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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329211

ABSTRACT

Numerous mutations in the spike protein of SARS-CoV-2 B.1.1.529 Omicron variant pose a crisis for antibody-based immunotherapies. The efficacy of emergency use authorized (EUA) antibodies that developed in early SARS-CoV-2 pandemic seems to be in flounder. In this work, we examined the Omicron variant neutralization using an early B cell antibody repertoire as well as several EUA antibodies in pseudovirus and authentic virus systems. More than half of the antibodies in the repertoire that showed good activity against WA1/2020 previously had completely lost neutralizing activity against Omicron, while antibody 8G3 from our early B cell repertoire displayed non-regressive activity. EUA antibodies Etesevimab, Casirivimab, Imdevimab and Bamlanivimab neutralized authentic WA1/2020 virus with low half maximal inhibitory concentration (IC50) values, but were entirely desensitized by Omicron. Only Sotrovimab targeting the non-ACE2 overlap epitope showed activity but with a dramatic decrease. Interestingly, antibody 8G3 efficiently neutralized Omicron in pseudovirus and authentic virus systems. 8G3 also showed excellent activity against other variants of concern (VOCs). Collectively, our results suggest that neutralizing antibodies with breadth remains broad neutralizing activity in tackling SARS-CoV-2 infection despite the universal evasion from EUA antibodies by Omicron variant.

2.
Buildings ; 12(3):257, 2022.
Article in English | MDPI | ID: covidwho-1699222

ABSTRACT

The construction industry is the backbone of most countries, but its carbon emissions are huge and growing rapidly, constraining the achievement of global carbon-peaking and carbon-neutrality goals. China’s carbon emissions are the highest in the world, and the construction industry is the largest contributor. Due to significant differences between provinces in pressure, potential, and motivation to reduce emissions, the “one-size-fits-all”emission reduction policy has failed to achieve the desired results. This paper empirically investigates the spatial and temporal evolution of carbon emissions in China’s construction industry and their decoupling relationship with economic growth relying on GIS tools and decoupling model in an attempt to provide a basis for the formulation of differentiated construction emission reduction policies and plans in China. The study shows that, firstly, the changes in carbon emissions and carbon intensity in the provincial construction industry are becoming increasingly complex, with a variety of types emerging, such as declining, “inverted U-shaped”, growing, “U-shaped”, and smooth fluctuating patterns. Secondly, the coefficient of variation is higher than 0.65 for a long time, indicating high spatial heterogeneity. However, spatial agglomeration and correlation are low, with only a few cluster-like agglomerations formed in the Pearl River Delta, Yangtze River Delta, Bohai Bay, Northeast China, and Loess and Yunnan–Guizhou Plateau regions. Thirdly, most provinces have not reached peak carbon emissions from the construction industry, with 25% having reached peak and being in the plateau stage, respectively. Fourthly, the decoupling relationship between carbon emissions from the construction industry and economic growth, as well as their changes, is increasingly diversified, and most provinces are in a strong and weak decoupling state. Moreover, a growing number of provinces that have achieved decoupling are moving backward to re-coupling, due to the impact of economic transformation and the outbreaks of COVID-19, with the degraded regions increasingly concentrated in the northeast and northwest. Fifthly, we classify China’s 30 provinces into Leader, Intermediate, and Laggard policy zones and further propose differentiated response strategies. In conclusion, studying the trends and patterns of carbon-emission changes in the construction industry in different regions, revealing their spatial differentiation and correlation, and developing a classification management strategy for low carbonized development of the construction industry help significantly improve the reliability, efficiency, and self-adaptability of policy design and implementation.

3.
Cell Discov ; 8(1): 16, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1692632

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325249

ABSTRACT

Background: The availability of vaccines provides a promising solution to containing the COVID-19 pandemic. However, it remains unclear whether the large-scale vaccination can succeed in containing the COVID-19 pandemic and how soon. We develop an epidemiological model named SUVQC (Suceptible-Unquarantined-Vaccined-Quarantined-Confirmed) to quantitatively analyze and predict the epidemic dynamics of COVID-19 under vaccination. Methods: In addition to the impact of non-pharmaceutical interventions (NPIs), our model explicitly parameterizes key factors related to vaccination, including the duration of immunity, vaccine efficacy, and daily vaccination rate etc. The model is applied to the daily released numbers of confirmed cases of Israel and United States of America to explore and predict the trend under vaccination based on their current epidemic status and intervention measures. We further provide a formula for designing a practical vaccination strategy, which simultaneously considers the effects of the basic reproductive number of COVID-19, intensity of NPIs, duration of immunological memory after vaccination, vaccine efficacy and daily vaccination rate. Findings: For Israel, of which 53.83% of the population was fully vaccinated, under the current intensity of NPIs and vaccination scheme, the pandemic is predicted to end between May 14, 2021 to May 16, 2021 depending on an immunity duration between 180 days and 365 days;Assuming no NPIs after March 24, 2021, the pandemic will ends later, between July 4, 2021 to August 26, 2021. For USA, if we assume the current vaccination rate (0.268% per day) and intensity of NPIs, the pandemic will end between February 3, 2022 and August 17, 2029 depending on an immunity duration between 180 days and 365 days. However, assuming an immunity duration of 180 days and with no NPIs, the pandemic will not end, and instead reach an equilibrium state with a proportion of the population remaining actively infected. Interpretation: Overall the daily vaccination rate should be chosen according to the vaccine efficacy and the immunity duration to achieve herd immunity. In some situations, vaccination alone cannot stop the pandemic, and NPIs are necessary both to supplement vaccination and accelerate the end of the pandemic. Considering that vaccine efficacy and duration of immunity may be reduced for new mutant strains, it is necessary to remain cautiously optimistic about the prospect of the pandemic under vaccination. Funding: National Key R&D Program of China, and National Natural Science Foundation of China.Declaration of Interests: None to declare.

5.
Int J Environ Res Public Health ; 19(3)2022 01 26.
Article in English | MEDLINE | ID: covidwho-1686732

ABSTRACT

Humans are exposed to a diverse mixture of chemical and non-chemical exposures across their lifetimes. Well-designed epidemiology studies as well as sophisticated exposure science and related technologies enable the investigation of the health impacts of mixtures. While existing statistical methods can address the most basic questions related to the association between environmental mixtures and health endpoints, there were gaps in our ability to learn from mixtures data in several common epidemiologic scenarios, including high correlation among health and exposure measures in space and/or time, the presence of missing observations, the violation of important modeling assumptions, and the presence of computational challenges incurred by current implementations. To address these and other challenges, NIEHS initiated the Powering Research through Innovative methods for Mixtures in Epidemiology (PRIME) program, to support work on the development and expansion of statistical methods for mixtures. Six independent projects supported by PRIME have been highly productive but their methods have not yet been described collectively in a way that would inform application. We review 37 new methods from PRIME projects and summarize the work across previously published research questions, to inform methods selection and increase awareness of these new methods. We highlight important statistical advancements considering data science strategies, exposure-response estimation, timing of exposures, epidemiological methods, the incorporation of toxicity/chemical information, spatiotemporal data, risk assessment, and model performance, efficiency, and interpretation. Importantly, we link to software to encourage application and testing on other datasets. This review can enable more informed analyses of environmental mixtures. We stress training for early career scientists as well as innovation in statistical methodology as an ongoing need. Ultimately, we direct efforts to the common goal of reducing harmful exposures to improve public health.


Subject(s)
National Institute of Environmental Health Sciences (U.S.) , Research Design , Environmental Exposure/analysis , Epidemiologic Methods , Epidemiologic Studies , Humans , Risk Assessment , United States
6.
JAMA Intern Med ; 182(4): 386-395, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1653126

ABSTRACT

Importance: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates. Objective: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease. We tested the hypothesis that the APOL1 high-risk group is associated with a higher-risk of COVID-19-associated AKI and death. Design, Setting, and Participants: This retrospective cohort study included 990 participants with African ancestry enrolled in the Million Veteran Program who were hospitalized with COVID-19 between March 2020 and January 2021 with available genetic information. Exposures: The primary exposure was having 2 APOL1 risk variants (RV) (APOL1 high-risk group), compared with having 1 or 0 risk variants (APOL1 low-risk group). Main Outcomes and Measures: The primary outcome was AKI. The secondary outcomes were stages of AKI severity and death. Multivariable logistic regression analyses adjusted for preexisting comorbidities, medications, and inpatient AKI risk factors; 10 principal components of ancestry were performed to study these associations. We performed a subgroup analysis in individuals with normal kidney function prior to hospitalization (estimated glomerular filtration rate ≥60 mL/min/1.73 m2). Results: Of the 990 participants with African ancestry, 905 (91.4%) were male with a median (IQR) age of 68 (60-73) years. Overall, 392 (39.6%) patients developed AKI, 141 (14%) developed stages 2 or 3 AKI, 28 (3%) required dialysis, and 122 (12.3%) died. One hundred twenty-five (12.6%) of the participants were in the APOL1 high-risk group. Patients categorized as APOL1 high-risk group had significantly higher odds of AKI (adjusted odds ratio [OR], 1.95; 95% CI, 1.27-3.02; P = .002), higher AKI severity stages (OR, 2.03; 95% CI, 1.37-2.99; P < .001), and death (OR, 2.15; 95% CI, 1.22-3.72; P = .007). The association with AKI persisted in the subgroup with normal kidney function (OR, 1.93; 95% CI, 1.15-3.26; P = .01). Data analysis was conducted between February 2021 and April 2021. Conclusions and Relevance: In this cohort study of veterans with African ancestry hospitalized with COVID-19 infection, APOL1 kidney risk variants were associated with higher odds of AKI, AKI severity, and death, even among individuals with prior normal kidney function.


Subject(s)
Acute Kidney Injury , COVID-19 , Veterans , Acute Kidney Injury/genetics , African Americans/genetics , Aged , Apolipoprotein L1/genetics , Cohort Studies , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
7.
Immunity ; 54(11): 2632-2649.e6, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1549842

ABSTRACT

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.


Subject(s)
Apolipoprotein L1/genetics , COVID-19/genetics , Genetic Predisposition to Disease/genetics , Sepsis/genetics , Animals , Apolipoprotein L1/blood , COVID-19/pathology , DNA, Mitochondrial/metabolism , Endothelial Cells/metabolism , Humans , Inflammation/genetics , Inflammation/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Knockout , Mitophagy/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Risk Factors , Sepsis/pathology , Severity of Illness Index , /statistics & numerical data
8.
Biosaf Health ; 2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1509610

ABSTRACT

By re-analzying public metagenomic data from 101 patients infected with influenza A virus during the 2007-2012 H1N1 flu seasons in France, we identified 22 samples with SARS-CoV sequences. In 3 of them, the SARS genome sequences could be fully assembled out of each. These sequences are highly similar (99.99% and 99.7%) to the artificially constructed recombinant SARS-CoV (SARSr-CoV) strains generated by the J. Craig Venter Institute in the USA. Moreover, samples from different flu seasons have different SARS-CoV strains, and the divergence between these strains cannot be explained by natural evolution. Our study also shows that retrospective studies using public metagenomic data from past major epidemic outbreaks serve as a genomic strategy for researching the origins or spread of infectious diseases.

9.
Genomics Proteomics Bioinformatics ; 2021 Oct 23.
Article in English | MEDLINE | ID: covidwho-1474586

ABSTRACT

COVID-19 has swept globally and Pakistan is no exception. To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan, we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1, 2020. We identified a total of 347 mutated positions, 31 of which were over-represented in Pakistan. Meanwhile, we found over 1000 intra-host single-nucleotide variants (iSNVs). Several of them occurred concurrently, indicating possible interactions among them or coevolution. Some of the high-frequency iSNVs in Pakistan were not observed in the global population, suggesting strong purifying selections. The genomic epidemiology revealed five distinctive spreading clusters. The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure, indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation (G8371T in ORF1ab) of this cluster. Furthermore, 28 putative international introductions were identified, several of which are consistent with the epidemiological investigations. In all, this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan, which could aid ongoing and future viral surveillance and COVID-19 control.

10.
Front Med (Lausanne) ; 8: 764493, 2021.
Article in English | MEDLINE | ID: covidwho-1450820

ABSTRACT

[This corrects the article DOI: 10.3389/fmed.2020.584342.].

12.
J Clin Nurs ; 2021 Sep 27.
Article in English | MEDLINE | ID: covidwho-1438025

ABSTRACT

AIMS AND OBJECTIVE: To explore the experiences of frontline nurses through analyzing nurse online diaries during the pandemic. BACKGROUND: Over 42,600 healthcare professionals took care of patients with COVID-19 in Wuhan in the initial months between 23 January 2020 and 8 April 2020. Many used to write online diaries on Sina Microblog and still wrote about their experiences in the front line on this site. However, there has been little research on frontline nurses' experiences in the initial months of the pandemic through analyzing their narratives. DESIGN: A qualitative descriptive design. METHODS: A qualitative content analysis was used to analyze online diaries written by frontline nurses in Wuhan. A total of 205 entries in online diaries were collected from 12 frontline nurses, as accessible to those who subscribed to Sina Microblog social media site, between 23 January 2020 and 8 April 2020. NVivo12 was used to help analyze the data, and COREQ reporting guidelines were also used in this study. RESULTS: Two themes were identified: constructing a better self and constructing a strong support network. A better self was constructed in describing positive emotions, commitment to care, pride and achievements, and whole-person growth. A strong support network was constructed through social support via different sources and gaining self-support via narrating their personal experiences in diaries. CONCLUSIONS: Frontline nurses demonstrated personal growth, psychological well-being, and professionalism in the process of constructing a better self and a strong support network. RELEVANCE TO CLINICAL PRACTICE: The findings indicate that frontline nurses can use narratives as debriefing opportunities and a way of gaining self-support. We suggest that online communities of professional support be used as an essential platform for sharing narratives and gaining a more comprehensive understanding of frontline nurses in the COVID-19 pandemic and other global public health events.

13.
Signal Transduct Target Ther ; 6(1): 343, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415924

ABSTRACT

SARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Y330 could be synergistically combined with either W19 or W27, whereas W19 and W27 are mutually unbeneficial. The structures of SARS-CoV-2 S-RBD bound to the ACE2 mutants reveal that the enhanced binding is mainly contributed by the van der Waals interactions mediated by the aromatic side-chains from W19, W27, and Y330. While Y330 and W19/W27 are distantly located and devoid of any steric interference, W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts, explaining their incompatibility. Finally, using pseudotyped SARS-CoV-2 viruses, we demonstrate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses. Taken together, our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W, T27W, and N330Y mutations in ACE2, paving the way for potential application of these mutants in clinical treatment of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , COVID-19 , Molecular Dynamics Simulation , Mutation, Missense , SARS-CoV-2/chemistry , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/chemistry , Antibodies, Viral/metabolism , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
15.
Nucleic Acids Res ; 49(9): 5382-5392, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1387965

ABSTRACT

The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.


Subject(s)
Biocatalysis , Exoribonucleases/chemistry , Exoribonucleases/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/metabolism , Binding Sites , Crystallography, X-Ray , Exoribonucleases/genetics , Guanine , Methyltransferases/chemistry , Methyltransferases/deficiency , Methyltransferases/genetics , Methyltransferases/metabolism , Models, Molecular , Protein Domains/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics , Viral Regulatory and Accessory Proteins/genetics
17.
Lancet Respir Med ; 9(7): 712-720, 2021 07.
Article in English | MEDLINE | ID: covidwho-1337036

ABSTRACT

BACKGROUND: Whether young adults who are infected with SARS-CoV-2 are at risk of subsequent infection is uncertain. We investigated the risk of subsequent SARS-CoV-2 infection among young adults seropositive for a previous infection. METHODS: This analysis was performed as part of the prospective COVID-19 Health Action Response for Marines study (CHARM). CHARM included predominantly male US Marine recruits, aged 18-20 years, following a 2-week unsupervised quarantine at home. After the home quarantine period, upon arrival at a Marine-supervised 2-week quarantine facility (college campus or hotel), participants were enrolled and were assessed for baseline SARS-CoV-2 IgG seropositivity, defined as a dilution of 1:150 or more on receptor-binding domain and full-length spike protein ELISA. Participants also completed a questionnaire consisting of demographic information, risk factors, reporting of 14 specific COVID-19-related symptoms or any other unspecified symptom, and brief medical history. SARS-CoV-2 infection was assessed by PCR at weeks 0, 1, and 2 of quarantine and participants completed a follow-up questionnaire, which included questions about the same COVID-19-related symptoms since the last study visit. Participants were excluded at this stage if they had a positive PCR test during quarantine. Participants who had three negative swab PCR results during quarantine and a baseline serum serology test at the beginning of the supervised quarantine that identified them as seronegative or seropositive for SARS-CoV-2 then went on to basic training at Marine Corps Recruit Depot-Parris Island. Three PCR tests were done at weeks 2, 4, and 6 in both seropositive and seronegative groups, along with the follow-up symptom questionnaire and baseline neutralising antibody titres on all subsequently infected seropositive and selected seropositive uninfected participants (prospective study period). FINDINGS: Between May 11, 2020, and Nov 2, 2020, we enrolled 3249 participants, of whom 3168 (98%) continued into the 2-week quarantine period. 3076 (95%) participants, 2825 (92%) of whom were men, were then followed up during the prospective study period after quarantine for 6 weeks. Among 189 seropositive participants, 19 (10%) had at least one positive PCR test for SARS-CoV-2 during the 6-week follow-up (1·1 cases per person-year). In contrast, 1079 (48%) of 2247 seronegative participants tested positive (6·2 cases per person-year). The incidence rate ratio was 0·18 (95% CI 0·11-0·28; p<0·001). Among seropositive recruits, infection was more likely with lower baseline full-length spike protein IgG titres than in those with higher baseline full-length spike protein IgG titres (hazard ratio 0·45 [95% CI 0·32-0·65]; p<0·001). Infected seropositive participants had viral loads that were about 10-times lower than those of infected seronegative participants (ORF1ab gene cycle threshold difference 3·95 [95% CI 1·23-6·67]; p=0·004). Among seropositive participants, baseline neutralising titres were detected in 45 (83%) of 54 uninfected and in six (32%) of 19 infected participants during the 6 weeks of observation (ID50 difference p<0·0001). INTERPRETATION: Seropositive young adults had about one-fifth the risk of subsequent infection compared with seronegative individuals. Although antibodies induced by initial infection are largely protective, they do not guarantee effective SARS-CoV-2 neutralisation activity or immunity against subsequent infection. These findings might be relevant for optimisation of mass vaccination strategies. FUNDING: Defense Health Agency and Defense Advanced Research Projects Agency.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , COVID-19/epidemiology , SARS-CoV-2/immunology , Adolescent , COVID-19/diagnosis , COVID-19 Serological Testing , Cohort Studies , Female , Humans , Male , Prospective Studies , Quarantine , Risk Assessment , Young Adult
18.
Adv Sci (Weinh) ; 8(14): e2100230, 2021 07.
Article in English | MEDLINE | ID: covidwho-1318679

ABSTRACT

Rapid advancements of artificial intelligence of things (AIoT) technology pave the way for developing a digital-twin-based remote interactive system for advanced robotic-enabled industrial automation and virtual shopping. The embedded multifunctional perception system is urged for better interaction and user experience. To realize such a system, a smart soft robotic manipulator is presented that consists of a triboelectric nanogenerator tactile (T-TENG) and length (L-TENG) sensor, as well as a poly(vinylidene fluoride) (PVDF) pyroelectric temperature sensor. With the aid of machine learning (ML) for data processing, the fusion of the T-TENG and L-TENG sensors can realize the automatic recognition of the grasped objects with the accuracy of 97.143% for 28 different shapes of objects, while the temperature distribution can also be obtained through the pyroelectric sensor. By leveraging the IoT and artificial intelligence (AI) analytics, a digital-twin-based virtual shop is successfully implemented to provide the users with real-time feedback about the details of the product. In general, by offering a more immersive experience in human-machine interactions, the proposed remote interactive system shows the great potential of being the advanced human-machine interface for the applications of the unmanned working space.

19.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 10.
Article in English | MEDLINE | ID: covidwho-1292829

ABSTRACT

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.


Subject(s)
Hematopoietic Stem Cell Transplantation , Pneumonia , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Pneumonia/diagnosis , Prognosis , Retrospective Studies , Transplantation, Homologous
20.
Nucleic Acids Res ; 49(9): 5382-5392, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1217861

ABSTRACT

The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1', which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.


Subject(s)
Biocatalysis , Exoribonucleases/chemistry , Exoribonucleases/metabolism , SARS-CoV-2/chemistry , SARS-CoV-2/enzymology , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Viral Regulatory and Accessory Proteins/chemistry , Viral Regulatory and Accessory Proteins/metabolism , Binding Sites , Crystallography, X-Ray , Exoribonucleases/genetics , Guanine , Methyltransferases/chemistry , Methyltransferases/deficiency , Methyltransferases/genetics , Methyltransferases/metabolism , Models, Molecular , Protein Domains/genetics , SARS-CoV-2/genetics , Viral Nonstructural Proteins/genetics , Viral Regulatory and Accessory Proteins/genetics
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