CoVEffect: interactive system for mining the effects of SARS-CoV-2 mutations and variants based on deep learning.

BACKGROUND: Literature about SARS-CoV-2 widely discusses the effects of variations that have spread in the past 3 years. Such information is dispersed in the texts of several research articles, hindering the possibility of practically integrating it with related datasets (e.g., millions of SARS-CoV-2 sequences available to the community). We aim to fill this gap, by mining literature abstracts to extract-for each variant/mutation-its related effects (in epidemiological, immunological, clinical, or viral kinetics terms) with labeled higher/lower levels in relation to the nonmutated virus. RESULTS: The proposed framework comprises (i) the provisioning of abstracts from a COVID-19-related big data corpus (CORD-19) and (ii) the identification of mutation/variant effects in abstracts using a GPT2-based prediction model. The above techniques enable the prediction of mutations/variants with their effects and levels in 2 distinct scenarios: (i) the batch annotation of the most relevant CORD-19 abstracts and (ii) the on-demand annotation of any user-selected CORD-19 abstract through the CoVEffect web application (http://gmql.eu/coveffect), which assists expert users with semiautomated data labeling. On the interface, users can inspect the predictions and correct them; user inputs can then extend the training dataset used by the prediction model. Our prototype model was trained through a carefully designed process, using a minimal and highly diversified pool of samples. CONCLUSIONS: The CoVEffect interface serves for the assisted annotation of abstracts, allowing the download of curated datasets for further use in data integration or analysis pipelines. The overall framework can be adapted to resolve similar unstructured-to-structured text translation tasks, which are typical of biomedical domains.

Vaccines Alone Cannot Slow the Evolution of SARS-CoV-2.

The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public-health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here, we examined that proposition using stochastic computational models of viral transmission and mutation. Specifically, we looked at the likelihood of emergence of immune escape variants requiring multiple mutations and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains, if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured.

Targeting viral ORF3a protein: A new approach to mitigate COVID- 19 induced Immune cell apoptosis and associated respiratory complications

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a growing concern to the global well-being of the public at present. Different amino acid mutations alter the biological and epidemiological characteristics, as well as immune resistance of SARS-CoV-2. The virus-induced pulmonary impairment and inflammatory cytokine storm are directly related to its clinical manifestations. But, the fundamental mechanisms of inflammatory responses are found to be the reason for the death of immune cells which render the host immune system failure. Apoptosis of immune cells is one of the most common forms of programmed cell death induced by the virus for its survival and virulence property. ORF3a, a SARS-CoV-2 accessory viral protein, induces apoptosis in host cells and suppress the defense mechanism. This suggests, inhibiting SARS-CoV-2 ORF3a protein is a good therapeutic strategy for the treatment in COVID-19 infection by promoting the host immune defense mechanism.Copyright © 2023 Tabriz University of Medical Sciences. All rights reserved.

The Novel SARS-CoV-2: An Overview on its Detection, Prevention and Control

On 30 January 2020, the World Health Organization (WHO) characterized the novel severe acute respiratory syndrome Coronavirus 2 (SARSCoV- 2) outbreak as a Public Health Emergency of International Concern. Subsequently, on 11 March 2020, WHO declared the global spread of Coronavirus disease 2019 (COVID-19) as a pandemic triggered by this causative virus. This COVID-19 pandemic has impacted lives and livelihoods worldwide, resulting in unprecedented social disruption and economic losses. In order to design and develop effective diagnostics, vaccines and therapeutic interventions against SARS-CoV-2, it is imperative to understand the molecular and cellular mechanisms underpinning the complex interactions between this virus, its variants, and its infected hosts. This chapter provides an overview on the classification, genomic organization and evolution of SARS-CoV-2 (including the emergence of variants from Alpha to Omicron), and summarizes existing and emerging testing strategies. With unprecedented speed, an array of conventional and new COVID-19 vaccines has been developed, evaluated in clinical trials, and administered to billions worldwide. Current and novel antiviral drugs and immunomodulatory approaches are discussed for the therapeutic and prophylactic management of SARS-CoV-2 infections. Finally, much remains for humanity to discover and learn as the world must continue to adapt and live with endemic COVID-19 and SARSCoV- 2 evolution. © 2023 by World Scientific Publishing Co. Pte. Ltd.

Highly Selective Aptamer-Molecularly Imprinted Polymer Hybrids for Recognition of SARS-CoV-2 Spike Protein Variants.

Virus recognition has been driven to the forefront of molecular recognition research due to the COVID-19 pandemic. Development of highly sensitive recognition elements, both natural and synthetic is critical to facing such a global issue. However, as viruses mutate, it is possible for their recognition to wane through changes in the target substrate, which can lead to detection avoidance and increased false negatives. Likewise, the ability to detect specific variants is of great interest for clinical analysis of all viruses. Here, a hybrid aptamer-molecularly imprinted polymer (aptaMIP), that maintains selective recognition for the spike protein template across various mutations, while improving performance over individual aptamer or MIP components (which themselves demonstrate excellent performance). The aptaMIP exhibits an equilibrium dissociation constant of 1.61 nM toward its template which matches or exceeds published examples of imprinting of the spike protein. The work here demonstrates that "fixing" the aptamer within a polymeric scaffold increases its capability to selectivity recognize its original target and points toward a methodology that will allow variant selective molecular recognition with exceptional affinity.

Targeting the Fusion Process of SARS-CoV-2 Infection by Small Molecule Inhibitors.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a serious threat to global public health, underscoring the urgency of developing effective therapies. Therapeutics and, more specifically, direct-acting antiviral development are still very much in their infancy. Here, we report that two hepatitis C virus (HCV) fusion inhibitors identified in our previous study, dichlorcyclizine and fluoxazolevir, broadly block human coronavirus entry into various cell types. Both compounds were effective against various human-pathogenic CoVs in multiple assays based on vesicular stomatitis virus (VSV) pseudotyped with the spike protein and spike-mediated syncytium formation. The antiviral effects were confirmed in SARS-CoV-2 infection systems. These compounds were equally effective against recently emerged variants, including the delta variant. Cross-linking experiments and structural modeling suggest that the compounds bind to a hydrophobic pocket near the fusion peptide of S protein, consistent with their potential mechanism of action as fusion inhibitors. In summary, these fusion inhibitors have broad-spectrum antiviral activities and may be promising leads for treatment of SARS-CoV-2, its variants, and other pathogenic CoVs. IMPORTANCE SARS-CoV-2 is an enveloped virus that requires membrane fusion for entry into host cells. Since the fusion process is relatively conserved among enveloped viruses, we tested our HCV fusion inhibitors, dichlorcyclizine and fluoxazolevir, against SARS-CoV-2. We performed in vitro assays and demonstrated their effective antiviral activity against SARS-CoV-2 and its variants. Cross-linking experiments and structural modeling suggest that the compounds bind to a hydrophobic pocket in spike protein to exert their inhibitory effect on the fusion step. These data suggest that both dichlorcyclizine and fluoxazolevir are promising candidates for further development as treatment for SARS-CoV-2.

India's covid catastrophe

In 2020 editor-in-chief (Andrew Malekoff) issued a special call for papers for group work stories on pandemic 2020. Among the 28 stories accepted for the series there were 16 from India, 9 from the United States, 2 from Canada and 1 from Israel. General submissions from the U.S., Canada and Israel were typical for the journal. Atypical are submissions from India. Rather than publish the stories in one special issue of the Journal, he decided to spread them out over several issues through 2022. In the course of organizing the special series (with a December 2021 deadline) he continued communication with a few of the authors from India, with particular interest and concern in the deteriorating situation as 2021 unfolded. Although the present commentary is not about group work per se, it is an update by Ajay Saini, Nancy and Andrew Malekoff on the current state of affairs in India, with some contrast to the situation in the U.S., that offers continuing context for the stories in the series. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

An updated review of SARS-CoV-2 detection methods in the context of a novel coronavirus pandemic.

The World Health Organization has reported approximately 430 million confirmed cases of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), worldwide, including nearly 6 million deaths, since its initial appearance in China in 2019. While the number of diagnosed cases continues to increase, the need for technologies that can accurately and rapidly detect SARS-CoV-2 virus infection at early phases continues to grow, and the Federal Drug Administration (FDA) has licensed emergency use authorizations (EUAs) for virtually hundreds of diagnostic tests based on nucleic acid molecules and antigen-antibody serology assays. Among them, the quantitative real-time reverse transcription PCR (qRT-PCR) assay is considered the gold standard for early phase virus detection. Unfortunately, qRT-PCR still suffers from disadvantages such as the complex test process and the occurrence of false negatives; therefore, new nucleic acid detection devices and serological testing technologies are being developed. However, because of the emergence of strongly infectious mutants of the new coronavirus, such as Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529), the need for the specific detection of mutant strains is also increasing. Therefore, this article reviews nucleic acid- and antigen-antibody-based serological assays, and compares the performance of some of the most recent FDA-approved and literature-reported assays and associated kits for the specific testing of new coronavirus variants.

No magic bullet: Limiting in-school transmission in the face of variable SARS-CoV-2 viral loads.

In the face of a long-running pandemic, understanding the drivers of ongoing SARS-CoV-2 transmission is crucial for the rational management of COVID-19 disease burden. Keeping schools open has emerged as a vital societal imperative during the pandemic, but in-school transmission of SARS-CoV-2 can contribute to further prolonging the pandemic. In this context, the role of schools in driving SARS-CoV-2 transmission acquires critical importance. Here we model in-school transmission from first principles to investigate the effectiveness of layered mitigation strategies on limiting in-school spread. We examined the effect of masks and air quality (ventilation, filtration and ionizers) on steady-state viral load in classrooms, as well as on the number of particles inhaled by an uninfected person. The effectiveness of these measures in limiting viral transmission was assessed for variants with different levels of mean viral load (ancestral, Delta, Omicron). Our results suggest that a layered mitigation strategy can be used effectively to limit in-school transmission, with certain limitations. First, poorly designed strategies (insufficient ventilation, no masks, staying open under high levels of community transmission) will permit in-school spread even if some level of mitigation is present. Second, for viral variants that are sufficiently contagious, it may be difficult to construct any set of interventions capable of blocking transmission once an infected individual is present, underscoring the importance of other measures. Our findings provide practical recommendations; in particular, the use of a layered mitigation strategy that is designed to limit transmission, with other measures such as frequent surveillance testing and smaller class sizes (such as by offering remote schooling options to those who prefer it) as needed.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors.

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.

A Comprehensive Review on the Current Vaccines and Their Efficacies to Combat SARS-CoV-2 Variants.

Since the first case of Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, SARS-CoV-2 infection has affected many individuals worldwide. Eventually, some highly infectious mutants-caused by frequent genetic recombination-have been reported for SARS-CoV-2 that can potentially escape from the immune responses and induce long-term immunity, linked with a high mortality rate. In addition, several reports stated that vaccines designed for the SARS-CoV-2 wild-type variant have mixed responses against the variants of concern (VOCs) and variants of interest (VOIs) in the human population. These results advocate the designing and development of a panvaccine with the potential to neutralize all the possible emerging variants of SARS-CoV-2. In this context, recent discoveries suggest the design of SARS-CoV-2 panvaccines using nanotechnology, siRNA, antibodies or CRISPR-Cas platforms. Thereof, the present comprehensive review summarizes the current vaccine design approaches against SARS-CoV-2 infection, the role of genetic mutations in the emergence of new viral variants, the efficacy of existing vaccines in limiting the infection of emerging SARS-CoV-2 variants, and efforts or challenges in designing SARS panvaccines.

Vaccination Rates and the Emergence of Viral Variants: An Evolutionary Strategies-Inspired Model

The emergence of variants of concern (VOC) has produced challenges in bringing the ongoing COVID-19 pandemic under control, and has created obstacles in the ultimate transition to endemicity;indeed, the omicron variant of SARS-CoV-2, the virus that causes COVID-19, caused a wave of unprecedented levels of infection throughout the globe. Although the available COVID-19 vaccines offer significant protection from infection, hospitalization, and death, challenges in vaccine availability globally have limited the efficacy of mass inoculation in controlling viral spread. The present study utilizes an evolutionary strategies (ES)-inspired model to examine the effect of vaccination upon the emergence of viral variants. The kinetics of the evolution of an idealized RNA virus are modelled in the details of the mutation of an ES population, and the emergence of variants is formulated as an optimization problem. A binary fitness function is optimized such that it achieves a maximum upon the condition that a single viral genome exhibits the requisite number of mutations such that it may be considered a variant of concern. Results demonstrate that vaccination is extremely effective in delaying the emergence of viral variants, and that vaccination rates are highly correlated with delayed variant emergence (R= 0.8399) and requisite viral genetic diversity for consideration as a variant of concern (R=0.8583). Time to emergence of a variant of concern for 0%, 25%, 50%, and 80% vaccination rates of the population are 17.46\pm 1.61 generations, 20.51\pm 2.12 generations, 33.67\pm 5.18 generations, and 226.12\pm 114.41 generations, respectively. It is shown that the delay in emergence of a variant of concern with higher vaccination rates may be attributable to a decrease in the number of infections, thus requiring a higher degree of genetic diversity in the viral genome. © 2022 IEEE.

[Update on collaborative autopsy-based research in German pathology, neuropathology, and forensic medicine]. / Update zur kooperativen autopsiebasierten Forschung in der deutschen Pathologie, Neuropathologie und Gerichtsmedizin.

BACKGROUND: Autopsies are a valuable tool for understanding disease, including COVID-19. MATERIALS AND METHODS: The German Registry of COVID-19 Autopsies (DeRegCOVID), established in April 2020, serves as the electronic backbone of the National Autopsy Network (NATON), launched in early 2022 following DEFEAT PANDEMIcs. RESULTS: The NATON consortium's interconnected, collaborative autopsy research is enabled by an unprecedented collaboration of 138 individuals at more than 35 German university and non-university autopsy centers through which pathology, neuropathology, and forensic medicine autopsy data including data on biomaterials are collected in DeRegCOVID and tissue-based research and methods development are conducted. More than 145 publications have now emerged from participating autopsy centers, highlighting various basic science and clinical aspects of COVID-19, such as thromboembolic events, organ tropism, SARS-CoV­2 detection methods, and infectivity of SARS-CoV-2 at autopsy. CONCLUSIONS: Participating centers have demonstrated the high value of autopsy and autopsy-derived data and biomaterials to modern medicine. The planned long-term continuation and further development of the registry and network, as well as the open and participatory design, will allow the involvement of all interested partners.

Functionality of Monoclonal Antibody Therapy in SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic emerged as a world crisis in 2019 and started a global search for optimal therapeutic regimen including vaccines, antiviral agents, and recently monoclonal antibody therapy. Clinical trials are currently underway for the efficacy of several neutralizing monoclonal antibodies against COVID-19. The evolution of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune evasion capacity has created a challenge for the healthcare workers with urgent need for prospective studies to determine functionality of monoclonal antibody therapy and their role in the reduction of hospitalization for disease severity. Herein, we report three cases of COVID-19 during the beginning of the spread of Omicron variants that were hospitalized after treatment with monoclonal antibody therapy in the emergency department. All the patients showed progression of the disease on imaging and were treated with dexamethasone, remdesivir and anticoagulation based on the symptoms and contraindications. Two of the patients recovered and were discharged with out-patient follow-up; however, one patient expired in the hospital. Monoclonal antibody therapy is a promising treatment to limit the progression of COVID-19 and reduce the hospital strain specifically in small community hospitals. Limited information is available about their efficacy in the new viral variants. These cases emphasize the need of future prospective study and randomized controlled trials to illustrate the utilization of monoclonal antibodies as a therapeutic modality in patients infected with the variants of SARS-CoV-2.

Boosting with Multiple Doses of mRNA Vaccine after Priming with Two Doses of Protein Subunit Vaccine MVC-COV1901 Elicited Robust Humoral and Cellular Immune Responses against Emerging SARS-CoV-2 Variants.

Confronted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as Delta and Omicron, with high infectivity and immune evasion capacity, vaccination remains the most effective tool to prevent infection and severe illness. However, heterologous vaccination of mRNA vaccines primed with protein subunit vaccines had not been evaluated before the current study. Since subunit vaccine MVC-COV1901 (MVC) has been granted emergency use authorization in Taiwan, in this study, we explored the humoral and cellular immune responses to additional third (2× MVC/Mod) and fourth (2× MVC/2× Mod) doses of mRNA-1273 (Mod) after priming with two doses of subunit vaccine MVC against the emerging variants. We found a 12.3- to 16.1-fold increase in antibodies targeting the receptor binding domain (RBD) of the Delta variant with 2× MVC/Mod compared to two doses of MVC (2× MVC) or AZD1222 (2× AZ) regimens and a 26- to 32.2-fold improvement in neutralizing potency against the Omicron variant (BA.1). Besides, the numbers of gamma interferon (IFN-γ)-secreting T cells induced by 2× MVC/Mod were also elevated 3.5-fold and 3.7- to 4.3-fold for the wild type and Delta variant. However, boosting with a fourth dose of Mod (2× MVC/2× Mod) after the 2× MVC/Mod regimen failed to significantly improve the immune responses. Moreover, all vaccination schedules showed reduced neutralizing activity against the Omicron variant. Collectively, our results suggested that the third or fourth dose booster vaccination with mRNA vaccine after priming with two doses of protein subunit vaccine could elicit stronger humoral and cellular immune responses. These findings could provide a future global heterologous boosting strategy against COVID-19. IMPORTANCE Vaccination is the most important strategy to combat the COVID-19 outbreak; however, it remains to be determined whether heterologous prime-boost regimens could induce equal or even stronger immune responses against SARS-CoV-2. Here, we showed that boosting the additional doses of mRNA-1273 (Mod) priming with two doses of MVC-COV1901 (MVC) (2× MVC/Mod) improved humoral and cellular immunity compared to two doses of AZD1222 (2× AZ) or MVC (2× MVC) against SARS-CoV-2 variants. However, the Omicron variant showed strong immune evasion ability for all vaccination schedules. Our findings provided evidence supporting that heterologous vaccination by boosting with mRNA vaccine after priming with two doses of protein subunit vaccine could strongly promote humoral and cellular immune responses against the emerging SARS-CoV-2 variants.

Serosurvey in SARS-CoV-2 inactivated vaccine-elicited neutralizing antibodies against authentic SARS-CoV-2 and its viral variants.

Various variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been emerging and circulating in different parts of the world. Millions of vaccine doses have been administered globally, which reduces the morbidity and mortality of coronavirus disease-2019 efficiently. Here, we assess the immune responses of individuals after two shots of BBIBP-CorV or CoronaVac inactivated vaccine. We measured neutralizing antibody responses after the second vaccination by using authentic SARS-CoV-2 and its viral variants. All the serum samples efficiently neutralized SARS-CoV-2 wild-type lineage, in contrast, a part of serum samples failed to neutralize Alpha, Beta, Gamma, Delta, or Eta lineages, and only several serum samples were able to neutralize Omicron lineage virus strains (BA.1 and BA.2) with low neutralization titer. As compared with the neutralization of SARS-CoV-2 wild-type lineage, the neutralization of all other SARS-CoV-2 variant lineages was significantly lower. Considering that all the SARS-CoV-2 mutation viruses challenged the antibody neutralization induced by BBIBP-CorV and CoronaVac, it is necessary to carry out a third booster vaccination to increase the humoral immune response against the SARS-CoV-2 mutation viruses.

Appraisal of SARS-CoV-2 mutations and their impact on vaccination efficacy: an overview.

With the unexpected emergence of the novel 2019 Wuhan coronavirus, the world was faced with a sudden uproar that quickly shifted into a serious life-threatening pandemic. Affecting the lives of the global population and leaving drastic damage in various sections and systems, several measures have been constantly taken to tackle down this crisis. For instance, numerous vaccines have been developed in the past two years, some of which have been granted emergency use, thus providing sufficient immunity to the vaccinated individuals. However, the appearance of newly emerged SARS-CoV-2 variants with accelerated transmission and fatality has led the world towards another pandemic. Having undergone various mutations in genomic and/or amino acid profiles, some of the emerged variants of concern (VOCs) including Alpha, Beta, Gamma, and Delta have displayed immune evasion and pathogenicity even in the vaccinated population, hence raising concerns regarding the efficacy of current vaccines against new VOCs of COVID-19. Therefore, genomic investigations of SARS-CoV-2 mutations are expected to provide valuable insight into the evolution of SARS-CoV-2, while also determining the impact of different mutations on infection severity. This study was constructed with the aim of shining light on recent advances regarding mutations in major COVID-19 VOCs, as well as vaccination efficacy against those VOCs.

The significance of advanced COVID-19 diagnostic testing in pandemic control measures.

During the 2 years since the start of the novel coronavirus disease 2019 (COVID-19) pandemic, the scientific world made an enormous effort to fight against this disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has high transmissibility. Advancements in vaccine and treatment strategies have reduced both the hospitalization and mortality rates. However, the virus has shown its ability to evolve and evade from our COVID-19 combating armamentaria by the most common evolution mechanism-mutation. Diagnostic testing has been the first line of defense following the identification of the causative agent. Ever since, the scientific community has developed nuclei acid-based, antigen-based, and antibody-based diagnostic tests, and these testing methodologies are still playing a central role in slowing down viral transmission. These testing methods have different sensitivity and specificity and could be optimally used in areas facing different challenges owing to different level and conditions of COVID-19 outbreak. In this review, we discuss these testing methodologies as well as the considerations on how to apply these diagnostic tests optimally in the community to cope with the ever-changing pandemic conditions.

Recipients of COVID-19 vaccines face challenges of SARS-CoV-2 variants.

The coronavirus disease 19 (COVID-19) has been rampant since 2019, severely affecting global public health, and causing 5.75 million deaths worldwide. So far, many vaccines have been developed to prevent the infection of SARS-CoV-2 virus. However, the emergence of new variants may threat vaccine recipients as they might evade immunological surveillance that depends on the using of anti-SARS-CoV-2 antibody to neutralize the viral particles. Recent studies have found that recipients who received two doses of vaccination plus an additional booster shoot were able to quickly elevate neutralization response and immune response against wild-type SARS-CoV-2 virus and some initially appeared viral variants. In this review, we assessed the real-world effectiveness of different COVID-19 vaccines by population studies and neutralization assays and compared neutralization responses of booster vaccines in vitro. Finally, as the efficacy of COVID-19 vaccine is expected to decline over time, continued vaccination should be considered to achieve a long-term immune protection against coronavirus.