Global variation in prior exposure shapes antibody neutralization profiles of SARS-CoV-2 variants up to BA.2.86 (preprint)

The highly mutated SARS-CoV-2 variant, BA.2.86, and its descendants are now the most frequently sequenced variants of SARS-CoV-2. We analyze antibody neutralization data from eight laboratories from the UK, USA, Denmark, and China, including two datasets assessing the effect of XBB.1.5 vaccines, to determine the effect of infection and vaccination history on neutralization of variants up to and including BA.2.86, and produce antibody landscapes to describe these neutralization profiles. We find evidence for lower levels of immune imprinting on pre-Omicron variants in sera collected from Denmark and China, which may be explained by lower levels of circulation of the ancestral variant in these countries, and the use of an inactivated virus vaccine in China.

Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1 (preprint)

The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.

Bidirectional causal relationships between IgA nephropathy and COVID-19: genetic evidence from Mendelian randomization (preprint)

Purpose Previous studies have suggested that patients with IgA nephropathy (IgAN) was associated with an increased risk of coronavirus disease 2019 (COVID-19) infection. However, the findings were inconsistent, and whether there was a causality between IgAN and COVID-19 infection remains unknown. This study was performed to estimate the casual effect between IgAN and COVID-19 infection with the implementation of bidirectional Mendelian randomization (MR) analysis.Methods Genetic summary data of IgAN was derived from a large genome-wide association study (GWAS) that consisted of 14,361 cases and 43,923 controls. The genetic data of COVID-19 comprised of three phenotypes, including hospitalization, severity and infection, which had a population more than 20 million. The methods of inverse variance weighting (IVW), MR-Egger, weight median and weighted mode were applied for causal inference in MR analysis.Results In the forward direction, the IVW’s results proved that IgAN did not have causal relationships with hospitalization COVID-19 (OR = 1.077, 95%CI: 0.953–1.217, P = 0.236), severe COVID-19 (OR = 1.059, 95%CI: 0.878–1.278, P = 0.547) and COVID-19 infection (OR = 0.973, 95%CI: 0.929–1.109, P = 0.243). Furthermore, reverse MR analysis showed no evidence of causal associations of hospitalization COVID-19 (OR = 1.017, 95%CI: 0.968–1.069, P = 0.499), severe COVID-19 (OR = 1.005, 95%CI: 0.979–1.078, P = 0.781) and COVID-19 infection (OR = 1.030, 95%CI: 0.909–1.169, P = 0.641) with the risk of IgAN.Conclusion Our study does not support a casual association of IgAN with the risk of COVID-19 infection, nor does the causality between COVID-19 infection and IgAN risk.

Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through multiple mechanisms (preprint)

Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain (RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity could be recovered in the presence of heparin sulfate, which targets the N354 pocket to ease restrictions of conformational transition resulting in a RBD-up state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell-cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.

Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure (preprint)

While the BA.2.86 variant demonstrated significant antigenic drift and enhanced ACE2 binding affinity, its ability to evade humoral immunity was relatively moderate compared to dominant strains like EG.5 and HK.3. However, the emergence of a new subvariant, JN.1 (BA.2.86.1.1), which possesses an additional spike mutation, L455S, compared to BA.2.86, showed a markedly increased prevalence in Europe and North America, especially in France. Here, we found that L455S of JN.1 significantly enhances immune evasion capabilities at the expense of reduced ACE2 binding affinity. This mutation enables JN.1 to effectively evade Class 1 neutralizing antibodies, offsetting BA.2.86s susceptibility and thus allowing it to outcompete both its precursor BA.2.86 and the prevailing variants HV.1 (XBB.1.5+L452R+F456L) and JD.1.1 (XBB.1.5+L455F+F456L+A475V) in terms of humoral immune evasion. The rapid evolution from BA.2.86 to JN.1, similar to the earlier transition from BA.2.75 to CH.1.1, highlights the importance of closely monitoring strains with high ACE2 binding affinity and distinct antigenicity, despite their temporarily unremarkable immune evasion capabilities. Such strains could survive and transmit at low levels, since their large antigenic distance to dominant strains allow them to target distinct populations and accumulate immune-evasive mutations rapidly, often at the cost of receptor binding affinity.

Antigenicity and infectivity characterization of SARS-CoV-2 BA.2.86 (preprint)

The recently identified SARS-CoV-2 variant, BA.2.86, which carries a substantial number of Spike mutations, has raised a global alarm. An immediate assessment of its antigenic properties and infectivity is necessary. Here, we reveal the distinct antigenicity of BA.2.86 compared with previous variants including XBB.1.5. BA.2.86 significantly evades convalescent plasma from XBB breakthrough infection (BTI) and reinfections. Key mutations that mediate the enhanced resistance include N450D, K356T, L452W, A484K, V483del, and V445H on the RBD, while BA.2.86\'s NTD mutations and E554K on SD1 also largely contribute. However, we found that BA.2.86 pseudovirus exhibits compromised efficiency of infecting HEK293T-hACE2 cells compared to XBB.1.5 and EG.5, which may be caused by K356T, V483del, and E554K, and could potentially limit BA.2.86\'s transmissibility. In sum, it appears that BA.2.86 has traded its infectivity for higher immune evasion during long-term host-viral evolution. Close attention should be paid to monitoring additional mutations that could improve BA.2.86\'s infectivity.

Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455-456 enhances antibody evasion and ACE2 binding (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants like EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. Specifically, L455F and F456L evades Class 1 NAbs, which could reduce the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.

Knowledge Map of Climate Change and Transportation: A Bibliometric Analysis Based on CiteSpace

Climate change has become one of the leading problems around the world. The transport sector is one of the major contributors to climate change. At the same time, climate change is also affecting transportation facilities and travel behaviour. This study proposed a bibliometric approach to explore the structure evolution development trends of this knowledge domain with a broader search scope and more objective results compared with a manual review. A total of 4073 peer-reviewed articles were collected from the WoS core collection database to conduct scientometric analysis. The collaboration analysis shows that the US, China, and European countries dominate this field, and international organisations' and government agencies' reports on climate change form the basis of this research field. A total of 14 co-citation clusters were identified, and the research on climate change and transportation primarily focused on the topics of policy options, travel behaviour, the COVID-19 lockdown, environmental cost, and air quality. Keyword co-occurrence evolution analysis was also conducted to track the latest research trends. Based on the results, we propose trends in four areas for future research. This study provides a holistic knowledge map for climate change and transportation research's past, present, and future. [ABSTRACT FROM AUTHOR] Copyright of Atmosphere is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Repeated Omicron infection alleviates SARS-CoV-2 immune imprinting (preprint)

The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5’s immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven't been exposed to Omicron yet should receive two updated vaccine boosters.

Boron nitride nanocage as drug delivery systems for chloroquine, as an effective drug for treatment of coronavirus disease: A DFT study

Graphical Research has shown that chloroquine (CQ) can effectively help control COVID-19 infection. B24N24 nanocage is a drug delivery system. Thus, through density functional theory, the present study analyzed pristine nanocage-CQ interaction and CQ interaction with Si- and Al -doped nanocage. The findings revealed that nanocage doping, particularly with Si and Al, yields more satisfactory drug delivery for CQ due to their greater electronic and energetic characteristics with CQ.

Boron nitride nanocage as drug delivery systems for chloroquine, as an effective drug for treatment of coronavirus disease: A DFT study.

Research has shown that chloroquine (CQ) can effectively help control COVID-19 infection. B24N24 nanocage is a drug delivery system. Thus, through density functional theory, the present study analyzed pristine nanocage-CQ interaction and CQ interaction with Si- and Al -doped nanocage. The findings revealed that nanocage doping, particularly with Si and Al, yields more satisfactory drug delivery for CQ due to their greater electronic and energetic characteristics with CQ.

Ship carbon dioxide emission estimation in coastal domestic emission control areas using high spatial-temporal resolution data: A China case

It is necessary to accurately calculate ship carbon emissions for shipping suitability. The state-of-the-art approaches could arguably not be able to estimate ship carbon emissions accurately due to the uncertainties of Ship Technical Specification Database (STSD) and the geographical and temporal breakpoints in Automatic Identification System (AIS) data, hence requiring a new methodology to be developed to address such defects and further improve the accuracy of emission estimation. Firstly, a novel STSD iterative repair model is proposed based on the random forest algorithm by the incorporation of13 ship technical parameters. The repair model is scalable and can substantially improve the quality of STSD. Secondly, a new ship AIS trajectory segmentation algorithm based on ST-DBSCAN is developed, which effectively eliminates the impact of geographical and temporal AIS breakpoints on emission estimation. It can accurately identify the ships' berthing and anchoring trajectories and reasonably segment the trajectories. Finally, based on this proposed framework, the ship carbon dioxide emissions within the scope of domestic emission control areas (DECA) along the coast of China are estimated. The experiment results indicate that the proposed STSD repair model is highly credible due to the significant connections between ship technical parameters. In addition, the emission analysis shows that, within the scope of China's DECA, the berthing period of ships is longer owing to the joint effects of coastal operation features and the strict quarantine measures under the COVID-19 pandemic, which highlights the emissions produced by ship auxiliary engines and boilers. The carbon intensity of most coastal provinces in China is relatively high, reflecting the urgent demand for the transformation and updates of the economic development models. Based on the theoretical models and results, this study recommends a five-stage decarbonization scheme for China's DECA to advance its decarbonization process.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China:a retrospective analysis (preprint)

Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China (preprint)

Abstract Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2 after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76 and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared to BA.5, remain unclear. Here we show BA.2.75 exhibits substantially higher affinity for host receptor ACE2 than BA.5 and other variants. Structural analyses of BA.2.75 Spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the “up” conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma, but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75’s distinct neutralizing antibody escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations. Graphical SARS-CoV-2 BA.2.75 is growing rapidly and globally. Cao et al. solved the structure of BA.2.75 spike and show it has stronger binding to human ACE2 than previous variants. BA.2.75 also exhibited distinct antigenicity compared to BA.5, escaping neutralizing antibodies targeting various epitopes and evading convalescent plasma from BA.5 breakthrough infections.

Deep Learning-based Network Pharmacology for Exploring the Mechanism of Licorice for the Treatment of COVID-19 (preprint)

Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and the corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice and to collect information regarding different representative compounds. A graph convolutional neural network was used to construct a molecular map and a convolutional neural network was used to develop a Morgan fingerprint. Twenty core compounds and 6 core targets were predicted, among which 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were associated with SARS-CoV-2-infection, which were confirmed by previous studies. In addition, 2 new active compounds (glabrone and vestitol) and 2 new targets (PTEN and MAP3K8) were further validated by molecular docking, and the results showed that these active compounds bound to SARS-CoV-2 related targets, including the main protease (Mpro, also called 3CLpro), the spike protein (S protein), and the angiotensin-converting enzyme 2 (ACE2). Overall, we conclude that the findings of this study has the value of further exploration in the following experiment and clinical application.

Chemical characteristics and sources of PM2.5 in Hohhot, a semi-arid city in northern China: insight from the COVID-19 lockdown

A knowledge gap exists concerning how chemical composition and sources respond to implemented policy control measures for aerosols, particularly in a semi-arid region. To address this, a single year's offline measurement was conducted in Hohhot, a semi-arid city in northern China, to reveal the driving factors of severe air pollution in a semi-arid region and assess the impact of the COVID-19 lockdown measures on chemical characteristics and sources of PM2.5. Organic matter, mineral dust, sulfate and nitrate accounted for 31.5 %, 14.2 %, 13.4 % and 12.3 % of the total PM2.5 mass, respectively. Coal combustion, vehicular emission, crustal source and secondary inorganic aerosols were the main sources of PM2.5 in Hohhot, at 38.3 %, 35.0 %, 13.5 %, and 11.4 %, respectively. Due to the coupling effect of emission reduction and improved atmospheric conditions, the concentration of secondary inorganic components, organic matter and elemental carbon declined substantially from the pre-lockdown (pre-LD) period to the lockdown (LD) and post-lockdown (post-LD) periods. The source contribution of secondary inorganic aerosols increased (from 21.1 % to 37.8 %), whereas the contribution of vehicular emission reduced (from 35.5 % to 4.4 %) due to lockdown measures. The rapid generation of secondary inorganic components caused by unfavorable meteorological conditions during lockdown led to serious pollution. This study elucidates the complex relationship between air quality and environmental policy.

Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution (preprint)

Continuous evolution of Omicron has led to numerous subvariants that exhibits growth advantage over BA.5. Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented. Despite their rapidly divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots, including R346, R356, K444, L452, N460K and F486. The driving force and destination of such convergent evolution and its impact on humoral immunity established by vaccination and infection remain unclear. Here we demonstrate that these convergent mutations can cause striking evasion of convalescent plasma, including those from BA.5 breakthrough infection, and existing antibody drugs, including Evusheld and Bebtelovimab. BA.2.75.2 is the most evasive strain tested, and only BQ.1.1 could compare. To clarify the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from convalescents of BA.2 and BA.5 breakthrough infection. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions of neutralizing antibody epitope diversity and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted the convergent RBD evolution. Additionally, the precise convergent RBD mutations and evolution trends of BA.2.75/BA.5 subvariants could be inferred by integrating the neutralization-weighted DMS profiles of mAbs from various immune histories (3051 mAbs in total). Moreover, we demonstrated that as few as five additional convergent mutations based on BA.5 or BA.2.75 could completely evade most plasma samples, including those from BA.5 breakthrough infections, while remaining sufficient hACE2-binding affinity. These results suggest herd immunity established by natural infection could hardly stop RBD evolution, and vaccine boosters using BA.5 may not provide sufficiently broad protection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be in high priority and the constructed convergent mutants could serve to examine their effectiveness in advance.