Enhancing food supply chain in green logistics with multi-level processing strategy under disruptions

Food supply chains (FSCs) have long been exposed to environmental variability and shock events caused by various economic, political, and infrastructural factors. The outbreak of the COVID-19 pandemic has further exposed and identified the vulnerability of FSCs, and promoted integrated optimization approaches for building resilience. However, existing works focusing on general supply chains (SCs) and FSCs have not been fully aware of the distinct characteristics of FSCs in green logistics, i.e., the expiration of fresh products. In reality, perishable food materials can be processed into products of different processing levels (i.e., multi-level processing) for longer shelf lives, which can serve as a timely and economic strategy to increase safety stocks for mitigating disruption risks. Motivated by this fact, we study the problem of enhancing FSC with a multi-level processing strategy. An integrated location, inventory, and distribution planning model for a multi-echelon FSC under COVID-19-related disruptions is formulated to maximize the total profit over a finite planning horizon. Specifically, a two-stage stochastic programming model is presented to hedge against disruption risks, where scenarios are generated to characterize geographical impact induced by source-region disruptions. For small-scale problems, the model can be solved with commercial solvers. To exactly and efficiently solve the large-scale instances, we design an integer L-shaped method. Numerical experiments are conducted on a case study and randomly generated instances to show the efficiency of our model and solution method. Based on the case study, managerial insights are drawn.

Anti-Coronaviral Nanocluster Restrain Infections of SARS-CoV-2 and Associated Mutants through Virucidal Inhibition and 3CL Protease Inactivation.

Antivirals that can combat coronaviruses, including SARS-CoV-2 and associated mutants, are urgently needed but lacking. Simultaneously targeting the viral physical structure and replication cycle can endow antivirals with sustainable and broad-spectrum anti-coronavirus efficacy, which is difficult to achieve using a single small-molecule antiviral. Thus, a library of nanomaterials on GX_P2V, a SARS-CoV-2-like coronavirus of pangolin origin, is screened and a surface-functionalized gold nanocluster (TMA-GNC) is identified as the top hit. TMA-GNC inhibits transcription- and replication-competent SARS-CoV-2 virus-like particles and all tested pseudoviruses of SARS-CoV-2 variants. TMA-GNC prevents viral dissemination through destroying membrane integrity physically to enable a virucidal effect, interfering with viral replication by inactivating 3CL protease and priming the innate immune system against coronavirus infection. TMA-GNC exhibits biocompatibility and significantly reduces viral titers, inflammation, and pathological injury in lungs and tracheas of GX_P2V-infected hamsters. TMA-GNC may have a role in controlling the COVID-19 pandemic and inhibiting future emerging coronaviruses or variants.

NSUN2-mediated M5c methylation of IRF3 mRNA negatively regulates type I interferon responses during various viral infections.

5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-ß production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the antiviral innate response is more dramatically enhanced in Nsun2+/- mice than in Nsun2+/+ mice. The highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation enhanced cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), or Zika virus (ZIKV) resulted in a reduction of endogenous NSUN2 levels. Especially, SARS-CoV-2 infection (WT strain and BA.1 omicron variant) also decreased endogenous levels of NSUN2 in COVID-19 patients and K18-hACE2 KI mice, further increasing type I interferon and downstream ISGs. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease during SARS-CoV-2 and various viral infections to boost antiviral responses for effective elimination of viruses.

Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Community Mitigation of COVID-19 and Portrayal of Testing on TikTok: Descriptive Study.

BACKGROUND: COVID-19 testing remains an essential element of a comprehensive strategy for community mitigation. Social media is a popular source of information about health, including COVID-19 and testing information. One of the most popular communication channels used by adolescents and young adults who search for health information is TikTok-an emerging social media platform. OBJECTIVE: The purpose of this study was to describe TikTok videos related to COVID-19 testing. METHODS: The hashtag #covidtesting was searched, and the first 100 videos were included in the study sample. At the time the sample was drawn, these 100 videos garnered more than 50% of the views for all videos cataloged under the hashtag #covidtesting. The content characteristics that were coded included mentions, displays, or suggestions of anxiety, COVID-19 symptoms, quarantine, types of tests, results of test, and disgust/unpleasantness. Additional data that were coded included the number and percentage of views, likes, and comments and the use of music, dance, and humor. RESULTS: The 100 videos garnered more than 103 million views; 111,000 comments; and over 12.8 million likes. Even though only 44 videos mentioned or suggested disgust/unpleasantness and 44 mentioned or suggested anxiety, those that portrayed tests as disgusting/unpleasant garnered over 70% of the total cumulative number of views (73,479,400/103,071,900, 71.29%) and likes (9,354,691/12,872,505, 72.67%), and those that mentioned or suggested anxiety attracted about 60% of the total cumulative number of views (61,423,500/103,071,900, 59.59%) and more than 8 million likes (8,339,598/12,872,505, 64.79%). Independent one-tailed t tests (α=.05) revealed that videos that mentioned or suggested that COVID-19 testing was disgusting/unpleasant were associated with receiving a higher number of views and likes. CONCLUSIONS: Our finding of an association between TikTok videos that mentioned or suggested that COVID-19 tests were disgusting/unpleasant and these videos' propensity to garner views and likes is of concern. There is a need for public health agencies to recognize and address connotations of COVID-19 testing on social media.

It is time to acknowledge coronavirus transmission via frozen and chilled foods: Undeniable evidence from China and lessons for the world.

Since the broke out of the novel coronavirus disease at the end of 2019, nearly 650 million people have been infected around the globe, and >6.6 million have died from this disease. The first wave of infections in mainland China had been effectively controlled within a short period, with no domestic cases of infection for 56 consecutive days from April 16, 2020. Nonetheless, the re-emergence of several outbreaks in multiple Chinese cities posed a new challenge for public health authorities after new cases of infections were found in Xinfadi Market in Beijing on June 11, 2020. In the following series of re-emergent outbreaks, findings from epidemiological investigations suggested that more than twenty re-emergent outbreaks were caused by fomite transmission, predominantly via imported frozen and chilled foods contaminated by the SARS-CoV-2 virus. Seven of the eleven incidents involving frozen and chilled foods were identified by screening individuals with occupational exposure to imported cold-chain foods and associated individuals. Evidence showed that low temperatures and poor ventilation typically maintained through cold-chain logistics create amenable environments for the survival of SARS-CoV-2, making transnational cold chain logistics a congenial vehicle to spread the virus through global transport of consumer goods. To address this gap, here we present a scrutiny of the findings from epidemiological investigations in recent re-emergent outbreaks in China caused by fomite transmission via imported foods and goods. A national regime of traceable cold-chain foods and reinforced customs inspection protocols were established by public health authorities in mainland China as emergency responses to recurring outbreaks from fomite transmission via imported goods. We urge that more attention needs to be given to this specific route of pathogenic transmission to ensure biosecurity and to increase the preparedness for epidemic or pandemic scenarios by the global food industry and logistics carriers.

Enhancing Food Supply Chain in Green Logistics with Multi-Level Processing Strategy under Disruptions

Food supply chains (FSCs) have long been exposed to environmental variability and shock events caused by various economic, political, and infrastructural factors. The outbreak of the COVID-19 pandemic has further exposed and identified the vulnerability of FSCs, and promoted integrated optimization approaches for building resilience. However, existing works focusing on general supply chains (SCs) and FSCs have not been fully aware of the distinct characteristics of FSCs in green logistics, i.e., the expiration of fresh products. In reality, perishable food materials can be processed into products of different processing levels (i.e., multi-level processing) for longer shelf lives, which can serve as a timely and economic strategy to increase safety stocks for mitigating disruption risks. Motivated by this fact, we study the problem of enhancing FSC with a multi-level processing strategy. An integrated location, inventory, and distribution planning model for a multi-echelon FSC under COVID-19-related disruptions is formulated to maximize the total profit over a finite planning horizon. Specifically, a two-stage stochastic programming model is presented to hedge against disruption risks, where scenarios are generated to characterize geographical impact induced by source-region disruptions. For small-scale problems, the model can be solved with commercial solvers. To exactly and efficiently solve the large-scale instances, we design an integer L-shaped method. Numerical experiments are conducted on a case study and randomly generated instances to show the efficiency of our model and solution method. Based on the case study, managerial insights are drawn.

Airport terminal passenger forecast under the impact of COVID-19 outbreaks: A case study from China

Passengers significantly affect airport terminal energy consumption and indoor environmental quality. Accurate passenger forecasting provides important insights for airport terminals to optimize their operation and management. However, the COVID-19 pandemic has greatly increased the uncertainty in airport passenger since 2020. There are insufficient studies to investigate which pandemic-related variables should be considered in forecasting airport passenger trends under the impact of COVID-19 outbreaks. In this study, the interrelationship between COVID-19 pandemic trends and passenger traffic at a major airport terminal in China was analyzed on a day-by-day basis. During COVID-19 outbreaks, three stages of passenger change were identified and characterized, i.e., the decline stage, the stabilization stage, and the recovery stage. A typical "sudden drop and slow recovery” pattern of passenger traffic was identified. A LightGBM model including pandemic variables was developed to forecast short-term daily passenger traffic at the airport terminal. The SHapley Additive exPlanations (SHAP) values was used to quantify the contribution of input pandemic variables. Results indicated the inclusion of pandemic variables reduced the model error by 27.7% compared to a baseline model. The cumulative numbers of COVID-19 cases in previous weeks were found to be stronger predictors of future passenger traffic than daily COVID-19 cases in the most recent week. In addition, the impact of pandemic control policies and passengers' travel behavior was discussed. Our empirical findings provide important implications for airport terminal operations in response to the on-going COVID-19 pandemic.

Engineering probiotic-derived outer membrane vesicles as functional vaccine carriers to enhance immunity against SARS-CoV-2.

Because of the continued emergence of SARS-CoV-2 variants, there has been considerable interest in how to display multivalent antigens efficiently. Bacterial outer membrane vesicles (OMVs) can serve as an attractive vaccine delivery system because of their self-adjuvant properties and the ability to be decorated with antigens. Here we set up a bivalent antigen display platform based on engineered OMVs using mCherry and GFP and demonstrated that two different antigens of SARS-CoV-2 could be presented simultaneously in the lumen and on the surface of OMVs. Comparing immunogenicity, ClyA-NG06 fusion and the receptor-binding domain (RBD) of the spike protein in the OMV lumen elicited a stronger humoral response in mice than OMVs presenting either the ClyA-NG06 fusion or RBD alone. Taken together, we provided an efficient approach to display SARS-CoV-2 antigens in the lumen and on the surface of the same OMV and highlighted the potential of OMVs as general multi-antigen carriers.

Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a mortal threat to human health. The elucidation of the relationship between peripheral immune cells and the development of inflammation is essential for revealing the pathogenic mechanism of COVID-19 and developing related antiviral drugs. The immune cell metabolism-targeting therapies exhibit a desirable anti-inflammatory effect in some treatment cases. In this study, based on differentially expressed gene (DEG) analysis, a genome-scale metabolic model (GSMM) was reconstructed by integrating transcriptome data to characterize the adaptive metabolic changes in peripheral blood mononuclear cells (PBMCs) in severe COVID-19 patients. Differential flux analysis revealed that metabolic changes such as enhanced aerobic glycolysis, impaired oxidative phosphorylation, fluctuating biogenesis of lipids, vitamins (folate and retinol), and nucleotides played important roles in the inflammation adaptation of PBMCs. Moreover, the main metabolic enzymes such as the solute carrier (SLC) family 2 member 3 (SLC2A3) and fatty acid synthase (FASN), responsible for the reactions with large differential fluxes, were identified as potential therapeutic targets. Our results revealed the inflammation regulation potentials of partial metabolic reactions with differential fluxes and their metabolites. This study provides a reference for developing potential PBMC metabolism-targeting therapy strategies against COVID-19.

Higher Education Students’ Perspectives on Using an Urban On-campus Food Pantry During COVID-19: A Qualitative Study

Background The rate of food insecurity (FI) in those pursuing higher education is three times higher than the national average. Many institutions have established food pantry (FP) programs in response to widespread campus FI. The pandemic has amplified financial stress for students and has altered many on-campus policies. Little is known about higher education students’ use of food pantries during COVID-19. Objective To explore the motivators and barriers that influence higher education students’ use of FPs during COVID-19. Study Design, Setting, Participants Eighteen unmarried/single undergraduate and graduate students at a private university in New York City who used an on-campus FP were interviewed by using a semi-structured script from April to October 2021. Measurable Outcome/Analysis Taking an inductive approach, audio-recorded interviews were transcribed and coded using NVivo v12. Four researchers collaboratively developed the codebook and used thematic analysis to identify themes and subthemes. Results While FP use was initially motivated by financial incentives and pre-pandemic FP experience, these motivations were reinforced by positive interactions with volunteers, satisfaction with food items, and COVID-19 safety protocols. However, students encountered several barriers that limited FP use, including eligibility concerns, logistical and communication issues, and lack of food variety. In addition, feelings of stigma, level of FI awareness, and familiarity with the US food system were major determinants of FP use. Notably, students with pre-pandemic FP experience identified assistance more quickly, expressed more complex feelings, and demonstrated a deeper understanding of FI than novice FP users. Conclusions The motivators and barriers of FP use during COVID-19 were influenced by students’ pre-pandemic experiences with FI. This study reveals that the on-campus FP requires systemic support to reduce FI stigma and increase food access. Furthermore, these findings indicate the need for more holistic institutional and governmental support for FI in higher education. Funding None

Development and evaluation of time-resolved fluorescent immunochromatographic assay for quantitative detection of SARS-CoV-2 spike antigen.

BACKGROUND: The spread of COVID-19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15-minute time-resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS-CoV-2 spike protein receptor-binding domain (S1-RBD). OBJECTIVES: Our objective was to develop an efficient method of detecting SARS-CoV-2 within 15 min of sample collection. METHODS: We constructed and evaluated a portable, disposable lateral flow device, which detected the S1-RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1-RBD, which can be captured by an automated TRF instrument. RESULTS: The TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1-RBD antigen. CONCLUSION: The new S1-RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR-based methodology in nasopharyngeal swab samples, showing that the detected S1-RBD antigen levels correlate with SARS-CoV-2 virus load. Therefore, the new TRF lateral flow test for S1-RBD has potential application in point-of-care settings.

Understanding the content of COVID-19 vaccination and pregnancy videos on YouTube: An analysis of videos published at the start of the vaccine rollout.

Over 2 years into the COVID-19 pandemic, information on the safety and efficacy of COVID-19 vaccination, particularly for people in high-risk populations, has become a popular topic of discussion. The purpose of this study was to analyze the content and characteristics of YouTube videos related to COVID-19 vaccination and pregnancy. The 50 most viewed English language videos on pregnancy and COVID-19 vaccination were included in this study. The 50 YouTube videos were viewed 4,589,613 times, with 6% uploaded by consumers, 40% by medical professionals, and 44% by television or internet-based news. Videos from consumer sources more often mentioned a human trial of the COVID-19 vaccine (75% of consumer videos vs. 65% of medical professional videos and 31.8% of television or internet-based news videos, P = .036) and more often mentioned anti-vaccination sentiment, fear, or distrust of the vaccines (37.5% of consumer videos vs 5.0% of medical professional videos and 4.5% of television or internet-based news videos, P = .018). Videos uploaded by medical professionals more often mentioned emergency use of the COVID-19 vaccines (P = .016), passive immunity in general (P = .011), and that the COVID-19 vaccine is either unlikely to or will not cause harm in breastfeeding more often than did videos from consumer or television-based news sources (P = .034). New information regarding COVID-19 vaccination and pregnancy is continuing to emerge, and this study highlights that the information found in the most viewed YouTube videos on this topic can quickly become outdated.

Hyperglycemia and blood glucose deterioration are risk factors for severe COVID-19 with diabetes: A two-center cohort study.

We aimed to assess whether blood glucose control can be used as predictors for the severity of 2019 coronavirus disease (COVID-19) and to improve the management of diabetic patients with COVID-19. A two-center cohort with a total of 241 confirmed cases of COVID-19 with definite outcomes was studied. After the diagnosis of COVID-19, the clinical data and laboratory results were collected, the fasting blood glucose levels were followed up at initial, middle stage of admission and discharge, the severity of the COVID-19 was assessed at any time from admission to discharge. Hyperglycemia patients with COVID-19 were divided into three groups: good blood glucose control, fair blood glucose control, and blood glucose deterioration. The relationship of blood glucose levels, blood glucose control status, and severe COVID-19 were analyzed by univariate and multivariable regression analysis. In our cohort, 21.16% were severe cases and 78.84% were nonsevere cases. Admission hyperglycemia (adjusted odds ratio [aOR], 1.938; 95% confidence interval [95% CI], 1.387-2.707), mid-term hyperglycemia (aOR, 1.758; 95% CI, 1.325-2.332), and blood glucose deterioration (aOR, 22.783; 95% CI, 2.661-195.071) were identified as the risk factors of severe COVID-19. Receiver operating characteristic (ROC) curve analysis, reaching an area under ROC curve of 0.806, and a sensitivity and specificity of 80.40% and 68.40%, respectively, revealed that hyperglycemia on admission and blood glucose deterioration of diabetic patients are potential predictive factors for severe COVID-19. Our results indicated that admission hyperglycemia and blood glucose deterioration were positively correlated with the risk factor for severe COVID-19, and deterioration of blood glucose may be more likely to the occurrence of severe illness in COVID-19.

A New Method Based on LAMP-CRISPR-Cas12a-Lateral Flow Immunochromatographic Strip for Detection.

INTRODUCTION: Carbapenemase-mediated antimicrobial resistance is currently a hot spot of global concern. Carbapenem-resistant organisms are highly prevalent in hospitals associated with difficult-to-treat infections, resulting in poor clinical outcome due to limited treatment options. It is urgently needed to have a rapid, efficient, and convenient molecular assay for identifying such resistant strains. METHODS: For this end, we developed a new laboratory assay targeting Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-ß-lactamase (NDM) based on loop-mediated isothermal amplification, CRISPR-Cas12a, and lateral flow immunochromatographic strip (CRISPR-Cas-LAMP-lateral flow strip). The method was designed to use a guide RNA (gRNA) to recognize the target DNA and guide Cas12a to cleave the target DNA, and simultaneously cleave any single-stranded DNA within the cleavage reaction system. RESULTS: The cleavage products are visible to the naked eye on the lateral flow strip. This method is highly sensitive in direct detection of bacteria in samples containing at least 3×105 CFU/mL without the need for bacterial culture. DISCUSSION: It provides shorter turnaround time and higher specificity than the conventional bacterial culture and susceptibility testing method. This new assay is applicable for extensive use in hospital infection control, as well as identification and treatment of resistant strains due to simple operation and inexpensive apparatuses.

The spike-ACE2 binding assay: An in vitro platform for evaluating vaccination efficacy and for screening SARS-CoV-2 inhibitors and neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a worldwide pandemic, and there is a pressing need for the rapid development of novel therapeutic strategies. SARS-CoV-2 viral entry is mediated by interaction between the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein and host cellular receptor, human angiotensin converting enzyme 2 (ACE2). The lack of a high throughput screening (HTS) platform for candidate drug screening means that no targeted COVID-19 treatments have been developed to date. To overcome this limitation, we developed a novel, rapid, simple, and HTS binding assay platform to screen potential inhibitors of the RBD-ACE2 complex. Three "neutralizing" mouse monoclonal antibodies capable of blocking the RBD-ACE2 interaction were identified using our binding assay and pseudovirus neutralization assay followed by further validation with the Focus Reduction Neutralization Test (FRNT), which analyzes the neutralization capacity of samples in the presence of live SARS-CoV-2. Furthermore, the consistency of our binding assay and FRNT results (R2 = 0.68) was demonstrated by patients' serum, of which were COVID-19 positive (n = 34) and COVID-19 negative (n = 76). Several small molecules selected for their potential to inhibit the Spike-ACE2 complex in silico were also confirmed with the binding assay. In addition, we have evaluated vaccine efficacy using binding assay platform and validated through pseudovirus neutralization assay. The correlation between binding assay & psuedovirus assay of the post vaccinated serum showed well correlated (R2 = 0.09) Moreover, our binding assay platform successfully validated different Spike RBD mutants. These results indicate that our binding assay can be used as a platform for in vitro screening of small molecules and monoclonal antibodies, and high-throughput assessment of antibody levels after vaccination. When conducting drug screening, computer virtual screening lacks actual basis, construction of pseudoviruses is relatively complicated, and even FRNT requires a P3 laboratory. There are few methods to determine the competitiveness of the target drug and SRBD or ACE2. Our binding assay can fill this gap and accelerate the process and efficiency of COVID-19 drug screening.

Correction: Community Mitigation of COVID-19 and Portrayal of Testing on TikTok: Descriptive Study.

[This corrects the article DOI: 10.2196/29528.].

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma.

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization.

Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.