, napping two or three times per week, resting more than one day after shifts, intervals of 8 days or more between shifts, and taking turns to rest during the night shift were associated with decreased odds of shift work sleep disorder. Conclusions: Shift work sleep disorder may be associated with scheduling strategies and personal behavior during the COVID-19 pandemic. To reduce the incidence of shift work sleep disorders in nurses, nursing managers should increase night shift staffing, extend rest days after shift, increase night shift spacing, and reduce overtime, and nurses need to seek more family and social support and control their sleep schedules and diet.


Subject(s)
COVID-19 , Sleep Disorders, Circadian Rhythm , Cross-Sectional Studies , Humans , Pandemics , SARS-CoV-2 , Sleep Disorders, Circadian Rhythm/epidemiology , Work Schedule Tolerance
17.
Cell Rep ; 38(3): 110256, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1588136

ABSTRACT

Inoculation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing worldwide. However, the emergence of SARS-CoV-2 variants could cause immune evasion. We developed a bivalent nanoparticle vaccine that displays the receptor binding domains (RBDs) of the D614G and B.1.351 strains. With a prime-boost or a single-dose strategy, this vaccine elicits a robust neutralizing antibody and full protection against infection with the authentic D614G or B.1.351 strain in human angiotensin-converting enzyme 2 transgene mice. Interestingly, 8 months after inoculation with the D614G-specific vaccine, a new boost with this bivalent vaccine potently elicits cross-neutralizing antibodies for SARS-CoV-2 variants in rhesus macaques. We suggest that the D614G/B.1.351 bivalent vaccine could be used as an initial single dose or a sequential enforcement dose to prevent infection with SARS-CoV-2 and its variants.


Subject(s)
COVID-19/prevention & control , Cross Protection , SARS-CoV-2/immunology , Vaccines, Combined/therapeutic use , Animals , CHO Cells , COVID-19 Vaccines/chemical synthesis , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Chlorocebus aethiops , Cricetulus , Cross Protection/immunology , Female , HEK293 Cells , Humans , Macaca mulatta , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Nanoparticles , Vaccination/methods , Vaccines, Combined/chemical synthesis , Vaccines, Combined/immunology , Vero Cells
18.
Signal Transduct Target Ther ; 6(1): 420, 2021 12 14.
Article in English | MEDLINE | ID: covidwho-1585885

ABSTRACT

COVID-19 is identified as a zoonotic disease caused by SARS-CoV-2, which also can cross-transmit to many animals but not mice. Genetic modifications of SARS-CoV-2 or mice enable the mice susceptible to viral infection. Although neither is the natural situation, they are currently utilized to establish mouse infection models. Here we report a direct contact transmission of SARS-CoV-2 variant B.1.351 in wild-type mice. The SARS-CoV-2 (B.1.351) replicated efficiently and induced significant pathological changes in lungs and tracheas, accompanied by elevated proinflammatory cytokines in the lungs and sera. Mechanistically, the receptor-binding domain (RBD) of SARS-CoV-2 (B.1.351) spike protein turned to a high binding affinity to mouse angiotensin-converting enzyme 2 (mACE2), allowing the mice highly susceptible to SARS-CoV-2 (B.1.351) infection. Our work suggests that SARS-CoV-2 (B.1.351) expands the host range and therefore increases its transmission route without adapted mutation. As the wild house mice live with human populations quite closely, this possible transmission route could be potentially risky. In addition, because SARS-CoV-2 (B.1.351) is one of the major epidemic strains and the mACE2 in laboratory-used mice is naturally expressed and regulated, the SARS-CoV-2 (B.1.351)/mice could be a much convenient animal model system to study COVID-19 pathogenesis and evaluate antiviral inhibitors and vaccines.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/transmission , Host-Pathogen Interactions/genetics , Receptors, Virus/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Gene Expression , HEK293 Cells , Host-Pathogen Interactions/immunology , Humans , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Protein Binding , Protein Domains , Receptors, Virus/immunology , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/immunology , Virus Replication
19.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-297101

ABSTRACT

It is challenging to quantitatively clarify the determining medical and social factors of COVID-19 mortality, which varied by 2-3 orders of magnitude across countries. Here, we present evidence that the whole-cycle patterns of mortality follow a logistic law for 52 countries. A universal linear law is found between the ICU time in the early stage and the most important quantity regarding the epidemic: its duration. Saturation mortality is found to have a power law relationship with median age and bed occupancy, which quantitatively explains the great variation in mortality based on the two key thresholds of median age (=38) and bed occupancy (=15%). We predict that deaths will be reduced by 36% when the number of beds is doubled for countries with older populations. Facing the next wave of the epidemic, this model can make early predictions on the epidemic duration and medical supply reservation.

20.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296426

ABSTRACT

Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analyzing the multi-level clinical data, including viral dynamics, immune response, and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses demonstrates that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells leads to more significant inflammation, proposing an explanation for the monotonous increase of COVID-19 mortality with age and higher mortality for males. We conclude that T cells play a crucial role in the immunity against COVID-19, which reveals a new direction——improvement of T cell number for advancing current prevention and treatment.

SELECTION OF CITATIONS
SEARCH DETAIL