Effect of the Timing of Amubarvimab/Romlusevimab (BRII-196/198) Administration on Progression to Severe Disease in Elderly Patients with COVID-19 Infection: A Retrospective Cohort Study

Objective Early intervention with neutralizing antibodies is considered to be effective in preventing disease progression in patients with mild to moderate COVID-19 infection. Elderly patients are the most susceptible and at a higher risk of COVID-19 infection. The present study aimed to assess the necessity and possible clinical benefits of the early administration of Amubarvimab/Romlusevimab (BRII-196/198) in the elderly population. Methods The present study was designed as a retrospective, multi-center cohort study conducted with 90 COVID-19 patients aged over 60, who were divided into two groups based on the timing of the administration of BRII-196/198 (administration at ≤ 3 days or > 3 days from the onset of infection symptoms). Results The ≤ 3 days group exhibited a greater positive effect (HR 5.94, 95% CI, 1.42–24.83;P < 0.01), with only 2 patients among 21 patients (9.52%) exhibiting disease progression, compared to the 31 patients among the 69 patients (44.93%) of the > 3 days group who exhibited disease progression. The multivariate Cox regression analysis revealed low flow oxygen support prior to BRII-196/198 administration (HR 3.53, 95% CI 1.42–8.77, P < 0.01) and PLT class (HR 3.68, 95% CI 1.37–9.91, P < 0.01) as independent predictors of disease progression. Conclusions In elderly patients with mild or moderate COVID-19 disease, who do not require oxygen support and had the risk factors for disease progression to severe COVID-19 disease, the administration of BRII-196/198 within 3 days resulted in a beneficial trend in terms of preventing disease progression.

Better therapeutic effect of oral administration of GS441524 compared with GC376.

FIP is a fatal feline disease caused by FIPV. Two drugs (GS441524 and GC376) target FIPV and have good therapeutic effect when administered by subcutaneous injection. However, subcutaneous injection has limitations compared with oral administration. Additionally, the oral efficacy of the two drugs has not been determined. Here, GS441524 and GC376 were shown to efficiently inhibit FIPV-rQS79 (recombination virus with a full-length field type I FIPV and the spike gene replaced with type II FIPV) and FIPV II (commercially available type II FIPV 79-1146) at a noncytotoxic concentration in CRFK cells. Moreover, the effective oral dose was determined via the in vivo pharmacokinetics of GS441524 and GC376. We conducted animal trials in three dosing groups and found that while GS441524 can effectively reducing the mortality of FIP subjects at a range of doses, GC376 only reducing the mortality rate at high doses. Additionally, compared with GC376, oral GS441524 has better absorption, slower clearance and a slower rate of metabolism. Furthermore, there was no significant difference between the oral and subcutaneous pharmacokinetic parameters. Collectively, our study is the first to evaluate the efficacy of oral GS441524 and GC376 using a relevant animal model. We also verified the reliability of oral GS441524 and the potential of oral GC376 as a reference for rational clinical drug use. Furthermore, the pharmacokinetic data provide insights into and potential directions for the optimization of these drugs.

Prevalence of inappropriate use of nirmatrelvir-ritonavir antiviral therapy in hospitalized patients: A multi-centre retrospective study in China.

BACKGROUND: Nirmatrelvir-ritonavir (NMVr) is a recently developed antiviral agent for treating coronavirus disease 2019 (COVID-19); however, data describing its appropriate use are scarce. This study examined the prevalence of inappropriate use of NMVr in a Chinese hospital setting. METHODS: A multi-centre retrospective chart review was performed for all hospitalized patients who received NMVr between 15 December 2022 and 15 February 2023 in four university-affiliated hospitals in Hangzhou, China. A multi-disciplinary team of experts developed the evaluation criteria. A group of senior clinical pharmacists examined and verified the suitability of NMVr prescriptions. RESULTS: In total, 247 patients received NMVr during the study period, of which 13.4% (n=31) met all the criteria for appropriate use of NMVr. The main types of inappropriate use of NMVr were delayed initiation of treatment (n=147, 59.5%), no dose adjustment for moderate renal impairment (n=46, 18.6%), use in patients with severe-to-critical COVID-19 (n=49, 19.8%), presence of contra-indicated drug‒drug interactions with other medications (n=36, 14.6%), and prescription for patients without a confirmed diagnosis of COVID-19 (n=36, 14.6%). CONCLUSIONS: The proportion of inappropriate use of NMVr was particularly high in the Chinese hospital setting, highlighting the urgent need to improve the appropriate use of NMVr.

Nirmatrelvir/ritonavir use in patients with COVID-19 on hemodialysis: a case series

Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to four patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.

Clinical Features and Blood Indicators for Severity and Prognosis in COVID-19 Patients.

BACKGROUND: This study aimed to analyze the clinical manifestations and blood indicators to deepen the understanding of Coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients admitted to C10 West Ward, Tongji Hospital in Wuhan City ("West Ward") between January 31 and March 28, 2020, were retrospectively analyzed. RESULTS: A total of 61 COVID-19 patients were hospitalized, wherein the non-critical Group had 30 cases, while the critical group had 31 (including 14 survivors and 17 deaths). Age, the proportion of fever cases, white blood cell (WBC), basophils, red blood cell (RBC), hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP), high-sensitivity troponin, pro-BNP (brain natriuretic peptide), prothrombin time (PT), and D-dimer were higher in the critical group while lymphocytes, eosinophils, albumin were lower compared with those of the non-critical group (all p < 0.05). WBC (p = 0.008), basophils (p = 0.034), and LDH (p = 0.005) of the death subgroup climbed remarkably in comparison with those of the survival subgroup. CONCLUSIONS: Advanced age, high fever, increases in indicators such as WBC, basophils, CRP, LDH, high-sensitivity troponin, pro-BNP, and D-dimer, and decreases in indicators, including lymphocytes, eosinophils, and albumin, might forebode a critical condition.

Removal Performance and Mechanism of Emerging Pollutant Chloroquine Phosphate from Water by Iron and Magnesium Co-Modified Rape Straw Biochar.

Chloroquine phosphate (CQP) is effective in treating coronavirus disease 2019 (COVID-19); thus, its usage is rapidly increasing, which may pose a potential hazard to the environment and living organisms. However, there are limited findings on the removal of CQP in water. Herein, iron and magnesium co-modified rape straw biochar (Fe/Mg-RSB) was prepared to remove CQP from the aqueous solution. The results showed that Fe and Mg co-modification enhanced the adsorption efficiency of rape straw biochar (RSB) for CQP with the maximum adsorption capacity of 42.93 mg/g (at 308 K), which was about two times higher than that of RSB. The adsorption kinetics and isotherms analysis, as well as the physicochemical characterization analysis, demonstrated that the adsorption of CQP onto Fe/Mg-RSB was caused by the synergistic effect of pore filling, π-π interaction, hydrogen bonding, surface complexation, and electrostatic interaction. In addition, although solution pH and ionic strength affected the adsorption performance of CQP, Fe/Mg-RSB still had a high adsorption capability for CQP. Column adsorption experiments revealed that the Yoon-Nelson model better described the dynamic adsorption behavior of Fe/Mg-RSB. Furthermore, Fe/Mg-RSB had the potential for repeated use. Therefore, Fe and Mg co-modified biochar could be used for the remediation of CQP from contaminated water.

Applicability of risk compensation to the relationship between health behaviors and COVID-19 vaccination among inpatients in Taizhou, China

Aim Based on the risk compensation theory, this study was designed to investigate the relationship between health behaviors of inpatients and COVID-19 vaccination during the epidemic with regard to the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taizhou, China. Subject and methods We conducted an online self-administered survey with a group of inpatients in a grade III, class A hospital in Taizhou, China, from February 27, 2022, to March 8, 2022. A total of 562 complete questionnaires were collected, and 18 questionnaires completed in under 180 seconds were rejected, leaving a total of 544 (96.8%) valid questionnaires collected. The participants who had received a COVID-19 vaccine were asked to describe the differences in their health behaviors before and after the vaccination, and the data were analyzed using SPSS Statistics version 22.0 software. Results There were significant differences in the percentage of individuals wearing masks (97.2% and 78.9%, P < 0.001) and the percentage of hand washing after taking off the mask (89.1% and 63.2%, P < 0.001) between the inoculated group and the uninoculated group;however, there were no significant differences in other health behaviors. The participants showed better health behaviors (handwashing and wearing a mask) after the vaccination than prior to it. Conclusions Our findings suggest that the Peltzman effect did not increase risk behaviors during the Omicron epidemic. There was no reduction in health behaviors among inpatients after the COVID-19 vaccine, which may have even improved their health behaviors.

Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak

Introduction The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak.

Introduction: The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods: Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results: We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion: Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

A full genome tiling array enhanced the inspection and quarantine of SARS-CoV-2.

As the worldwide spreading epidemic of SARS-CoV-2, quick inspection and quarantine of passengers for SARS-CoV-2 infection are essential for controlling the spread of SARS-CoV-2, especially the cross-border transmission. This study reports a SARS-CoV-2 genome sequencing method based on a re-sequencing tiling array successfully used in border inspection and quarantine. The tiling array chip has four cores, with one core of 240,000 probes dedicated to the whole genome sequencing of the SAR-CoV-2 genome. The assay protocol has been improved to reduce the detection time to within one day and can detect 96 samples in parallel. The detection accuracy has been validated. This fast and simple procedure is also of low cost and high accuracy, and it is particularly suitable for the rapid tracking of viral genetic variants in custom inspection applications. Combining these properties means this method has significant application potential in the clinical investigation and quarantine of SARS-CoV-2. We used this SARS-CoV-2 genome re-sequencing tiling array to inspect and quarantine China's entry and exit ports in the Zhejiang Province. From November 2020 to January 2022, we observed the gradual shift of SARS-CoV-2 variants from the D614G type to the Delta Variant, and then to the dominance of the Omicron variant recently, consistently with the global emergency pattern of the new SARS-CoV-2 variant.

Applicability of risk compensation to the relationship between health behaviors and COVID-19 vaccination among inpatients in Taizhou, China.

Aim: Based on the risk compensation theory, this study was designed to investigate the relationship between health behaviors of inpatients and COVID-19 vaccination during the epidemic with regard to the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taizhou, China. Subject and methods: We conducted an online self-administered survey with a group of inpatients in a grade III, class A hospital in Taizhou, China, from February 27, 2022, to March 8, 2022. A total of 562 complete questionnaires were collected, and 18 questionnaires completed in under 180 seconds were rejected, leaving a total of 544 (96.8%) valid questionnaires collected. The participants who had received a COVID-19 vaccine were asked to describe the differences in their health behaviors before and after the vaccination, and the data were analyzed using SPSS Statistics version 22.0 software. Results: There were significant differences in the percentage of individuals wearing masks (97.2% and 78.9%, P < 0.001) and the percentage of hand washing after taking off the mask (89.1% and 63.2%, P < 0.001) between the inoculated group and the uninoculated group; however, there were no significant differences in other health behaviors. The participants showed better health behaviors (handwashing and wearing a mask) after the vaccination than prior to it. Conclusions: Our findings suggest that the Peltzman effect did not increase risk behaviors during the Omicron epidemic. There was no reduction in health behaviors among inpatients after the COVID-19 vaccine, which may have even improved their health behaviors.

COVID-19 and Gut Injury.

COVID-19 induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic and it has led to more than 620 million patients with 6.56 million deaths globally. Males are more susceptible to COVID-19 infection and associated with a higher chance to develop severe COVID-19 than females. Aged people are at a high risk of COVID-19 infection, while young children have also increased cases. COVID-19 patients typically develop respiratory system pathologies, however symptoms in the gastrointestinal (GI) tract are also very common. Inflammatory cell recruitments and their secreted cytokines are found in the GI tract in COVID-19 patients. Microbiota changes are the key feature in COVID-19 patients with gut injury. Here, we review all current known mechanisms of COVID-19-induced gut injury, and the most acceptable one is that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) receptor on host cells in the GI tract. Interestingly, inflammatory bowel disease (IBD) is an inflammatory disorder, but the patients with IBD do not have the increased risk to develop COVID-19. There is currently no cure for COVID-19, but anti-viruses and monoclonal antibodies reduce viral load and shorten the recovery time of the disease. We summarize current therapeutics that target symptoms in the GI tract, including probiotics, ACE2 inhibitors and nutrients. These are promising therapeutic options for COVID-19-induced gut injury.

COVID-19 Vaccination as a Trigger of IgA Vasculitis: Truth or Illusion?

We read with great interest the recent article by Ramdani and colleagues in The Journal of Rheumatology on a nationwide multicenter, retrospective study conducted in France describing the status of the occurrence of IgA vasculitis (IgAV) after coronavirus disease 2019 (COVID-19) vaccination.1 We support and appreciate the authors' work and agree with their conclusions that IgA vasculitis following COVID-19 vaccination is usually benign and that a fortuitous link cannot be ruled out and now requires a worldwide pharmacovigilance study, but there are some concerns about some of the details in the article.

Surveillance of SARS-CoV-2 at the Huanan Seafood Market.

SARS-CoV-2, the causative agent of COVID-19, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases had a history of contact with the Huanan Seafood Market. Here we present the results of surveillance for SARS-CoV-2 within the market. From January 1st 2020, after closure of the market, 923 samples were collected from the environment. From 18th January, 457 samples were collected from 18 species of animals, comprising of unsold contents of refrigerators and freezers, swabs from stray animals, and the contents of a fish tank. Using RT-qPCR, SARS-CoV-2 was detected in 73 environmental samples, but none of the animal samples. Three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.99% to 100% with the human isolate HCoV-19/Wuhan/IVDC-HB-01/2019. SARS-CoV-2 lineage A (8782T and 28144C) was found in an environmental sample. RNA-seq analysis of SARS-CoV-2 positive and negative environmental samples showed an abundance of different vertebrate genera at the market. In summary, this study provides information about the distribution and prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stages of the COVID-19 outbreak.

Multilayer information spillover networks between oil shocks and banking sectors: Evidence from oil-rich countries

There is no doubt that oil price shocks significantly affect oil-producing countries' macroeconomic fundamentals and financial stability, mainly in crisis times. The recent oil price shocks, coupled with the COVID-19 pandemic, motivated us to investigate the connectedness and risk transmission among oil shocks and banking sectors in the Gulf Cooperation Council (GCC) economies from June 30, 2006, to September 9, 2021. Thus, we construct multilayer information spillover networks between oil price shocks and GCC banking sectors. The empirical results show that the Bahrain banking sector depicts the highest connectedness and risk transmission with oil price shocks on the extreme risk spillover layer. In addition, Kuwait and the United Arab Emirates are highly connected to oil demand shocks. Furthermore, we find a substantial increase in extreme risk spillover and volatility spillover layers during the COVID-19 period. The results of this paper have some important implications for regional portfolio risk management, alleviating systemic risk, and developing hedging and investment strategies.

Efficacy and safety of Reyanning mixture in patients infected with SARS-CoV-2 Omicron variant: A prospective, open-label, randomized controlled trial.

BACKGROUND: A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. STUDY DESIGN AND METHODS: This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. RESULTS: A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p = 0.012), coughing (12.2% vs. 14.8%, p = 0.046), and expectoration (6.0% vs. 8.0%, p = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. CONCLUSION: RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

BiT-MAC: Mortality prediction by bidirectional time and multi-feature attention coupled network on multivariate irregular time series.

Mortality prediction is crucial to evaluate the severity of illness and assist in improving the prognosis of patients. In clinical settings, one way is to analyze the multivariate time series (MTSs) of patients based on their medical data, such as heart rates and invasive mean arterial blood pressure. However, this suffers from sparse, irregularly sampled, and incomplete data issues. These issues can compromise the performance of follow-up MTS-based analytic applications. Plenty of existing methods try to deal with such irregular MTSs with missing values by capturing the temporal dependencies within a time series, yet in-depth research on modeling inter-MTS couplings remains rare and lacks model interpretability. To this end, we propose a bidirectional time and multi-feature attention coupled network (BiT-MAC) to capture the temporal dependencies (i.e., intra-time series coupling) and the hidden relationships among variables (i.e., inter-time series coupling) with a bidirectional recurrent neural network and multi-head attention, respectively. The resulting intra- and inter-time series coupling representations are then fused to estimate the missing values for a more robust MTS-based prediction. We evaluate BiT-MAC by applying it to the missing-data corrupted mortality prediction on two real-world clinical datasets, i.e., PhysioNet'2012 and COVID-19. Extensive experiments demonstrate the superiority of BiT-MAC over cutting-edge models, verifying the great value of the deep and hidden relations captured by MTSs. The interpretability of features is further demonstrated through a case study.

Visual Detection of COVID-19 from Materials Aspect.

Abstract: In the recent COVID-19 pandemic, World Health Organization emphasized that early detection is an effective strategy to reduce the spread of SARS-CoV-2 viruses. Several diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR) and lateral flow immunoassay (LFIA), have been applied based on the mechanism of specific recognition and binding of the probes to viruses or viral antigens. Although the remarkable progress, these methods still suffer from inadequate cellular materials or errors in the detection and sampling procedure of nasopharyngeal/oropharyngeal swab collection. Therefore, developing accurate, ultrafast, and visualized detection calls for more advanced materials and technology urgently to fight against the epidemic. In this review, we first summarize the current methodologies for SARS-CoV-2 diagnosis. Then, recent representative examples are introduced based on various output signals (e.g., colorimetric, fluorometric, electronic, acoustic). Finally, we discuss the limitations of the methods and provide our perspectives on priorities for future test development.

Effective vaccination strategy using SARS-CoV-2 spike cocktail against Omicron and other variants of concern.

The SARS-CoV-2 Omicron variant harbors more than 30 mutations in its spike (S) protein. Circulating Omicron subvariants, particularly BA5 and other variants of concern (VOCs), show increased resistance to COVID-19 vaccines that target the original S protein, calling for an urgent need for effective vaccines to prevent multiple SARS-CoV-2 VOCs. Here, we evaluated the neutralizing activity and protection conferred by a BA1-S subunit vaccine when combined with or used as booster doses after, administration of wild-type S protein (WT-S). A WT-S/BA1-S cocktail, or WT-S prime and BA1-S boost, induced significantly higher neutralizing antibodies against pseudotyped Omicron BA1, BA2, BA2.12.1, and BA5 subvariants, and similar or higher neutralizing antibodies against the original SARS-CoV-2, than the WT-S protein alone. The WT-S/BA1-S cocktail also elicited higher or significantly higher neutralizing antibodies than the WT-S-prime-BA1-S boost, WT-S alone, or BA1-S alone against pseudotyped SARS-CoV-2 Alpha, Beta, Gamma, and Delta VOCs, and SARS-CoV, a closely related beta-coronavirus using the same receptor as SARS-CoV-2 for viral entry. By contrast, WT-S or BA1-S alone failed to induce potent neutralizing antibodies against all these viruses. Similar to the WT-S-prime-BA1-S boost, the WT-S/BA1-S cocktail completely protected mice against the lethal challenge of a Delta variant with negligible weight loss. Thus, we have identified an effective vaccination strategy that elicits potent, broadly, and durable neutralizing antibodies against circulating SARS-CoV-2 Omicron subvariants, other VOCs, original SARS-CoV-2, and SARS-CoV. These results will provide useful guidance for developing efficacious vaccines that inhibit current and future SARS-CoV-2 variants to control the COVID-19 pandemic.