Efficacy and safety of acupuncture for post-COVID-19 depression: a protocol for systematic review and meta-analysis.

INTRODUCTION: Post-COVID-19 depression (PCD) is a possible sequela of COVID-19. Some doctors have used acupuncture to treat PCD, but no systematic review or meta-analysis has yet evaluated its efficacy and safety for the treatment of PCD. The aim of this systematic review is to assess the efficacy and safety of acupuncture therapy for PCD. METHODS AND ANALYSIS: Two reviewers will independently search the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (PubMed), Excerpt Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and Wan-Fang Database from inception to 24 January 2023. Study selection, data extraction and assessment of study quality will be independently performed by two reviewers. If a meta-analysis is appropriate, Review Manager V.5.3 will be used for data synthesis; otherwise, a descriptive analysis will be conducted. Data will be synthesised using a fixed-effects or random-effects model, according to the results of a heterogeneity test. The results will be presented as risk ratios with 95% CIs for dichotomous data, and weighted mean differences or standardised mean differences with 95% CIs for continuous data. ETHICS AND DISSEMINATION: The entire process used for this systematic review does not use private information, so ethical approval is not required. The results of this meta-analysis will be disseminated through publication in a peer-reviewed journal and/or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022379312.

Anxiety, depression, and sleep disturbances among people on long-term efavirenz-based treatment for HIV: a cross-sectional study in Beijing, China.

BACKGROUND: Efavirenz (EFV)-induced neuropsychiatric toxicity bothers people living with HIV (PLHIV). Neuropsychiatric adverse effects of EFV may differ by length of time on EFV-based antiretroviral treatment (ART). METHODS: A cross-sectional, single-center study was conducted at Beijing Ditan Hospital in China from June-August 2020 among ART-experienced PLHIV who were on long-term EFV-based ART. 424 eligible virological suppressed participants were enrolled and divided into four groups according to time on EFV-based ART: group A (0.5 ≤ ART < 2 year), B (2 ≤ ART < 4 year), C (4 ≤ ART < 6 year), and D (ART ≥ 6 year). The questionnaires about 12-item Short Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) were administered to assess neuropsychiatric adverse events of EFV among different groups. RESULTS: Overall mental component summary scores (MCS) of SF-12 in PLHIV was 50.2, which was lower than general population. Overall prevalence of anxiety, depression and sleep disturbances was 15.6%, 15.3% and 58%, respectively. Prevalence of anxiety, depression and sleep disturbances did not vary significantly between the time-on-ART groups. Anxiety, depression, sleep disturbances had no correlation with time on EFV-based ART or CD4+ T cells counts. CONCLUSIONS: In ART-experienced PLHIV in China, neuropsychiatric adverse events exist persistently and prevalence do not significantly change with prolonged time on EFV-based ART. The prevalence of sleep disturbances was high, suggesting that clinicians should pay more attention to long-standing psychiatric health to perform early and effective interventions.

A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry.

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

The Acceptance Behavior of Blended Learning in Secondary Vocational School Students: Based on the Modified UTAUT Model

With the COVID-19 pandemic, the importance of online learning for students and teachers in schools across the country has become more crucial than ever. Blended learning, combining online and offline learning, has gradually developed into a new normal mode in primary and secondary schools. However, the factors influencing the acceptance behavior of secondary vocational school students have been inadequately investigated and have failed to address if secondary vocational students are willing to accept this learning model. This study aimed to analyze the influential factors and measure the behavioral acceptance of blended learning. This study adopted the modified model of the unified theory of acceptance use of technology (UTAUT) to understand the behavioral acceptance of blended learning from secondary vocational school students. Multiple-item scales were established, based on validated previous measurement scales and adjusted following the characteristics of secondary vocational school students. Data from 240 valid samples were analyzed statistically, applying the partial least square structural equation modelling. The results indicated that the acceptance intention was positively influenced by students' perceptions of social influence, facilitating conditions, perceived joyfulness, self-learning management and self-efficacy. Meanwhile, performance expectancy and effort expectation were insignificant. Personal characteristics, such as gender, grade, voluntariness and experience, insignificantly adjusted the influence of all factors on the acceptance of blended learning. The conclusion of this study can provide some theoretical support and practical guidance for the improvement of blended learning quality in secondary vocational schools. The results indicated that students' perceptions of SI, FC, PJ, SM, and SE could positively anticipate the UA to accept blended learning, having a relatively strong influence from SE and PJ.

A triple-RBD-based mucosal vaccine provides broad protection against SARS-CoV-2 variants of concern.

The rapid mutation and spread of SARS-CoV-2 variants urge the development of effective mucosal vaccines to provide broad-spectrum protection against the initial infection and thereby curb the transmission potential. Here, we designed a chimeric triple-RBD immunogen, 3Ro-NC, harboring one Delta RBD and two Omicron RBDs within a novel protein scaffold. 3Ro-NC elicits potent and broad RBD-specific neutralizing immunity against SARS-CoV-2 variants of concern. Notably, intranasal immunization with 3Ro-NC plus the mucosal adjuvant KFD (3Ro-NC + KFDi.n) elicits coordinated mucosal IgA and higher neutralizing antibody specificity (closer antigenic distance) against the Omicron variant. In Omicron-challenged human ACE2 transgenic mice, 3Ro-NC + KFDi.n immunization significantly reduces the tissue pathology in the lung and lowers the viral RNA copy numbers in both the lung (85.7-fold) and the nasal turbinate (13.6-fold). Nasal virologic control is highly correlated with RBD-specific secretory IgA antibodies. Our data show that 3Ro-NC plus KFD is a promising mucosal vaccine candidate for protection against SARS-CoV-2 Omicron infection, pathology and transmission potential.

The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.

Ecological study of cave nectar bats reveals low risk of direct transmission of bat viruses to humans.

Bats are reservoirs of various viruses. The widely distributed cave nectar bat ( Eonycteris spelaea) is known to carry both filoviruses and coronaviruses. However, the potential transmission of theses bat viruses to humans is not fully understood. In this study, we tracked 16 E. spelaea bats in Mengla County, Yunnan Province, China, using miniaturized GPS devices to investigate their movements and potential contact with humans. Furthermore, to determine the prevalence of coronavirus and filovirus infections, we screened for the nucleic acids of the Menglà virus (MLAV) and two coronaviruses (GCCDC1-CoV and HKU9-CoV) in anal swab samples taken from bats and for antibodies against these viruses in human serum samples. None of the serum samples were found to contain antibodies against the bat viruses. The GPS tracking results showed that the bats did not fly during the daytime and rarely flew to residential areas. The foraging range of individual bats also varied, with a mean cumulative nightly flight distance of 25.50 km and flight speed of up to 57.4 km/h. Taken together, these results suggest that the risk of direct transmission of GCCDC1-CoV, HKU9-CoV, and MLAV from E. spelaea bats to humans is very low under natural conditions.

Single-Cell Landscape of Lungs Reveals Key Role of Neutrophil-Mediated Immunopathology during Lethal SARS-CoV-2 Infection.

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.

Inactivated SARS-CoV-2 Vaccine Shows Cross-Protection against Bat SARS-Related Coronaviruses in Human ACE2 Transgenic Mice.

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.

ACE2-independent infection of T lymphocytes by SARS-CoV-2.

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

Characteristics of SARS-CoV-2 transmission in a medium-sized city with traditional communities during the early COVID-19 epidemic in China.

The nationwide COVID-19 epidemic ended in 2020, a few months after its outbreak in Wuhan, China at the end of 2019. Most COVID-19 cases occurred in Hubei Province, with a few local outbreaks in other provinces of China. A few studies have reported the early SARS-CoV-2 epidemics in several large cities or provinces of China. However, information regarding the early epidemics in small and medium-sized cities, where there are still traditionally large families and community culture is more strongly maintained and thus, transmission profiles may differ, is limited. In this study, we characterized 60 newly sequenced SARS-CoV-2 genomes from Anyang as a representative of small and medium-sized Chinese cities, compared them with more than 400 reference genomes from the early outbreak, and studied the SARS-CoV-2 transmission profiles. Genomic epidemiology revealed multiple SARS-CoV-2 introductions in Anyang and a large-scale expansion of the epidemic because of the large family size. Moreover, our study revealed two transmission patterns in a single outbreak, which were attributed to different social activities. We observed the complete dynamic process of single-nucleotide polymorphism development during community transmission and found that intrahost variant analysis was an effective approach to studying cluster infections. In summary, our study provided new SARS-CoV-2 transmission profiles representative of small and medium-sized Chinese cities as well as information on the evolution of SARS-CoV-2 strains during the early COVID-19 epidemic in China.

Antibody-Dependent Enhancement of SARS-CoV-2 Infection of Human Immune Cells: In Vitro Assessment Provides Insight in COVID-19 Pathogenesis.

Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.

COVID-19 Vaccination in People Living with HIV (PLWH) in China: A Cross Sectional Study of Vaccine Hesitancy, Safety, and Immunogenicity.

The administration of COVID-19 vaccines is the primary strategy used to prevent further infections by COVID-19, especially in people living with HIV (PLWH), who are at increased risk for severe symptoms and mortality. However, the vaccine hesitancy, safety, and immunogenicity of COVID-19 vaccines among PLWH have not been fully characterized. We estimated vaccine hesitancy and status of COVID-19 vaccination in Chinese PLWH, explored the safety and impact on antiviral therapy (ART) efficacy and compared the immunogenicity of an inactivated vaccine between PLWH and healthy controls (HC). In total, 27.5% (104/378) of PLWH hesitated to take the vaccine. The barriers included concerns about safety and efficacy, and physician counselling might help patients overcome this vaccine hesitancy. A COVID-19 vaccination did not cause severe side effects and had no negative impact on CD4+ T cell counts and HIV RNA viral load. Comparable spike receptor binding domain IgG titer were elicited in PLWH and HC after a second dose of the CoronaVac vaccine, but antibody responses were lower in poor immunological responders (CD4+ T cell counts < 350 cells/µL) compared with immunological responders (CD4+ T cell counts ≥ 350 cells/µL). These data showed that PLWH have comparable safety and immune response following inactivated COVID-19 vaccination compared with HC, but the poor immunological response in PLWH is associated with impaired humoral response.

Genomic Characterization of Diverse Bat Coronavirus HKU10 in Hipposideros Bats.

Bats have been identified as natural reservoirs of a variety of coronaviruses. They harbor at least 19 of the 33 defined species of alpha- and betacoronaviruses. Previously, the bat coronavirus HKU10 was found in two bat species of different suborders, Rousettus leschenaultia and Hipposideros pomona, in south China. However, its geographic distribution and evolution history are not fully investigated. Here, we screened this viral species by a nested reverse transcriptase PCR in our archived samples collected over 10 years from 25 provinces of China and one province of Laos. From 8004 bat fecal samples, 26 were found to be positive for bat coronavirus HKU10 (BtCoV HKU10). New habitats of BtCoV HKU10 were found in the Yunnan, Guangxi, and Hainan Provinces of China, and Louang Namtha Province in Laos. In addition to H. pomona, BtCoV HKU10 variants were found circulating in Aselliscus stoliczkanus and Hipposideros larvatus. We sequenced full-length genomes of 17 newly discovered BtCoV HKU10 strains and compared them with previously published sequences. Our results revealed a much higher genetic diversity of BtCoV HKU10, particularly in spike genes and accessory genes. Besides the two previously reported lineages, we found six novel lineages in their new habitats, three of which were located in Yunnan province. The genotypes of these viruses are closely related to sampling locations based on polyproteins, and correlated to bat species based on spike genes. Combining phylogenetic analysis, selective pressure, and molecular-clock calculation, we demonstrated that Yunnan bats harbor a gene pool of BtCoV HKU10, with H. pomona as a natural reservoir. The cell tropism test using spike-pseudotyped lentivirus system showed that BtCoV HKU10 could enter cells from human and bat, suggesting a potential interspecies spillover. Continuous studies on these bat coronaviruses will expand our understanding of the evolution and genetic diversity of coronaviruses, and provide a prewarning of potential zoonotic diseases from bats.

Discovery of Bat Coronaviruses through Surveillance and Probe Capture-Based Next-Generation Sequencing.

Coronaviruses (CoVs) of bat origin have caused two pandemics in this century. Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV both originated from bats, and it is highly likely that bat coronaviruses will cause future outbreaks. Active surveillance is both urgent and essential to predict and mitigate the emergence of these viruses in humans. Next-generation sequencing (NGS) is currently the preferred methodology for virus discovery to ensure unbiased sequencing of bat CoVs, considering their high genetic diversity. However, unbiased NGS is an expensive methodology and is prone to missing low-abundance CoV sequences due to the high background level of nonviral sequences present in surveillance field samples. Here, we employ a capture-based NGS approach using baits targeting most of the CoV species. Using this technology, we effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.IMPORTANCE Active surveillance is both urgent and essential to predict and mitigate the emergence of bat-origin CoV in humans and livestock. However, great genetic diversity increases the chance of homologous recombination among CoVs. Performing targeted PCR, a common practice for many surveillance studies, would not reflect this diversity. NGS, on the other hand, is an expensive methodology and is prone to missing low-abundance CoV sequences. Here, we employ a capture-based NGS approach using baits targeting all CoVs. Our work demonstrates that targeted, cost-effective, large-scale, genome-level surveillance of bat CoVs is now highly feasible.