Exercise Adherence in Older and Middle-Aged Adults With Coronary Artery Disease Before and During COVID-19.

BACKGROUND: Regular exercise is advised for individuals given a diagnosis of cardiovascular disease. COVID-19 presented challenges to exercise adherence. OBJECTIVE: The objective of this study was to determine long-term exercise adherence and whether individuals with cardiovascular disease adhered to American Heart Association/American College of Cardiology Foundation guidelines before and during the COVID-19 pandemic. METHODS: This is an observational cross-sectional study in which men (73%) and women discharged from a multiwide hospital system after an acute coronary event were enrolled. Participants completed 3 questionnaires, including the Exercise Adherence Rating Scale. RESULTS: Five hundred eighty-two individuals (mean [SD] age, 67 [9.8] years) completed the survey. Fifty-three percent of participants met minimum exercise guidelines during COVID-19. Exercise days per week decreased significantly during COVID-19 in women (P = .013) but not significant for men (P = .301). Categorized by age, the decrease was significant for middle-aged women (P = .002), not older women (P = .336). Men exercised more minutes per session (P = .034), and had greater exercise adherence (P = .003) and greater exercise intensity (P < .001). Overall, women participated less in cardiac rehabilitation (P = .046) and reported the greatest disparity in exercise adherence and intensity. CONCLUSION: Exercise after an acute event is beneficial, and the percentage of individuals meeting recommended guidelines should be higher considering the relationship between exercise and the possibility of future cardiac events. On the basis of the many physical and mental benefits of maintaining exercise, healthcare practitioners are encouraged to screen all patients for exercise adherence with a major emphasis on educating women and older adults.

The role of booster vaccination in decreasing COVID-19 age-adjusted case fatality rate: Evidence from 32 countries.

Background: The global COVID-19 pandemic is still ongoing, and cross-country and cross-period variation in COVID-19 age-adjusted case fatality rates (CFRs) has not been clarified. Here, we aimed to identify the country-specific effects of booster vaccination and other features that may affect heterogeneity in age-adjusted CFRs with a worldwide scope, and to predict the benefit of increasing booster vaccination rate on future CFR. Method: Cross-temporal and cross-country variations in CFR were identified in 32 countries using the latest available database, with multi-feature (vaccination coverage, demographic characteristics, disease burden, behavioral risks, environmental risks, health services and trust) using Extreme Gradient Boosting (XGBoost) algorithm and SHapley Additive exPlanations (SHAP). After that, country-specific risk features that affect age-adjusted CFRs were identified. The benefit of booster on age-adjusted CFR was simulated by increasing booster vaccination by 1-30% in each country. Results: Overall COVID-19 age-adjusted CFRs across 32 countries ranged from 110 deaths per 100,000 cases to 5,112 deaths per 100,000 cases from February 4, 2020 to Jan 31, 2022, which were divided into countries with age-adjusted CFRs higher than the crude CFRs and countries with age-adjusted CFRs lower than the crude CFRs (n = 9 and n = 23) when compared with the crude CFR. The effect of booster vaccination on age-adjusted CFRs becomes more important from Alpha to Omicron period (importance scores: 0.03-0.23). The Omicron period model showed that the key risk factors for countries with higher age-adjusted CFR than crude CFR are low GDP per capita and low booster vaccination rates, while the key risk factors for countries with higher age-adjusted CFR than crude CFR were high dietary risks and low physical activity. Increasing booster vaccination rates by 7% would reduce CFRs in all countries with age-adjusted CFRs higher than the crude CFRs. Conclusion: Booster vaccination still plays an important role in reducing age-adjusted CFRs, while there are multidimensional concurrent risk factors and precise joint intervention strategies and preparations based on country-specific risks are also essential.

Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus.

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Phase separation drives the formation of biomolecular condensates in the immune system.

When the external conditions change, such as the temperature or the pressure, the multi-component system sometimes separates into several phases with different components and structures, which is called phase separation. Increasing studies have shown that cells condense related biomolecules into independent compartments in order to carry out orderly and efficient biological reactions with the help of phase separation. Biomolecular condensates formed by phase separation play a significant role in a variety of cellular processes, including the control of signal transduction, the regulation of gene expression, and the stress response. In recent years, many phase separation events have been discovered in the immune response process. In this review, we provided a comprehensive and detailed overview of the role and mechanism of phase separation in the innate and adaptive immune responses, which will help the readers to appreciate the advance and importance of this field.

Born or not: A moderated mediation model of the relationship between work-family conflict and female employees' wellbeing based on fertility intention during the COVID-19 pandemic

The previous academic research on work-family conflict mainly focused on the relevant elements in the work field. This study concludes that elements of the family domain have a significant impact on the relationship between work-family conflict and employee wellbeing. Female employees' perceptions of wellbeing largely depend on their willingness to have children when they take on family roles. During COVID-19, employees had more time to fulfill both work and family roles in the family sphere due to the epidemic blockade, the contribution of the female employee's significant other (husband) in family matters had a significant impact on Fertility intention. This study using SPSS 24.0 AMOS 20.0 and M plus 7.4 statistical analysis tools to test the proposed hypotheses. In the paired data of 412 working female employees and husbands of Chinese dual-earner families with different occupational backgrounds, hypothesis testing results support that female employees' work → family conflict is negatively related to female employees' fertility intentions, and female employees' fertility intentions are positively related to wellbeing;female employees' family → work conflict is negatively related to female employees' wellbeing;husband's flexible work stress is negatively related to husband's share of housework;husband's share of housework moderated the front, rear and overall mediating effects by the fertility intention. When formulating policies, the managers should consider not only the direct effects of policies, but also the indirect effects that policies may have on other family members of employees. Managers should develop management policies during an epidemic that are more responsive to the actual needs of employees during an epidemic. The management of female employees should give due consideration to the family status of female employees and the enterprises should recognize the importance of childcare for female employees.

COVID-19 infections among passengers in an inbound flight to Beijing

Objective To understand the epidemiological characteristics and laboratory test results of COVID-19 infections among passengers in an inbound flight to Beijing, and to provide reference for the management of imported COVID-19 cases. Methods Flight information, centralized quarantine sites, transfer vehicle, laboratory test results, clinical progression and outcome and other information of all passengers in an inbound flight to Beijing on August 6, 2021 were collected and analyzed. Results A total of 15 passengers were COVID-19 positive. They were all tested negative for nucleic acid 48 h before boarding. The earliest positive was on the day of entry, and the longest was on the 13th day of entry, with the median of being the 3rd day after entry. There were inconsistent nucleic acid test results of 8 positive passengers reported by two institutions and the CT values were close to cutoff. The initial serum antibody levels were higher than 100（s/co） in 6 positive passengers. Nobody was infected during transportation and quarantine. Conclusions Nucleic acid testing before boarding the flight should be able to identify majority of positive cases. Accordingly, joint screening strategy such as blood serum antibody test for inbound passengers with suspicious preliminary screening results of COVID-19 should be implemented to determine the infection history of the case.

Born or not: A moderated mediation model of the relationship between work-family conflict and female employees' wellbeing based on fertility intention during the COVID-19 pandemic.

The previous academic research on work-family conflict mainly focused on the relevant elements in the work field. This study concludes that elements of the family domain have a significant impact on the relationship between work-family conflict and employee wellbeing. Female employees' perceptions of wellbeing largely depend on their willingness to have children when they take on family roles. During COVID-19, employees had more time to fulfill both work and family roles in the family sphere due to the epidemic blockade, the contribution of the female employee's significant other (husband) in family matters had a significant impact on Fertility intention. This study using SPSS 24.0 AMOS 20.0 and M plus 7.4 statistical analysis tools to test the proposed hypotheses. In the paired data of 412 working female employees and husbands of Chinese dual-earner families with different occupational backgrounds, hypothesis testing results support that female employees' work → family conflict is negatively related to female employees' fertility intentions, and female employees' fertility intentions are positively related to wellbeing; female employees' family → work conflict is negatively related to female employees' wellbeing; husband's flexible work stress is negatively related to husband's share of housework; husband's share of housework moderated the front, rear and overall mediating effects by the fertility intention. When formulating policies, the managers should consider not only the direct effects of policies, but also the indirect effects that policies may have on other family members of employees. Managers should develop management policies during an epidemic that are more responsive to the actual needs of employees during an epidemic. The management of female employees should give due consideration to the family status of female employees and the enterprises should recognize the importance of childcare for female employees.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Effective multidimensional approach for practical management of the emergency department in a COVID-19 designated children's hospital in east China during the Omicron pandemic: a cross-sectional study.

Background: Characterized by rapid transmission but lower severity, the new Omicron wave brought about an acute increase in local corona virus disease 2019 (COVID-19) cases in Shanghai, followed by stricter infection prevention and control strategies. Inevitably, more time was required for emergency consultation and treatment of children with critical illnesses. Therefore, a multidimensional approach was designed to streamline the emergency service and reduce the incidence of nosocomial infection of sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron wave for the emergency department (ED) at the Children's Hospital of Fudan University (CHFU). Methods: A multidimensional approach was implemented in the ED to help achieve a balance between the demand for emergency services and pandemic control, consisting of ED layout adjustment; electronic screening (E-screening) measures; standard management processes for patients, medical staff, and goods transfer; reliable disinfection measures; and a surveillance system for infection prevention and control. To evaluate the effect of the management strategy, the data on nosocomial infection cases and occupational exposure episodes among staff in the ED were collected. The demographic and clinical characteristics of level I/II children by the five-level pediatric triage tool and their mean duration of stay in the resuscitation room were collected. Results: There were 12,114 ED visitors from March 1 to May 31 in 2022, among which 53.24% were medical emergencies (6,449/12,114) and 46.76% were surgical emergencies (5,665/12,114). Twenty-nine patients were sent to the buffer zone, four of whom were transferred to the pediatric intensive care unit (PICU) because of the critical situation. Six patients tested positive for COVID-19 after entering ED, including three in the buffer zone and three in the ED clinic, causing a temporary closure of the ED for disinfection. There were no reports on medical care delays, unintended deaths, staff with COVID-19 infection, or occupational exposures to COVID-19. Conclusions: Our findings highlight the effectiveness of the multidimensional approach, which can simultaneously meet the emergency care needs of patients as well as pandemic prevention and control. However, the results were obtained against the proportional decrease in clinic visitors due to the Shanghai lockdown. Dynamic assessment and further optimization may be adopted to cope with the pre-pandemic visit volume.

Monkeypox outbreaks in the context of the COVID-19 pandemic: Network and clustering analyses of global risks and modified SEIR prediction of epidemic trends.

Background: Ninety-eight percent of documented cases of the zoonotic disease human monkeypox (MPX) were reported after 2001, with especially dramatic global spread in 2022. This longitudinal study aimed to assess spatiotemporal risk factors of MPX infection and predict global epidemiological trends. Method: Twenty-one potential risk factors were evaluated by correlation-based network analysis and multivariate regression. Country-level risk was assessed using a modified Susceptible-Exposed-Infectious-Removed (SEIR) model and a risk-factor-driven k-means clustering analysis. Results: Between historical cases and the 2022 outbreak, MPX infection risk factors changed from relatively simple [human immunodeficiency virus (HIV) infection and population density] to multiple [human mobility, population of men who have sex with men, coronavirus disease 2019 (COVID-19) infection, and socioeconomic factors], with human mobility in the context of COVID-19 being especially key. The 141 included countries classified into three risk clusters: 24 high-risk countries mainly in West Europe and Northern America, 70 medium-risk countries mainly in Latin America and Asia, and 47 low-risk countries mainly in Africa and South Asia. The modified SEIR model predicted declining transmission rates, with basic reproduction numbers ranging 1.61-7.84 in the early stage and 0.70-4.13 in the current stage. The estimated cumulative cases in Northern and Latin America may overtake the number in Europe in autumn 2022. Conclusions: In the current outbreak, risk factors for MPX infection have changed and expanded. Forecasts of epidemiological trends from our modified SEIR models suggest that Northern America and Latin America are at greater risk of MPX infection in the future.

Monkeypox outbreaks in the context of the COVID-19 pandemic: Network and clustering analyses of global risks and modified SEIR prediction of epidemic trends

Background Ninety-eight percent of documented cases of the zoonotic disease human monkeypox (MPX) were reported after 2001, with especially dramatic global spread in 2022. This longitudinal study aimed to assess spatiotemporal risk factors of MPX infection and predict global epidemiological trends. Method Twenty-one potential risk factors were evaluated by correlation-based network analysis and multivariate regression. Country-level risk was assessed using a modified Susceptible-Exposed-Infectious-Removed (SEIR) model and a risk-factor-driven k-means clustering analysis. Results Between historical cases and the 2022 outbreak, MPX infection risk factors changed from relatively simple [human immunodeficiency virus (HIV) infection and population density] to multiple [human mobility, population of men who have sex with men, coronavirus disease 2019 (COVID-19) infection, and socioeconomic factors], with human mobility in the context of COVID-19 being especially key. The 141 included countries classified into three risk clusters: 24 high-risk countries mainly in West Europe and Northern America, 70 medium-risk countries mainly in Latin America and Asia, and 47 low-risk countries mainly in Africa and South Asia. The modified SEIR model predicted declining transmission rates, with basic reproduction numbers ranging 1.61–7.84 in the early stage and 0.70–4.13 in the current stage. The estimated cumulative cases in Northern and Latin America may overtake the number in Europe in autumn 2022. Conclusions In the current outbreak, risk factors for MPX infection have changed and expanded. Forecasts of epidemiological trends from our modified SEIR models suggest that Northern America and Latin America are at greater risk of MPX infection in the future.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine composed of STFK and STFK1628x elicited high titers of broad-spectrum neutralizing antibodies to 19 circulating SARS-CoV-2 variants, including Omicron sublineages BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, and BA.4/5. Furthermore, this vaccine conferred robust protection against intranasal challenges by either SARS-CoV-2 ancestral strain or immune-evasive Beta and Omicron BA.1. Strikingly, vaccination with the bivalent vaccine in hamsters effectively blocked within-cage virus transmission of ancestral SARS-CoV-2, Beta variant, and Omicron BA.1 to unvaccinated sentinels. Thus, our study provided insight and antigen candidates for the development of next-generation COVID-19 vaccines.

A Heterologous Challenge Rescues the Attenuated Immunogenicity of SARS-CoV-2 Omicron BA.1 Variant in Syrian Hamster Model.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.

Climate Change Drives the Transmission and Spread of Vector-Borne Diseases: An Ecological Perspective.

Climate change affects ecosystems and human health in multiple dimensions. With the acceleration of climate change, climate-sensitive vector-borne diseases (VBDs) pose an increasing threat to public health. This paper summaries 10 publications on the impacts of climate change on ecosystems and human health; then it synthesizes the other existing literature to more broadly explain how climate change drives the transmission and spread of VBDs through an ecological perspective. We highlight the multi-dimensional nature of climate change, its interaction with other factors, and the impact of the COVID-19 pandemic on transmission and spread of VBDs, specifically including: (1) the generally nonlinear relationship of local climate (temperature, precipitation and wind) and VBD transmission, with temperature especially exhibiting an n-shape relation; (2) the time-lagged effect of regional climate phenomena (the El Niño-Southern Oscillation and North Atlantic Oscillation) on VBD transmission; (3) the u-shaped effect of extreme climate (heat waves, cold waves, floods, and droughts) on VBD spread; (4) how interactions between non-climatic (land use and human mobility) and climatic factors increase VBD transmission and spread; and (5) that the impact of the COVID-19 pandemic on climate change is debatable, and its impact on VBDs remains uncertain. By exploring the influence of climate change and non-climatic factors on VBD transmission and spread, this paper provides scientific understanding and guidance for their effective prevention and control.

Nasal irrigation efficiently attenuates SARS-CoV-2 Omicron infection, transmission and lung injury in the Syrian hamster model.

Recently, a new variant lineage of SARS-CoV-2, namely Omicron, became the dominant global circulating strain. The multiple antigenic mutations of Omicron largely decrease the efficiency of current vaccines and neutralizing antibodies, which highlights the need for more potent and reachable medical countermeasures. Here, we hypothesize that direct viral clearance by nasal irrigation might be a convenient and alternative option, and perform proof-of-concept experiments in the Syrian hamster model. Interestingly, Omicron shows a different dynamic in the changes of viral RNA, viral titers, and proinflammatory cytokines in nasal rinsing samples when compared with the prototype. Meanwhile, the levels of viral load and proinflammatory cytokines in nasal rinsing samples can indicate the severity of lung injury. Of note, daily nasal irrigation efficiently attenuates inflammation and lung injury in Omicron-infected hamsters by decreasing the viral loads in the respiratory tract organs. Moreover, daily nasal irrigation effectively suppresses viral transmission by close contact.

Infection, pathology and interferon treatment of the SARS-CoV-2 Omicron BA.1 variant in juvenile, adult and aged Syrian hamsters.

The new predominant circulating SARS-CoV-2 variant, Omicron, can robustly escape current vaccines and neutralizing antibodies. Although Omicron has been reported to have milder replication and disease manifestations than some earlier variants, its pathogenicity in different age groups has not been well elucidated. Here, we report that the SARS-CoV-2 Omicron BA.1 sublineage causes elevated infection and lung pathogenesis in juvenile and aged hamsters, with more body weight loss, respiratory tract viral burden, and lung injury in these hamsters than in adult hamsters. Juvenile hamsters show a reduced interferon response against Omicron BA.1 infection, whereas aged hamsters show excessive proinflammatory cytokine expression, delayed viral clearance, and aggravated lung injury. Early inhaled IFN-α2b treatment suppresses Omicron BA.1 infection and lung pathogenesis in juvenile and adult hamsters. Overall, the data suggest that the diverse patterns of the innate immune response affect the disease outcomes of Omicron BA.1 infection in different age groups.

The neutralizing breadth of antibodies targeting diverse conserved epitopes between SARS-CoV and SARS-CoV-2.

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2.

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.