Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 168
Filter
Add filters

Year range
2.
J Mater Chem B ; 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1634680

ABSTRACT

In this study, we developed a crystal-reconstructed-BiVO4 aptamer photoelectrochemical (PEC) biosensor by a high-energy laser treatment technique. This biosensor achieves a limit of detection (LOD) (0.82 ag mL-1), linear detection range (1 ag mL-1 to 2 ng mL-1), and resolution ratio (∼18 molecules per mL) for prostate-specific antigen (PSA) tumor biomarker detection. Furthermore, reconstructed surface microstructure and oxygen vacancy doping energy formation after crystal reconstruction induce the stereo-hindrance effect and photogenerated hole energy is reduced during PSA target detection. In this case, a photocurrent inhibition phenomenon for PSA detection is noticed. Based on this photocurrent inversion phenomenon, some dysoxidizable nucleonic acid tumor (miRNA-21) and virus biomarkers (RdRp-COVID) can be detected with a LOD level of ∼10-16 M by linking the corresponding base paring probe on the surface of the crystal-reconstructed photoanode. In addition to high sensitivity, this PEC biosensor presents high detection specificity, stability, and accuracy in clinical verification. Thus, this crystal-reconstructed PEC biosensor shows application potential in the fields of multi-tumor or viral biomarker detection.

3.
Hum Brain Mapp ; 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1627415

ABSTRACT

The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta-burst stimulation (iTBS) can improve WM. In this within-subject randomized controlled study, under the guidance of fMRI-identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K-score were then calculated to reflect neural and behavioral WM improvement. Repeated-measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere-by-iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated-measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.

4.
Preprint in English | bioRxiv | ID: ppbiorxiv-475291

ABSTRACT

Emerging SARS-CoV-2 variants are threatening the efficacy of antibody therapies. Combination treatments including ACE2-Fc have been developed to overcome the evasion of neutralizing antibodies (NAbs) in individual cases. Here we conducted a comprehensive evaluation of this strategy by combining ACE2-Fc with NAbs of diverse epitopes on the RBD. NAb+ACE2-Fc combinations efficiently neutralized HIV-based pseudovirus carrying the spike protein of the Delta or Omicron variants, achieving a balance between efficacy and breadth. In an antibody escape assay using replication-competent VSV-SARS-CoV-2-S, all the combinations had no escape after fifteen passages. By comparison, all the NAbs without combo with ACE2-Fc had escaped within six passages. Further, the VSV-S variants escaped from NAbs were neutralized by ACE2-Fc, revealing the mechanism of NAb+ACE2-Fc combinations survived after fifteen passages. We finally examined ACE2-Fc neutralization against pseudovirus variants resistant to the therapeutic antibodies that have currently been in clinic. Our results suggest ACE2-Fc is a universal combination partner to combat SARS-CoV-2 variants including Delta and Omicron.

5.
BMC Psychiatry ; 22(1): 33, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1622219

ABSTRACT

BACKGROUND: A global public health emergency triggered by the Coronavirus Disease 2019 (COVID-19) epidemic may have are markable psychological impact on the population. There is still limited psychological research on police officers, especially prison officers in the process of enforcing the law. The present study aims to identify prevalence and influencing factors on mental health status among frontline prison officers in China during the prevention and control of the COVID-19 epidemic. METHODS: A cross-sectional survey with a sample of 981 frontline prison officers was conducted using snowball sampling approach. The self-administered questionnaire consisted of 4 parts: (i) informed consent form; (ii) socio-demographic section; (iii) work and life situations during the prevention and control of the COVID-19 epidemic; (iv) the Chinese version of the 12-item General Health Questionnaire (GHQ-12). Univariate analysis and multivariable logistic regression were performed to identify factors influencing mental health status. RESULTS: The prevalence of being prone to mental health problems (GHQ-12 score ≥ 4) was 33.43% among frontline prison officers. The results of GHQ-12 factors analysis indicated that the prison officers suffered from psychological issues was related to anxiety and depression, which main symptoms were unhappy and depressed, lost sleep over worry and constantly under strain. Multivariate logistic regression analysis revealed that male (OR = 1.573, 95% CI:1.385-1.853), lockdown shift inside the prison(OR = 2.203, 95% CI:2.139-2.297), more night shifts (OR = 2.163, 95% CI:2.031-2.317; OR = 2.749, 95% CI:2.194-2.901), more smoking (OR = 1.100, 95% CI:1.037-2.168), poor self-reported physical condition (OR = 1.947, 95% CI:1.478-2.250), chronic or serious illness history(OR = 1.870, 95% CI:1.314-2.660; OR = 2.214, 95% CI:1.460-2.812) were risk factors for mental health among frontline prison officers, while regular diet (OR = 0.779, 95% CI:0.539-0.928), more physical exercise (OR = 0.702, 95% CI:0.548-0.899; OR = 0.641, 95% CI:0.316-0.887), more communication with family members (OR = 0.437, 95% CI:0.295-0.616) were protective factors. CONCLUSION: Chinese frontline prison officers experienced different psychological stress coming from the prevention and control of this epidemic. Therefore, continued surveillance of psychological problems and targeted mental health care for frontline prison officers were urgent.


Subject(s)
COVID-19 , Prisons , Anxiety , China/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Depression , Health Status , Humans , Male , SARS-CoV-2 , Surveys and Questionnaires
6.
Preprint in English | medRxiv | ID: ppmedrxiv-22269182

ABSTRACT

Patients with chronic kidney disease (CKD) are at higher risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. However, a significant portion of CKD patients showed hesitation toward vaccination in telephone survey of our center. Yet no serial data available on humoral response in patients with CKD, especially those on immunosuppression. We conducted a pilot, prospective study to survey the safety and humoral response to inactivated SARS-CoV-2 vaccine in CKD patients receiving a 2-dose immunization of inactivated SARS-CoV-2 vaccine. We found the neutralizing antibody titers in CKD patients was significantly lower than that in healthy controls, hypertension patients, and diabetes patients. Notably, immunosuppressive medication rather than eGFR levels or disease types showed effect on the reduction of immunogenicity. Interestingly, a third dose significantly boosted neutralizing antibody in CKD patients while immunosuppressants impeded the boosting effects. In conclusion, our data demonstrates that CKD patients, even for those on immunosuppression treatment, can benefit from a third vaccination boost by improving their humoral immunity.

7.
Biosaf Health ; 2021 Dec 25.
Article in English | MEDLINE | ID: covidwho-1588184

ABSTRACT

Although significant achievements have shown that the COVID-19 resurgence in Beijing, China, was initiated by contaminated frozen products and transported via cold chain transportation, international travelers with asymptomatic symptoms or false-negative nucleic acid may have another possible transmission mode that spread the virus into Beijing. One of the key differences between these two assumptions was whether the virus actively replicated since, so far, no reports showed viruses could stop evolution in alive hosts. We studied SARS-CoV-2 sequences in this outbreak by a modified leaf-dating method with the Bayes factor. The numbers of single nucleotide variants (SNVs) found in SARS-CoV-2 sequences were significantly lower than those called from B.1.1 records collected at the matching time worldwide (p = 0.047). In addition, results of the Leaf-dating method showed ages of viruses sampled from this outbreak were earlier than their recorded dates of collection (Bayes factors > 10), while control sequences (selected randomly with ten replicates) showed no differences in their collection dates (Bayes factors < 10). Our results which indicated that the re-emergence of SARS-CoV-2 in Beijing in June 2020 was caused by a virus that exhibited a lack of evolutionary changes compared to viruses collected at the corresponding time, provided evolutionary evidence to the contaminated imported frozen food should be responsible for the reappearance of COVID-19 cases in Beijing. The method developed here might also be helpful to provide the very first clues for potential sources of COVID-19 cases in the future.

8.
J Clin Epidemiol ; 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1587327

ABSTRACT

AIM: To describe the current status of COVID-19 vaccine guidelines. STUDY DESIGN AND SETTING: We searched databases, Google and guideline platforms to retrieve COVID-19 vaccine guidelines published between January 1, 2020 and July 8, 2021. We worked in pairs to identify the eligible guidelines and extract data of whether the methodology, funding, and conflict of interests were assessed/reported, and so on. Results were presented descriptively. RESULTS: A total of 106 COVID-19 vaccine guidelines were included. In the first half of 2021, on average 15 guidelines were published every month. Fifty (47.2%) guidelines addressed the vaccination of people with specific medical conditions, and 18 (17.0%) guidelines focused on adverse effects after vaccination. Only 28 (26.4%) guidelines reported the methodology they used. Four (3.8%) of guidelines assessed both the quality of evidence and strength of recommendations; 42 (39.6%) and 65 (61.3%) guidelines reported their funding sources and conflict of interest, respectively. Most guidelines were published in English (n=92, 86.8%). CONCLUSION: A high number of guidelines on COVID-19 vaccines have been published in the recent months, but most of them lack clear and transparent reporting of methodology, funding, and conflicts of interest. Rigorous methodological and reporting quality evaluation of these guidelines is needed.

9.
PLoS One ; 16(12): e0261236, 2021.
Article in English | MEDLINE | ID: covidwho-1581757

ABSTRACT

In the past year, the global epidemic situation is still not optimistic, showing a trend of continuous expansion. With the research and application of vaccines, there is an urgent need to develop some optimal vaccination strategies. How to make a reasonable vaccination strategy to determine the priority of vaccination under the limited vaccine resources to control the epidemic and reduce human casualties? We build a dynamic model with vaccination which is extended the classical SEIR model. By fitting the epidemic data of three countries-China, Brazil, Indonesia, we have evaluated age-specific vaccination strategy for the number of infections and deaths. Furthermore, we have evaluated the impact of age-specific vaccination strategies on the number of the basic reproduction number. At last, we also have evaluated the different age structure of the vaccination priority. It shows that giving priority to vaccination of young people can control the number of infections, while giving priority to vaccination of the elderly can greatly reduce the number of deaths in most cases. Furthermore, we have found that young people should be mainly vaccinated to reduce the number of infections. When the emphasis is on reducing the number of deaths, it is important to focus vaccination on the elderly. Simulations suggest that appropriate age-specific vaccination strategies can effectively control the epidemic, both in terms of the number of infections and deaths.

10.
Anal Biochem ; 635: 114445, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1565506

ABSTRACT

The outbreak of COVID-19 makes epidemic prevention and control become a growing global concern. Nucleic acid amplification testing (NAAT) can realize early and rapid detection of targets, thus it is considered as an ideal approach for detecting pathogens of severe acute infectious diseases. Rapid acquisition of high-quality target nucleic acid is the prerequisite to ensure the efficiency and accuracy of NAAT. Herein, we proposed a simple system in which magnetic nanoparticles (MNPs) based nucleic acid extraction was carried out in a plastic Pasteur pipette. Different from traditional approaches, this proposed system could be finished in 15 min without the supports of any electrical instruments. Furthermore, this system was superior to traditional MNPs based extraction methods in the aspects of rapid extraction and enhancing the sensitivity of a NAAT method, accelerated denaturation bubbles mediated strand exchange amplification (ASEA), to the pathogens from various artificial samples. Finally, this Pasteur pipette system was utilized for pathogen detection in actual samples of throat swabs, cervical swabs and gastric mucosa, the diagnosis results of which were identical with that provided by hospital. This rapid, easy-performing and efficiency extraction method ensures the applications of the NAAT in pathogen detection in regions with restricted resources.

11.
Biomed Signal Process Control ; 73: 103415, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1559225

ABSTRACT

The quick and precise identification of COVID-19 pneumonia, non-COVID-19 viral pneumonia, bacterial pneumonia, mycoplasma pneumonia, and normal lung on chest CT images play a crucial role in timely quarantine and medical treatment. However, manual identification is subject to potential misinterpretations and time-consumption issues owing the visual similarities of pneumonia lesions. In this study, we propose a novel multi-scale attention network (MSANet) based on a bag of advanced deep learning techniques for the automatic classification of COVID-19 and multiple types of pneumonia. The proposed method can automatically pay attention to discriminative information and multi-scale features of pneumonia lesions for better classification. The experimental results show that the proposed MSANet can achieve an overall precision of 97.31%, recall of 96.18%, F1-score of 96.71%, accuracy of 97.46%, and macro-average area under the receiver operating characteristic curve (AUC) of 0.9981 to distinguish between multiple classes of pneumonia. These promising results indicate that the proposed method can significantly assist physicians and radiologists in medical diagnosis. The dataset is publicly available at https://doi.org/10.17632/rf8x3wp6ss.1.

12.
Sci Rep ; 11(1): 23465, 2021 Dec 06.
Article in English | MEDLINE | ID: covidwho-1556248

ABSTRACT

Human coronavirus NL63 (HCoV-NL63) mainly affects young children and immunocompromised patients, causing morbidity and mortality in a subset of patients. Since no specific treatment is available, this study aims to explore the anti-SARS-CoV-2 agents including favipiravir and remdesivir for treating HCoV-NL63 infection. We first successfully modelled the 3D structure of HCoV-NL63 RNA-dependent RNA polymerase (RdRp) based on the experimentally solved SARS-CoV-2 RdRp structure. Molecular docking indicated that favipiravir has similar binding affinities to SARS-CoV-2 and HCoV-NL63 RdRp with LibDock scores of 75 and 74, respectively. The LibDock scores of remdesivir to SARS-CoV-2 and HCoV-NL63 were 135 and 151, suggesting that remdesivir may have a higher affinity to HCoV-NL63 compared to SARS-CoV-2 RdRp. In cell culture models infected with HCoV-NL63, both favipiravir and remdesivir significantly inhibited viral replication and production of infectious viruses. Overall, remdesivir compared to favipiravir is more potent in inhibiting HCoV-NL63 in cell culture. Importantly, there is no evidence of resistance development upon long-term exposure to remdesivir. Furthermore, combining favipiravir or remdesivir with the clinically used antiviral cytokine interferon-alpha resulted in synergistic effects. These findings provided a proof-of-concept that anti-SARS-CoV-2 drugs, in particular remdesivir, have the potential to be repurposed for treating HCoV-NL63 infection.

13.
Preprint in English | EuropePMC | ID: ppcovidwho-296391

ABSTRACT

mRNA vaccine was approved clinically in 2020. Future development includes delivering mRNA to dendritic cells (DCs) specifically to improve effectiveness and avoid off-target cytotoxicity. Here, we developed virus-like particles (VLPs) as a DC tropic mRNA vaccine vector and showed the prophylactic effects in both SARS-CoV-2 and HSV-1 infection models. The VLP mRNA vaccine elicited strong cytotoxic T cell immunity and durable antibody response with the spike-specific antibodies that lasted for more than 9 months. Importantly, we were able to target mRNA to DCs by pseudotyping VLP with engineered Sindbis virus glycoprotein and found the DC-targeting mRNA vaccine significantly enhanced the titer of antigen-specific IgG, protecting the hACE-2 mice from SARS-CoV-2 infection. Additionally, we showed DC-targeted mRNA vaccine also protected mice from HSV-1 infection when co-delivering the gB and gD mRNA. Thus, the VLP may serve as an in situ DC vaccine and accelerate the further development of mRNA vaccines.

14.
Preprint in English | EuropePMC | ID: ppcovidwho-294684

ABSTRACT

COVID-19 has become a global pandemic and is still posing a severe health risk to the public. Accurate and efficient segmentation of pneumonia lesions in CT scans is vital for treatment decision-making. We proposed a novel unsupervised approach using cycle consistent generative adversarial network (cycle-GAN) which automates and accelerates the process of lesion delineation. The workflow includes lung volume segmentation, "synthetic" healthy lung generation, infected and healthy image subtraction, and binary lesion mask creation. The lung volume volume was firstly delineated using a pre-trained U-net and worked as the input for the later network. The cycle-GAN was developed to generate synthetic "healthy" lung CT images from infected lung images. After that, the pneumonia lesions are extracted by subtracting the synthetic "healthy" lung CT images from the "infected" lung CT images. A median filter and K-means clustering were then applied to contour the lesions. The auto segmentation approach was validated on two public datasets (Coronacases and Radiopedia). The Dice coefficients reached 0.748 and 0.730, respectively, for the Coronacases and Radiopedia datasets. Meanwhile, the precision and sensitivity for lesion segmentationdetection are 0.813 and 0.735 for the Coronacases dataset, and 0.773 and 0.726 for the Radiopedia dataset. The performance is comparable to existing supervised segmentation networks and outperforms previous unsupervised ones. The proposed unsupervised segmentation method achieved high accuracy and efficiency in automatic COVID-19 lesion delineation. The segmentation result can serve as a baseline for further manual modification and a quality assurance tool for lesion diagnosis. Furthermore, due to its unsupervised nature, the result is not influenced by physicians' experience which otherwise is crucial for supervised methods.

15.
PLoS One ; 16(12): e0260940, 2021.
Article in English | MEDLINE | ID: covidwho-1551304

ABSTRACT

The resilience and vulnerability of airport networks are significant challenges during the COVID-19 global pandemic. Previous studies considered node failure of networks under natural disasters and extreme weather. Herein, we propose a complex network methodology combined with data-driven to assess the resilience of airport networks toward global-scale disturbance using the Chinese airport network (CAN) and the European airport network (EAN) as a case study. The assessment framework includes vulnerability and resilience analyses from the network- and node-level perspectives. Subsequently, we apply the framework to analyze the airport networks in China and Europe. Specifically, real air traffic data for 232 airports in China and 82 airports in Europe are selected to form the CAN and EAN, respectively. The complex network analysis reveals that the CAN and the EAN are scale-free small-world networks, that are resilient to random attacks. However, the connectivity and vulnerability of the CAN are inferior to those of the EAN. In addition, we select the passenger throughput from the top-50 airports in China and Europe to perform a comparative analysis. By comparing the resilience evaluation of individual airports, we discovered that the factors of resilience assessment of an airport network for global disturbance considers the network metrics and the effect of government policy in actual operations. Additionally, this study also proves that a country's emergency response-ability towards the COVID-19 has a significantly affectes the recovery of its airport network.

16.
Int J Infect Dis ; 2021 Dec 02.
Article in English | MEDLINE | ID: covidwho-1549834

ABSTRACT

IMPORTANCE: Since January 2020, Singapore has implemented comprehensive measures to suppress SARS-CoV-2. Despite this, the country has experienced contrasting epidemics, with limited transmission in the community and explosive outbreaks in migrant worker dormitories. OBJECTIVE: To estimate SARS-CoV-2 infection incidence among migrant workers and the general population in Singapore. DESIGN: Prospective serological cohort studies. SETTING: Two cohort studies in a migrant worker dormitory and in the general population in Singapore. PARTICIPANTS: We followed up 478 residents of a SARS-CoV-2 affected migrant worker dormitory between May and July 2020, collecting blood samples at recruitment and after two and six weeks. We also recruited 937 community-dwelling adult Singapore residents for whom pre-pandemic sera were available. These individuals also provided a serum sample at recruitment in November/December 2020. EXPOSURE: Exposure to SARS-CoV-2 in a densely populated migrant worker dormitory and in the general population. MAIN OUTCOMES AND MEASURES: The main outcome measures were the incidence of SARS-CoV-2 infection in migrant workers and in the general population, as determined by the detection of neutralising antibodies against SARS-CoV-2 and adjusting for assay sensitivity and specificity using a Bayesian modelling framework. RESULTS: We found no evidence of community SARS-CoV-2 exposure in Singapore prior to September 2019. We estimated that <2 per 1000 adult residents in the community were infected with SARS-CoV-2 in 2020 (cumulative seroprevalence: 0.16% (95% CrI: 0.008% - 0.72%). Comparison with comprehensive national case notification data suggests that around 1 in 4 infections in the general population is associated with symptoms. In contrast, in the migrant worker cohort, nearly two-thirds had been infected by July 2020 (cumulative seroprevalence: 63.8% (95% CrI: 57.9% - 70.3%); no symptoms were reported in almost all of these infections. CONCLUSIONS AND RELEVANCE: Our findings demonstrate that SARS-CoV-2 suppression is possible with strict and rapid implementation of border restrictions, case isolation, contact tracing, quarantining and social distancing measures. However, the risk of large-scale epidemics in densely-populated environments requires specific consideration in preparedness planning. Prioritisation of these settings in vaccination strategies should minimise risk of future resurgences and potential spillover of transmission to the wider community.

17.
Preprint in English | EuropePMC | ID: ppcovidwho-293476

ABSTRACT

mRNA vaccine was approved clinically in 2020. Future development includes delivering mRNA to dendritic cells (DCs) specifically to improve effectiveness and avoid off-target cytotoxicity. Here, we developed virus-like particles (VLPs) as a DC tropic mRNA vaccine vector and showed the prophylactic effects in both SARS-CoV-2 and HSV-1 infection models. The VLP mRNA vaccine elicited strong cytotoxic T cell immunity and durable antibody response with the spike-specific antibodies that lasted for more than 9 months. Importantly, we were able to target mRNA to DCs by pseudotyping VLP with engineered Sindbis virus glycoprotein and found the DC-targeting mRNA vaccine significantly enhanced the titer of antigen-specific IgG, protecting the hACE-2 mice from SARS-CoV-2 infection. Additionally, we showed DC-targeted mRNA vaccine also protected mice from HSV-1 infection when co-delivering the gB and gD mRNA. Thus, the VLP may serve as an in situ DC vaccine and accelerate the further development of mRNA vaccines.

18.
Journal of Advanced Research ; 2021.
Article in English | ScienceDirect | ID: covidwho-1536633

ABSTRACT

Introduction The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1,034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results Nonsurvivors (n=955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n=79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Conclusions Our findings might have important implications for improving clinical management of COVID-19 patients.

19.
Preprint in English | EuropePMC | ID: ppcovidwho-292882

ABSTRACT

Inhibitors of Bromodomain and Extra-terminal domain (BET) proteins are possible anti-SARS-CoV-2 prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here, we show that BET proteins should not be inactivated therapeutically as they are critical antiviral factors at the post-entry level. Knockouts of BRD3 or BRD4 in cells overexpressing ACE2 exacerbate SARS-CoV-2 infection;the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection, and not before. Viral replication and mortality are also enhanced in BET inhibitor-treated mice overexpressing ACE2. BET inactivation suppresses interferon production induced by SARS-CoV-2, a process phenocopied by the envelope (E) protein previously identified as a possible "histone mimetic." E protein, in an acetylated form, directly binds the second bromodomain of BRD4. Our data support a model where SARS-CoV-2 E protein evolved to antagonize interferon responses via BET protein inhibition;this neutralization should not be further enhanced with BET inhibitor treatment.

20.
Emerg Microbes Infect ; 10(1): 2141-2150, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1532382

ABSTRACT

BACKGROUND: We studied humoral and cellular responses against SARS-CoV-2 longitudinally in a homogeneous population of healthy young/middle-aged men of South Asian ethnicity with mild COVID-19. METHODS: In total, we recruited 994 men (median age: 34 years) post-COVID-19 diagnosis. Repeated cross-sectional surveys were conducted between May 2020 and January 2021 at six time points - day 28 (n = 327), day 80 (n = 202), day 105 (n = 294), day 140 (n = 172), day 180 (n = 758), and day 280 (n = 311). Three commercial assays were used to detect anti-nucleoprotein (NP) and neutralizing antibodies. T cell response specific for Spike, Membrane and NP SARS-CoV-2 proteins was tested in 85 patients at day 105, 180, and 280. RESULTS: All serological tests displayed different kinetics of progressive antibody reduction while the frequency of T cells specific for different structural SARS-CoV-2 proteins was stable over time. Both showed a marked heterogeneity of magnitude among the studied cohort. Comparatively, cellular responses lasted longer than humoral responses and were still detectable nine months after infection in the individuals who lost antibody detection. Correlation between T cell frequencies and all antibodies was lost over time. CONCLUSION: Humoral and cellular immunity against SARS-CoV-2 is induced with differing kinetics of persistence in those with mild disease. The magnitude of T cells and antibodies is highly heterogeneous in a homogeneous study population. These observations have implications for COVID-19 surveillance, vaccination strategies, and post-pandemic planning.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Antibodies, Neutralizing/blood , Cross-Sectional Studies , Humans , Male , Nucleocapsid Proteins/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...