Stability and WBE biomarkers possibility of 17 antiviral drugs in sewage and gravity sewers.

Wastewater-based epidemiology (WBE) is a promising technique for monitoring the rapidly increasing use of antiviral drugs during the COVID-19 pandemic. It is essential to evaluate the in-sewer stability of antiviral drugs in order to determine appropriate biomarkers. This study developed an analytical method for quantification of 17 typical antiviral drugs, and investigated the stability of target compounds in sewer through 4 laboratory-scale gravity sewer reactors. Nine antiviral drugs (lamivudine, acyclovir, amantadine, favipiravir, nevirapine, oseltamivir, ganciclovir, emtricitabine and telbivudine) were observed to be stable and recommended as appropriate biomarkers for WBE. As for the other 8 unstable drugs (abacavir, arbidol, ribavirin, zidovudine, ritonavir, lopinavir, remdesivir and efavirenz), their attenuation was driven by adsorption, biodegradation and diffusion. Moreover, reaction kinetics revealed that the effects of sediments and biofilms were regarded to be independent in gravity sewers, and the rate constants of removal by biofilms was directly proportional to the ratio of surface area against wastewater volume. The study highlighted the potential importance of flow velocity for compound stability, since an increased flow velocity significantly accelerated the removal of unstable biomarkers. In addition, a framework for graded evaluation of biomarker stability was proposed to provide reference for researchers to select suitable WBE biomarkers. Compared with current classification method, this framework considered the influences of residence time and different removal mechanisms, which additionally screened four antiviral drugs as viable WBE biomarkers. This is the first study to report the stability of antiviral drugs in gravity sewers.

Effective risk management in the shadow of COVID-19 pandemic: The evidence of Indonesian listed corporations.

The study uses COVID-19 to identify the treatment group as the difference in change of non-financial corporations (NFCs) risk management ratios over time to investigate the causal effect of the NFCs' effective risk management (ERM) practices on operational efficiency (OE). ERM was measured by solvency and liquidity ratios, while the risk management theory was developed to refine the scope of the study. The data were collected from the central bank of Indonesia to map the empirical analysis, and the difference in difference (DID) technique was used to illustrate how NFCs react to mitigate the negative impact of COVID-19 and generate OE. Specifically, a quasi-natural experiment was used to size the effect of ERM practices on corporate OE during the COVID-19 pandemic. The descriptive analysis revealed that the COVID-19 pandemic effect has been unequal across different industrial sectors. Moreover, the empirical findings showed that corporate risk management during COVID-19 is the source of structural change, which affects its existence and operational efficiency. While debt amount and age may affect corporate credit score, ERM practices led the indebted corporation to the flexibility of debt refinancing or/and restructuring, which offers them the ability to prevent bankruptcy and adapt to the changes while operating efficiently. The finding revealed evidence of the important role of long-term debt in offering protection to NFCs during the credit supply shock brought in by the COVID-19 pandemic. Furthermore, the findings show that long-term debt is negatively associated with corporate OE. This was expected given that corporations use long-term debt financing for long-term investment, while short-term debt funds the working capital. Thus, to assess the effect of debts on corporate OE, managers should consider their maturity structure, among other factors.

An ultrasensitive electrochemical sensor for detecting porcine epidemic diarrhea virus based on a Prussian blue-reduced graphene oxide modified glassy carbon electrode.

This study developed a novel, ultrasensitive sandwich-type electrochemical immunosensor for detecting the porcine epidemic diarrhea virus (PEDV). By electrochemical co-deposition of graphene and Prussian blue, a Prussian blue-reduced graphene oxide-modified glassy carbon electrode was made, further modified with PEDV-monoclonal antibodies (mAbs) to create a new PEDV immunosensor using the double antibody sandwich technique. The electrochemical characteristics of several modified electrodes were investigated using cyclic voltammetry (CV). We optimized the pH levels and scan rate. Additionally, we examined specificity, reproducibility, repeatability, accuracy, and stability. The study indicates that the immunosensor has good performance in the concentration range of 1 × 101.88 to 1 × 105.38 TCID50/mL of PEDV, with a detection limit of 1 × 101.93 TCID50/mL at a signal-to-noise ratio of 3σ. The composite membranes produced via co-deposition of graphene and Prussian blue effectively increased electron transport to the glassy carbon electrode, boosted response signals, and increased the sensitivity, specificity, and stability of the immunosensor. The immunosensor could accurately detect PEDV, with results comparable to real-time quantitative PCR. This technique was applied to PEDV detection and served as a model for developing additional immunosensors for detecting hazardous chemicals and pathogenic microbes.

A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections.

Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections. Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters. Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy. Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.

Rapid, Sensitive, Label-Free Electrical Detection of SARS-CoV-2 in Nasal Swab Samples.

Rapid diagnosis of coronavirus disease 2019 (COVID-19) is key for the long-term control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) amid renewed threats of mutated SARS-CoV-2 around the world. Here, we report on an electrical label-free detection of SARS-CoV-2 in nasopharyngeal swab samples directly collected from outpatients or in saliva-relevant conditions by using a remote floating-gate field-effect transistor (RFGFET) with a 2-dimensional reduced graphene oxide (rGO) sensing membrane. RFGFET sensors demonstrate rapid detection (<5 min), a 90.6% accuracy from 8 nasal swab samples measured by 4 different devices for each sample, and a coefficient of variation (CV) < 6%. Also, RFGFET sensors display a limit of detection (LOD) of pseudo-SARS-CoV-2 that is 10 000-fold lower than enzyme-linked immunosorbent assays, with a comparable LOD to that of reverse transcription-polymerase chain reaction (RT-PCR) for patient samples. To achieve this, comprehensive systematic studies were performed regarding interactions between SARS-CoV-2 and spike proteins, neutralizing antibodies, and angiotensin-converting enzyme 2, as either a biomarker (detection target) or a sensing probe (receptor) functionalized on the rGO sensing membrane. Taken together, this work may have an immense effect on positioning FET bioelectronics for rapid SARS-CoV-2 diagnostics.

The latest research progress in asymptomatic and pre-symptomatic patients with COVID-19

The asymptomatic and pre-symptomatic infections of coronavirus disease 2019 (COVID-19) has no perceptible clinical symptoms and signs, and it is not easy to be detected. The transmission of the virus carried by asymptomatic and pre-symptomatic patients is insidious, which brings great challenges to the control of the epidemic. Due to the length of the incubation period, some studies have failed to distinguish between asymptomatic and pre-symptomatic infections, resulting in a higher proportion of asymptomatic infections. This article reviews the latest research progress of characteristics, transmission, detection and control of asymptomatic and pre-symptomatic infection.

AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity.

Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.

Source tracing of the COVID-19 infection case in Guangxi, China

The study describing the process of discovery and source tracing of a native case of coronavirus disease 2019 (COVID-19) infection on Jan 2021, in Guangxi, China, to provide methodology for source investigation better in the future. Following the Epidemiological Investigation Plan for COVID-19 (version 7), information of the native COVID-19 case and related close contacts were collected. Real time reverse transcription-quantitative polymerase chain reaction was performed to detect the nucleic acids of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in samples collected from the infection case, related close contacts, and the environment, combined with serum specific antibody detection. The positive nucleic acid samples were undergone whole genome sequencing, phylogenetic analysis and analyses of variation of amino acids. The whole genome sequence from the native case and the imported asymptomatic infected case from Indonesia containing 25 nucleotide mutation sites belong to L-Lineage European Branch II. 3. The imported asymptomatic case was the source of infection of this native case. The possible route of infection was that native case was exposed to contaminated environment by imported case, due to improper personal protective equipment. A focus on local outbreaks of COVID-19 caused by SARS-CoV-2-infected people from outside China is needed.

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection.

Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination ('hybrid immunity') further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.

A Novel, Cleaved Probe-Based Reverse Transcription Loop-Mediated Isothermal Amplification Method for Specific and Sensitive Detection of Porcine Deltacoronavirus.

Porcine deltacoronavirus (PDCoV) causes watery diarrhea, vomiting, and 30-40% mortality in newborn piglets. A simple, rapid, and sensitive method for PDCoV detection is valuable in its surveillance and control. Here, we developed a novel, cleaved probe-based reverse transcription loop-mediated isothermal amplification (CP-RT-LAMP) method for PDCoV detection. A cleaved probe with a ribonucleotide insertion that targeted the N gene of PDCoV was designed. During the reaction, the enzyme ribonuclease H2 is activated only when the cleaved probe is perfectly complementary to the template, leading to the hydrolytic release of a quencher moiety and signal output. This method can be easily used on a real-time fluorescence quantitative equipment or an on-site isothermal instrument combined with a smartphone. The specificity assay showed no cross-reactivity with other porcine enteric pathogens. This method had a detection limit of 25 copies/µL, suggesting comparable sensitivity with reverse transcription quantitative PCR (RT-qPCR). In detecting 100 clinical samples (48 fecal swab specimens and 52 intestinal specimens), the detection rate of the CP-RT-LAMP method (26%) was higher than that of RT-qPCR (17%). Thus, it is a highly specific and sensitive diagnostic method for PDCoV, with a great application potential for monitoring PDCoV in the laboratory or point-of-care testing in the field.

Remote Floating-Gate Field-Effect Transistor with 2-Dimensional Reduced Graphene Oxide Sensing Layer for Reliable Detection of SARS-CoV-2 Spike Proteins.

Despite intensive research of nanomaterials-based field-effect transistors (FETs) as a rapid diagnostic tool, it remains to be seen for FET sensors to be used for clinical applications due to a lack of stability, reliability, reproducibility, and scalability for mass production. Herein, we propose a remote floating-gate (RFG) FET configuration to eliminate device-to-device variations of two-dimensional reduced graphene oxide (rGO) sensing surfaces and most of the instability at the solution interface. Also, critical mechanistic factors behind the electrochemical instability of rGO such as severe drift and hysteresis were identified through extensive studies on rGO-solution interfaces varied by rGO thickness, coverage, and reduction temperature. rGO surfaces in our RFGFET structure displayed a Nernstian response of 54 mV/pH (from pH 2 to 11) with a 90% yield (9 samples out of total 10), coefficient of variation (CV) < 3%, and a low drift rate of 2%, all of which were calculated from the absolute measurement values. As proof-of-concept, we demonstrated highly reliable, reproducible, and label-free detection of spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a saliva-relevant media with concentrations ranging from 500 fg/mL to 5 µg/mL, with an R2 value of 0.984 and CV < 3%, and a guaranteed limit of detection at a few pg/mL. Taken together, this new platform may have an immense effect on positioning FET bioelectronics in a clinical setting for detecting SARS-CoV-2.

Improved integration of single-cell transcriptome and surface protein expression by LinQ-View

Summary Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting results. Finally, we utilized this method to integrate single-cell transcriptional and protein expression data from SARS-CoV-2-infected patients, revealing antigen-specific B cell subsets after infection. Our results suggest LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations (e.g., B cells). Graphical Highlights • LinQ-View integrates mRNA and protein expression data to reveal cell heterogeneity• LinQ-View prevents single dominant ADT features from affecting clustering• LinQ-View presents a quantitative purity metric for CITE-seq data• LinQ-View is specialized in handling CITE-seq data with fewer ADT features Motivation Multimodal single-cell sequencing enables multiple aspects for characterizing the dynamics of cell states and developmental processes. Properly integrating information from multiple modalities is a crucial step for interpreting cell heterogeneity. Here, we present LinQ-View, a computational workflow that provides an effective solution for integrating multiple modalities of CITE-seq data for downstream interpretation. LinQ-View balances information from multiple modalities to achieve accurate clustering results and is specialized in handling CITE-seq data with routine numbers of surface protein features. Li et al. present LinQ-View, a computational workflow that provides an effective solution for integrating multiple modalities of CITE-seq data and quantitative assessment of cluster purity. LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations.

CHARM: COVID-19 Health Action Response for Marines-Association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test.

SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses against S, N and M proteins in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were enrolled in an immune response sub-study. FluoroSpot interferon-gamma (IFN-γ) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-γ responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-γ responses were significantly (p = 0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic but not symptomatic subjects. Asymptomatic IFN-γ responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but not symptomatic participants. The frequencies of IFN-γ responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-γ and IL2 responses to the N+M pool were significantly correlated with IFN-γ and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-γ and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

Argonaute-integrated isothermal amplification for rapid, portable, multiplex detection of SARS-CoV-2 and influenza viruses.

Isothermal amplification methods are a promising trend in virus detection because of their superiority in rapidity and sensitivity. However, the generation of false positives and limited multiplexity are major bottlenecks that must be addressed. In this study, we developed a multiplex Argonaute (Ago)-based nucleic acid detection system (MULAN) that integrates rapid isothermal amplification with the multiplex inclusiveness of a single Ago for simultaneous detection of multiple targets such as SARS-CoV-2 and influenza viruses. Owing to its high specificity, MULAN can distinguish targets at a single-base resolution for mutant genotyping. Moreover, MULAN also supports portable and visible devices with a limit of detection of five copies per reaction. Validated by SARS-CoV-2 pseudoviruses and clinical samples of influenza viruses, MULAN showed 100% agreement with quantitative reverse-transcription PCR. These results demonstrated that MULAN has great potential to facilitate reliable, easy, and quick point-of-care diagnosis for promoting the control of infectious diseases.

Artificial intelligence for stepwise diagnosis and monitoring of COVID-19.

BACKGROUND: Main challenges for COVID-19 include the lack of a rapid diagnostic test, a suitable tool to monitor and predict a patient's clinical course and an efficient way for data sharing among multicenters. We thus developed a novel artificial intelligence system based on deep learning (DL) and federated learning (FL) for the diagnosis, monitoring, and prediction of a patient's clinical course. METHODS: CT imaging derived from 6 different multicenter cohorts were used for stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. Patients with more than 3 consecutive CT images were trained for the monitoring algorithm. FL has been applied for decentralized refinement of independently built DL models. RESULTS: A total of 1,552,988 CT slices from 4804 patients were used. The model can diagnose COVID-19 based on CT alone with the AUC being 0.98 (95% CI 0.97-0.99), and outperforms the radiologist's assessment. We have also successfully tested the incorporation of the DL diagnostic model with the FL framework. Its auto-segmentation analyses co-related well with those by radiologists and achieved a high Dice's coefficient of 0.77. It can produce a predictive curve of a patient's clinical course if serial CT assessments are available. INTERPRETATION: The system has high consistency in diagnosing COVID-19 based on CT, with or without clinical data. Alternatively, it can be implemented on a FL platform, which would potentially encourage the data sharing in the future. It also can produce an objective predictive curve of a patient's clinical course for visualization. KEY POINTS: • CoviDet could diagnose COVID-19 based on chest CT with high consistency; this outperformed the radiologist's assessment. Its auto-segmentation analyses co-related well with those by radiologists and could potentially monitor and predict a patient's clinical course if serial CT assessments are available. It can be integrated into the federated learning framework. • CoviDet can be used as an adjunct to aid clinicians with the CT diagnosis of COVID-19 and can potentially be used for disease monitoring; federated learning can potentially open opportunities for global collaboration.

ISGylation in Innate Antiviral Immunity and Pathogen Defense Responses: A Review.

The interferon-stimulating gene 15 (ISG15) protein is a ubiquitin-like protein induced by interferons or pathogens. ISG15 can exist in free form or covalently bind to the target protein through an enzymatic cascade reaction, which is called ISGylation. ISGylation has been found to play an important role in the innate immune responses induced by type I interferon, and is, thus, critical for the defense of host cells against RNA, DNA, and retroviruses. Through covalent binding with the host and viral target proteins, ISG15 inhibits the release of viral particles, hinder viral replication, and regulates the incubation period of viruses, thereby exerting strong antiviral effects. The SARS-CoV-2 papain-like protease, a virus-encoded deubiquitinating enzyme, has demonstrated activity on both ubiquitin and ISG15 chain conjugations, thus playing a suppressive role against the host antiviral innate immune response. Here we review the recent research progress in understanding ISG15-type ubiquitin-like modifications, with an emphasis on the underlying molecular mechanisms. We provide comprehensive references for further studies on the role of ISG15 in antiviral immunity, which may enable development of new antiviral drugs.

Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy (Adv. Mater. 49/2021)

COVID-19 Therapy In their work reported in article number 2103471, Long Zhang, Fangfang Zhou, and co-workers fuse the S-palmitoylation-dependent plasma membrane (PM) targeting sequence with angiotensin converting enzyme 2 (ACE2) and engineer extracellular vesicles (EVs) on their surface enriched with palmitoylated ACE2 (PM-ACE2-EVs). The PM-ACE2-EVs can bind to the SARS-CoV-2 S-RBD with high affinity and block its interaction with cell-surface ACE2, thereby preventing SARS-CoV-2 from entering the host cell. This study provides a novel EV-based candidate for prophylactic and therapeutic treatment against COVID-19.

The way of SARS-CoV-2 vaccine development: success and challenges.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). To halt the pandemic, multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide. With novel SARS-CoV-2 variants emerging and circulating widely, whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion. Moreover, some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity. Thus, in this review, we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern. We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials. Furthermore, we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines, such as special disease conditions, sex, and pre-existing immunity, with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.

A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2.

The outbreak of 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic. Despite intensive research, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high-affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS-CoV-2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS-CoV-2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS-CoV-2 and its variants.