Impact of the COVID-19 pandemic on outpatient appointments of rheumatic patients in a low- and medium-risk area of China (preprint)

Background We aimed to determine the impact of different strategies of outpatient appointments of rheumatic patients in a low- and medium-risk area of China against the COVID-19 pandemic.Methods Three hospitals in Shandong Province were investigated to compare the number of outpatient appointments of rheumatic patients before and after the COVID-19 pandemic.Results The number of outpatient appointments of rheumatic patients in 2020 decreased significantly under strict restrictive COVID-19 prevention measures compared to prior to the pandemic. The impact on Western medicine hospitals was greater than that on a traditional Chinese medicine (TCM) hospital. After COVID-19, first-level public health emergency responses were degraded, and the number of outpatient appointments increased rapidly, exceeding the numbers in 2019 before the COVID-19 pandemic.Conclusion In the early stage of the pandemic, severe restrictive policies were effective measures in limiting the spread of COVID-19, but outpatient appointments in the three hospitals were significantly affected. The impacts on these three hospitals were different, with the designated Western medicine hospital for COVID-19 treatment suffering the greatest impact.

The silver lining of the pandemic in surgical education: virtual surgical education and recommendations for best practices

Virtual education is an evolving field within the realm of surgical training. Since the onset of the COVID-19 pandemic, the application of virtual technologies in surgical education has undergone significant exploration and advancement. While originally developed to supplement in-person curricula for the development of clinical decision-making, virtual surgical education has expanded into the realms of clinical decision-making, surgical, and non-surgical skills acquisition. This manuscript aims to discuss the various applications of virtual surgical education as well as the advantages and disadvantages associated with each education modality, while offering recommendations on best practices and future directions.

Sub genomic analysis of SARS-CoV-2 using short read amplicon-based sequencing

The novel coronavirus disease 2019 (COVID-19) pandemic poses a serious public health risk. In this report, we present a modified sequencing workflow using short tiling (280bp) amplicons library preparation method paired with Illumina's iSeq100 desktop sequencer. We demonstrated the utility of our workflow in identifying gapped reads that capture characteristics of subgenomic RNA junctions within our patient cohort. These analytical and library preparation approaches allow a versatile, small footprint and decentralized deployment that can facilitate comprehensive genetics characterizations during outbreaks. Based on the sequencing data, Taqman assays were designed to accurately capture the quantity of subgenomic ORF5 and ORF7a RNA from patient samples and demonstrated utility in tracking subgenomic titres in patient samples when combined with a standard COVID-19 qRT-PCR assay.

COVID-19 and isolated oculomotor nerve palsy: Clinical features and outcomes.

AIM: This study aims to describe the clinical characteristics of patients with isolated oculomotor nerve palsy from COVID-19 infection, and provide guidance on their treatment and management. METHODS: We performed a systematic review and retrospective analysis on the clinical features and outcomes of patients with isolated oculomotor nerve palsy from COVID-19 reported in literature over the past three years. RESULTS: We analyzed a total of 11 cases; 9 identified in literature from January 2020 to September 2022, together with our two patients. Their median age was 46 years (range 2-65), and three were children. More than half (6/11, 55 %) were without medical history. Oculomotor nerve palsies tended to occur early (longest interval of 16 days), but they can also occur concurrently (2/11, 18 %) or before the appearance of COVID-19 symptoms (1/11, 9 %). COVID-19 symptoms tended to be mild (8/11, 73 %). Oculomotor nerve palsies, however, displayed neither a clear gender predilection, nor consistent clinical features in terms of the severity of extraocular weakness and the involvement of pupillary light responses. Nearly two-thirds (7/11, 64 %) received no pharmacological treatment. Regardless, recovery was complete in nearly all (9/10, 90 %), with most occurring within a month (8/9, 89 %) CONCLUSION: Isolated oculomotor nerve palsies are early but uncommon complications of COVID-19. They affect patients with mild infections, and can be the first symptom. Prognosis is excellent, with recovery being often complete and early. Early discharge and outpatient clinical review, with or without short courses of oral steroids, are reasonable treatment measures.

Sub genomic analysis of SARS-CoV-2 using short read amplicon-based sequencing.

The novel coronavirus disease 2019 (COVID-19) pandemic poses a serious public health risk. In this report, we present a modified sequencing workflow using short tiling (280bp) amplicons library preparation method paired with Illumina's iSeq100 desktop sequencer. We demonstrated the utility of our workflow in identifying gapped reads that capture characteristics of subgenomic RNA junctions within our patient cohort. These analytical and library preparation approaches allow a versatile, small footprint and decentralized deployment that can facilitate comprehensive genetics characterizations during outbreaks. Based on the sequencing data, Taqman assays were designed to accurately capture the quantity of subgenomic ORF5 and ORF7a RNA from patient samples and demonstrated utility in tracking subgenomic titres in patient samples when combined with a standard COVID-19 qRT-PCR assay.

Changes in endemic patterns of respiratory syncytial virus infection in pediatric patients under the pressure of nonpharmaceutical interventions for COVID-19 in Beijing, China.

A series of nonpharmaceutical interventions (NPIs) was launched in Beijing, China, on January 24, 2020, to control coronavirus disease 2019. To reveal the roles of NPIs on the respiratory syncytial virus (RSV), respiratory specimens collected from children with acute respiratory tract infection between July 2017 and Dec 2021 in Beijing were screened by capillary electrophoresis-based multiplex PCR (CEMP) assay. Specimens positive for RSV were subjected to a polymerase chain reaction (PCR) and genotyped by G gene sequencing and phylogenetic analysis using iqtree v1.6.12. The parallel and fixed (paraFix) mutations were analyzed with the R package sitePath. Clinical data were compared using SPSS 22.0 software. Before NPIs launched, each RSV endemic season started from October/November to February/March of the next year in Beijing. After that, the RSV positive rate abruptly dropped from 31.93% in January to 4.39% in February 2020; then, a dormant state with RSV positive rates ≤1% from March to September, a nearly dormant state in October (2.85%) and November (2.98%) and a delayed endemic season in 2020, and abnormal RSV positive rates remaining at approximately 10% in summer until September 2021 were detected. Finally, an endemic RSV season returned in October 2021. There was a game between Subtypes A and B, and RSV-A replaced RSV-B in July 2021 to become the dominant subtype. Six RSV-A and eight RSV-B paraFix mutations were identified on G. The percentage of severe pneumonia patients decreased to 40.51% after NPIs launched. NPIs launched in Beijing seriously interfered with the endemic season of RSV.

Multiple-Inputs Convolutional Neural Network for COVID-19 Classification and Critical Region Screening From Chest X-ray Radiographs: Model Development and Performance Evaluation

Background The COVID-19 pandemic is becoming one of the largest, unprecedented health crises, and chest X-ray radiography (CXR) plays a vital role in diagnosing COVID-19. However, extracting and finding useful image features from CXRs demand a heavy workload for radiologists. Objective The aim of this study was to design a novel multiple-inputs (MI) convolutional neural network (CNN) for the classification of COVID-19 and extraction of critical regions from CXRs. We also investigated the effect of the number of inputs on the performance of our new MI-CNN model. Methods A total of 6205 CXR images (including 3021 COVID-19 CXRs and 3184 normal CXRs) were used to test our MI-CNN models. CXRs could be evenly segmented into different numbers (2, 4, and 16) of individual regions. Each region could individually serve as one of the MI-CNN inputs. The CNN features of these MI-CNN inputs would then be fused for COVID-19 classification. More importantly, the contributions of each CXR region could be evaluated through assessing the number of images that were accurately classified by their corresponding regions in the testing data sets. Results In both the whole-image and left- and right-lung region of interest (LR-ROI) data sets, MI-CNNs demonstrated good efficiency for COVID-19 classification. In particular, MI-CNNs with more inputs (2-, 4-, and 16-input MI-CNNs) had better efficiency in recognizing COVID-19 CXRs than the 1-input CNN. Compared to the whole-image data sets, the efficiency of LR-ROI data sets showed approximately 4% lower accuracy, sensitivity, specificity, and precision (over 91%). In considering the contributions of each region, one of the possible reasons for this reduced performance was that nonlung regions (eg, region 16) provided false-positive contributions to COVID-19 classification. The MI-CNN with the LR-ROI data set could provide a more accurate evaluation of the contribution of each region and COVID-19 classification. Additionally, the right-lung regions had higher contributions to the classification of COVID-19 CXRs, whereas the left-lung regions had higher contributions to identifying normal CXRs. Conclusions Overall, MI-CNNs could achieve higher accuracy with an increasing number of inputs (eg, 16-input MI-CNN). This approach could assist radiologists in identifying COVID-19 CXRs and in screening the critical regions related to COVID-19 classifications.

How Innovation Ecosystem Synergy Degree Influences Technology Innovation Performance—Evidence from China’s High-Tech Industry

The technology innovation of high-tech industries has become an important support for the innovation-driven strategy. This study introduces innovation ecosystem synergy as a moderating variable from a systemic and holistic perspective based on the traditional perspective of innovation factor input-output, and helps construct a technology innovation performance driving model based on the Cobb–Douglas knowledge production function, which enriches the discussion perspective and theoretical model research on technology innovation performance. With a sample of 28 provinces in mainland China, this study empirically analyzed the moderating mechanism of innovation performance by innovation synergy in high-tech industries during the two stages of technology development and technology transformation. The findings of the study are as follows: (1) Independent research and development has a positive and significant impact on technology development performance;product innovation has a positive and significant impact on technology transformation performance;(2) Technology introduction can weaken technology development performance due to technology dependence and the inhibitory effect on independent innovation, and inefficient technology renovation can negatively and significantly affect technology transformation performance.;(3) The degree of synergy has a positive and significant impact on the performance of technology development innovation and technology transformation innovation. The degree of synergy has a positive moderating effect on the innovation performance of independent R&D and technology development, as well as product innovation and technology renovation, and a negative moderating effect on the innovation performance of technology introduction and technology development, but no significant moderating effect on technology renovation and technology transformation performance. The research results can provide a reference for the improvement of the technology innovation performance of regional high-tech industries.

Social Media Data for Omicron Detection from Unscripted Voice Samples (preprint)

Social media data can boost artificial intelligence (AI) systems designed for clinical applications by expanding data sources that are otherwise limited in size. Currently, deep learning methods applied to large social media datasets are used for a variety of biomedical tasks, including forecasting the onset of mental illness and detecting outbreaks of new diseases. However, exploration of online data as a training component for diagnostics tools remains rare, despite the deluge of information that is available through various APIs. In this study, data from YouTube was used to train a model to detect the Omicron variants of SARS-CoV-2 from changes in the human voice. According to the ZOE Health Study, laryngitis and hoarse voice were among the most common symptoms of the Omicron variant, regardless of vaccination status. Omicron is characterized by pre-symptomatic transmission as well as mild or absent symptoms. Therefore, impactful screening methodologies may benefit from speed, convenience, and non-invasive ergonomics. We mined YouTube to collect voice data from individuals with self-declared positive COVID-19 tests during time periods where the Omicron variant (or sub-variants, including BA.4/5) consisted of more than 95% of cases. Our dataset contained 183 distinct Omicron samples (28.39 hours), 192 healthy samples (33.90 hours), 138 samples from other upper respiratory infections (8.09 hours), and 133 samples from non-Omicron variants of COVID-19 (22.84 hours). We used a flexible data collection protocol and implemented a simple augmentation strategy that leveraged intra-sample variance arising from the diversity of unscripted speech (different words, phrases, and tones). This approach led to enhanced model generalization despite a relatively small number of samples. We trained a DenseNet model to detect Omicron in subjects with self-declared positive COVID-19 tests. Our model achieved 86% sensitivity and 81% specificity when detecting healthy voices (asymptomatic negative vs. all positive). We also achieved 76% sensitivity and 70% specificity separating between symptomatic negative samples and all positive samples. This result showed that social media data may be used to counterbalance the limited amount of well-curated data commonly available for deep learning tasks in clinical medicine. Our work demonstrates the potential of digital, non-invasive diagnostic methods trained with public online data and explores novel design paradigms for diagnostic tools that rely on audio data.

Viral inhibition of ER-phagy is critical to membrane remodelling for biogenesis of (+)RNA virus replication organelles (preprint)

Infection by (+)RNA viruses are accompanied by induction of ER-expansion and membrane remodelling to form viral replication organelles, followed by assembly and secretion of viral progenies. We previously identified that virus triggered lipophagy was critical for the process of flaviviral assembly, driven by the lipid droplet associated protein Ancient ubiquitin protein 1 (Aup1). A ubiquitin conjugating protein Ube2g2 that functions as a co-factor for Aup1 was also identified as a host dependency factor in our study. Here we characterized its function: Ube2g2-deficient cells displayed a dramatic reduction in production of flavi- and coronaviruses, which could be rescued by reconstituting the wild-type but not the catalytically deficient (C89K) mutant of Ube2g2, suggesting that its enzymatic activity is necessary. Ube2g2 deficiency did not affect entry of virus particles but resulted in a profound loss in formation of replication organelles, and production of infectious progenies. This phenomenon resulted from its dual activity in (i) triggering lipophagy in conjunction with Aup1, and (ii) degradation of ER chaperones such as Herpud1, SEL1L, Hrd1 to restrict ER-phagy upon Xbp1-IRE1 triggered ER expansion. Ube2g2-deficient cells were impaired in lipophagy, while undergoing wide-spread Sec62 and Chmp4 dependent ER-phagy, inhibiting membrane remodelling required for biogenesis of viral replication organelles. Our results therefore underscore a virus-driven exquisite fine-tuning of selective autophagy of organelles that drive host membrane reorganization during +RNA virus infection to enable biogenesis of viral replication organelles.

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants (preprint)

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Clinical evaluation and application of detection of IgM and IgG antibodies against SARS-CoV-2 using a colloidal gold immunochromatography assay

The pandemic of the novel coronavirus (SARS-CoV-2) infection has seriously threated global public health, a rapid and easy operated method for coronavirus disease (COVID-19) diagnosis is needed. To evaluate the clinical application efficacy of the colloidal gold rapid test kit for detection of the IgM/IgG antibodies to SARS-CoV-2, a total of 304 clinical diagnosed case, 138 health donor (of which 114 showed SARS-CoV-2) viral RNA negative and 64 other fever patients with respiratory symptoms were selected for the study and the plasma or serum samples were tested for both IgM and IgG with the kit. The comparison of the detection coincidence of the samples from whole blood and plasma or serum were also performed;Furthermore, the time distribution of SARS-CoV-2 viral RNA and IgM/IgG antibodies detections were analyzed. The results showed that, of the 304 clinical diagnosed cases, 105 cases were positive for viral RNA detection, among which the detection sensitivity of IgM and IgG antibodies to SARS-CoV-2 by colloidal gold rapid assay was 76.2% (80/105) and 86.6% (91/105), respectively, and the overall coincidence rate of IgM/IgG antibody was 96.1% (101/105);and 73 cases were negative for both nucleic acid and antibody detection. Of the remaining 126 clinical diagnosed cases, the positive rate of IgM and IgG was 69.2% (87/126) and 98.3% (125/126), respectively, and the overall coincidence rate of IgM/IgG antibody was 100% (126/126). In detections for healthy and other fever patients, the specificity of IgM and IgG was 99% (200/202) and 98% (198/202), respectively, and the total coincidence rate of antibody detection results of homologous whole blood and plasma samples was 99%, indicating a high degree of consistency. In this study, the detection assay of SARS-CoV-2 antibodies using colloidal gold method showed satisfactory detection effect, and it could be used for clinical auxiliary diagnosis and epidemiological investigation, which could be applied in a wide range of scenarios and play a valuable role in the prevention and control of SARS-CoV-2 pandemic.

Prussian Blue@Zeolitic Imidazolate Framework Composite Toward Solar-triggered Biodecontamination

Metal-organic frameworks (MOFs) featuring composition and bandstructure diversity, are an emerging class of photoresponsive disinfectants. In this study, we demonstrated the superiority of core-shell arranged photoactive MOFs (prussian blue (PB) and zeolitic imidazolate framework (ZIF-8)) for pathogen inactivation in terms of biocidal efficiency and broad-spectrum sensitivity. Reactive oxygen species (ROS) production was significantly promoted after the integration of PB due to the photosensitization effect and initiation of in situ Fenton reaction. Favorably, another inactivation channel was also opened owing to the unique photothermal effect of PB. Attributed to the facilitated ROS intracellular penetration by heat, the composite outperforms not only individual component but anatase TiO2 in pathogen elimination. Specifically, the Staphylococcus aureus (S. aureus) inactivation efficiency of the composite (6.6 log) is 2, 1.8 and 5.1 times higher than that of PB (3.3 log), ZIF-8 (3.7 log) and TiO2 (1.3 log) over 45 min of simulated sunlight illumination. Significantly, the infectivity of Bacillus anthracis and murine coronavirus in droplets on composite-coated filter surface could be greatly reduced (approximately 3 log reduction in colony number/coronavirus titer) within few minutes of solar exposure, indicative of the great potential of MOF composites toward life-threatening microbial infection prevention.

Computer-Aided and AILDE Approaches to Design Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a pivotal enzyme in tocopherol and plastoquinone synthesis and a potential target for novel herbicides. Thirty-five pyridine derivatives were selected to establish a Topomer comparative molecular field analysis (Topomer CoMFA) model to obtain correlation information between HPPD inhibitory activity and the molecular structure. A credible and predictive Topomer CoMFA model was established by "split in two R-groups" cutting methods and fragment combinations (q2 = 0.703, r2 = 0.957, ONC = 6). The established model was used to screen out more active compounds and was optimized through the auto in silico ligand directing evolution (AILDE) platform to obtain potential HPPD inhibitors. Twenty-two new compounds with theoretically good HPPD inhibition were obtained by combining the high-activity contribution substituents in the existing molecules with the R-group search via Topomer search. Molecular docking results revealed that most of the 22 fresh compounds could form stable π-π interactions. The absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction and drug-like properties made 9 compounds potential HPPD inhibitors. Molecular dynamics simulation indicated that Compounds Y12 and Y14 showed good root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values and stability. According to the AILDE online verification, 5 new compounds with potential HPPD inhibition were discovered as HPPD inhibitor candidates. This study provides beneficial insights for subsequent HPPD inhibitor design.

What drives attitude towards remote palliative care among tumor patients amid the COVID-19 Pandemic ? A survey (preprint)

Background: To understand the status of cancer patients’ awareness and demand for remote palliative care service and to provide a reference for promoting the formulation of remote palliative care policy. Methods: : A small across-section design involved a sample of 148 cancer adults in the First Affiliated Hospital of Guangxi Medical University, who were conducted by self-designed questionnaire via the Questionnaire Star. The questionnaire contained basic information (14 items) and the attitude towards the remote palliative care (6 items). Results: : The rate of patients who supported to take remote palliative care was 41.2%. It related with age, education level, occupation, family income, insurance type, self-care ability, smartphone and communication app using, and the using time(p＜0.05). Most of them hoped to get remote palliative care 24 hours. Almost half of the patients would like to be charged by items and they hoped the price of remote palliative care be cheap. Most of the patients didn’t really care about the working years and title of the care provider, but half of them more believed Grade 3, Class A hospital. The top three demand of remote palliative care were pain reducing, nutrition counseling, and nursing instruction. Conclusion: Remote palliative care has a good application prospect for cancer patients, but there are still some challenges, which need further exploration and development, including appropriate infrastructure, reasonable price and sufficient personnel to provide remote palliative care services.

Rapid PCR-Based Nanopore Adaptive Sequencing Improves Sensitivity and Timeliness of Viral Clinical Detection and Genome Surveillance

Nanopore sequencing has been widely used for the real-time detection and surveillance of pathogens with portable MinION. Nanopore adaptive sequencing can enrich on-target sequences without additional pretreatment. In this study, the performance of adaptive sequencing was evaluated for viral genome enrichment of clinical respiratory samples. Ligation-based nanopore adaptive sequencing (LNAS) and rapid PCR-based nanopore adaptive sequencing (RPNAS) workflows were performed to assess the effects of enrichment on nasopharyngeal swab samples from human adenovirus (HAdV) outbreaks. RPNAS was further applied for the enrichment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from nasopharyngeal swab samples to evaluate sensitivity and timeliness. The RPNAS increased both the relative abundance (7.87–12.86-fold) and data yield (1.27–2.15-fold) of HAdV samples, whereas the LNAS increased only the relative abundance but had no obvious enrichment on the data yield. Compared with standard nanopore sequencing, RPNAS detected the SARS-CoV-2 reads from two low-abundance samples, increased the coverage of SARS-CoV-2 by 36.68–98.92%, and reduced the time to achieve the same coverage. Our study highlights the utility of RPNAS for virus enrichment directly from clinical samples, with more on-target data and a shorter sequencing time to recover viral genomes. These findings promise to improve the sensitivity and timeliness of rapid identification and genomic surveillance of infectious diseases.

ROS-Ethereum: A Convenient Tool to Bridge ROS and Blockchain (Ethereum)

Robot Operating System (ROS) has received widespread utilization with the development of robotics, self-driving, etc., recently. Meanwhile, the other technology blockchain is frequently applied to various fields with its trustworthy characteristics and immutability in data storage. However, ROS has no ability to interact with the blockchain, which hinders research in related fields. Therefore, we wonder if we can develop a convenient tool to bridge ROS and blockchain. Inspired by this, we propose ROS-Ethereum. It bridges ROS and Ethereum, a widely used blockchain platform. ROS-Ethereum is based on the User Datagram Protocol (UDP) communication mechanism and the SM algorithm family along with Ethereum technology. Simply put, ROS-Ethereum allows users to invoke the contract when interacting with the blockchain, which makes this process easier and safer. We conduct experiments in real robots to verify the effectiveness of ROS-Ethereum and evaluate it from the following metrics: (1) the encryption efficiency and stability of the algorithm and (2) ROS-Ethereum transaction response time and packet loss rate.

Evaluation of multiplex combined real-time PCR detection kit for nucleic acid detection of 22 respiratory pathogens

Objective: To evaluate the detection consistency and power of a multiplex combined real-time PCR detection kits, and provide reference for the prevention and control of influenza plus SARS-CoV-2 infection.

A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants (preprint)

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Safety and immunogenicity of a hybrid-type vaccine booster in BBIBP-CorV recipients: a randomized controlled phase 2 trial (preprint)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.