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1.
J Infect ; 2020 Mar 03.
Article in English | MEDLINE | ID: covidwho-1639594

ABSTRACT

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

2.
BMC Pediatr ; 22(1): 53, 2022 Jan 20.
Article in English | MEDLINE | ID: covidwho-1638111

ABSTRACT

BACKGROUND: After the outbreak of COVID-19, many families equip with 75% ethanol to inactivate the SARS-CoV-2, which increases the risk of exposure to ethanol. CASE PRESENTATION: We reported a 25-day-old newborn who was diagnosed with neonatal acute ethanol intoxication with a presenting complaint of accidental consumption about 15 ml formula milk containing 75% ethanol. His main clinical manifestations were irritability, flushed skin, tachycardia, tachypnea, and toxicology analysis detected ethanol. After timely gastric lavage and intravenous fluid replacement, he was cured and discharged. CONCLUSIONS: During the COVID-19 epidemic, high concentration ethanol used for inactivating SARS-COV-2 should be placed reasonably and neonatal feeding safety should be emphasized. Timely diagnosis and symptomatic treatment are essential for the prevention and management of acute ethanol intoxication in newborns.

4.
PLoS One ; 17(1): e0261216, 2022.
Article in English | MEDLINE | ID: covidwho-1622335

ABSTRACT

BACKGROUND: The global epidemic of novel coronavirus pneumonia (COVID-19) has resulted in substantial healthcare resource consumption. Since patients' hospital length of stay (LoS) is at stake in the process, an investigation of COVID-19 patients' LoS and its risk factors becomes urgent for a better understanding of regional capabilities to cope with COVID-19 outbreaks. METHODS: First, we obtained retrospective data of confirmed COVID-19 patients in Sichuan province via National Notifiable Diseases Reporting System (NNDRS) and field surveys, including their demographic, epidemiological, clinical characteristics and LoS. Then we estimated the relationship between LoS and the possibly determinant factors, including demographic characteristics of confirmed patients, individual treatment behavior, local medical resources and hospital grade. The Kaplan-Meier method and the Cox Proportional Hazards Model were applied for single factor and multi-factor survival analysis. RESULTS: From January 16, 2020 to March 4, 2020, 538 human cases of COVID-19 infection were laboratory-confirmed, and were hospitalized for treatment, including 271 (50%) patients aged ≥ 45, 285 (53%) males, and 450 patients (84%) with mild symptoms. The median LoS was 19 (interquartile range (IQR): 14-23, range: 3-41) days. Univariate analysis showed that age and clinical grade were strongly related to LoS (P<0.01). Adjusted multivariate analysis showed that the longer LoS was associated with those aged ≥ 45 (Hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.60-0.91), admission to provincial hospital (HR: 0.73, 95% CI: 0.54-0.99), and severe illness (HR: 0.66, 95% CI: 0.48-0.90). By contrast, the shorter LoS was linked with residential areas with more than 5.5 healthcare workers per 1,000 population (HR: 1.32, 95% CI: 1.05-1.65). Neither gender factor nor time interval from illness onset to diagnosis showed significant impact on LoS. CONCLUSIONS: Understanding COVID-19 patients' hospital LoS and its risk factors is critical for governments' efficient allocation of resources in respective regions. In areas with older and more vulnerable population and in want of primary medical resources, early reserving and strengthening of the construction of multi-level medical institutions are strongly suggested to cope with COVID-19 outbreaks.

6.
J Med Chem ; 2022 Jan 10.
Article in English | MEDLINE | ID: covidwho-1616927

ABSTRACT

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

8.
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
10.
Biosens Bioelectron ; 200: 113925, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1588208

ABSTRACT

The current COVID-19 pandemic caused by SARS-CoV-2 is raging, seriously threatening people's lives. The establishment of rapid and accurate pathogen detection technology is not only critical in this epidemic, but also a reminder that we must always be prepared for possible future outbreaks. Therefore, we developed a Palm Germ-Radar (PaGeR) device for rapid and simple detection of COVID-19 from extracted patient sample RNA by RT-LAMP. The whole procedure of rapid COVID-19 detection is based on 4 simple steps: inactivation, extraction, amplification, and detection. SARS-CoV-2 down to 1 copy/µL could be detected selectively with naked-eye. Three detection methods (colorimetric, fluorometric and lateral dipstick readout) could be performed in PaGeR instrument. By employing the PaGeR, we successfully detected SARS-CoV-2 in clinical RNA samples isolated from swab specimens. The results showed that 15 out of 17 COVID-19 patients were diagnosed as positive while all 55 normal samples were diagnosed as negative. Therefore, the developed PaGeR instrument can realize the detection of COVID-19 with easily visualized results, providing a promising instrument for rapid detection in the community as well as at home.


Subject(s)
Biosensing Techniques , COVID-19 , Humans , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Pandemics , RNA, Viral/genetics , Radar , Reverse Transcription , SARS-CoV-2 , Sensitivity and Specificity
11.
Preprint | EuropePMC | ID: ppcovidwho-296808

ABSTRACT

Air pollution is the result of comprehensive evolution of a dynamic and complex system composed of emission sources, topography, meteorology and other environmental factors. The establishment of spatiotemporal evolution model is of great significance for the study of air pollution mechanism, trend prediction, identification of pollution sources and pollution control. In this paper, the air pollution system is described based on cellular automata and restricted agents, and a Swarm Intelligence based Air Pollution SpatioTemporal Evolution (SI-APSTE) model is constructed. Then the spatiotemporal evolution analysis method of air pollution is studied. Taking Henan Province before and after COVID-19 pandemic as an example, the NO 2 products of TROPOMI and OMI were analysed based on SI-APSTE model. The tropospheric NO 2 Vertical Column Densities (VCDs) distribution characteristics of spatiotemporal variation of Henan province before COVID-19 pandemic were studied. Then the tropospheric NO 2 VCDs of TROPOMI was used to study the pandemic period, month-on-month and year-on-year in 18 urban areas of Henan Province. The results show that SI-APSTE model can effectively analyse the spatiotemporal evolution of air pollution by using environmental big data and swarm intelligence, and also can establish a theoretical basis for pollution source identification and trend prediction.

12.
Preprint | EuropePMC | ID: ppcovidwho-296703

ABSTRACT

Emergence of SARS-CoV-2 variants of concern (VOC), including the highly transmissible delta strain, has posed challenges to current COVID-19 vaccines that principally target the viral spike protein (S). Here, we report a nucleoside-modified mRNA vaccine that expresses the more conserved viral nucleoprotein (mRNA-N). We show that mRNA-N alone was able to induce a modest but significant control of SARS-CoV-2 in mice and hamsters. Critically, by combining mRNA-N with the clinically approved S-expressing mRNA vaccine (mRNA-S-2P), we found that combinatorial mRNA vaccination (mRNA-S+N) led to markedly enhanced protection against the SARS-CoV-2 delta variant compared to mRNA-S. In a hamster model, we demonstrated that while mRNA-S alone elicited significant control of the delta strain in the lungs (~45-fold reduction in viral loads compared to un-vaccinated control), its effectiveness in the upper respiratory tract was weak, whereas combinatorial mRNA-S+N vaccination induced markedly more robust control of the delta variant infection in the lungs (~450-fold reduction) as well as in the upper respiratory tract (~20-fold reduction). Immune analyses indicated that induction of N-specific immunity as well as augmented S-specific T-cell response and neutralizing antibody activity were collectively associated the enhanced protection against SARS-CoV-2 delta strain by combinatorial mRNA vaccination. These findings suggest that the combined effects of protection in the lungs and upper respiratory tract could both reduce the risk of severe disease as well as of infection and transmission.

13.
IEEE J Biomed Health Inform ; PP2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1570201

ABSTRACT

The pathogen of the ongoing coronavirus disease 2019 (COVID-19) pandemic is a newly discovered virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Testing individuals for SARS-CoV-2 plays a critical role in containing COVID-19. For saving medical personnel and consumables, many countries are implementing group testing against SARS-CoV-2. However, existing group testing methods have the following limitations: (1) The group size is determined without theoretical analysis, and hence is usually not optimal. This adversely impacts the screening efficiency. (2) These methods neglect the fact that mixing samples together usually leads to substantial dilution of the SARS-CoV-2 virus, which seriously impacts the sensitivity of tests. In this paper, we aim to screen individuals infected with COVID-19 with as few tests as possible, under the premise that the sensitivity of tests is high enough. We propose an eXpectation Maximization based Adaptive Group Testing (XMAGT) method. The basic idea is to adaptively adjust its testing strategy between a group testing strategy and an individual testing strategy such that the expected number of samples identified by a single test is larger. During the screening process, the XMAGT method can estimate the ratio of positive samples. With this ratio, the XMAGT method can determine a group size under which the group testing strategy can achieve a maximal expected number of negative samples and the sensitivity of tests is higher than a user-specified threshold. Experimental results show that the XMAGT method outperforms existing methods in terms of both efficiency and sensitivity.

14.
Chem Eng J ; 432: 134160, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1568555

ABSTRACT

Wearing surgical masks remains the most effective protective measure against COVID-19 before mass vaccination, but insufficient comfortability and low antibacterial/antiviral activities accelerate the replacement frequency of surgical masks, resulting in large amounts of medical waste. To solve this problem, we report new nanofiber membrane masks with outstanding comfortability and anti-pathogen functionality prepared using fluorinated carbon nanofibers/carbon fiber (F-CNFs/CF). This was used to replace commercial polypropylene (PP) nonwovens as the core layer of face masks. The through-plane and in-plane thermal conductivity of commercial PP nonwovens were only 0.12 and 0.20 W/m K, but the F-CNFs/CF nanofiber membranes reached 0.62 and 5.23 W/m K, which represent enhancements of 380% and 2523%, respectively. The surface temperature of the PP surgical masks was 23.9 ℃ when the wearing time was 15 min, while the F-CNFs/CF nanocomposite fibrous masks reached 27.3 ℃, displaying stronger heat dissipation. Moreover, the F-CNFs/CF nanofiber membranes displayed excellent electrical conductivity and produced a high-temperature layer that killed viruses and bacteria in the masks. The surface temperature of the F-CNFs/CF nanocomposite fibrous masks reached 69.2 ℃ after being connected to a portable power source for 60 s. Their antibacterial rates were 97.9% and 98.6% against E. coli and S. aureus, respectively, after being connected to a portable power source for 30 min.

15.
Preprint in English | EuropePMC | ID: ppcovidwho-296466

ABSTRACT

The surgical masks have been essential consumables for public in the COVID-19 pandemic. However, long-time wearing masks will make wearers feel uncomfortable and massive discarded non-biodegradable masks lead to a heavy burden on our environment. In this paper, we adopt degradable chitosan@silver (CS@Ag) core-shell fibers and plant fibers to prepare an eco-friendly mask with excellent thermal comfort, self-sterilization, and antiviral effects. The thermal network of CS@Ag core-shell fibers highly improves the in-plane thermal conductivity of masks, which is 4.45 times higher than that of commercial masks. Because of the electrical conductivity of Ag, the fabricated mask can be electrically heated to warm the wearer in a cold environment and disinfect COVID-19 facilely at room temperature. Meanwhile, the in-situ reduced silver nanoparticles (AgNPs) endow the mask with superior antibacterial properties. Therefore, this mask shows a great potential to address the urgent need for a thermally comfortable, antibacterial, antiviral, and eco-friendly mask.

16.
Preprint in English | Other preprints | ID: ppcovidwho-296160

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein, spike, for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live attenuated, recombinant human respiratory syncytial virus (RSV) expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200- fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunity in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against two virus variants of concern. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in phase 1 clinical trials as a single-dose intranasal COVID-19 vaccine.

17.
Preprint in English | Other preprints | ID: ppcovidwho-296045

ABSTRACT

ABSTRACT BACKGROUND SARS-CoV-2 causes COVID-19 through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns (DAMPs) and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) is able to blunt the broad inflammatory response induced by DAMPs in multiple models. A recent randomized phase III trial evaluating the impact of CD24Fc in patients with severe COVID-19 demonstrated encouraging clinical efficacy. METHODS We studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial ( NCT04317040 ) collected before and after treatment with CD24Fc or placebo. We performed high dimensional spectral flow cytometry analysis of peripheral blood mononuclear cells and measured the levels of a broad array of cytokines and chemokines. A systems analytical approach was used to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. FINDINGS Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found systemic hyper-activation of multiple cellular compartments in the placebo group, including CD8 + T cells, CD4 + T cells, and CD56 + NK cells. By contrast, CD24Fc-treated patients demonstrated blunted systemic inflammation, with a return to homeostasis in both NK and T cells within days without compromising the ability of patients to mount an effective anti-Spike protein antibody response. A single dose of CD24Fc significantly attenuated induction of the systemic cytokine response, including expression of IL-10 and IL-15, and diminished the coexpression and network connectivity among extensive circulating inflammatory cytokines, the parameters associated with COVID-19 disease severity. INTERPRETATION Our data demonstrates that CD24Fc treatment rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19. FUNDING NIH

18.
Preprint in English | Other preprints | ID: ppcovidwho-295334

ABSTRACT

In type II CRISPR systems, the guide RNA (gRNA) consists of a CRISPR RNA (crRNA) and a hybridized trans-acting CRISPR RNA (tracrRNA) which interacts directly with Cas9 and is essential to its guided DNA targeting function. Though tracrRNAs are diverse in sequences and structures across type II CRISPR systems, the programmability of crRNA-tracrRNA hybridization for particular Cas9 has not been studied adequately. Here, we revealed the high programmability of crRNA-tracrRNA hybridization for Streptococcus pyogenes Cas9. By reprogramming the crRNA-tracrRNA hybridized sequence, reprogrammed tracrRNAs can repurpose various RNAs as crRNAs to trigger CRISPR function. We showed that the engineered crRNA-tracrRNA pairs enable design of orthogonal cellular computing devices and hijacking of endogenous RNAs as crRNAs. We next designed novel RNA sensors that can monitor the transcriptional activity of specific genes on the host genome and detect SARS-CoV-2 RNA in vitro . The engineering potential of crRNA-tracrRNA interaction has therefore redefined the capabilities of CRISPR/Cas9 system.

19.
Preprint in English | EuropePMC | ID: ppcovidwho-294793

ABSTRACT

Background Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. Methods In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of R t , a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. Findings We observe a relationship between reductions in human mobility and decreases in R t during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Interpretation Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity and monitor the impact of NPI policies. Research in Context Evidence before this study We searched PubMed and preprint archives for articles published in English that contained information about the COVID-19 pandemic published up to Nov 1, 2021, using the search terms “coronavirus”, “CoV”, “COVID-19”, “mobility”, “movement”, and “flow”. The data thus far suggests that NPI measures including physical distancing, reduction of travel, and use of personal protective equipment have been demonstrated to reduce COVID-19 transmission. Much of the existing research focuses on comparisons of NPI stringency with COVID-19 transmission among different high-income countries, or on high-income countries, leaving critical questions about the applicability of these findings to low- and middle-income settings. Added value of this study We used a detailed COVID-19 surveillance dataset from Ghana, and unique high resolution spatial data on human mobility from Vodafone Ghana as well as Google smartphone GPS location data. We show how human mobility and NPI stringency were associated with changes in the effective reproduction number (R t ). We further demonstrate how this association was strongest in the early COVID-19 outbreak in Ghana, decreasing after the relaxation of national restrictions. Implications of all the available evidence The change in association between human mobility, NPI stringency, and R t may reflect a “decoupling” of NPI stringency and human mobility from disease transmission in Ghana as the COVID-19 epidemic progressed. This finding provides public health decision makers with important insights for the understanding of the utility of mobility data for predicting the spread of COVID-19.

20.
Preprint in English | EuropePMC | ID: ppcovidwho-294352

ABSTRACT

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning, to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) problem in statistical machine learning. Here, we have implemented Portal Learning to predict chemicalprotein interactions on a genome-wide scale. Systematic studies demonstrate that Portal Learning can effectively assign ligands to unexplored gene families (unknown functions), versus existing state-of-the-art methods. Compared with AlphaFold2-based protein-ligand docking, Portal Learning significantly improved the performance by 79% in PR-AUC and 27% in ROC-AUC, respectively. The superior performance of Portal Learning allowed us to target previously “undruggable” proteins and design novel polypharmacological agents for disrupting interactions between SARS-CoV-2 and human proteins. Portal Learning is general-purpose and can be further applied to other areas of scientific inquiry.

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