Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 25
Filter
1.
Cell Reports ; : 110864, 2022.
Article in English | ScienceDirect | ID: covidwho-1821172

ABSTRACT

Summary The pathological and immune response of individuals with COVID-19 display different dynamics in lung and intestine. Here, we depict the single-cell transcriptional atlas of longitudinally collected lung and intestinal tissue samples from SARS-CoV-2-infected monkeys at 3 to 10 dpi. We find that intestinal enterocytes are degraded at 3 days post-infection but recovered rapidly, revealing that infection has mild effects on the intestine. Crucially, we observe suppression of the inflammatory response and tissue damage related to B-cell and Paneth cell accumulation in the intestines, although T cells are activated in the SARS-CoV-2 infection. Compared with that in the lung, the expression of interferon response-related genes is inhibited, and inflammatory factor secretion is reduced in the intestines. Our findings indicate an imbalance of immune dynamic in intestinal mucosa during SARS-CoV-2 infection, which may underlie ongoing rectal viral shedding and mild tissue damage.

2.
Sensors and Actuators B: Chemical ; : 131974, 2022.
Article in English | ScienceDirect | ID: covidwho-1815176

ABSTRACT

The outbreak of COVID-19 caused by SARS-CoV-2 urges the development of rapid and accurate diagnostic methods. Here, one high-sensitivity and point-of-care detection method based on magnetic SERS biosensors composed of Fe3O4-Au nanocomposite and Au nanoneedles array was developed to detect SARS-CoV-2 directly. Among, the magnetic Fe3O4-Au nanocomposite is applied to capture and separate virus from nasopharyngeal swabs and enhance the Raman signals of SARS-CoV-2. The magnetic SERS biosensor possessed high sensitivity by optimizing the Fe3O4-Au nanocomposite. More significantly, the on-site detection of inactivated SARS-CoV-2 virus was achieved based on the magnetic SERS biosensor with ultra-low limitation of detection of 100 copies/mL during 15mins. Furthermore, the contaminated throat and nasal swabs samples were identified by support vector machine, and the diagnostic accuracy of 100% was obtained. The magnetic SERS biosensor combined with support vector machine provides giant potential as the point-of-care detection tool for SARS-CoV-2.

3.
Signal Transduct Target Ther ; 7(1): 61, 2022 02 25.
Article in English | MEDLINE | ID: covidwho-1758178

ABSTRACT

Variants are globally emerging very quickly following pandemic prototypic SARS-CoV-2. To evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants, we vaccinated rhesus monkeys with three doses of prototypic SARS-CoV-2 inactivated vaccine, followed by challenging with emerging SARS-CoV-2 variants of concern (VOCs). These vaccinated animals produced neutralizing antibodies against Alpha, Beta, Delta, and Omicron variants, although there were certain declinations of geometric mean titer (GMT) as compared with prototypic SARS-CoV-2. Of note, in vivo this prototypic vaccine not only reduced the viral loads in nasal, throat and anal swabs, pulmonary tissues, but also improved the pathological changes in the lung infected by variants of Alpha, Beta, and Delta. In summary, the prototypic SARS-CoV-2 inactivated vaccine in this study protected against VOCs to certain extension, which is of great significance for prevention and control of COVID-19.


Subject(s)
Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Cross Protection , SARS-CoV-2/drug effects , Vaccination/methods , Vaccines, Inactivated/administration & dosage , Anal Canal/virology , Animals , B-Lymphocytes/immunology , B-Lymphocytes/virology , COVID-19/immunology , COVID-19/virology , Humans , Immunogenicity, Vaccine , Lung/virology , Macaca mulatta , Male , Nasal Cavity/virology , Pharynx/virology , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/virology , Viral Load/drug effects
4.
Signal Transduct Target Ther ; 7(1): 69, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721495

ABSTRACT

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the world. To investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain (RBD) (PS-RBD) and whole inactivated virus particle vaccine (IV) against the variant strains, in this study, rhesus macaques were immunized with PS-RBD or IV vaccine, followed by a Beta variant (B.1.351) challenge. Although neutralizing activity against the Beta variant was reduced compared with that against the prototype, the decreased viral load in both upper and lower respiratory tracts, milder pathological changes, and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque model. Furthermore, PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha, Beta, Delta, and Omicron variants in our study, though the neutralizing antibody (NAb) titers declined by varying degrees, demonstrating potential protection of PS-RBD against current circulating variants of concern (VOCs). Interestingly, although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant, it still showed reduction for viral load and significantly alleviated pathological change. Other correlates of vaccine-induced protection (CoP) like antibody-dependent cellular cytotoxicity (ADCC) and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , Humans , Macaca mulatta , Vaccines, Inactivated/immunology , Vaccines, Inactivated/pharmacology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/pharmacology
5.
Matter ; 5(2): 694-709, 2022 Feb 02.
Article in English | MEDLINE | ID: covidwho-1670871

ABSTRACT

The current COVID-19 pandemic urges us to develop ultra-sensitive surface-enhanced Raman scattering (SERS) substrates to identify the infectiousness of SARS-CoV-2 virions in actual environments. Here, a micrometer-sized spherical SnS2 structure with the hierarchical nanostructure of "nano-canyon" morphology was developed as semiconductor-based SERS substrate, and it exhibited an extremely low limit of detection of 10-13 M for methylene blue, which is one of the highest sensitivities among the reported pure semiconductor-based SERS substrates. Such ultra-high SERS sensitivity originated from the synergistic enhancements of the molecular enrichment caused by capillary effect and the charge transfer chemical enhancement boosted by the lattice strain and sulfur vacancies. The novel two-step SERS diagnostic route based on the ultra-sensitive SnS2 substrate was presented to diagnose the infectiousness of SARS-CoV-2 through the identification standard of SERS signals for SARS-CoV-2 S protein and RNA, which could accurately identify non-infectious lysed SARS-CoV-2 virions in actual environments, whereas the current PCR methods cannot.

6.
Int J Environ Res Public Health ; 19(3)2022 01 25.
Article in English | MEDLINE | ID: covidwho-1648638

ABSTRACT

Vaccination plays an essential role in the fight against Coronavirus Disease 2019 (COVID-19). The currently insufficient vaccine production capacity makes it difficult to balance supply with demand, which has led to a contradiction between command demand and limited supply. According to analysis based on game theory, the attributes of COVID-19 vaccines vary with supply strategies formulated by vaccine-producing countries. This means that vaccine-receiving countries can only be motivated to prepare operable vaccine distribution plans through the supply of COVID-19 vaccines as global public goods. The rational distribution of global public goods must be guaranteed by a global supply institution system. To that end, Elinor Ostrom's eight design principles provide a basis for designing such a global supply system. This paper proposes a nested institution solution for guaranteeing the global supply of COVID-19 vaccines based on the design principles, which include clearly defined boundaries, proportional equivalence between benefits and costs, collective-choice arrangements, monitoring, graduated sanctions, conflict-resolution mechanisms, minimal recognition of rights to organize, and nested enterprises. To win this global fight against COVID-19, COVID-19 vaccines must not only be treated as global public goods, but countries must also be urged to coordinate cooperation in global institutional design, thus ensuring that COVID-19 vaccines can truly benefit all mankind.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
7.
J Infect Dev Ctries ; 15(12): 1808-1812, 2021 12 31.
Article in English | MEDLINE | ID: covidwho-1639503

ABSTRACT

Beginning in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly resulted in a worldwide pandemic. Many patients with coronavirus disease-19 (COVID-19) require invasive ventilation due to severe respiratory failure. However, many medical hospitals experienced shortages of personal protective equipment, increasing the risk of healthcare workers contracting an infection. However, we report a case of acute respiratory distress syndrome during the early stage of COVID-19 treated at a university hospital outside of Wuhan, China. We described the optimization of healthcare worker personal protection and a procedure for airway management in the context of insufficient personal protective equipment. This report may provide a reference for resource-limited settings in low- and middle-income countries, even countries where healthcare systems have been overwhelmed by the pandemic.


Subject(s)
COVID-19/transmission , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Personal Protective Equipment/supply & distribution , COVID-19/epidemiology , China/epidemiology , Fatal Outcome , Humans , Intubation, Intratracheal/adverse effects , Male , Middle Aged , Pandemics , SARS-CoV-2
9.
Open forum infectious diseases ; 8(Suppl 1):S361-S361, 2021.
Article in English | EuropePMC | ID: covidwho-1564485

ABSTRACT

Background BRII-196 and BRII-198 are human monoclonal antibodies (mAb) with an extended half-life targeting distinct epitopes of the spike protein on SARS-CoV-2. Mutations in these epitope regions are continuously emerging, potentially conferring resistance to COVID-19 therapeutics in development. Individual phase I studies showed that BRII-196 or BRII-198 alone were safe and well tolerated in healthy subjects. The BRII-196 and BRII-198 cocktail is currently under evaluation in Phase 2/3 studies for the treatment of COVID-19. Methods Preclinical study: BRII-196 and BRII-198 were evaluated in the microneutralization assay using pseudo-viruses encoding mutations identified in the spike protein of a panel of SARS-CoV-2 variants of concerns, including strains originating in UK, SA, BR, CA, and India. The fold-change in neutralization IC50 titers relative to wild-type virus was calculated. Phase 1 study: healthy adults received sequential IV BRII-196 and BRII-198 (n=9) or placebo (n=3);and were followed for 180 days. Two dose levels (750mg/750mg and 1500mg/1500mg) were evaluated for safety, pharmacokinetics and immunogenicity. Interim analysis results are presented. Results Preclinical: BRII-196 and BRII-198 exhibited neutralizing activity against pseudo-virus variants that contained spike mutations of a panel of variants including B.1.1.7 (UK), B.1.351(SA), P.1(BR), B.1.427/429 (CA), B.1.526 (NY), and B.1.617 (IN), comparable to that against wild-type virus. Phase I study: BRII-196 plus BRII-198 was well tolerated with no dose-limiting adverse events (AEs), deaths, serious adverse events, or infusion reactions. The majority of AEs were isolated asymptomatic grade 1-2 laboratory abnormalities. (Table 1). Each mAb displayed pharmacokinetic characteristics expected of extended half-life YTE-antibodies. Conclusion The BRII-196 and BRII-198 cocktail was well-tolerated, and maintains neutralization against currently reported circulating variants of concern. These preclinical and clinical results support further development of BRII-196 and BRII-198 as a therapeutic or prophylactic option for SARS-CoV-2. Disclosures David A. Margolis, MD MPH, Brii Biosciences (Employee) Yao Zhang, MD, Brii Biosciences (Employee) Yun Ji, PhD, Brii Biosciences (Employee, Shareholder)

10.
Infect Drug Resist ; 14: 4641-4655, 2021.
Article in English | MEDLINE | ID: covidwho-1523538

ABSTRACT

OBJECTIVE: COVID-19 may have a demonstrable influence on disease patterns. However, it remained unknown how tuberculosis (TB) epidemics are impacted by the COVID-19 outbreak. The purposes of this study are to evaluate the impacts of the COVID-19 outbreak on the decreases in the TB case notifications and to forecast the epidemiological trends in China. METHODS: The monthly TB incidents from January 2005 to December 2020 were taken. Then, we investigated the causal impacts of the COVID-19 pandemic on the TB case reductions using intervention analysis under the Bayesian structural time series (BSTS) method. Next, we split the observed values into different training and testing horizons to validate the forecasting performance of the BSTS method. RESULTS: The TB incidence was falling during 2005-2020, with an average annual percentage change of -3.186 (95% confidence interval [CI] -4.083 to -2.281), and showed a peak in March-April and a trough in January-February per year. The BSTS method assessed a monthly average reduction of 14% (95% CI 3.8% to 24%) in the TB case notifications from January-December 2020 owing to COVID-19 (probability of causal effect=99.684%, P=0.003), and this method generated a highly accurate forecast for all the testing horizons considering the small forecasting error rates and estimated a continued downward trend from 2021 to 2035 (annual percentage change =-2.869, 95% CI -3.056 to -2.681). CONCLUSION: COVID-19 can cause medium- and longer-term consequences for the TB epidemics and the BSTS model has the potential to forecast the epidemiological trends of the TB incidence, which can be recommended as an automated application for public health policymaking in China. Considering the slow downward trend in the TB incidence, additional measures are required to accelerate the progress of the End TB Strategy.

12.
Infect Drug Resist ; 14: 3849-3862, 2021.
Article in English | MEDLINE | ID: covidwho-1459502

ABSTRACT

OBJECTIVE: We aim to examine the adequacy of an innovation state-space modeling framework (called TBATS) in forecasting the long-term epidemic seasonality and trends of hemorrhagic fever with renal syndrome (HFRS). METHODS: The HFRS morbidity data from January 1995 to December 2020 were taken, and subsequently, the data were split into six different training and testing segments (including 12, 24, 36, 60, 84, and 108 holdout monthly data) to investigate its predictive ability of the TBATS method, and its forecasting performance was compared with the seasonal autoregressive integrated moving average (SARIMA). RESULTS: The TBATS (0.27, {0,0}, -, {<12,4>}) and SARIMA (0,1,(1,3))(0,1,1)12 were selected as the best TBATS and SARIMA methods, respectively, for the 12-step ahead prediction. The mean absolute deviation, root mean square error, mean absolute percentage error, mean error rate, and root mean square percentage error were 91.799, 14.772, 123.653, 0.129, and 0.193, respectively, for the preferred TBATS method and were 144.734, 25.049, 161.671, 0.203, and 0.296, respectively, for the preferred SARIMA method. Likewise, for the 24-, 36-, 60-, 84-, and 108-step ahead predictions, the preferred TBATS methods produced smaller forecasting errors over the best SARIMA methods. Further validations also suggested that the TBATS model outperformed the Error-Trend-Seasonal framework, with little exception. HFRS had dual seasonal behaviors, peaking in May-June and November-December. Overall a notable decrease in the HFRS morbidity was seen during the study period (average annual percentage change=-6.767, 95% confidence intervals: -10.592 to -2.778), and yet different stages had different variation trends. Besides, the TBATS model predicted a plateau in the HFRS morbidity in the next ten years. CONCLUSION: The TBATS approach outperforms the SARIMA approach in estimating the long-term epidemic seasonality and trends of HFRS, which is capable of being deemed as a promising alternative to help stakeholders to inform future preventive policy or practical solutions to tackle the evolving scenarios.

14.
J Psychosoc Nurs Ment Health Serv ; 60(1): 17-22, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1305848

ABSTRACT

The current study aimed to identify the main stressors inherent to caring for patients with coronavirus disease 2019 (COVID-19) and associated mental health outcomes among frontline health care workers. Data were collected via an online questionnaire from 651 frontline health care workers providing direct medical services for patients with suspected or confirmed COVID-19. Participants reported the stressors inherent to caring for patients with COVID-19, including depression, anxiety, and insomnia. Data were analyzed using descriptive statistics and multivariable logistic regression analysis. The most common stressors were "Worry about being negligent and endangering coworkers" (76.2%), "Worry about getting infected" (74.7%), and "Protective gear causing physical discomfort" (73.6%). "Conflict between duty and safety" and "Protective gear causing physical discomfort" were linked to high risk of depression, anxiety, and insomnia. Findings suggest that frontline health care workers may develop adverse mental health outcomes in the face of certain stressors, requiring targeted interventions. [Journal of Psychosocial Nursing and Mental Health Services, 60(1), 17-22.].


Subject(s)
COVID-19 , Anxiety , China , Cross-Sectional Studies , Depression , Health Personnel , Humans , Mental Health , Outcome Assessment, Health Care , SARS-CoV-2
15.
Front Psychol ; 12: 679661, 2021.
Article in English | MEDLINE | ID: covidwho-1295699

ABSTRACT

Since the end of 2019, the outbreak of the COVID-19 pandemic has engendered widespread fear and anxiety across China. Nearly half a million international students pursuing their studies in Chinese universities have also been exposed to the psychological distress triggered by the unfolding crisis. In addition to government and medical institutions' efforts, universities have also endeavored to mitigate concerns among these students under quarantine on campus by providing reliable information as well as medical, monetary, and emotional support. In this study, international students' trust in university management teams and its role in remediating their anxieties were evaluated using an online survey conducted after 10 days of the lockdown of Wuhan, China. The empirical analysis incorporates quantitative data from 180 international students. Ordinary least squares regression and probit regression were used in the analysis with the non-robust and robust models. The study found students' perception of trust in university management to be negatively associated with their anxiety levels. Additionally, having trust in university management was found to positively influence students' commitment to the self-quarantine guidelines. These results reinforce the important role of universities and their relationship with international students during public health emergencies.

16.
Bioconjug Chem ; 32(5): 1034-1046, 2021 05 19.
Article in English | MEDLINE | ID: covidwho-1217668

ABSTRACT

SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 µg of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross-neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 × 105 CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Nanoparticles/chemistry , Spike Glycoprotein, Coronavirus/metabolism , T-Lymphocytes/immunology , Animals , Antibodies, Neutralizing/immunology , Binding Sites , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Ferritins/chemistry , Ferritins/metabolism , Immunity, Humoral , Macaca mulatta , Male , Nanoparticles/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/metabolism , Ultracentrifugation
17.
Medicine (Baltimore) ; 99(51): e23547, 2020 Dec 18.
Article in English | MEDLINE | ID: covidwho-1010676

ABSTRACT

ABSTRACT: This study aims to investigate the clinical characteristics and viral shedding kinetics of asymptomatic patients with coronavirus disease 2019 (COVID-19).The data of 38 asymptomatic patients positive for SARS-CoV-2 nucleic acid were collected from February to March 2020 in Tuanfeng County, Huanggang, Hubei, China. The epidemiology, laboratory examination, chest imaging, viral nucleic acid test results, clinical characteristics, and viral shedding time were summarized in this retrospective study.The study included 20 family members of patients with COVID-19, 10 medical personnel participating in COVID-19 treatment or working in a fever clinic, 6 personnel from quarantine places, 1 individual with a close contact history with confirmed patients, and 1 local epidemic prevention personnel. All were positive for SARS-CoV-2 nucleic acid. The white blood cell (WBC) count, the absolute value of lymphocytes, C-reactive protein (CRP), and D-dimer were normal. Pneumonia manifestations were not found in the chest computed tomography (CT) scan of 36 patients; the remaining 2 cases included a 1-year-old child and a pregnant woman, and they did not undergo chest CT. The viral shedding time was 6 days.All asymptomatic patients with COVID-19 had a history of close contact or exposure. Laboratory tests were normal. Chest imaging did not show any pneumonia manifestation. The viral shedding time was <10 days, which is shorter than that of patients with COVID-19. A timely discovery of such asymptomatic infections is crucial for blocking the spread of the virus and strengthening the prevention and control measures.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19/virology , SARS-CoV-2 , Virus Shedding , Adolescent , Adult , Asymptomatic Infections/therapy , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/epidemiology , Child , China/epidemiology , Female , Humans , Indoles/therapeutic use , Infant , Male , Medicine, Chinese Traditional , Middle Aged , Radiography, Thoracic , Retrospective Studies , Young Adult
18.
PLoS Pathog ; 16(11): e1008949, 2020 11.
Article in English | MEDLINE | ID: covidwho-922716

ABSTRACT

The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5-7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1ß), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1ß/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Pneumonia, Viral/pathology , Animals , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Cytokines/immunology , Disease Models, Animal , Lung/immunology , Lung/pathology , Macaca mulatta , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Viral Load/methods , Virulence , Virus Shedding
20.
SSRN; 2020.
Preprint | SSRN | ID: ppcovidwho-1686

ABSTRACT

Background: To investigate the clinical characteristics and viral shedding kinetics of asymptomatic patients with COVID-19. brbrMethods: The data of 38 asy

SELECTION OF CITATIONS
SEARCH DETAIL