Ongoing positive selection drives the evolution of SARS-CoV-2 genomes.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively through world populations since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30, 2021, we demonstrate with population genetic evidence that during the course of SARS-CoV-2 pandemic in humans, (i) SARS-CoV-2 genomes are overall conserved under purifying selection, especially for the 14 genes related to viral RNA replication, transcription, and assembly; (ii) Ongoing positive selection is actively driving the evolution of 6 genes (e.g., S, ORF3a, and N) that play critical roles in molecular processes involving pathogen-host interactions, including viral invasion into and egress from host cells, viral inhibition, or evasion of host immune response, possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution. According to an established haplotype phylogenetic relationship of 138 viral clusters, a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters, of which multiple mutations potentially conferring alterations in viral transmissibility, pathogenicity, and virulence of SARS-CoV-2 are highlighted, warranting attentions.

Towards Exploring Large Molecular Space: An Efficient Chemical Genetic Algorithm.

Generating molecules with desired properties is an important task in chemistry and pharmacy. An efficient method may have a positive impact on finding drugs to treat diseases like COVID-19. Data mining and artificial intelligence may be good ways to find an efficient method. Recently, both the generative models based on deep learning and the work based on genetic algorithms have made some progress in generating molecules and optimizing the molecule's properties. However, existing methods need to be improved in efficiency and performance. To solve these problems, we propose a method named the Chemical Genetic Algorithm for Large Molecular Space (CALM). Specifically, CALM employs a scalable and efficient molecular representation called molecular matrix. Then, we design corresponding crossover, mutation, and mask operators inspired by domain knowledge and previous studies. We apply our genetic algorithm to several tasks related to molecular property optimization and constraint molecular optimization. The results of these tasks show that our approach outperforms the other state-of-the-art deep learning and genetic algorithm methods, where the z tests performed on the results of several experiments show that our method is more than 99% likely to be significant. At the same time, based on the experimental results, we point out the insufficiency in the experimental evaluation standard which affects the fair evaluation of previous work. Supplementary Information: The online version contains supplementary material available at 10.1007/s11390-021-0970-3.

Linear Regression Analysis of Sleep Quality in People with Insomnia in Wuhan City during the COVID-19 Pandemic.

Objective: COVID-19 has evolved into a major global public health event. The number of people reporting insomnia is growing exponentially during the pandemic. This study aimed to explore the relationship between aggravated insomnia and COVID-19-induced psychological impact on the public, lifestyle changes, and anxiety about the future. Methods: In this cross-sectional study, we used the questionnaires from 400 subjects who were obtained from the Department of Encephalopathy of the Wuhan Hospital of Traditional Chinese Medicine between July 2020 and July 2021. The data collected for the study included demographic characteristics of the participants and psychological scales consisting of the Spiegel Sleep Questionnaire, the Fear of COVID-19 Scale (FCV-19S), the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS). The independent sample t-test and one-way ANOVA were used to compare the results. Correlation analysis of variables affecting insomnia was performed using Pearson correlation analysis. The degree of influence of the variables on insomnia was determined using linear regression, and a regression equation was derived. Results: A total of 400 insomnia patients participated in the survey. The median age was 45.75 ± 15.04 years. The average score of the Spiegel Sleep Questionnaire was 17.29 ± 6.36, that of SAS was 52.47 ± 10.39, that of SDS was 65.89 ± 8.72, and that of FCV-19S was 16.09 ± 6.81. The scores of FCV-19S, SAS, and SDS were closely related to insomnia, and the influencing degree was in the following order: fear, depression, and anxiety (OR = 1.30, 0.709, and 0.63, respectively). Conclusion: Fear of COVID-19 can be one of the primary contributors to worsening insomnia.

The impact of covid-19 on coaching practice: Results from a global coach survey

ABSTRACT This paper presents the results from a global coach survey of 1266 coaches from 79 nations conducted in Summer 2021, when the world emerged from global lockdowns and the 18-month COVID-19 pandemic. In addition to sharing data on the composition of the global coach community (national residence, gender, race, ethnicity, sexual orientation and disability), this study focuses on the impact of the global pandemic on the coaching industry using a quantitative analysis. The findings indicate that age, platform association, pre-pandemic online coaching experiences and average fee were significant predictors of the total impact of the COVID-19 pandemic on coaches. Those least able to adjust and transition to an online environment, or with the least experience working online, reported the greatest detrimental impact. Moreover, the data confirm coaching's transition towards online delivery, with the pandemic accelerating this process to a point where we believe that this trajectory will continue post-pandemic. To enable the success of this shift, coach supervisors, peer support and professional coach training need to recognise the need for this digital transition and adjust training, support and practices to reflect this new reality. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Effects of High Temperature on COVID‐19 Deaths in U.S. Counties

The United States of America (USA) was afflicted by extreme heat in the summer of 2021 and some states experienced a record‐hot or top‐10 hottest summer. Meanwhile, the United States was also one of the countries impacted most by the coronavirus disease 2019 (COVID‐19) pandemic. Growing numbers of studies have revealed that meteorological factors such as temperature may influence the number of confirmed COVID‐19 cases and deaths. However, the associations between temperature and COVID‐19 severity differ in various study areas and periods, especially in periods of high temperatures. Here we choose 119 US counties with large counts of COVID‐19 deaths during the summer of 2021 to examine the relationship between COVID‐19 deaths and temperature by applying a two‐stage epidemiological analytical approach. We also calculate the years of life lost (YLL) owing to COVID‐19 and the corresponding values attributable to high temperature exposure. The daily mean temperature is approximately positively correlated with COVID‐19 deaths nationwide, with a relative risk of 1.108 (95% confidence interval: 1.046, 1.173) in the 90th percentile of the mean temperature distribution compared with the median temperature. In addition, 0.02 YLL per COVID‐19 death attributable to high temperature are estimated at the national level, and distinct spatial variability from −0.10 to 0.08 years is observed in different states. Our results provide new evidence on the relationship between high temperature and COVID‐19 deaths, which might help us to understand the underlying modulation of the COVID‐19 pandemic by meteorological variables and to develop epidemic policy response strategies. Key Points This study explores the relationship between COVID‐19 deaths and temperature by applying a two‐stage epidemiological analytical approach during the summer of 2021 in the Unites States The daily mean temperature is approximately positively correlated with COVID‐19 deaths nationwide, with different shapes of temperature–mortality curves noted at the regional level Evaluation of temperature‐mortality relationship is important in controlling COVID‐19 severity

Transcriptomic signatures and repurposing drugs for COVID-19 patients: findings of bioinformatics analyses.

The novel coronavirus SARS-CoV-2 is damaging the world's social and economic fabrics seriously. Effective drugs are urgently needed to decrease the high mortality rate of COVID-19 patients. Unfortunately, effective antiviral drugs or vaccines are currently unavailable. Herein, we systematically evaluated the effect of SARS-CoV-2 on gene expression of both lung tissue and blood from COVID-19 patients using transcriptome profiling. Differential gene expression analysis revealed potential core mechanism of COVID-19-induced pneumonia in which IFN-α, IFN-ß, IFN-γ, TNF and IL6 triggered cytokine storm mediated by neutrophil, macrophage, B and DC cells. Weighted gene correlation network analysis identified two gene modules that are highly correlated with clinical traits of COVID-19 patients, and confirmed that over-activation of immune system-mediated cytokine release syndrome is the underlying pathogenic mechanism for acute phase of COVID-19 infection. It suggested that anti-inflammatory therapies may be promising regimens for COVID-19 patients. Furthermore, drug repurposing analysis of thousands of drugs revealed that TNFα inhibitor etanercept and γ-aminobutyric acid-B receptor (GABABR) agonist baclofen showed most significant reversal power to COVID-19 gene signature, so we are highly optimistic about their clinical use for COVID-19 treatment. In addition, our results suggested that adalimumab, tocilizumab, rituximab and glucocorticoids may also have beneficial effects in restoring normal transcriptome, but not chloroquine, hydroxychloroquine or interferons. Controlled clinical trials of these candidate drugs are needed in search of effective COVID-19 treatment in current crisis.

Effects of High Temperature on COVID-19 Deaths in U.S. Counties.

The United States of America (USA) was afflicted by extreme heat in the summer of 2021 and some states experienced a record-hot or top-10 hottest summer. Meanwhile, the United States was also one of the countries impacted most by the coronavirus disease 2019 (COVID-19) pandemic. Growing numbers of studies have revealed that meteorological factors such as temperature may influence the number of confirmed COVID-19 cases and deaths. However, the associations between temperature and COVID-19 severity differ in various study areas and periods, especially in periods of high temperatures. Here we choose 119 US counties with large counts of COVID-19 deaths during the summer of 2021 to examine the relationship between COVID-19 deaths and temperature by applying a two-stage epidemiological analytical approach. We also calculate the years of life lost (YLL) owing to COVID-19 and the corresponding values attributable to high temperature exposure. The daily mean temperature is approximately positively correlated with COVID-19 deaths nationwide, with a relative risk of 1.108 (95% confidence interval: 1.046, 1.173) in the 90th percentile of the mean temperature distribution compared with the median temperature. In addition, 0.02 YLL per COVID-19 death attributable to high temperature are estimated at the national level, and distinct spatial variability from -0.10 to 0.08 years is observed in different states. Our results provide new evidence on the relationship between high temperature and COVID-19 deaths, which might help us to understand the underlying modulation of the COVID-19 pandemic by meteorological variables and to develop epidemic policy response strategies.

Characterizing the cellular and molecular variabilities of peripheral immune cells in healthy recipients of BBIBP-CorV inactivated SARS-CoV-2 vaccine by single-cell RNA sequencing.

Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4+ T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4+ T cells (but not CD8+ T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4+ T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4+ T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4+ T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).

Development of Bivalent mRNA Vaccines against SARS-CoV-2 Variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions of individuals and is the cause of the current global coronavirus disease 2019 (COVID-19) pandemic. We previously developed an mRNA vaccine (LVRNA009) based on the S protein of the Wuhan-Hu-1 strain; the phases I and II clinical trials showed that LVRNA009 has a promising safety and immunogenicity profile. In order to counteract the immune escape by SARS-CoV-2 variants of concern, a panel of mRNA vaccines was developed based on the S proteins of the Wuhan-Hu-1, Delta, Omicron BA.1, BA.2, and BA.5 strains, and each vaccine's protective potency against the virus variants was evaluated. Furthermore, to achieve excellent neutralization against SARS-CoV-2 variants, bivalent vaccines were developed and tested against the variants. We found that the monovalent Wuhan-Hu-1 or the Delta vaccines could induce high level of neutralization antibody and protect animals from the infection of the SARS-CoV-2 Wuhan-Hu-1 or Delta strains, respectively. However, serum samples from mice immunized with monovalent Delta vaccine showed relatively low virus neutralization titers (VNTs) against the pseudotyped virus of the Omicron strains. Serum samples from mice immunized with bivalent Delta/BA.1 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, and BA.1 strains but low VNTs against BA.2 and BA.5 (p < 0.05). Serum samples from mice immunized with Delta/BA.2 vaccine had high VNTs against the pseudotyped Wuhan-Hu-1, Delta, BA.1 and BA.2 strains but low VNTs against BA.5. Finally, serum samples from mice immunized with Delta/BA.5 vaccine had high VNTs against all the tested pseudotyped SARS-CoV-2 strains including the Wuhan-Hu-1, Delta, and Omicron variants (p > 0.05). Therefore, a bivalent mRNA vaccine with Delta/BA.5 combination is promising to provide broad spectrum immunity against all VOCs.

Perceptions, precautions, and vaccine acceptance related to monkeypox in the public in China: A cross-sectional survey.

BACKGROUND: The World Health Organization declared monkeypox as a Public Health Emergency of International Concern. A cross-sectional online survey was conducted to understand beliefs, attitudes, perceived preventive measures, and vaccination acceptance related to monkeypox in the public in China. METHODS: Between August 30 and September 15, 2022, we recruited adults through an online survey platform. Demographic characteristics, perceptions, common knowledge, concerns, attitudes, willingness to adopt preventive measures (including hygiene practices, social distancing, and travel avoidance), and vaccination acceptance related to monkeypox were collected. Logistic regression was used to assess correlates of concerns about monkeypox, willingness to adopt preventive measures, and vaccination acceptance. RESULTS: 2135 participants were recruited (median age: 31.4 years). 62.7% were concerned about monkeypox. 33.2% were more concerned about monkeypox compared to COVID-19. Males (aOR 0.61, 95%CI 0.50-0.74), accessing monkeypox information from the Internet (0.77, 0.61-0.98), and willingness to adopt monkeypox vaccine (2.9, 2.38-3.53) were associated with concerns about monkeypox. Most participants were willing to adopt precautions (76.3% hygiene practices, 68.2% social distancing, 85.9% travel avoidance). Individuals who were concerned about monkeypox (hygiene practices: 2.09, 1.69-2.59; social distancing: 1.78, 1.46-2.16; travel avoidance: 1.74, 1.34-2.26) and had better knowledge about monkeypox (hygiene practices: 1.85, 1.48-2.31; social distancing: 2.17, 1.77-2.66; travel avoidance: 1.74, 1.34-2.26) were more likely to adopt precautions. 68.8% were willing to adopt monkeypox vaccine. Participants with older age (aged 40-49: 0.57, 0.38-0.85; aged 50 +: 0.50, 0.31-0.81), and higher income (¥6000-10,000: 0.61, 0.39-0.95; ≥¥10,000: 0.48, 0.30-0.77) were less likely to adopt the monkeypox vaccine. Being concerned more about monkeypox compared to COVID-19 (1.63, 1.31-2.02), and having better knowledge about monkeypox (1.34, 1.09-1.66) were associated with willingness to adopt vaccination. CONCLUSIONS: Compared with COVID-19, monkeypox attracted significantly less attention in the public in China, who currently have insufficient monkeypox knowledge. Interventions aimed at improving monkeypox knowledge and precautions among different groups of individuals in China are needed.

Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai.

Objective: To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods: A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result: Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8-15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8-15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50-64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions: Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Hematopoietic stem cell transplantation activity in China 2020-2021 during the SARS-CoV-2 pandemic: a report from the Chinese Blood and Marrow Transplantation Registry Group.

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplant teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplant teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (AA) (13%). The PB stem cell source accounted for 41% of HIDs and 75% of MSDs. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and TBI-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.

Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai

Objective To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8–15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8–15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50–64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. METHODS: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. RESULTS: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). CONCLUSION: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022.

Perceptions and worries about monkeypox, and attitudes towards monkeypox vaccination among medical workers in China: A cross-sectional survey.

BACKGROUND: The World Health Organization (WHO) declared monkeypox a "public health emergency of international concern" on 23 June 2022. However, there is a lack of data on monkeypox perceptions among medical workers. The purposes of this study were to evaluate perceptions, worries about monkeypox, attitudes towards monkeypox vaccination and their correlates among medical workers in China. METHODS: Data were collected from medical practitioners using an online survey questionnaire between September 1 and September 30, 2022 in China. All the subjects completed an online questionnaire including general characteristics, perceptions/knowledge/worries about monkeypox, and attitudes towards monkeypox vaccination. Logistic regression was employed to examine the correlates of perceptions, worries about monkeypox, and attitudes toward monkeypox vaccination. RESULTS: In total, this study sample included 639 medical workers. The mean age was 37.9 ± 9.4 years old. Approximately 71.8% of individuals reported perceptions of monkeypox, 56.7% worried about monkeypox, and 64.9% supported the promotion of monkeypox vaccination. Medical workers who were older than 50 years (aOR 3.73, 95%CI 1.01-13.85), worked in the Infectious Diseases/Dermatology/Venereal Diseases departments (3.09, 1.61-5.91), and provided correct answer to monkeypox transmission route (10.19, 5.42-19.17) were more likely to know about monkeypox/monkeypox virus before investigation. 30.7% reported that they were more worried about monkeypox than the coronavirus (COVID-19). Participants reported that the key population most in need of monkeypox vaccination were health practitioners (78.2%) and people with immunodeficiency (74.3%), followed by children (65.4%) and older adults (63.2%). CONCLUSION: Awareness of monkeypox was high and attitude towards the promotion of monkeypox vaccination was positive among medical staff in China. Further targeted dissemination of monkeypox common knowledge among health care providers might improve their precaution measures and improve the promotion of monkeypox vaccination among key populations.

Robustness of Significant Dichotomous Outcomes in Randomized Controlled Trials in the Treatment of Patients with COVID-19: A Systematic Analysis.

Purpose: Significant results of randomized controlled trials (RCTs) should be properly weighed. This study adopted fragility index (FI) to evaluate the robustness of significant dichotomous outcomes from RCTs on coronavirus disease 2019 (COVID-19) treatment. Materials and methods: ClinicalTrials.gov and PubMed were searched from inception to July 31, 2021. FIs were calculated and their distribution was depicted. FI's categorical influential factors were analyzed. Spearman correlation coefficient (r s) was reported for the relationship between FI and the continuous characteristics of RCTs. Results: Fifty RCTs with 120 outcomes in 7869 patients were included. The FI distribution was abnormal with median 3 (interquartile range 1-7, P = 0.0001). The FIs and robustness were affected by the outcomes of interest, various patient populations, and interventions (T = 18.215,16.667, 23.107; P = 0.02,0.0001, 0.001, respectively). A cubic relationship between the FIs and absolute difference of events between groups with R square of 0.848 (T = 215.828, P = 0.0001, R square = 0.865) was observed. A strong negative logarithmic relationship existed between FI and the P value with R square = - 0.834. Conclusion: The robustness of significant dichotomous outcomes of COVID-19 treatments was fragile and affected by the outcomes of interest, patients, interventions, P value, and absolute difference of events between the groups. FI was an useful quantitative metric for the binary significant outcomes on COVID-19 treatments. Registration: PROSPERO (CRD42021272455). Supplementary Information: The online version contains supplementary material available at 10.1007/s44231-022-00027-y.

Towards Exploring Large Molecular Space: An Efficient Chemical Genetic Algorithm

Generating molecules with desired properties is an important task in chemistry and pharmacy. An efficient method may have a positive impact on finding drugs to treat diseases like COVID-19. Data mining and artificial intelligence may be good ways to find an efficient method. Recently, both the generative models based on deep learning and the work based on genetic algorithms have made some progress in generating molecules and optimizing the molecule's properties. However, existing methods need to be improved in efficiency and performance. To solve these problems, we propose a method named the Chemical Genetic Algorithm for Large Molecular Space (CALM). Specifically, CALM employs a scalable and efficient molecular representation called molecular matrix. Then, we design corresponding crossover, mutation, and mask operators inspired by domain knowledge and previous studies. We apply our genetic algorithm to several tasks related to molecular property optimization and constraint molecular optimization. The results of these tasks show that our approach outperforms the other state-of-the-art deep learning and genetic algorithm methods, where the z tests performed on the results of several experiments show that our method is more than 99% likely to be significant. At the same time, based on the experimental results, we point out the insufficiency in the experimental evaluation standard which affects the fair evaluation of previous work. Supplementary Information The online version contains supplementary material available at 10.1007/s11390-021-0970-3.

Alterations of the gut microbiota in coronavirus disease 2019 and its therapeutic potential.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global health. SARS-CoV-2 infects host cells primarily by binding to angiotensin-converting enzyme 2, which is coexpressed in alveolar type 2 cells and gut epithelial cells. It is known that COVID-19 often presents with gastrointestinal symptoms and gut dysbiosis, mainly characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. In recent years, multiple studies have comprehensively explored gut microbiota alterations in COVID-19 and highlighted the clinical correlation between dysbiosis and COVID-19. SARS-CoV-2 causes gastrointestinal infections and dysbiosis mainly through fecal-oral transmission and the circulatory and immune pathways. Studies have shown that the gut microbiota and its metabolites can regulate the immune response and modulate antiviral effects. In addition, the gut microbiota is closely related to gastrointestinal symptoms, such as diarrhea, a common gastrointestinal symptom among COVID-19. Therefore, the contribution of the gut microbiota in COVID-19 should not be overlooked. Strategies targeting the gut microbiota via probiotics, prebiotics and fecal microbiota transplantation should be considered to treat this patient population in the future. However, the specific alterations and mechanisms as well as the contributions of gut microbiota in COVID-19 should be urgently further explored.