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The SARS-CoV-2 Omicron variant is characterized by its high transmissibility, which has caused a worldwide epidemiological event. Yet, it turns ominous once the disease progression degenerates into severe pneumonia and sepsis, presenting a horrendous lethality. To elucidate the alveolar immune or inflammatory landscapes of Omicron critical-ill patients, we performed single-cell RNA-sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) from the patients with critical pneumonia caused by Omicron infection, and analyzed the correlation between the clinical severity scores and different immune cell subpopulations. In the BALF of Omicron critical patients, the alveolar violent myeloid inflammatory environment was determined. ISG15 + neutrophils and CXCL10 + macrophages, both expressed the interferon-stimulated genes (ISGs), were negatively correlated with clinical pulmonary infection score, while septic CST7 + neutrophils and inflammatory VCAN + macrophages were positively correlated with sequential organ failure assessment. The percentages of ISG15 + neutrophils were associated with more protective alveolar epithelial cells, and may reshape CD4 + T cells to the exhaustive phenotype, thus preventing immune injuries. The CXCL10 + macrophages may promote plasmablast/plasma cell survival and activation as well as the production of specific antibodies. As compared to the previous BALF scRNA-seq data from SARS-CoV-2 wild-type/Alpha critical patients, the subsets of neutrophils and macrophages with pro-inflammatory and immunoregulatory features presented obvious distinctions, suggesting an immune disparity in Omicron variants. Overall, this study provides a BALF single-cell atlas of Omicron critical patients, and suggests that alveolar interferon-responsive neutrophils and macrophages may extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis., (© 2024 Wiley Periodicals LLC.)

Abstract: COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The immune dysregulation associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) severity was investigated through single-cell RNA sequencing (scRNA-seq) of 5 peripheral blood samples from 3 patients with moderate and severe CRKP pneumonia. Additionally, scRNA-seq datasets from two individuals with COVID-19 were included for comparative analysis. The dynamic characterization and functional properties of each immune cell type were examined by delineating the transcriptional profiles of immune cells throughout the transition from moderate to severe conditions. Overall, most immune cells in CRKP patients exhibited a robust interferon-α response and inflammatory reaction compared to healthy controls, mirroring observations in COVID-19 patients. Furthermore, cell signatures associated with NK cells, macrophages, and monocytes were identified in CRKP progression including PTPRCAP for NK cells, C1QB for macrophages, and S100A12 for both macrophages and monocytes. In summary, this study offers a comprehensive scRNA-seq resource for illustrating the dynamic immune response patterns during CRKP progression, thereby shedding light on the associations between CRKP and COVID-19., Competing Interests: Declaration of competing interest All authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since the outbreak of corona virus disease 2019 (COVID-19), this pandemic has caused severe death and infection worldwide. Owing to its strong infectivity, long incubation period, and nonspecific symptoms, the early diagnosis is essential to reduce risk of the severe illness. The electrochemical biosensor, as a fast and sensitive technique for quantitative analysis of body fluids, has been widely studied to diagnose different biomarkers caused at different infective stages of COVID-19 virus (SARS-CoV-2). Recently, many reports have proved that nanomaterials with special architectures and size effects can effectively promote the biosensing performance on the COVID-19 diagnosis, there are few comprehensive summary reports yet. Therefore, in this review, we will pay efforts on recent progress of advanced nanomaterials-facilitated electrochemical biosensors for the COVID-19 detections. The process of SARS-CoV-2 infection in humans will be briefly described, as well as summarizing the types of sensors that should be designed for different infection processes. Emphasis will be supplied to various functional nanomaterials which dominate the biosensing performance for comparison, expecting to provide a rational guidance on the material selection of biosensor construction for people. Finally, we will conclude the perspective on the design of superior nanomaterials-based biosensors facing the unknown virus in future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This hemodialysis center experienced the pandemic from December 2022 to January 2023. Therefore, we sought to describe the clinical characteristics and mortality outcomes in hemodialysis patients during this Omicron surge., Methods: According to whether they are infected, they are divided into two groups: SARS-CoV-2-positive and SARS-CoV-2-negative. The SARS-CoV-2-positive group was divided into a survival group and a non-survival group for comparison., Results: 366 of 457 hemodialysis patients were infected with SARS-CoV-2. The most common symptoms observed were fever (43.2%) and cough (29.8%), Followed by diarrhea (1.4%). Hemodialysis patients with hypertension were more susceptible to SARS-CoV-2 infection. The lymphocyte count, serum creatinine, serum potassium, and serum phosphorus in the SARS-CoV-2-positive group were significantly lower than those in the SARS-CoV-2-negative group. The all-cause mortality rate for infection with SARS-CoV-2 was 5.2%. Only 7 of 366 SARS-CoV-2-positive patients were admitted to the intensive care unit, but 6 of them died. Intensive care unit hospitalization rates were significantly higher in the non-survival group compared with the survival group. White blood cells count, neutrophil count, C-reactive protein, AST, and D-dimer in the non-survival group were higher than those in the survival group. The lymphocyte count, hemoglobin concentration, serum creatinine, serum albumin, serum phosphorus and parathyroid hormone in the non-survival group were lower than those in the survival group. Age > 65 years, elevated C-reactive protein and AST are independent risk factors for death. Finally, no significant difference in vaccination status was found between the SARS-CoV-2-positive group and the negative group., Conclusions: Hemodialysis patients are at high risk for SARS-CoV-2 infection. Ensuring the adequacy of hemodialysis treatment and maintaining good physical condition of patients are the top priorities., (© 2024. The Author(s).)

Introduction: Despite the extensive neurological symptoms induced by COVID-19 and the identification of SARS-CoV-2 in post-mortem brain samples from COVID-19 patients months after death, the precise mechanisms of SARS-CoV-2 invasion into the central nervous system remain unclear due to the lack of research models., Methods: We collected glioma tissue samples from glioma patients who had a recent history of COVID-19 and examined the presence of the SARS-CoV-2 spike protein. Subsequently, spatial transcriptomic analyses were conducted on normal brain tissues, glioma tissues, and glioma tissues from glioma patients with recent COVID-19 history. Additionally, single-cell sequencing data from both glioma tissues and glioma organoids were collected and analyzed. Glioma organoids were utilized to evaluate the efficacy of potential COVID-19 blocking agents., Results: Glioma tissues from glioma patients with recent COVID-19 history exhibited the presence of the SARS-CoV-2 spike protein. Differences between glioma tissues from glioma patients who had a recent history of COVID-19 and healthy brain tissues primarily manifested in neuronal cells. Notably, neuronal cells within glioma tissues of COVID-19 history demonstrated heightened susceptibility to Alzheimer's disease, depression, and synaptic dysfunction, indicative of neuronal aberrations. Expressions of SARS-CoV-2 entry factors were confirmed in both glioma tissues and glioma organoids. Moreover, glioma organoids were susceptible to pseudo-SARS-CoV-2 infection and the infections could be partly blocked by the potential COVID-19 drugs., Conclusions: Gliomas had inherent traits that render them susceptible to SARS-CoV-2 infection, leading to their representability of COVID-19 neurological symptoms. This established a biological foundation for the rationality and feasibility of utilization of glioma organoids as research and blocking drug testing model in SARS-CoV-2 infection within the central nervous system., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS-CoV-2 spike (S) protein-conjugated nanoparticles (NPs) in combination with cyclic GMP-AMP (cGAMP) (S-NPs-cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S-NPs-cGAMP group exhibits a 16-fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S-NPs-cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus-specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3 + CD4 + and CD3 + CD8 + T lymphocytes, as well as B220 + CD19 + and CD3 - CD49b + NK lymphocytes, show an upward trend, indicating a positive cellular immune response. Moreover, the S-NPs-cGAMP demonstrates promising results against the Delta strain and exhibits good cross-neutralization potential against other variants. These findings suggest that pDMDAAC NPs is potential adjuvant and could serve as a versatile platform for future vaccine development., (© 2024 Wiley‐VCH GmbH.)

Objective: Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China., Methods: GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively., Results: The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P < 0.001). More COVID-GBS patients (11/13) presented AIDP subtype than non-COVID-GBS cases (10/27, P = 0.003). The mean interval between onset of infective symptoms and GBS was longer in COVID-GBS (21.54 ± 11.56 days) than in non-COVID-GBS (5.76 ± 3.18 days, P < 0.001)., Conclusions: COVID-19 significantly increased the incidence of GBS. Most COVID-GBS patients fell into the category of AIDP, responded well to IVIg, and had a favorable prognosis., (© 2024. The Author(s).)

Since the COVID-19 outbreak, raccoon dogs have been suggested as a potential intermediary in transmitting SARS-CoV-2 to humans. To understand their role in the COVID-19 pandemic and the species barrier for SARS-CoV-2 transmission to humans, we analyzed how their ACE2 protein interacts with SARS-CoV-2 spike protein. Biochemical data showed that raccoon dog ACE2 is an effective receptor for SARS-CoV-2 spike protein, though not as effective as human ACE2. Structural comparisons highlighted differences in the virus-binding residues of raccoon dog ACE2 compared to human ACE2 (L24Q, Y34H, E38D, T82M, R353K), explaining their varied effectiveness as receptors for SARS-CoV-2. These variations contribute to the species barrier that exists between raccoon dogs and humans regarding SARS-CoV-2 transmission. Identifying these barriers can help assess the susceptibility of other mammals to SARS-CoV-2. Our research underscores the potential of raccoon dogs as SARS-CoV-2 carriers and identifies molecular barriers that affect the virus's ability to jump between species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hsueh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The COVID-19 pandemic, together with the subsequent social distancing measures, could lead to shifts in family and fertility planning. This study aimed to explore the associations between the COVID-19 pandemic and changes in fertility intentions among an international sample of reproductive-aged women., Methods: A multi-country, cross-sectional study based on data from 10 672 women aged 18-49 years who participated in the International Sexual Health And REproductive Health (I-SHARE) study, which organised an international online survey between July 2020 and February 2021. Factors associated with changes in fertility intentions were explored using multinomial probit regression models. Cluster-robust standard errors were used to calculate model parameters., Results: Of 10 672 included reproductive-aged women, 14.4% reported changing their fertility intentions due to the pandemic, with 10.2% postponement and 4.2% acceleration. Women who had ever been isolated/quarantined were more likely to postpone their fertility intentions (adjusted odds ratio (AOR)=1.41; 95% CI 1.18 to 1.69) compared with those who had not; women who lived with a steady partner were more likely to want children sooner (AOR=1.57; 95% CI 1.10 to 2.23) compared with those who did not; and those who reported a higher frequency of getting angry, feeling frustrated, or worrying about their finances were more likely to postpone their fertility intentions. The main findings were robust in the sensitivity analyses., Conclusions: Most women who changed fertility intentions because of the pandemic have postponed intentions to expand their families. The pandemic-induced exposures were associated with these postponements., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

We analyzed the characteristics, risk factors, outcomes, and post-coronavirus disease 2019 (COVID-19) symptoms in liver transplant recipients in China's late 2022 COVID-19 wave. Recipients with COVID-19 were enrolled from December 1, 2022, to January 31, 2023, and followed up until May 31, 2023. Baseline and characteristic data were collected. A total of 930 recipients were included, with a vaccination rate (non-mRNA) of 40.0%. Among 726 (78.1%) recipients with COVID-19, 641 (88.3%) patients were treated at home, 81 (11.2%) patients required hospitalization in general wards, 4 (0.6%) patients required intensive care, and 1 (0.1%) patient died because of COVID-19. Severe acute respiratory syndrome coronavirus 2 infection was related to close contact with confirmed cases (P < .001) and the condition of end-stage kidney disease (P < .046). Older age, male sex, less vaccination, and hypertension were independent risk factors for hospitalization. Fatigue (36.9%) was the most common symptom post-COVID-19, followed by memory loss (35.7%) and sleep disturbance (23.9%). Two doses of vaccines had a protective effect against these post-COVID-19 symptoms (P < .05). During this Omicron outbreak, liver transplant recipients were susceptible to COVID-19, with frequent hospitalization but low mortality. Two doses of non-mRNA COVID-19 vaccines could protect against liver transplant recipient hospitalization and post-COVID-19 symptoms., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2β1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2β1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Veterans may be especially susceptible to increased alcohol consumption following the COVID-19 pandemic. We aim to evaluate trends in alcohol use among US Veterans prior to, during, and following the onset of the COVID-19 pandemic., Methods: All US Veterans utilizing Veterans Affairs health care facilities in the United States from March 1, 2018 to February 28, 2023 with ≥1 AUDIT-C score were categorized into 1) No alcohol use (AUDIT-C = 0), 2) Low-risk alcohol use (AUDIT-C 1-2 for women, 1-3 for men), and 3) High-risk alcohol use (AUDIT-C ≥ 3 for women, ≥ 4 for men). Trends in the proportion of Veterans reporting high-risk alcohol use, stratified by sex, age, race/ethnicity, and urbanicity were evaluated., Results: Among a cohort of 2.15 to 2.60 million Veterans, 15.5% reported high-risk alcohol use during March 2018-February 2019, which decreased to 14.6% during the first year of the pandemic, increased to 15.2% in the second year, and then decreased to 14.9% from March 2022-February 2023. Among non-Hispanic whites, African Americans, Asians, and Hispanics, the proportion of women reporting high-risk alcohol use surpassed that of men during the onset of the pandemic and beyond. The greatest proportion of high-risk alcohol use was observed among young Veterans ages 18-39 years (17%-27%), which was consistent across all race/ethnic groups., Conclusions: High-risk alcohol use among US Veterans has increased since the COVID-19 pandemic onset, and in the third year following pandemic onset, 15% of Veterans overall and over 20% of young Veterans ages 18-39 years reported high-risk alcohol use., (Published by Elsevier Inc.)

Introduction: Guillain-Barré syndrome (GBS) is a group of acute immune-mediated disorders in the peripheral nervous system. Both infectious and noninfectious factors are associated with GBS, which may act as triggers of autoimmune responses leading to neural damage and dysfunction., Areas Covered: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines as well as flaviviruses have been associated with GBS, although a robust conclusion has yet to be reached. Immunomodulatory treatments, including intravenous immunoglobulins (IVIg) and plasma exchange (PE), have long been the first-line therapies for GBS. Depending on GBS subtype and severity at initial presentation, the efficacy of IVIg and PE can be variable. Several new therapies showing benefits to experimental animals merit further investigation before translation into clinical practice. We review the state-of-the-art knowledge on the immunopathogenesis of GBS in the context of coronavirus disease 2019 (COVID-19). Immunomodulatory therapies in GBS, including IVIg, PE, corticosteroids, and potential therapies, are summarized., Expert Opinion: The association with SARS-CoV-2 remains uncertain, with geographical differences that are difficult to explain. Evidence and guidelines are lacking for the decision-making of initiating immunomodulatory therapies in mildly affected patients or patients with regional subtypes of GBS.

Background: It is unclear about the mutual impact of COVID-19 related psychological stress and infection on mental health of adolescent and youth students. This study aimed to explore the mutual impact of COVID-19 related psychological stress and infection on mental health problems among students., Methods: This study was conducted from December 14, 2022 to February 28, 2023 in Sichuan, China. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, PTSD Checklist for DSM-5, Insomnia Severity Index, and Internet Addiction Test were used. Participants were grouped by COVID-19 infection and psychological stress level. The differences among groups were compared, and logistic regression analysis was used to investigate risk factors for depression, anxiety, PTSD and insomnia among groups., Results: Of 90,118 participants, 82,873 (92.0 %) finished the questionnaires and were included in the study. Of 82,873 participants, 33,314 (40.2 %) reported to be infected with COVID-19. Participants had depression symptoms (38.1 %), anxiety symptoms (31.8 %), PTSD (33.9 %), insomnia (34.0 %), and internet addiction (60.3 %). Compared with participants uninfected with low psychological stress level, the risk for symptoms of depression, anxiety, PTSD and insomnia increased by 9.6 %, 12.3 %, 6.6 %, and 12.0 % in participants infected with low psychological stress level (p < 0.001), 106.8 %, 125.9 %, 125.2 %, and 95.7 % in participants uninfected with high psychological stress level (p < 0.001), and 147.3 %, 161.1 %, 158.7 %, and 141.0 % in participants infected with high psychological stress level (p < 0.001)., Limitation: This study is a cross-sectional design, and no causal associations should be inferred. Infection status was based on self-report of participants with infectious symptoms., Conclusion: COVID-19 related psychological stress and infection per se have mutually overlapping impacts on mental health problems among students. Further health policies and psychosocial interventions should be developed to reduce mutually overlapping impact and improve the long-term mental health among students., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A lack of health resources is a common problem after the outbreak of infectious diseases, and resource optimization is an important means to solve the lack of prevention and control capacity caused by resource constraints. This study systematically evaluated the similarities and differences in the application of coronavirus disease (COVID-19) resource allocation models and analyzed the effects of different optimal resource allocations on epidemic control., Methods: A systematic literature search was conducted of CNKI, WanFang, VIP, CBD, PubMed, Web of Science, Scopus and Embase for articles published from January 1, 2019, through November 23, 2023. Two reviewers independently evaluated the quality of the included studies, extracted and cross-checked the data. Moreover, publication bias and sensitivity analysis were evaluated., Results: A total of 22 articles were included for systematic review; in the application of optimal allocation models, 59.09% of the studies used propagation dynamics models to simulate the allocation of various resources, and some scholars also used mathematical optimization functions (36.36%) and machine learning algorithms (31.82%) to solve the problem of resource allocation; the results of the systematic review show that differential equation modeling was more considered when testing resources optimization, the optimization function or machine learning algorithm were mostly used to optimize the bed resources; the meta-analysis results showed that the epidemic trend was obviously effectively controlled through the optimal allocation of resources, and the average control efficiency was 0.38(95%CI 0.25-0.51); Subgroup analysis revealed that the average control efficiency from high to low was health specialists 0.48(95%CI 0.37-0.59), vaccines 0.47(95%CI 0.11-0.82), testing 0.38(95%CI 0.19-0.57), personal protective equipment (PPE) 0.38(95%CI 0.06-0.70), beds 0.34(95%CI 0.14-0.53), medicines and equipment for treatment 0.32(95%CI 0.12-0.51); Funnel plots and Egger's test showed no publication bias, and sensitivity analysis suggested robust results., Conclusion: When the data are insufficient and the simulation time is short, the researchers mostly use the constructor for research; When the data are relatively sufficient and the simulation time is long, researchers choose differential equations or machine learning algorithms for research. In addition, our study showed that control efficiency is an important indicator to evaluate the effectiveness of epidemic prevention and control. Through the optimization of medical staff and vaccine allocation, greater prevention and control effects can be achieved., (© 2024. The Author(s).)

Background: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19., Objective: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China., Methods: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023., Results: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94)., Conclusions: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough., (©Tingting Xu, Yuehan Chen, Wenzhi Zhan, Kian Fan Chung, Zhongmin Qiu, Kewu Huang, Ruchong Chen, Jiaxing Xie, Gang Wang, Min Zhang, Xuefen Wang, Hongmei Yao, Xiuqing Liao, Yunhui Zhang, Guojun Zhang, Wei Zhang, Dejun Sun, Jia Zhu, Shujuan Jiang, Juntao Feng, Jianping Zhao, Gengyun Sun, Huaqiong Huang, Jianyong Zhang, Lingwei Wang, Feng Wu, Suyun Li, Pusheng Xu, Chunhua Chi, Ping Chen, Mei Jiang, Wen He, Lianrong Huang, Wei Luo, Shiyue Li, Nanshan Zhong, Kefang Lai, China Cough Coalition. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 05.02.2024.)

To analyze the post-COVID-19 construction and management of fever clinics targeted to prevention and control of healthcare-associated respiratory viral infections in medical institutions at all levels in China, and to provide a basis for promoting their standardized construction, we conducted this survey on the construction of fever clinics in 429 medical institutions of Jiangsu Province from July to December 2020. Contents of the questionnaire included the general situation of medical institutions, the construction status and future construction plans of fever clinics. We find the construction rate of fever clinic in medical institutions of Jiangsu province was 75.3%. All construction indicators, quality management systems and processes fail to fully meet the requirements of documents and standards. Jiangsu province actively promotes the construction of fever clinic layout, but there is still a gap with the construction standard. As a result, it is necessary to further promote standardized construction of fever clinic, and necessary financial input should be increased to expand all constructions of fever clinic in primary medical institutions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19., Methods: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed., Findings: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients)., Interpretation: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns., Funding: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JM, BX, and KZ are employees of Shanghai Junshi Biosciences. Shanghai JunTop Biosciences is an affiliated company of Shanghai Junshi Biosciences; Shanghai Vinnerna Biosciences, the sponsor of this study, is the subsidiary of Shanghai JunTop Biosciences and Vigonvita Life Sciences. All aspects of this study were done by Shanghai Junshi Biosciences. The remaining authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

COVID-19 patients commonly present with signs of central nervous system and/or peripheral nervous system dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection of DA neurons triggers an inflammatory and cellular senescence response. High-throughput screening in hPSC-derived DA neurons identified several FDA-approved drugs that can rescue the cellular senescence phenotype by preventing SARS-CoV-2 infection. We also identified the inflammatory and cellular senescence signature and low levels of SARS-CoV-2 transcripts in human substantia nigra tissue of COVID-19 patients. Furthermore, we observed reduced numbers of neuromelanin+ and tyrosine-hydroxylase (TH)+ DA neurons and fibers in a cohort of severe COVID-19 patients. Our findings demonstrate that hPSC-derived DA neurons are susceptible to SARS-CoV-2, identify candidate neuroprotective drugs for COVID-19 patients, and suggest the need for careful, long-term monitoring of neurological problems in COVID-19 patients., Competing Interests: Declaration of interests R.E.S. is on the scientific advisory board of Miromatrix Inc. and Lime Therapeutics Inc. and is a paid consultant and speaker for Alnylam Inc. L.S. is a scientific cofounder and paid consultant of BlueRock Therapeutics Inc. and a co-founder of DaCapo Brainscience Inc. S.C. is the co-founder of OncoBeat, LLC and a paid consultant of Vesalius Therapeutics., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) continues to impact global public health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become less virulent as it mutates, prompting China to ease restrictions at the end of 2022. With the complete reopening, a surge in COVID-19 cases has ensued. Therefore, we conducted a study to explore the correlation between plasma antibody levels and baseline conditions or clinical outcomes in severe and critical patients. We collected the basic information of 79 included patients. Enzyme-linked immunosorbent assay (ELISA) tests were performed on plasma samples. The receptor-binding domain (RBD) IgG antibody level of the mild group was significantly higher than that of the severe/critical group (P = 0.00049). And in the severe/critical group, there existed an association between plasma antibody levels and age (P < 0.001, r = - 0.471), as well as plasma antibody levels and vaccination status (P = 0.00147, eta 2  = 0.211). Besides, the level of plasma antibody seemed to be moderately correlated with the age, indicating the need for heightened attention to infections in the elderly. And plasma antibody levels were strongly associated with vaccination status in the severe/critical patients., (© 2024. The Author(s).)

To investigate the interannual evolution of air pollution in summer and the impact of the COVID-19 lockdown on local pollution in Chengdu, China, single aerosol particles were continuously measured in three summer periods: the regular period in 2020 (RP2020); the regular period in 2022 (RP2022); and the lockdown period in 2022 (LP2022). It was found that, from RP2020 to RP2022, the mass concentrations of PM 2.5 , PM 10 , SO 2 and NO 2 decreased by 25.6 %, 24.7 %, 28.8 % and 38.5 %, respectively, while the concentration of O 3 increased by 11.0 %. Affected by regional transport, there was no significant decrease in the concentrations of various pollutants during LP2022. All single aerosol particles could be classified into seven categories: vehicle emissions (VE), dust, biomass burning (BB), coal combustion (CC), K mixed with sulfate (KSO 4 ), K mixed with nitrate (KNO 3 ) and K mixed with sulfate and nitrate (KSN) particles. From RP2020 to RP2022, the contributions of BB and CC particles decreased by 12.1 % and 0.9 %, respectively, while VE and dust particles increased by 3.6 % and 2.5 %, respectively; and compared to RP2022, the contributions of VE, dust and CC particles in LP2022 decreased by 22.2 %, 11.0 % and 12.7 %, respectively. The high PM 2.5 pollution events in RP2020 and RP2022 were mainly caused by combustion sources (BB and CC, 51.6 %) and VE (38.3 %) particles, respectively, while the pollution event in LP2022 was contributed by BB (27.0 %) and secondary inorganic (KSO 4 , KNO 3 and KSN, 60.2 %) particles. The formation mechanisms of different pollution events were further validated by WRF-Chem results. Although the potential source areas of particles showed a shrinking trend from RP2020 to RP2022, regional transport still caused high PM 2.5 pollution events during LP2022. Photochemical processes dominated the formation of KSO 4 particles, while the KNO 3 and KSN particles were mainly generated by liquid-phase reactions, and this effect increased year by year., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen., Competing Interests: Declaration of Competing Interest Yang Yang, Shao-Ping Peng, Yu-Mei Yang, Pan Shu, Pei-Jin Li, Shan Li, Hong-Lin Hu and Ren-Hong Tang are employees of Jiangsu Simcere Pharmaceutical Co., Ltd. Yan Xu is employee of Simcere of America. Other authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Immense attention has been given to the outcome of COVID-19 infection. However, comprehensive studies based on large populational cohort with long-term follow-up are still lacking. This study aimed to investigate the risk of various short-term comorbidities (within one month) and long-term sequelae (above one month) after COVID-19 infection., Methods: In this large prospective cohort study with 14 months follow-up information based on UK biobank, we included 16,776 COVID-19-positive participants and 58,281 COVID-19-negative participants matched for comparison. The risk of each comorbidity and sequela was evaluated by multivariable logistic regression analysis and presented as hazard ratio (HR) and 95% confidence interval (95% CI)., Results: COVID-19-positive individuals had a higher risk of 47 types of comorbidities within one month following COVID-19 infection, especially those who were older, male, overweight/obese, ever-smoked, with more pre-existing comorbidities and hospitalized. About 70.37% of COVID-19 patients with comorbidities had more than one co-occurring comorbidities. Additionally, only 6 high-risk sequelae were observed after one month of COVID-19 infection, and the incidence was relatively low (< 1%)., Conclusion: In addition to long-term sequelae following COVID-19 infection, plenty of comorbidities were observed, especially in patients with older age, male gender, overweight/obese, more pre-existing comorbidities and severe COVID-19, indicating that more attention should be given to these susceptible persons within this period., (© 2023. The Author(s).)

Introduction: In the middle of December 2022, the Chinese government adjusted the lockdown policy on coronavirus disease 2019 (COVID-19), a large number of infected patients flooded into the emergency department. The emergency medical staff encountered significant working and mental stress while fighting the COVID-19 pandemic. We aimed to investigate the workload change, and the prevalence and associated factors for depression symptoms among emergency medical staff after the policy adjustment., Methods: We conducted a cross-sectional online survey of emergency medical staff who fought against COVID-19 in Shandong Province during January 16 to 31, 2023. The respondents' sociodemographic and work information were collected, and they were asked to complete the 9-item Patient Health Questionnaire (PHQ-9) then. Univariate and multivariate logistic regression analyses were applied to identify the potential associated factors for major depression., Results: Nine hundred and sixteen emergency medical personnel from 108 hospitals responded to this survey. The respondents' weekly working hours (53.65 ± 17.36 vs 49.68 ± 14.84) and monthly night shifts (7.25 ± 3.85 vs 6.80 ± 3.77) increased after the open policy. About 54.3% of the respondents scored more than 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. In univariate analysis, being doctors, living with family members aged ≤16 or ≥ 65 years old, COVID-19 infection and increased weekly working hours after the open policy were significantly associated with a PHQ-9 score ≥ 10 points. In the multivariate analysis, only increased weekly working hours showed significant association with scoring ≥10 points., Conclusion: Emergency medical staff' workload had increased after the open policy announcement, which was strongly associated with a higher PHQ-9 scores, indicating a very high risk for major depression. Emergency medical staff working as doctors or with an intermediate title from grade-A tertiary hospitals had higher PHQ-9 scores, while COVID-19 infection and weekly working hours of 60 or more after the open policy were associated with higher PHQ-9 scores for those from grade-B tertiary hospitals. Hospital administrators should reinforce the importance of targeted emergency medical staff support during future outbreaks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Feng, Bian, Zhang, Meng, Gong, Ma, Su, Zhou, Xu, Zhang, Zhang, Zhou and Shang.)

The main proteases (M pro ) are highly conserved cysteine-rich proteins that can be covalently modified by numerous natural and synthetic compounds. Herein, we constructed an integrative approach to efficiently discover covalent inhibitors of M pro from complex herbal matrices. This work begins with biological screening of 60 clinically used antiviral herbal medicines, among which Lonicera japonica Flos (LJF) demonstrated the strongest anti-M pro effect (IC 50  = 37.82 μg/mL). Mass spectrometry (MS)-based chemical analysis and chemoproteomic profiling revealed that LJF extract contains at least 50 constituents, of which 22 exhibited the capability to covalently modify M pro . We subsequently verified the anti-M pro effects of these covalent binders. Gallic acid and quercetin were found to potently inhibit severe acute respiratory syndrome coronavirus 2 M pro in dose- and time- dependent manners, with the IC 50 values below 10 µM. The inactivation kinetics, binding affinity and binding mode of gallic acid and quercetin were further characterized by fluorescence resonance energy transfer, surface plasmon resonance, and covalent docking simulations. Overall, this study established a practical approach for efficiently discovering the covalent inhibitors of M pro from herbal medicines by integrating target-based high-throughput screening and MS-based assays, which would greatly facilitate the discovery of key antiviral constituents from medicinal plants., (© 2023 Wiley Periodicals LLC.)

The excessive use of quaternary ammonium compounds (QACs) following the COVID-19 pandemic has raised substantial concerns regarding their biosafety. Overuse of QACs has been associated with chronic biological adverse effects, including genotoxicity or carcinogenicity. In particular, inadvertent intravascular administration or oral ingestion of QACs can lead to fatal acute toxicity. To enhance the biosafety and antimicrobial efficacy of QACs, this study reports a new series of QACs, termed as PACs, with the alkyl chain of benzalkonium substituted by a phthalocyanine moiety. Firstly, the rigid phthalocyanine moiety enhances the selectivity of QACs to bacteria over human cells and reduces alkyl chain's entropic penalty of binding to bacterial membranes. Furthermore, phthalocyanine neutralizes hemolysis and cytotoxicity of QACs by binding with albumin in plasma. Our experimental results demonstrate that PACs inherit the optical properties of phthalocyanine and validate the broad-spectrum antibacterial activity of PACs in vitro. Moreover, the intravascular administration of the most potent PAC, PAC1a, significantly reduced bacterial burden and ameliorated inflammation level in a bacteria-induced septic mouse model. This study presents a new strategy to improve the antimicrobial efficacy and biosafety of QACs, thus expanding their range of applications to the treatment of systemic infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The existing therapeutic approaches for combating tumors are insufficient in completely eradicating malignancy, as cancer facilitates tumor relapse and develops resistance to treatment interventions. The potential mechanistic connection between SARS-CoV-2 and ESCC has received limited attention. Therefore, our objective was to investigate the characteristics of SARS-CoV-2-related-genes (SCRGs) in esophageal squamous cancer (ESCC)., Methods: Raw data were obtained from the TCGA and GEO databases. Clustering of SCRGs from the scRNA-seq data was conducted using the Seurat R package. A risk signature was then generated using Lasso regression, incorporating prognostic genes related to SCRGs. Subsequently, a nomogram model was developed based on the clinicopathological characteristics and the risk signature., Results: Eight clusters of SCRGs were identified in ESCC utilizing scRNA-seq data, of which three exhibited prognostic implications. A risk signature was then made up with bulk RNA-seq, which displayed substantial correlations with immune infiltration. The novel signature was verified to have excellent prognostic efficacy., Conclusion: The utilization of risk signatures based on SCRGs can efficiently forecast the prognosis of ESCC. A thorough characterization of the SCRGs signature in ESCC could facilitate the interpretation of ESCC's response to immunotherapy and offer innovative approaches to cancer therapy.

Background: The objective of this bibliometric inquiry was to scrutinize domains that delve into the repercussions of the 2019 coronavirus disease (COVID-19) pandemic on individuals afflicted with autism spectrum disorder (ASD), worldwide scholarly findings of interrelated research, and forthcoming trajectories., Methods: To conduct a literature analysis, use the web of science core collection database, search for ASD and COVID-19-related literature published Utilize CiteSpace and VosViewer to visually analyze documents and create networks of authors, organizations. The CiteSpace and VosViewer to visually analyze documents and create networks of authors, organizations, countries, and keywords., Results: This study collected 771 papers and shows an increasing trend in publications. The United States had the most relevant literature (281), followed by the United Kingdom (115) and Italy (76). The United States had the most relevant literature (281), followed by the United Kingdom (115) and Italy (76). The University of London had the most papers (53, 6.87%), and Happe&#95;Francesca was the most productive researcher (6). J AUTISM DEV DISORD was the main journal for research on the impact of COVID-19 on ASD, with 22 related articles. Keyword co-occurrence analysis has revealed that "parenting stress," "enhancing adherence," "acute stress disorder," "COVID-19 Italian lockdown," "neurodevelopmental disorder," and "occupational therapy" have garnered significant attention recently. Notably, the burst keywords suggest that "interventions," "qualitative research," "Disabilities Monitoring Network," "neurodevelopmental disabilities," "perceived stress," and "barriers" are potential areas of investigation for future research., Conclusion: This bibliometric analysis delineates the fundamental structure for assessing the impact of COVID-19 on ASD by scrutinizing crucial indicators such as Our analysis reveals that COVID-19 impact on autism has garnered the interest of an Future research could explore the stress, anxiety, and strategies for individuals with ASD and their The use of telemedicine can be studied in depth, as a new idea for ASD diagnosis and intervention training, it is worthwhile. The use of telemedicine can be studied in depth, as a new idea for ASD diagnosis and intervention training, it is worth exploring, such as Disabilities Monitoring Network, etc., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC 50 value of 18.79 μM, while other compounds were devoid of noticeable activity (IC 50  > 50 μM)., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Four new stilbenes (1-4) and one new flavonoid (5), named cajanines D-H, together with three known stilbenes (6-8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1-4 bore an isopentyl side chain, and further hydroxylation of compounds 1-3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1-8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC 50 values of compounds 5-7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background: COVID-19 could develop severe respiratory symptoms in certain infected patients, especially in the patients with immune disorders. Gut microbiome and plasma metabolome act important immunological modulators in the human body and could contribute to the immune responses impacting the progression of COVID-19. However, the causal relationship between specific intestinal bacteria, metabolites and severe COVID-19 remains not clear., Methods: Based on two-sample Mendelian randomization (MR) framework, the causal effects of 131 intestinal taxa and 452 plasma metabolites on severe COVID-19 were evaluated. Single nucleotide polymorphisms (SNPs) strongly associated with the abundance of intestinal taxa and the concentration of plasma metabolites had been utilized as the instrument variables to infer whether they were causal factors of severe COVID-19. In addition, mediation analysis was conducted to find the potential association between the taxon and metabolite, and further colocalization analysis had been performed to validate the causal relationships., Results: MR analysis identified 13 taxa and 53 metabolites, which were significantly associated with severe COVID-19 as causal factors. Mediation analysis revealed 11 mediated relationships. Myo-inositol, 2-stearoylglycerophosphocholine, and alpha-glutamyltyrosine, potentially contributed to the association of Howardella and Ruminiclostridium 6 with severe COVID-19, respectively. Butyrivibrio and Ruminococcus gnavus could mediate the association of myo-inositol and N-acetylalanine, respectively. In addition, Ruminococcus torques abundance was colocalized with severe COVID-19 (PP.H4 = 0.77) and the colon expression of permeability related protein RASIP1 (PP.H4 = 0.95)., Conclusions: Our study highlights the potential causal relationships between gut microbiome, plasma metabolome and severe COVID-19, which potentially serve as clinical biomarkers for risk stratification and prognostication and benefit the mechanism mechanistic investigation of severe COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Zhao, Huang, Xie, Cai, Qu, Zhang, Luo, Zhang and Li.)

Understanding the roots of Covid-19 vaccine hesitancy in at-risk groups, such as persons living with HIV (PLWH), is of utmost importance. We developed a modified Vaccine Hesitancy Scale (VHS) questionnaire using items from the National Advisory Committee on Immunization Acceptability Matrix. To examine factors associated with receiving COVID-19 vaccine and the link between vaccine attitudes and beliefs with vaccine behavior, PLWH were recruited via social media and community-based organizations (February-May 2022). Descriptive statistics were used to summarize results. Total VHS score was generated by adding Likert scale scores and linear regression models used to compare results between participants who received or did not receive COVID-19 vaccines. Logistic regression models were used to identify factors associated with vaccine uptake. A total of 246 PLWH indicated whether they received a COVID-19 vaccine. 89% received ≥ 1 dose. Mean total VHS(SD) for persons having received ≥ 1 COVID-19 vaccine was 17.8(6.2) vs. 35.4(9.4) for participants not having received any COVID-19 vaccine. Persons who received ≥ 1 dose were significantly older than those who had not received any (48.4 ± 13.8 vs. 34.0 ± 7.7 years, p < 0.0001). The majority of participants considered COVID-19 vaccination important for their health(81.3%) and the health of others(84.4%). Multivariate logistic regression revealed the odds of taking ≥ 1dose were increased 2.4-fold [95% CI 1.6, 3.5] with each increase in age of 10 years (p < 0.0001). Sex and ethnicity were not different between groups. In conclusion, PLWH accept COVID-19 vaccines for both altruistic and individual reasons. With evolving recommendations and increasing numbers of booster vaccines, we must re-examine the needs of PLWH regularly., (© 2023. The Author(s).)

Objective: This study aimed to assess changes in social contact with family, friends and healthcare providers, as well as social participation in working, volunteering, religious services and other organized activities, among older adults during the COVID-19 pandemic while examining the role of pre-COVID sociodemographic characteristics or cognitive and physical limitations in changes in social contact and participation., Methods: We conducted secondary data analyses in the National Health and Aging Trends Study (NHATS) COVID-19 questionnaire, collected in 2020 during a period of workplace closures and social distancing guidelines. We linked data to pre-COVID sociodemographic and medical information collected in 2019 before COVID interrupted social life. The frequency of participants' social contact and social participation prior to and during the COVID-19 pandemic, were compared using paired t-tests for summed scores. Multivariate linear regression was used to relate participants' socio-demographic, prior physical and cognitive performance with levels of social contact and participation and with changes reported during the COVID-19 pandemic., Results: In total, results from 2,486 eligible participants revealed that COVID-19 was associated with decreased social contact among family and friends (change: -0.62; SE: 0.06; p<0.0001), and social participation among older adults (change: -0.58; SE: 0.02; p<0.0001). Pre-COVID characteristics including older age, lower educational attainment, poorer physical performance, and more chronic conditions were associated with lower social contact and social participation and with how older adults adapted their social lives during the COVID-19 pandemic., Discussion: These results emphasize the importance of increasing digital inclusion for older adults in a major crisis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Multiple SARS-CoV-2 Omicron sub-variants, such as BA.2, BA.2.12.1, BA.4, and BA.5, emerge one after another. BA.5 has become the dominant strain worldwide. Additionally, BA.2.75 is significantly increasing in some countries. Exploring their receptor binding and interspecies transmission risk is urgently needed. Herein, we examine the binding capacities of human and other 28 animal ACE2 orthologs covering nine orders towards S proteins of these sub-variants. The binding affinities between hACE2 and these sub-variants remain in the range as that of previous variants of concerns (VOCs) or interests (VOIs). Notably, R493Q reverse mutation enhances the bindings towards ACE2s from humans and many animals closely related to human life, suggesting an increased risk of cross-species transmission. Structures of S/hACE2 or RBD/hACE2 complexes for these sub-variants and BA.2 S binding to ACE2 of mouse, rat or golden hamster are determined to reveal the molecular basis for receptor binding and broader interspecies recognition., (© 2023. The Author(s).)

Now in the post-pandemic era, healthcare employers and leaders must navigate decisions around use of telework arrangements made popular during the COVID-19 pandemic. Among healthcare employees who teleworked during the pandemic, this study investigates preference to continue teleworking post-pandemic and the determinants of this preference. An overwhelming majority (99%) preferred to continue teleworking to some degree and the majority (52%) preferred to telework for all work hours. Healthcare employers should consider that most employees who teleworked during the pandemic prefer to continue teleworking for most or all work hours, and that hybrid work arrangements are especially important for clinical telework employees. In addition to space and resource allocation, management considerations include supports to promote productivity, work-life balance, and effective virtual communication while teleworking to promote positive employee health, recruitment, and retention outcomes.

Inflammasome activation is exclusively involved in sensing activation of innate immunity and inflammatory response during viral infection. Accumulating evidence suggests that the manipulation of inflammasome assembly or its interaction with viral proteins are critical factors in viral pathogenesis. Results from pilot clinical trials show encouraging results of NLRP3 inflammasome suppression in reducing mortality and morbidity in SARS-CoV-2-infected patients. In this article, we summarize the up-to-date understanding of inflammasomes, including NLRP3, AIM2, NLRP1, NLRP6, and NLRC4 in various viral infections, with particular focus on RNA viruses such as SARS-CoV-2, HIV, IAV, and Zika virus and DNA viruses such as herpes simplex virus 1. We also discuss the current achievement of the mechanisms involved in viral infection-induced inflammatory response, host defense, and possible therapeutic solutions.

Continuous surveillance of enteroviruses (EVs) in urban domestic sewage can timely reflect the circulation of EVs in the environment and crowds, and play a predictive and early warning role in EV-related diseases. To better understand the long-term epidemiological trends of circulating EVs and EV-related diseases, we conducted a 9-year (2013 to 2021) surveillance study of non-polio EVs (NPEVs) in urban sewage in Guangzhou city, China. After concentrating and isolating the viruses from the sewage samples, NPEVs were detected and molecular typing was performed. Twenty-one different NPEV serotypes were identified. The most isolated EVs were echovirus 11 (E11), followed by coxsackievirus (CV) B5, E6, and CVB3. EV species B prevailed in sewage samples, but variations in the annual frequency of different serotypes were also observed in different seasons, due to spatial and temporal factors. E11 and E6 were detected continuously before 2017, and the number of isolates was relatively stable during the surveillance period. However, after their explosive growth in 2018 and 2019, their numbers suddenly decreased significantly. CVB3 and CVB5 had alternating trends; CVB5 was most frequently detected in 2013 to 2014 and 2017 to 2018, while CVB3 was most frequently detected in 2015 to 2016 and 2020 to 2021. Phylogenetic analysis showed that at least two different transmission chains of CVB3 and CVB5 were prevalent in Guangzhou City. Our results show that in the absence of a comprehensive and systematic EV-related disease surveillance system in China, environmental surveillance is a powerful and effective tool to strengthen and further investigate the invisible transmission of EVs in the population. IMPORTANCE This study surveilled urban sewage samples from north China for 9 years to monitor enteroviruses. Samples were collected, processed, and viral identification and molecular typing were performed. We detected 21 different non-polio enteroviruses (NPEVs) with yearly variations in prevalence and peak seasons. In addition, this study is very important for understanding the epidemiology of EVs during the COVID-19 pandemic, as the detection frequency and serotypes of EVs in sewage changed considerably around 2020. We believe that our study makes a significant contribution to the literature because our results strongly suggest that environmental surveillance is an exceptionally important tool, which can be employed to detect and monitor organisms of public health concern, which would otherwise be missed and under-reported by case-based surveillance systems alone., Competing Interests: The authors declare no conflict of interest.

The extensive research into developing novel strategies for detecting respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens, especially the sensitive point-of-care testing method, is still urgently needed to reach rapid screening of viral infections. Herein, a new lateral flow immunoassay (LFIA) platform was reported for the detection of SARS-CoV-2 spike-S1 protein antigens, in which four sensitive and specific SARS-CoV-2 mouse monoclonal antibodies (MmAbs) were tailored by using quantum dot (QD)-loaded dendritic mesoporous silica nanoparticles modified further for achieving the -COOH group surface coating (named Q/S-COOH nanospheres). Importantly, compact QD adsorption was achieved in mesoporous channels of silica nanoparticles on account of highly accessible central-radial pores and electrostatic interactions, leading to significant signal amplification. As such, a limit of detection for SARS-CoV-2 spike-S1 testing was found to be 0.03 ng/mL, which is lower compared with those of AuNPs-LFIA (traditional colloidal gold nanoparticles, Au NPs) and enzyme-linked immunosorbent assay methods. These results show that optimizing the affinity of antibody and the intensity of fluorescent nanospheres simultaneously is of great significance to improve the sensitivity of LFIA.

The response to the COVID-19 pandemic in long-term care (LTC) has threatened to undo efforts to transform the culture of care from institutionalized to de-institutionalized models characterized by an orientation towards person- and relationship-centred care. Given the pandemic's persistence, the sustainability of culture-change efforts has come under scrutiny. Drawing on seven culture-change models implemented in Canada, we identify organizational prerequisites, facilitatory mechanisms, and frontline changes relevant to culture change that can strengthen the COVID-19 pandemic response in LTC homes. We contend that a reversal to institutionalized care models to achieve public health goals of limiting COVID-19 and other infectious disease outbreaks is detrimental to LTC residents, their families, and staff. Culture change and infection control need not be antithetical. Both strategies share common goals and approaches that can be integrated as LTC practitioners consider ongoing interventions to improve residents' quality of life, while ensuring the well-being of staff and residents' families.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines., (© 2023. Higher Education Press.)

Background: The 3C-like proteases (3CL pro s) are cysteine-rich homodimeric proteins and can be covalently modified by numerous natural and synthetic compounds, which in turn, block the proteolytic activity or the formation of enzymatically active dimeric forms. Although herbal medicines have been widely used to treat COVID-19, identification of the key herbal constituents that can covalently modify the 3CL pro s in β-coronaviruses (CoVs) remains a big challenge., Aims: To construct a comprehensive approach for efficient discovering the covalent SARS-CoV-2 3CL pro inhibitors from herbal medicines. To decipher the key anti-SARS-CoV-2 3CL pro constituents in Ginkgo biloba extract 50 (GBE50) and to study their anti-SARS-CoV-2 3CL pro mechanisms., Methods: SARS-CoV-2 3CL pro inhibition assay including time-dependent inhibition assays and inactivation kinetic analyses were conducted using a fluorescence-based biochemical assay. The constituents in GBE50 were analyzed by UHPLC-Q-Exactive Orbitrap HRMS. The peptides modified by herbal constituents were characterized by using nanoLC-MS/MS., Results: Following testing the anti-SARS-CoV-2 3CL pro effects of 104 herbal medicines, it was found that Ginkgo biloba extract 50 (GBE50) potently inhibited SARS-CoV-2 3CL pro in dose- and time-dependent manners. A total of 38 constituents were identified from GBE50 by UHPLC-Q-Exactive Orbitrap HRMS, while 26 peptides modified by 18 constituents were identified by chemoproteomic profiling. The anti-SARS-CoV-2 3CL pro effects of 18 identified covalent inhibitors were then validated by performing time-dependent inhibition assays. The results clearly demonstrated that most tested constituents showed time-dependent inhibition on SARS-CoV-2 3CL pro , while gallocatechin and sciadopitysin displayed the most potent anti-SARS-CoV-2 3CL pro effects., Conclusion: Collectively, GBE50 and some constituents in this herbal product could strongly inhibit SARS-CoV-2 3CL pro in dose- and time-dependent manner. Gallocatechin and sciadopitysin were identified as potent SARS-CoV-2 3CL pro inhibitors, which offers promising lead compounds for the development of novel anti-SARS-CoV-2 drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier GmbH.)

The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modeled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. We created deep-learning-based, epitope-aware vector embeddings to infer individual TCR specificity. Then we aggregated clonotype frequencies of TCRs to obtain a quantitative profile of repertoire specificity at epitope, antigen and organism levels. Applying TCRanno to 4195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, supporting the possibility of abortive infections. TCRanno discovered age-accumulated fraction of severe acute respiratory syndrome coronavirus 2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of coronavirus disease 2019. TCRanno also identified the encounter of Hepatitis B antigens as a potential trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In the era of coronavirus disease (COVID-19), wearing a mask could effectively protect people from the risk of infection and largely reduce transmission in public places. To prevent the spread of the virus, instruments are needed in public places to monitor whether people are wearing masks, which has higher requirements for the accuracy and speed of detection algorithms. To meet the demand for high accuracy and real-time monitoring, we propose a single-stage approach based on YOLOv4 to identify the face and whether to regulate the wearing of masks. In this approach, we propose a new feature pyramidal network based on the attention mechanism to reduce the loss of object information that can be caused by sampling and pooling in convolutional neural networks. The network is able to deeply mine the feature map for spatial and communication factors, and the multi-scale feature fusion makes the feature map equipped with location and semantic information. Based on the complete intersection over union (CIoU), a penalty function based on the norm is proposed to improve positioning accuracy, which is more accurate at the detection of small objects; the new bounding box regression function is called Norm CIoU (NCIoU). This function is applicable to various object-detection bounding box regression tasks. A combination of the two functions to calculate the confidence loss is used to mitigate the problem of the algorithm bias towards determinating no objects in the image. Moreover, we provide a dataset for recognizing faces and masks (RFM) that includes 12,133 realistic images. The dataset contains three categories: face, standardized mask and non-standardized mask. Experiments conducted on the dataset demonstrate that the proposed approach achieves mAP@.5:.95 69.70% and AP75 73.80%, outperforming the compared methods.

The increased prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide is particularly worrisome, as no medication has been approved to treat the disease. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first-line treatment for NAFLD. However, due to the lack of standard and scientific guidance and out-of-hospital supervision, long-term outcomes of lifestyle interventions for patients with NAFLD are often unsatisfactory. In addition, the COVID-19 pandemic aggravated this dilemma. At the same time, digital therapeutics (DTx) are expected to be a new method for the convenient management and treatment of patients with NAFLD and are attracting a great deal of attention. DTx, which provide evidence-based medicine through software programs for remote intervention in preventing, treating, or managing diseases, overcome the drawbacks of traditional treatment. The efficacy of the approach has already been demonstrated for some chronic diseases, but DTx have not been fully developed for NAFLD. This study reviews the concepts, clinical value, and practical applications related to DTx, with an emphasis on recommendations based on unmet needs for NAFLD. A better understanding of the current state will help clinicians and researchers develop high-quality, standardized, and efficient DTx products, with the aim of optimizing the prognosis of patients with NAFLD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

The coronavirus pandemic (COVID-19) has created challenging working conditions in coal-production activities. In addition to the massive loss of resources for miners, it has had a devastating impact on these individuals' mental health. Based on the conservation of resources (COR) theory and a resource-loss perspective, this study examined the impact of COVID-19 risk, life-safety risk, perceived job insecurity, and work-family conflict on miners' job performance. Moreover, this study investigated the mediating role of job anxiety (JA) and health anxiety (HA). The study data were collected through online structured questionnaires disseminated to 629 employees working in a coal mine in China. The data analysis and hypothesis generation were conducted using the structural equation modeling (partial least squares) method. The results demonstrated that the perception of COVID-19 risk, life-safety risk, job insecurity, and work-family conflict negatively and significantly impacted miners' job performance. In addition, JA and HA negatively mediated the relationships between the perception of COVID-19 risk, life-safety risk, perceived job insecurity, work-family conflict, and job performance. The findings of this study can give coal-mining companies and their staff useful insights into how to minimize the pandemic's effects on their operations.

Introduction: Since September 2020, Chinese populations aged > 3 years have been encouraged to receive a two-dose inoculation with vaccines against coronavirus disease 2019 (COVID-19). This study aims to evaluate the cost-effectiveness of the current vaccination strategy amongst the general population in mainland China from a societal perspective., Methods: In this study, we construct a decision tree with Markov models to compare the economic and health consequences of the current vaccination strategy versus a no-vaccination scenario, over a time horizon of one year and an annual discount rate of 5%. Transition probabilities, health utilities, healthcare costs, and productivity losses are estimated from literature. Outcome measures include infection rates, death rates, quality-adjusted life years (QALYs), and costs. The incremental cost-effectiveness ratio (ICER) is then calculated to evaluate the cost-effectiveness of the current vaccination strategy, and both one-way deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA) are applied to assess the impact of uncertainties on results., Results: Our simulation indicates that compared with a no-vaccination scenario, vaccination amongst the general population in mainland China would reduce the infection rate from 100% to 45.3% and decrease the death rate from 6.8% to 3.1%. Consequently, the strategy will lead to a saving of 37,664.77 CNY (US$5,256.70) and a gain of 0.50 QALYs per person per year on average (lifetime QALY and productivity loss due to immature death are included). The cost-saving for each QALY gain is 74,895.69 CNY (US$10,452.85). Result of the PSA indicates that vaccination is the dominating strategy with a probability of 97.9%, and the strategy is cost-effective with a probability of 98.5% when the willingness-to-pay (WTP) is 72,000 CNY (US$10,048.71) per QALY., Conclusion: Compared with a no-vaccination scenario, vaccination among the general population in mainland China is the dominating strategy from a societal perspective. The conclusion is considered robust in the sensitivity analyses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Ding, Han, Zhang, Liu, Jia, Yu and Zhang.)

Introduction: Since the implementation of national stay-at-home orders during the COVID-19 pandemic, there has been rising concerns regarding prolonged social isolation that many individuals face. Given the link between increased stress and alcohol and drug use, our study investigated admission trends and patterns of alcohol and drug use in trauma patients., Methods: This was a single center, retrospective cohort study comparing trauma patients admitted before the pandemic and during the first wave. We compared patient demographics, injury characteristics, and outcomes of substance screen negative, positive, and unscreened patients admitted. Patients screened positive if they had a positive urine drug screen (UDS) and/or a blood alcohol concentration (BAC) ≥10 mg/dL., Results: There were 3906 trauma admissions in the year prior to and 3469 patients in the first year of the pandemic. No significant demographic differences were presented across time periods. Rates of UDS and BAC screening remained consistent. Equivalent rates of alcohol and drug positivity occurred (34% versus 33%, 17% versus 18%, P = 0.49). The total prevalence of alcohol use disorders (4% versus 5%, P < 0.001) and psychiatric disorders (6% versus 7%, P = 0.02) increased during the pandemic., Conclusions: The prevalence of diagnosed alcohol use and psychiatric disorders in trauma patients increased during the COVID-19 pandemic while rates of acute alcohol and drug screen positivity remained the same. These observations suggest a possible link between pandemic stressors and exacerbation of alcohol use and psychiatric conditions in trauma patients. During a changing pandemic landscape, it remains pertinent to increased screening for these conditions regardless of substance screen positivity upon admission., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: This study aimed to examine the differences in health status between patients with confirmed COVID-19 and those suspected (other diagnosis) and to identify nursing diagnoses using a structured checklist from a hospital in China., Design: Cross-sectional study design was used., Methods: One hundred sixty COVID-19 confirmed, and suspected patients were conveniently selected. A structured survey and checklist were utilized. Independent t test and chi-square test were employed to compare the mean between patients with confirmed coronavirus infection and others. A two-sided p-value of .05 or less is considered statistically significant., Results: The study yielded a response rate of 93.6%. The result indicated that patients with confirmed coronavirus infection have a higher proportion of perceived General Health Status than inpatients with suspected (other) diagnoses. The finding also indicated that ineffective airway clearance, hyperthermia, imbalanced nutrition less than body requirement and sleep pattern disturbance were the main nursing diagnoses identified., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

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.