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1.
Topics in Antiviral Medicine ; 30(1 SUPPL):330, 2022.
Article in English | EMBASE | ID: covidwho-1880794

ABSTRACT

Background: Monitoring new mutations in SARS-CoV-2 is crucial for identifying diagnostic and therapeutic targets and important insights to achieve a more effective COVID-19 control strategy. Next-generation sequencing (NGS) has been widely used for whole-genome sequencing of SARS-CoV-2. However, NGS methods may be limited by the complexity of workflow, which limits scalability. Here, we address this limitation by designing a workflow optimized for high-throughput studies. Methods: We utilized modified ARTIC network v3 primers for SARS-CoV-2 whole-genome amplification. Similar to a previously reported tailed PCR approach, libraries were prepared by a 2-step PCR method but optimized to improve amplicon balance, integrate robotic liquid handlers, and minimize amplicon dropout for viral genomes harboring primer-binding site mutation(s). Sequencing was performed on the Illumina NovaSeq 6000 and the Illumina MiSeq. An in-house analysis pipeline utilized the BWA aligner and iVar software. Assay precision was assessed with unique clinical samples. Assay sensitivity was assessed with serial dilutions of clinical samples. Robustness was assessed by sequencing samples and controls on the NovaSeq from multiple prior ARTIC v3 runs. Results: Intra-assay (n=188) and inter-assay (n=168) precision at the amino acid substitution level was 99.8% and 99.5%, respectively. Over 98.2% (111/113) of samples with a cycle threshold (Ct) <28 yielded a near-complete (≥97%) consensus sequence, and 98.7% (147/149) of samples with a Ct <30 yielded ≥90% consensus coverage. 2,688 samples and controls were sequenced in a single NovaSeq run yielding a 94.3% (2,416/2,562) sample pass rate. The optimized workflow gave more complete SARS-CoV-2 genome consensus sequences for most viral clades than the original ARTIC v3 workflow (Table). From over 65,000 clinical samples sequenced in 2021, we observed clade and lineage prevalence in-line with those documented by the CDC in 2021, including the Alpha clade that peaked at 65.3% in May, and the Delta clade that attained near-100% prevalence in September. Conclusion: We present an optimized workflow to process up to 2,688 samples in a single NovaSeq 6000 run without compromising sensitivity or robustness and with fewer amplicon dropout events compared to the standard ARTIC protocol. We additionally report results for over 65,000 SARS-CoV-2 clinical specimens collected in the United States between January and September of 2021, as part of an ongoing national genomics surveillance effort.

2.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-338053

ABSTRACT

Introduction A small body of epidemiological research suggests that working in an essential sector is a risk factor for SARS-CoV-2 infection or subsequent disease or mortality. However, there is limited evidence to date on the US, or on how the risks associated with essential work differ across demographic subgroups defined by age, sex, and race/ethnicity. Methods Using publicly available data from the National Center for Health Statistics on deaths occurring in the US in 2020, we calculated per-capita COVID-19 mortality by industry and occupation. We additionally calculated per-capita COVID-19 mortality by essential industry—essential or not—by age group, sex, and race/ethnicity. Results Among non-military individuals and individuals with a known industry or occupation, there were 48,030 reported COVID-19 deaths, representing 25.1 COVID-19 deaths per 100,000 working-age individuals after age standardization. Per-capita age-standardized COVID-19 mortality was 1.96 times higher among essential workers than among workers in non-essential industries, representing an absolute difference of 14.9 per 100,000. Across industry, per-capita age-standardized COVID-19 mortality was highest in the following industries: accommodation and food services (45.4 per 100,000);transportation and warehousing (43.4);agriculture, forestry, fishing and hunting (42.3);mining (39.6);and construction (38.7). Discussion Given that SARS-CoV-2 is an airborne virus, we call for collaborative efforts to ensure that workplace settings are properly ventilated and that workers have access to effective masks. We also urge for paid sick leave, which can help increase vaccine access and minimize disease transmission.

3.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-334871

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.

4.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816903

ABSTRACT

Vimentin intermediate filament is involved in multiple steps of viral infection such as viral entry, trafficking and egress, as well as in various mechanisms of hyperinflammation such as the restraint of Treg cell functions and the activation of NLRP3 inflammasome. We evaluated a vimentin-binding small molecule compound ALD-R491 for its effects on cellular processes related to viral infection and for its efficacy in treating SARS-CoV2 infection in vitro and in vivo. In cultured cells, the compound could reduce endocytosis by 10%, endosomal trafficking by 40% and exosomal release by over 30%. In an infection system consisting of a lentiviral pseudotype bearing the SARS-CoV-2 spike protein and HEK293 cells over-expressing the human ACE2 receptor with multiplicity of infection (MOI) of 1, 10 and 100, the compound inhibited the infection up to a maximum of over 90%, with IC 50 < 50 nM, CC50 > 10 μM, and SI > 200. After oral administration of ALD-R491 in rats, the plasma concentration of the compound reached the peak (Tmax) at around 5 h with a half-life (T1/2) of about 5 h. The compound was widely distributed and enriched in tissues in vivo in rats with a volume of distribution (Vd) of over 2,000 ml/kg. The lung and the lymph nodes were among the tissues with high drug exposures. In rats receiving oral gavage of the compound at 30 mg/kg, the drug exposure in the lung and the lymph nodes maintained at levels over 1 μM from 1 h to 6 h after the oral dosing. In the syngeneic mouse tumor CT26 model, ALD-R491 was found to activate regulatory T cells (Tregs) in vivo and enhance de novo generation of Tregs in lymph nodes of the mice. In the Mouse-Adapted SARS-CoV2 model, aged mice (11-12 months) were used to provide a harder test of recovery from infection that reflects the severeness of COVID-19 in old patients. For therapeutic treatment, the mice were orally administered with the compound 24 h after the SARS-CoV2 infection once per day on Day 1, Day 2 and Day 4. At 10 mg/kg, ALD-R491 significantly reduced the body weight loss of the mice (p<0.01 on Day 5 post-infection). At both 3 mg/kg and 10 mg/kg, the compound significantly reduced the hemorrhagic score for the lungs (p<0.01 and p<0.05, respectively, on Day 5). These results indicate that vimentin intermediate filament is an effective host-directed antiviral target. Importantly, the vimentin-binding small molecule ALD-R491 impacts multiple aspects of SARS-CoV2 infection, has a favorable oral pharmacokinetics and a wide therapeutic window, and therefore may be a promising therapeutic candidate for treating COVID-19. Statement: Aluda Pharmaceuticals, Inc. has utilized the non-clinical and pre-clinical services program offered by the National Institute of Allergy and Infectious Diseases.

5.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333828

ABSTRACT

Escape variants of SARS-CoV-2 are threatening to prolong the COVID-19 pandemic. To address this challenge, we developed multivalent protein-based minibinders as potential prophylactic and therapeutic agents. Homotrimers of single minibinders and fusions of three distinct minibinders were designed to geometrically match the SARS-CoV-2 spike (S) trimer architecture and were optimized by cell-free expression and found to exhibit virtually no measurable dissociation upon binding. Cryo-electron microscopy (cryoEM) showed that these trivalent minibinders engage all three receptor binding domains on a single S trimer. The top candidates neutralize SARS-CoV-2 variants of concern with IC 50 values in the low pM range, resist viral escape, and provide protection in highly vulnerable human ACE2-expressing transgenic mice, both prophylactically and therapeutically. Our integrated workflow promises to accelerate the design of mutationally resilient therapeutics for pandemic preparedness. ONE-SENTENCE SUMMARY: We designed, developed, and characterized potent, trivalent miniprotein binders that provide prophylactic and therapeutic protection against emerging SARS-CoV-2 variants of concern.

6.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333778

ABSTRACT

Emergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 microg RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only ~2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development. SIGNIFICANCE STATEMENT: The emergence of SARS-CoV-2 variants of concern (VOC) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 Spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation, efficacious vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses exceeding those of current vaccines in terms of breadth and potency and protects against high-dose respiratory tract challenge. Neutralization activity against the B.1.351 VOC within two-fold of wild-type virus and against SARS-CoV-1 indicate exceptional breadth. Our results support consideration of RFN for SARS-like betacoronavirus vaccine development.

7.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333761

ABSTRACT

The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern. ONE SENTENCE SUMMARY: Protection against SARS-CoV-2 variants by a potently neutralizing vaccine-induced human monoclonal antibody.

8.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333760

ABSTRACT

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 micro g) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN's potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses. ONE-SENTENCE SUMMARY: A SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.

10.
IEEE Internet of Things Journal ; 2022.
Article in English | Scopus | ID: covidwho-1759122

ABSTRACT

Preventing COVID-19 disease from spreading in communities will require proactive and effective healthcare resources allocations, such as vaccinations. A fine-grained COVID-19 vulnerability map will be essential to detect the high-risk communities and guild the effective vaccine policy. A mobile-crowdsourcing-based self-reporting approach is a promising solution. However, an accurate mobile-crowdsourcing-based map construction requests participants to report their actual locations, raising serious privacy concerns. To address this issue, we propose a novel approach to effectively construct a reliable community-level COVID-19 vulnerability map based on mobile crowdsourced COVID-19 self-reports without compromising participants’location privacy. We design a geo-perturbation scheme where participants can locally obfuscate their locations with the geo-indistinguishability guarantee to protect their location privacy against any adversaries’prior knowledge. To minimize the data utility loss caused by location perturbation, we first design an unbiased vulnerability estimator and formulate the location perturbation probability generation into a convex optimization. Its objective is to minimize the estimation error of the direct vulnerability estimator under the constraints of geo-indistinguishability. Given the perturbed locations, we integrate the perturbation probabilities with the spatial smoothing method to obtain reliable community-level vulnerability estimations that are robust to a small-sampling-size problem incurred by location perturbation. Considering the fast-spreading nature of coronavirus, we integrate the vulnerability estimates into the modified susceptible-infected-removed (SIR) model with vaccination for building a future trend map. It helps to provide a guideline for vaccine allocation when supply is limited. Extensive simulations based on real-world data demonstrate the proposed scheme superiority over the peer designs satisfying geo-indistinguishability in terms of estimation accuracy and reliability. IEEE

11.
Global Journal of Environmental Science and Management ; 6(Special Issue):65-84, 2020.
Article in English | CAB Abstracts | ID: covidwho-1727154

ABSTRACT

COVID-19 has a severe and widespread impact, especially in Indonesia. COVID-19 was first reported in Indonesia on March 03, 2020 then rapidly spread to all 34 provinces by April 09, 2020. Since then, COVID-19 is declared a state of national disaster and health emergency. This research analyzes the difference of CO, HCHO, NO2, and SO2 density in Jakarta, West Java, Central Java, and South Sulawesi before and during the pandemic. Also, this study assesses the effect of large scale restrictions on the economic growth during COVID-19 pandemic in Indonesia. In a nutshell, the results on Wilcoxon and Fisher test by significance level a=5% as well as odds ratio showed that there are significant differences of CO density in all regions with highest odds ratio in East Java (OR=9.07), significant differences of HCHO density in DKI Jakarta, East Java, and South Sulawesi. There are significant differences of NO2 density before and during public activities limitation in DKI Jakarta, West Java, East Java, and South Sulawesi. However, the results show that there are no significant differences of SO2 density in all regions. In addition, this research shows that there are significant differences of retail, grocery and pharmacy, and residental mobility before and during the COVID-19 pandemic in Indonesia. This research also shows that during the COVID-19 pandemic there are severe economic losses, industry, companies, and real disruptions are severe for all levels of life due to large scale restrictions.

12.
European Respiratory Journal ; 58:2, 2021.
Article in English | Web of Science | ID: covidwho-1704115
13.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327041

ABSTRACT

The SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an “active” conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

14.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326943

ABSTRACT

COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.

15.
Medical Journal of Wuhan University ; 43(2):184-188, 2022.
Article in Chinese | Scopus | ID: covidwho-1687526

ABSTRACT

Objective: To assess the level of pulmonary ventilation function in patients with COVID‑19 after six months post⁃discharge and analyze the relevant influencing factors. Methods: In November 2020, patients with COVID‑19 were investigated in a district of Wuhan City, Hubei Province. Their pulmonary ventilation function indicators were measured, including forced vital capacity of percent predicted (FVC%pred), forced expiratory volume in one second of percent predicted (FEV1%pred), FEV1/FVC ratio (FEV1/FVC%), forced expiratory flow at 50% of percent predicted (FEF50%pred), forced expiratory flow at 75% of percent predicted (FEF75%pred), mean forced expiratory flow between 25% and 75% of percent predicted (MMEF%pred). The related factors affecting pulmonary ventilation function were analyzed. Results: A total of 151 discharged cases were recruited, which included 64 cases of mild illness, 87 cases of moderate illness. The average age of both men and women in the mild group was significantly higher than that in the moderate group (P<0.05). The mean values of the lung ventilation function indexes were all within the normal range. The FVC%pred in both male and female and FEV1%pred in female were better in the mild group than that in the moderate group (P<0.05). Some patients had mild abnormal pulmonary ventilation function and 11 cases in the mild group, 46 cases in the moderate group. Multi‑factor logistic regression analysis showed that women [OR=3.012, 95%CI(1.249,7.264)], the presence of a previous history of chronic disease [OR=2.739, 95%CI(1.186,6.326)], and cases of moderate illness [OR=6.365, 95%CI(2.730,14.840)] were the risk factors for abnormal pulmonary ventilation function after discharge. Conclusion: Half a year after discharge, the pulmonary ventilation function of both mild and moderate group patients recovered well. Women and those with chronic disease in the past should have more targeted health guidance during the post‑discharge recovery period. © 2022, Editorial Board of Medical Journal of Wuhan University. All right reserved.

16.
Current Directions in Biomedical Engineering ; 7(2):323-326, 2021.
Article in English | Scopus | ID: covidwho-1594328

ABSTRACT

The COVID-19 is a viral infection that causes respiratory complications. Infected lungs often present ground glass opacities, thus suggesting that medical imaging technologies could provide useful information for the disease diagnosis, treatment, and posterior recovery. The Electrical Impedance Tomography (EIT) is a non-invasive, radiationfree, and continuous technology that generates images by using a sequence of current injections and voltage measurements around the body, making it very appropriate for the study to monitor the regional behaviour of the lung. Moreover, this tool could also be used for a preliminary COVID-19 phenotype classification of the patients. This study is based on the monitoring of lung compliances of two COVID-19-infected patients: the results indicate that one of them could belong to the H-type, while the other is speculated belongs to L-type. It has been concluded that the EIT is a useful tool to obtain information regarding COVID-19 patients and could also be used to classify different phenotypes. © 2021 by Walter de Gruyter Berlin/Boston.

17.
Current Directions in Biomedical Engineering ; 7(2):276-278, 2021.
Article in English | Scopus | ID: covidwho-1592304

ABSTRACT

COVID-19 induced acute respiratory distress syndrome (ARDS) could have two different phenotypes, which might have different response and outcome to the traditional ARDS positive end-expiration pressure (PEEP) treatment. The identification of the different phenotypes in terms of the PEEP recruitment can help improve the patients' outcome. In this contribution we reported a COVID-19 patient with seven-day electrical impedance tomography monitoring. From the conductivity distribution difference image analysis of the data, a clear course developing trend can be observed in addition to the phenotype identification. This case might suggest that EIT can be a practical tool to identify phenotypes and to provide progressive information of COVID-19 pneumonia. © 2021 by Walter de Gruyter Berlin/Boston.

18.
Epidemiology and Infection ; 2021.
Article in English | EMBASE | ID: covidwho-1586095

ABSTRACT

COVID-19 elicits a range of different responses in patients and can manifest into mild to very severe cases in different individuals, depending on many factors. We aimed to establish a prediction model of severe risk in COVID-19 patients, to help clinicians achieve early prevention, intervention, and aid them in choosing effective therapeutic strategy. We selected confirmed COVID-19 patients who admitted to First Hospital of Changsha city between January 29 and February 15, 2020 and collected their clinical data. Multivariate logical regression was used to identify the factors associated with severe risk. These factors were incorporated into the nomogram to establish the model. The ROC curve, calibration plot and decision curve were used to assess the performance of the model. 228 patients were enrolled and 33 (14.47%) patients developed severe pneumonia. Univariate and multivariate analysis showed that shortness of breath, fatigue, creatine kinase, lymphocytes and h CRP were independent factors for severe risk in COVID-19 patients. Incorporating age, COPD and these factors, the nomogram achieved good concordance indexes of 0.89 (95% CI: 0.832-0.949), and well-fitted calibration plot curves (Hosmer-Lemeshow test: P=0.97). The model provided superior net benefit when clinical decision thresholds were between 15-85% predicted risk. Using the model, clinicians can intervene early, improve therapeutic effects and reduce the severity of COVID-19, thus ensuring more targeted and efficient use of medical resources.

19.
2d Materials ; 9(1):8, 2022.
Article in English | Web of Science | ID: covidwho-1585203

ABSTRACT

Recently, the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with major impact on public health. Novel methods that enable fast and efficient detection of the virus and the associated biomarkers, such as SARS-CoV-2 antibodies, may provide alterative opportunities for early diagnosis, disease status monitoring, and the development of vaccines. Here, we report the fabrication of a functionalized MoS2-field effect transistor (FET) for sensitive and quantitative detection of antibodies against SARS-CoV-2 spike protein receptor binding domain (S-RBD) in vaccinated serum specimens. The device was modified by SARS-CoV-2 S-RBD fusion protein on the surface and enabled rapid detection of SARS-CoV-2 antibodies. In addition, an on-chip calibration method was established for quantitative measurement. Furthermore, this method was applied to measure the levels of S-RBD antibodies in serum specimens from vaccinated donors. The devices showed no response to negative control samples from individuals who did not receive vaccination, suggesting the high specificity of this method. This study illustrated the successful fabrication of S-RBD functionalized MoS2-FET with potential clinical applications to facilitate vaccine development and efficacy evaluation.

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