Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern (preprint)

SARS-CoV-2 variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22995 and 28866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination.

Engineering Immunosuppressive Drug Resistant Armored (IDRA) SARS-CoV-2 T cells for cell therapy (preprint)

Solid organ transplant (SOT) recipients receive immunosuppressive drugs (ISDs) and are susceptible to develop severe COVID-19. Here, we analyzed the Spike-specific T cell response after 3 doses of mRNA vaccine in a group of SOT patients (n=136) treated with different ISDs. We demonstrated that combination of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone (Pred) treatment regimen displayed strong suppression of mRNA vaccine-induced Spike-specific cellular response. Such defects have clinical consequences since the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough infection. To then compensate the T cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients, we describe the production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T Cell Receptor (TCR)-T cells engineered using mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta, Delta, Gamma, and Omicron variants. This strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.

Lymphocyte–C-reactive protein ratio can differentiate disease severity of COVID-19 patients and serve as an assistant screening tool for hospital and ICU admission

In this study, we aimed to explore whether lymphocyte–C-reactive protein ratio (LCR) can differentiate disease severity of coronavirus disease 2019 (COVID-19) patients and its value as an assistant screening tool for admission to hospital and intensive care unit (ICU). A total of 184 adult COVID-19 patients from the COVID-19 Treatment Center in Heilongjiang Province at the First Affiliated Hospital of Harbin Medical University between January 2020 and March 2021 were included in this study. Patients were divided into asymptomatic infection group, mild group, moderate group, severe group, and critical group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data including gender, age, comorbidities, severity of COVID-19, white blood cell count (WBC), neutrophil proportion (NEUT%), lymphocyte count (LYMPH), lymphocyte percentage (LYM%), red blood cell distribution width (RDW), platelet (PLT), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), albumin (ALB), total bilirubin (TB), direct bilirubin (DBIL), indirect bilirubin (IBIL), and D-dimer were obtained and collated from medical records at admission, from which sequential organ failure assessment (SOFA) score and LCR were calculated, and all the above indicators were compared among the groups. Multiple clinical parameters, including LYMPH, CRP, and LCR, showed significant differences among the groups. The related factors to classify COVID-19 patients into moderate, severe, and critical groups included age, number of comorbidities, WBC, LCR, and AST. Among these factors, the number of comorbidities showed the greatest effect, and only WBC and LCR were protective factors. The area under the receiver operating characteristic (ROC) curve of LCR to classify COVID-19 patients into moderate, severe, and critical groups was 0.176. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 1,780.7050 and 84.6% and 66.2%, respectively. The related factors to classify COVID-19 patients into severe and critical groups included the number of comorbidities, PLT, LCR, and SOFA score. Among these factors, SOFA score showed the greatest effect, and LCR was the only protective factor. The area under the ROC curve of LCR to classify COVID-19 patients into severe and critical groups was 0.106. The cutoff value of LCR and the sensitivity and specificity of the ROC curve were 571.2200 and 81.3% and 90.0%, respectively. In summary, LCR can differentiate disease severity of COVID-19 patients and serve as a simple and objective assistant screening tool for hospital and ICU admission.

SARS-CoV-2 and Plasmodium falciparum Co-Infection in a Returning Traveler

Since December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has become a non-neglectable context for the whole healthcare system. Under the background of COVID-19, the detection and diagnosis of malaria cases are under challenge. Here, we reported a COVID-19 and malaria co-infection traveler who has a long living history in Cameroon. The case was administered with dihydroartemisinin and piperaquine tablets for malaria, Lopinavir and Ritonavir tablets, Arbidol, recombinant human interferon α-2b and Compound Maxing Yifei mixture for COVID-19, and Zolpidem Tartrate tablets, Diazepam, Paroxetine Hydrochloride tablets, Thymosin α1, and Lianhua Qinwen Jiaonang during the second hospitalization of the patient since the patient has a certain level of anxiety and insomnia with no evidence of inflammatory reactions. After being tested negative two times for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 48 h, the patient met China's COVID-19 discharge standards and was discharged with stable vital signs and mental state. Since most countries in the sub-Saharan region have a fragile health system, co-infection for both Plasmodium and SARS-CoV-2 may not be uncommon, and raise a challenge in diagnosis, treatment, and prevention for both diseases. We add to the literature on co-infection of P. falciparum malaria and COVID-19 and offer operational advice on diagnosis, prevention, and treatment for the co-infection.

Mixed-Reality-Enhanced Human–Robot Interaction with an Imitation-Based Mapping Approach for Intuitive Teleoperation of a Robotic Arm-Hand System

This paper presents an integrated mapping of motion and visualization scheme based on a Mixed Reality (MR) subspace approach for the intuitive and immersive telemanipulation of robotic arm-hand systems. The effectiveness of different control-feedback methods for the teleoperation system is validated and compared. The robotic arm-hand system consists of a 6 Degrees-of-Freedom (DOF) industrial manipulator and a low-cost 2-finger gripper, which can be manipulated in a natural manner by novice users physically distant from the working site. By incorporating MR technology, the user is fully immersed in a virtual operating space augmented by real-time 3D visual feedback from the robot working site. Imitation-based velocity-centric motion mapping is implemented via the MR subspace to accurately track operator hand movements for robot motion control and enables spatial velocity-based control of the robot Tool Center Point (TCP). The user control space and robot working space are overlaid through the MR subspace, and the local user and a digital twin of the remote robot share the same environment in the MR subspace. The MR-based motion and visualization mapping scheme for telerobotics is compared to conventional 2D Baseline and MR tele-control paradigms over two tabletop object manipulation experiments. A user survey of 24 participants was conducted to demonstrate the effectiveness and performance enhancements enabled by the proposed system. The MR-subspace-integrated 3D mapping of motion and visualization scheme reduced the aggregate task completion time by 48% compared to the 2D Baseline module and 29%, compared to the MR SpaceMouse module. The perceived workload decreased by 32% and 22%, compared to the 2D Baseline and MR SpaceMouse approaches.

Mutations of SARS-CoV-2 variants of concern escaping Spike-specific T cells (preprint)

The amino acid (AA) mutations that characterise the different variants of concern (VOCs), which replaced the ancestral SARS-CoV-2 Wuhan-Hu-1 isolate worldwide, provide biological advantages such as increased infectivity and partial escape from humoral immunity. Here we analysed the impact of these mutations on vaccination- and infection-induced Spike-specific T cells. We confirmed that, in the majority of infected or vaccinated individuals, different mutations present in a single VOC (Delta) or a combined mosaic of more than 30 AA substitutions and deletions found in Alpha, Beta, Gamma, Delta and Omicron VOCs cause modest alteration in the global Spike-specific T cell response. However, distinct numerically dominant Spike-specific CD4 and CD8 T cells preferentially targeted regions affected by AA mutations and do not recognise the mutated peptides. Importantly, some of these mutations, such as N501Y (present in Alpha, Beta, Gamma, and Omicron) and L452R (present in Delta), known to provide biological advantage to SARS-CoV-2 in terms of infectivity also abolished CD8 T cell recognition. Taken together, our data show that while global mRNA vaccine- and infection-induced Spike-specific T cells largely tolerate the diverse mutations present in VOCs, single Spike-specific T cells might contribute to the natural selection of SARS-CoV-2 variants.

Assessment to China's Recent Emission Pattern Shifts

Energy and emission data are crucial to climate change research and mitigation efforts. The accuracy of energy statistics is essential for mitigation strategies and evaluating the performance of low carbon energy transition efforts. This study provides the most up‐to‐date emission inventories for China and its provinces for 2018 and 2019. We also update the carbon dioxide (CO2) emission inventories of China and 30 provinces since 2012 based on the newly revised energy statistics. The inventories are compiled in a combined accounting approach of scope 1 (Intergovernmental Panel on Climate Change territorial emissions from 17 types of fossil fuel combustion and cement production by 47 socioeconomic sectors) and scope 2 (emissions from purchased electricity and heat consumption). The most recent energy revision led to an increase in reported national CO2 emissions by an average of 0.3% from 2014 to 2017. The results show that data revisions raised China's carbon intensity mitigation baseline (in 2005) by 5.1%–10.8% and thus made it more challenging to fulfill the mitigation pledges. However, the 2020 carbon intensity mitigation target was achieved ahead of schedule in 2018. A preliminary estimate of China's national emissions for 2020 shows that the COVID‐19 pandemic and lockdown was not able to offset China's annual increase in CO2 emissions. These emissions inventories provide an improved evidence base for China's policies toward net‐zero emissions.

Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2 (preprint)

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

Evolutionary analysis of SARS-CoV-2 spike protein for its different clades (preprint)

Objective: The spike protein of SARS-CoV-2 has become the main target for antiviral and vaccine development. Despite its relevance, there is scarce information about its evolutionary traces. The aim of this study was to investigate the diversification patterns of the spike for each clade of SARS-CoV-2 through different approaches. Methods: Two thousand and one hundred sequences representing the seven clades of the SARS-CoV-2 were included. Patterns of genetic diversifications and nucleotide evolutionary rate were estimated for the spike genomic region. Results: The haplotype networks showed a star shape, where multiple haplotypes with few nucleotide differences diverge from a common ancestor. Four hundred seventy nine different haplotypes were defined in the seven analyzed clades. The main haplotype, named Hap-1, was the most frequent for clades G (54%), GH (54%), and GR (56%) and a different haplotype (named Hap-252) was the most important for clades L (63.3%), O (39.7%), S (51.7%), and V (70%). The evolutionary rate for the spike protein was estimated as 1.08 x 10-3 nucleotide substitutions/site/year. Moreover, the nucleotide evolutionary rate after eight months of pandemic was similar for each clade. Conclusions: In conclusion, the present evolutionary analysis is relevant since the spike protein of SARS-CoV-2 is the target for most therapeutic candidates; besides, changes in this protein could have consequences on viral transmission, response to antivirals and efficacy of vaccines. Moreover, the evolutionary characterization of clades improves knowledge of SARS-CoV-2 and deserves to be assessed in more detail since re-infection by different phylogenetic clades has been reported.

Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 (preprint)

The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was ~100 PFU in aged, male BALB/c mice. Deep sequencing identified three amino acid mutations, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, which significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of mACE2 in complex with the RBD of MASCp36 at 3.7-angstrom resolution elucidates molecular basis for the receptor-binding switch driven by amino acid substitutions. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in mice.

SARS-CoV-2 infection causes transient olfactory dysfunction in mice (preprint)

Olfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman's gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19.

People’s Life and Psychological Change after Quarantining Wuhan: Influence of the Epidemic of Covid-19 (preprint)

The epidemic of Coronavirus Disease 2019 (Covid-19) has brought many changes to people's life. This study aims to analysis Chinese people's psychological change and life after quarantining Wuhan and explore the influencing factors. Based on data from a web-survey after quarantining Wuhan (N=3268), the principal-component-analysis (PCA), multiple-linear-regression (MLR), propensity-score-matching (PSM) were used to explore the psychological change of people in China and the influencing factors. 83.3% of the respondents said that the impact of the epidemic on their life had increased after quarantining Wuhan. A considerable proportion of people's anxiety increased, being reflected in negative emotion, behavioral response and physiological response. The proportion of people who said their anxiety had increased in Wuhan was higher than that in other regions (p <0.05). The anxiety of people who were in medical isolation increased less than those who were not (p <0.05). All three aspects of people’s anxiety were positively related with time of medical isolation and degree of the attention on the epidemic (p＜0.05) except the effect of attention degree on the physiological response (p＝0.06). The measure of medical isolation at home should be advocated. Yet people should reduce the concern for the epidemic while paying attention to self-protection.

Cohort profile: protocol and baseline survey for the Shanghai Suburban Adult Cohort and Biobank (SSACB) study

PURPOSE: The Shanghai Suburban Adult Cohort and Biobank (SSACB) was established to identify environmental, lifestyle and genetic risk factors for non-communicable chronic diseases (NCDs) in adults (20-74 years old) living in a suburban area of Shanghai with rapid urbanisation. PARTICIPANTS: Two of eight suburban district were purposely selected according to participant willingness, health service facilities, population, geographic region and electronic medical record system. From these suburban districts, four communities were selected based on economic level and population size. At stage three, one-third of the committees/villages were randomly selected from each community. All residents aged 20-74 years old were invited as study participants. FINDINGS TO DATE: The baseline data on demographics, lifestyle and physical health-related factors were collected using a face-to-face questionnaire interview. All participants completed physical examinations and had blood and urine tests. Blood and urine samples from these tests were stored in a biobank. From 6 April 2016 through 31 October 2017, we conducted face-to-face interviews and clinical examinations in 44 887 participants: 35 727 from Songjiang District and 9160 from Jiading District. The average age of participants was 56.4±11.2 years in Songjiang and 56.6±10.5 years in Jiading. The prevalence of hypertension, diabetes and dyslipidaemia was 34.0%, 8.2% and 11.1%, respectively. FUTURE PLANS: In-person surveys will be conducted every 5 years. For annual tracking, baseline data was linked to the local health information system, which was composed of an electronic medical record system, a chronic disease management system, a cancer registry system, an infectious disease report system and a death registry system. The data of the SSACB cohort is located in the School of Public Health, Fudan University. International and domestic collaborative research projects are encouraged and inherent in the project.

Using RIGHT (Reporting Items for Practice Guidelines in Healthcare) to evaluate the reporting quality of WHO guidelines

BACKGROUND: Without adequate reporting of research, valuable time and resources are wasted. In the same vein, adequate reporting of practice guidelines to optimise patient care is equally important. Our study examines the quality of reporting of published WHO guidelines, over time, using the RIGHT (Reporting Items for Practice Guidelines in HealThcare) reporting checklist. METHODS: We examined English-language guidelines approved by the WHO Guidelines Review Committee from inception of the committee in 2007 until 31 December 2017. Pairs of independent, trained reviewers assessed the reporting quality of these guidelines. Descriptive data were summarised with frequencies and percentages. RESULTS: We included 182 eligible guidelines. Overall, 25 out of the 34 RIGHT items were reported in 75% or more of the WHO guidelines. The reporting rates improved over time. Further, 90% of the guidelines reported document type in the title. The identification of evidence, the rationale for recommendations and the review process were reported in more than 80% of guidelines. The certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was assessed in 81% of the guidelines assessed. While 82% of guidelines reported funding sources, only 25% mentioned the role of funders. CONCLUSIONS: WHO guidelines provide adequate reporting of many of the RIGHT items and reporting has improved over time. WHO guidelines compare favourably to guidelines produced by other organisations. However, reporting can be further improved in a number of areas.

SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19 (preprint)

Long-term antibody responses and neutralizing activities following SARS-CoV-2 infections have not yet been elucidated. We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being infected. The positivity rate and magnitude of IgM-S and IgG-N responses increased rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset were associated with virus control and IgG-S titers correlated closely with the capacity to neutralize SARS-CoV-2. While specific IgM-S/N became undetectable 12 weeks after disease onset in most patients, IgG-S/N titers showed an intermediate contraction phase, but stabilized at relatively high levels over the six months observation period. At late time points the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies was still over 70%. Taken together, our data indicate sustained humoral immunity in recovered patients who suffer from symptomatic COVID-19, suggesting prolonged immunity.

Psychological Status and Associated Factors During the Lockdown Period of the COVID-19 Epidemic in China: A Web-Based Survey (preprint)

Background: The aim of this study was to survey the general public in China to better understand their levels of psychological state and its influencing factors after the Wuhan shutdown on 23 Jan. Methods: : A survey was conducted on Feb 20-24, using an online self-administrated questionnaire among 4071 participants. Data on subjective indicators of daily-life change was collected, and individual scores on changes in anxiety, depression, and stress were generated by 8-item, 11-item, and 6-item questions. After bivariate analyses, multiple linear regression analyses were conducted to investigate independent associations between socio-demographic variables, subjective indicators of changes in daily life， and summary scores including anxiety, depression, and stress scores. Results: : Information from 3803 participants was available for analysis. Multivariable regression analyses showed that the anxiety (B=-1.27, 95%CI=-1.71 to -0.82), depression (B=-1.47, 95%CI=-2.06 to -0.88), and stress (B=-0.79, 95%CI=-1.13 to -0.46) scores of people in rural areas are lower than those in urban areas. People living in the other regions except Hubei, higher education were independent correlates of less negative emotions, while people with relatively high incomes had poor psychological status in anxiety (B=0.73, 95%CI=0.08 to 1.38),depression (B=1.45, 95%CI=0.60 to 2.30) and stress (B=0.65, 95%CI=0.17 to 1.13). Married people were less anxious (B=-0.67, 95%CI=-1.30 to -0.05), depressed (B=-1.14, 95%CI=-1.96 to -0.33), and stressed (B=-0.47, 95%CI=-0.93 to 0.00) than single people. The level of attention, self-assessed infection risk, impact of the daily life and mental-health help-seeking tended to be positively associated with the scores of anxiety, depression, and stress (p<0.001). Conclusions: : Usual residence, education, marital status, monthly income, the level of attention, self-assessed infection risk, impact of the daily life and mental-health help-seeking are important correlates of the scores of anxiety, depression, and stress. Awareness of these relevant factors could help the government and related personnel to prevent more severe psychological trauma in the later period.

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody (preprint)

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19. One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.

Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy (preprint)

Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. SummaryThis study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.