Comparison of SARS-CoV-2 Omicron nucleic acid test for COVID-19 infection with real-time RT-PCR using different nasopharyngeal swabs (preprint)

Background: A new one SARS-CoV-2 Variant of Concern (VoC), Omicron, was born in a world weary of COVID-19, which anger and frustration with the pandemic was widespread, with wide-ranging negative impacts on health, social and economic well-being. The Omicron variant, which main types was BA5.2and BF.7 in China, in December 2022 to January 2023 leaded to off-target of the S and N genes, and the kits used were not adequately and independently evaluated when these agents are studied and developed. To ensure the accuracy of coronavirus test results, performance verification of commercial Real-Time quantitative PCR (RT-qPCR) was required. Objective: We performed a clinical evaluation for two Real Time SARS-CoV-2 assay, and to verify them based on different detection reagents and different clinical specimens. Methods: : We performed clinical evaluations of two existing Chinese SARS-CoV-2 RT-qPCR kits COVID-19 nucleic acid detection kits (e-Diagnostic Biomedical, Wuhan, China) and 2019-nCoV nucleic acid diagnostic kits (Fosun Biotechnology, Shanghai, China) using BSD ( Bondson) (Guangzhou Bondson Biotechnology Co. Ltd.;batch number 2022101), quality controls provided by the inspection center and a large number of clinically confirmed specimens. Overall, through the BDS performance verification reference product kit, It was best used to verify the performance of the reagent through a large number of clinical specimens for further verification. Results: : The coincidence rate for Fosun and e-Diagnostic kits were individually 95% and 100%. Verified that the detection limit for Fosun and e-Diagnostic kits was 300copies/mL. All were below the detection limit for Fosun reagent was 300copies/mL. e-Diagnostic was 500copies/mL. Fosun had the largest CV for ORF1ab and N gene at the the detection limit concentration(4.80%,3.49%), while e-Diagnostic had the smaller (0.93%,1.10%). Negative results were tested in cross-reactivity. During the verification of clinical samples, sequencing analyses had shown that Fosun single gene miss rate was relatively high, especially ORF1ab, followed by N gene miss rate. we survey that all N genes were detected in clinical specimens, ,ORFab dropout (i.e., a negative/low result) occurred in (10.8%) of 225 Omicron variant. Conclusions: : Our results endorse the use of these two commercial kits for the diagnosis of SARS-CoV-2 in China, as their clinical performance has been fully validated by a large number of clinically confirmed cases.

Preventive and therapeutic benefits of nelfinavir in rhesus macaques and human beings infected with SARS-CoV-2.

Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 µM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 µM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant.

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.

Risk Factors Associated with the Spatiotemporal Spread of the SARS-CoV-2 Omicron BA.2 Variant - Shanghai Municipality, China, 2022.

What is already known about this topic?: Previous studies have explored the spatial transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have assessed the associated risk factors. However, none of these studies have quantitatively described the spatiotemporal transmission patterns and risk factors for Omicron BA.2 at the micro (within-city) scale. What is added by this report?: This study highlights the heterogeneous spread of the 2022 Omicron BA.2 epidemic in Shanghai, and identifies associations between different metrics of spatial spread at the subdistrict level and demographic and socioeconomic characteristics of the population, human mobility patterns, and adopted interventions. What are the implications for public health practice?: Disentangling different risk factors might contribute to a deeper understanding of the transmission dynamics and ecology of coronavirus disease 2019 and an effective design of monitoring and management strategies.

Estimating Changes in Contact Patterns in China Over the First Year of the COVID-19 Pandemic: Implications for SARS-CoV-2 Spread - Four Cities, China, 2020.

Introduction: Previous studies have demonstrated significant changes in social contacts during the first-wave coronavirus disease 2019 (COVID-19) in Chinese mainland. The purpose of this study was to quantify the time-varying contact patterns by age in Chinese mainland in 2020 and evaluate their impact on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: Diary-based contact surveys were performed for four periods: baseline (prior to 2020), outbreak (February 2020), post-lockdown (March-May 2020), and post-epidemic (September-November 2020). We built a Susceptible-Infected-Recovered (SIR) model to evaluate the effect of reducing contacts on transmission. Results: During the post-epidemic period, daily contacts resumed to 26.7%, 14.8%, 46.8%, and 44.2% of the pre-COVID levels in Wuhan, Shanghai, Shenzhen, and Changsha, respectively. This suggests a moderate risk of resurgence in Changsha, Shenzhen, and Wuhan, and a low risk in Shanghai. School closure alone was not enough to interrupt transmission of SARS-CoV-2 Omicron BA.5, but with the addition of a 75% reduction of contacts at the workplace, it could lead to a 16.8% reduction of the attack rate. To control an outbreak, concerted strategies that target schools, workplaces, and community contacts are needed. Discussion: Monitoring contact patterns by age is key to quantifying the risk of COVID-19 outbreaks and evaluating the impact of intervention strategies.

The bioactivities of sclareol: A mini review.

Sclareol, a diterpene alcohol isolated from the herbal and flavor plant clary sage (Salvia sclarea L.), is far-famed as the predominant ingredient in the refined oil of Salvia sclarea (L.). The empirical medicine of Salvia sclarea L. focused on various diseases, such as arthritis, oral inflammation, digestive system diseases, whereas the sclareol possessed more extensive and characteristic bioactivities, including anti-tumor, anti-inflammation and anti-pathogenic microbes, even anti-diabetes and hypertension. However, there is a deficiency of literature to integrate and illuminate the pharmacological attributes of sclareol based on well-documented investigations. Interestingly, sclareol has been recently considered as the potential candidate against COVID-19 and Parkinson's disease. Accordingly, the bioactive attributes of sclareol in cancer, inflammation, even pharmacochemistry and delivery systems are reviewed for comprehensively dissecting its potential application in medicine.

Ultrasensitive detection of SARS-CoV-2 S protein with aptamers biosensor based on surface-enhanced Raman scattering.

A rapid and accurate diagnostic modality is essential to prevent the spread of SARS-CoV-2. In this study, we proposed a SARS-CoV-2 detection sensor based on surface-enhanced Raman scattering (SERS) to achieve rapid and ultrasensitive detection. The sensor utilized spike protein deoxyribonucleic acid aptamers with strong affinity as the recognition entity to achieve high specificity. The spherical cocktail aptamers-gold nanoparticles (SCAP) SERS substrate was used as the base and Au nanoparticles modified with the Raman reporter molecule that resonates with the excitation light and spike protein aptamers were used as the SERS nanoprobe. The SCAP substrate and SERS nanoprobes were used to target and capture the SARS-CoV-2 S protein to form a sandwich structure on the Au film substrate, which can generate ultra-strong "hot spots" to achieve ultrasensitive detection. Analysis of SARS-CoV-2 S protein was performed by monitoring changes in SERS peak intensity on a SCAP SERS substrate-based detection platform. This assay detects S protein with a LOD of less than 0.7 fg mL-1 and pseudovirus as low as 0.8 TU mL-1 in about 12 min. The results of the simulated oropharyngeal swab system in this study indicated the possibility of it being used for clinical detection, providing a potential option for rapid and accurate diagnosis and more effective control of SARS-CoV-2 transmission.

Cucurbitacin B: A review of its pharmacology, toxicity, and pharmacokinetics.

Cucurbitacin B (CuB, C32H46O8), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.

Rapid Point-of-Care Assay by SERS Detection of SARS-CoV-2 Virus and Its Variants.

Addressing the spread of coronavirus disease 2019 (COVID-19) has highlighted the need for rapid, accurate, and low-cost diagnostic methods that detect specific antigens for SARS-CoV-2 infection. Tests for COVID-19 are based on reverse transcription PCR (RT-PCR), which requires laboratory services and is time-consuming. Here, by targeting the SARS-CoV-2 spike protein, we present a point-of-care SERS detection platform that specifically detects SARS-CoV-2 antigen in one step by captureing substrates and detection probes based on aptamer-specific recognition. Using the pseudovirus, without any pretreatment, the SARS-CoV-2 virus and its variants were detected by a handheld Raman spectrometer within 5 min. The limit of detection (LoD) for the pseudovirus was 124 TU µL-1 (18 fM spike protein), with a linear range of 250-10,000 TU µL-1. Moreover, this assay can specifically recognize the SARS-CoV-2 antigen without cross reacting with specific antigens of other coronaviruses or influenza A. Therefore, the platform has great potential for application in rapid point-of-care diagnostic assays for SARS-CoV-2.

Efficiency of nicotinamide-based supportive therapy in lymphopenia for patients with ordinary or severe COVID-19: A randomized controlled trial.

BACKGROUND: This study aimed to investigate the efficiency of nicotinamide-based supportive therapy for lymphopenia in patients with coronavirus disease-2019 (COVID-19). METHODS: Twenty four patients diagnosed with COVID-19 were randomly divided into 2 groups (n = 12) during hospitalization in a ratio of 1:1. Based on conventional treatment, the treatment group was administered 100 mg nicotinamide 5 times a day for 2 days. The control group received routine treatment only. The primary endpoint was the change in the absolute lymphocyte count. The secondary endpoints included both in-hospital death and the composite endpoint of aggravation, according to upgraded oxygen therapy, improved nursing level, and ward rounds of superior physicians for changes in conditions. RESULTS: Full blood counts before and after nicotinamide administration were comparable in each group (all P > .05). Before and after receiving nicotinamide, mean absolute lymphocyte counts were similar between the two groups ([0.94 ± 0.26] × 109/L vs [0.89 ± 0.19] × 109/L, P = .565; [1.15 ± 0.48] × 109/L vs [1.02 ± 0.28] × 109/L, P = .445, respectively). Therefore, there was no statistically significant difference in the lymphocyte improvement rate between the two groups (23.08 ± 46.10 vs 16.52 ± 24.10, P = .67). There was also no statistically significant difference in the secondary endpoints between the two groups. CONCLUSION: Among patients with COVID-19, there was no statistically significant difference in the change of whole blood counts and absolute lymphocyte counts before and after intervention in both groups. Therefore, no new evidence has been found regarding the effect of niacinamide on lymphopenia in COVID-19 patients.

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial.

Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0µg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.

Modeling transmission of SARS-CoV-2 Omicron in China.

Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

Rapid and Accurate Detection of SARS Coronavirus 2 by Nanopore Amplicon Sequencing.

Objective: We aimed to evaluate the performance of nanopore amplicon sequencing detection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples. Method: We carried out a single-center, prospective cohort study in a Wuhan hospital and collected a total of 86 clinical samples, including 54 pharyngeal swabs, 31 sputum samples, and 1 fecal sample, from 86 patients with coronavirus disease 2019 (COVID-19) from Feb 20 to May 15, 2020. We performed parallel detection with nanopore-based genome amplification and sequencing (NAS) on the Oxford Nanopore Technologies (ONT) minION platform and routine reverse transcription quantitative polymerase chain reaction (RT-qPCR). In addition, 27 negative control samples were detected using the two methods. The sensitivity and specificity of NAS were evaluated and compared with those of RT-qPCR. Results: The viral read number and reference genome coverage were both significantly different between the two groups of samples, and the latter was a better indicator for SARS-CoV-2 detection. Based on the reference genome coverage, NAS revealed both high sensitivity (96.5%) and specificity (100%) compared with RT-qPCR (80.2 and 96.3%, respectively), although the samples had been stored for half a year before the detection. The total time cost was less than 15 h, which was acceptable compared with that of RT-qPCR (∼2.5 h). In addition, the reference genome coverage of the viral reads was in line with the cycle threshold value of RT-qPCR, indicating that this number could also be used as an indicator of the viral load in a sample. The viral load in sputum might be related to the severity of the infection, particularly in patients within 4 weeks after onset of clinical manifestations, which could be used to evaluate the infection. Conclusion: Our results showed the high sensitivity and specificity of the NAS method for SARS-CoV-2 detection compared with RT-qPCR. The sequencing results were also used as an indicator of the viral load to display the viral dynamics during infection. This study proved the wide application prospect of nanopore sequencing detection for SARS-CoV-2 and may more knowledge about the clinical characteristics of COVID-19.

Global Scientific Research Landscape on Medical Informatics From 2011 to 2020: Bibliometric Analysis.

BACKGROUND: With the emerging information and communication technology, the field of medical informatics has dramatically evolved in health care and medicine. Thus, it is crucial to explore the global scientific research landscape on medical informatics. OBJECTIVE: This study aims to present a visual form to clarify the overall scientific research trends of medical informatics in the past decade. METHODS: A bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze global scientific research trends on medical informatics, including publication year, journals, authors, institutions, countries/regions, references, and keywords, from January 1, 2011, to December 31, 2020. RESULTS: The data set recorded 34,742 articles related to medical informatics from WoSCC between 2011 and 2020. The annual global publications increased by 193.86% from 1987 in 2011 to 5839 in 2020. Journal of Medical Internet Research (3600 publications and 63,932 citations) was the most productive and most highly cited journal in the field of medical informatics. David W Bates (99 publications), Harvard University (1161 publications), and the United States (12,927 publications) were the most productive author, institution, and country, respectively. The co-occurrence cluster analysis of high-frequency author keywords formed 4 clusters: (1) artificial intelligence in health care and medicine; (2) mobile health; (3) implementation and evaluation of electronic health records; (4) medical informatics technology application in public health. COVID-19, which ranked third in 2020, was the emerging theme of medical informatics. CONCLUSIONS: We summarize the recent advances in medical informatics in the past decade and shed light on their publication trends, influential journals, global collaboration patterns, basic knowledge, research hotspots, and theme evolution through bibliometric analysis and visualization maps. These findings will accurately and quickly grasp the research trends and provide valuable guidance for future medical informatics research.

A convolutional neural network-based COVID-19 detection method using chest CT images.

Background: High-throughput population screening for the novel coronavirus disease (COVID-19) is critical to controlling disease transmission. Convolutional neural networks (CNNs) are a cutting-edge technology in the field of computer vision and may prove more effective than humans in medical diagnosis based on computed tomography (CT) images. Chest CT images can show pulmonary abnormalities in patients with COVID-19. Methods: In this study, CT image preprocessing are firstly performed using fuzzy c-means (FCM) algorithm to extracted the region of the pulmonary parenchyma. Through multiscale transformation, the preprocessed image is subjected to multi scale transformation and RGB (red, green, blue) space construction. After then, the performances of GoogLeNet and ResNet, as the most advanced CNN architectures, were compared in COVID-19 detection. In addition, transfer learning (TL) was employed to solve overfitting problems caused by limited CT samples. Finally, the performance of the models were evaluated and compared using the accuracy, recall rate, and F1 score. Results: Our results showed that the ResNet-50 method based on TL (ResNet-50-TL) obtained the highest diagnostic accuracy, with a rate of 82.7% and a recall rate of 79.1% for COVID-19. These results showed that applying deep learning technology to COVID-19 screening based on chest CT images is a very promising approach. This study inspired us to work towards developing an automatic diagnostic system that can quickly and accurately screen large numbers of people with COVID-19. Conclusions: We tested a deep learning algorithm to accurately detect COVID-19 and differentiate between healthy control samples, COVID-19 samples, and common pneumonia samples. We found that TL can significantly increase accuracy when the sample size is limited.

Assessing the transition of COVID-19 burden towards the young population while vaccines are rolled out in China.

SARS-CoV-2 infection causes most cases of severe illness and fatality in older age groups. Over 92% of the Chinese population aged ≥12 years has been fully vaccinated against COVID-19 (albeit with vaccines developed against historical lineages). At the end of October 2021, the vaccination programme has been extended to children aged 3-11 years. Here, we aim to assess whether, in this vaccination landscape, the importation of Delta variant infections could shift COVID-19 burden from adults to children. We developed an age-structured susceptible-infectious-removed model of SARS-CoV-2 transmission to simulate epidemics triggered by the importation of Delta variant infections and project the age-specific incidence of SARS-CoV-2 infections, cases, hospitalizations, intensive care unit admissions, and deaths. In the context of the vaccination programme targeting individuals aged ≥12 years, and in the absence of non-pharmaceutical interventions, the importation of Delta variant infections could have led to widespread transmission and substantial disease burden in mainland China, even with vaccination coverage as high as 89% across the eligible age groups. Extending the vaccination roll-out to include children aged 3-11 years (as it was the case since the end of October 2021) is estimated to dramatically decrease the burden of symptomatic infections and hospitalizations within this age group (39% and 68%, respectively, when considering a vaccination coverage of 87%), but would have a low impact on protecting infants. Our findings highlight the importance of including children among the target population and the need to strengthen vaccination efforts by increasing vaccine effectiveness.

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study.

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Multifunctional carbon nanomaterials for diagnostic applications in infectious diseases and tumors.

Infectious diseases (such as Corona Virus Disease 2019) and tumors pose a tremendous challenge to global public health. Early diagnosis of infectious diseases and tumors can lead to effective control and early intervention of the patient's condition. Over the past few decades, carbon nanomaterials (CNs) have attracted widespread attention in different scientific disciplines. In the field of biomedicine, carbon nanotubes, graphene, carbon quantum dots and fullerenes have the ability of improving the accuracy of the diagnosis by the improvement of the diagnostic approaches. Therefore, this review highlights their applications in the diagnosis of infectious diseases and tumors over the past five years. Recent advances in the field of biosensing, bioimaging, and nucleic acid amplification by such CNs are introduced and discussed, emphasizing the importance of their unique properties in infectious disease and tumor diagnosis and the challenges and opportunities that exist for future clinical applications. Although the application of CNs in the diagnosis of several diseases is still at a beginning stage, biosensors, bioimaging technologies and nucleic acid amplification technologies built on CNs represent a new generation of promising diagnostic tools that further support their potential application in infectious disease and tumor diagnosis.

Investigating vaccine-induced immunity and its effect in mitigating SARS-CoV-2 epidemics in China.

BACKGROUND: To allow a return to a pre-COVID-19 lifestyle, virtually every country has initiated a vaccination program to mitigate severe disease burden and control transmission. However, it remains to be seen whether herd immunity will be within reach of these programs. METHODS: We developed a compartmental model of SARS-CoV-2 transmission for China, a population with low prior immunity from natural infection. Two vaccination programs were tested and model-based estimates of the immunity level in the population were provided. RESULTS: We found that it is unlikely to reach herd immunity for the Delta variant given the relatively low efficacy of the vaccines used in China throughout 2021 and the lack of prior natural immunity. We estimated that, assuming a vaccine efficacy of 90% against the infection, vaccine-induced herd immunity would require a coverage of 93% or higher of the Chinese population. However, even when vaccine-induced herd immunity is not reached, we estimated that vaccination programs can reduce SARS-CoV-2 infections by 50-62% in case of an all-or-nothing vaccine model and an epidemic starts to unfold on December 1, 2021. CONCLUSIONS: Efforts should be taken to increase population's confidence and willingness to be vaccinated and to develop highly efficacious vaccines for a wide age range.

Predicting spike protein NTD mutations of SARS-CoV-2 causing immune evasion by molecular dynamics simulations.

The coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among all the potential targets studied for developing drugs and antibodies, the spike (S) protein is the most striking one, which is on the surface of the virus. In contrast with the intensively investigated immunodominant receptor-binding domain (RBD) of the protein, little is known about the neutralizing antibody binding mechanisms of the N-terminal domain (NTD), let alone the effects of NTD mutations on antibody binding and thereby the risk of immune evasion. Based on 400 ns molecular dynamics simulation for 11 NTD-antibody complexes together with other computational approaches in this study, we investigated critical residues for NTD-antibody binding and their detailed mechanisms. The results show that 36 residues on the NTD including R246, Y144, K147, Y248, L249 and P251 are critically involved in the direct interaction of the NTD with many monoclonal antibodies (mAbs), indicating that the viruses harboring these residue mutations may have a high risk of immune evasion. Binding free energy calculations and an interaction mechanism study reveal that R246I, which is present in the Beta (B.1.351/501Y.V2) variant, may have various impacts on current NTD antibodies through abolishing the hydrogen bonds and electrostatic interaction with the antibodies or affecting other interface residues. Therefore, special attention should be paid to the mutations of these key residues in future antibody and vaccine design and development.