Engineering customized viral receptors for various coronaviruses (preprint)

Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus amplification for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as amplification of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.

Engineering customized viral receptors for various coronaviruses (preprint)

Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models1,2. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus propagation for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as propagation of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A3. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.

Impacts of the COVID-19 pandemic on pediatric and adult patients with haemophilia (preprint)

Background:The COVID-19-associated mortality rate of haemophilia patients is similar to that of the general population, but the risk of hospitalization and bleeding is higher. However, the specific impact of this infection on haemophilia patients has not been reported yet. In this study, we aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the infection susceptibility, symptoms, drug use, and social intercourse of patients with haemophilia. Methods: A survey was distributed to a total of 265 patients with haemophilia [adult (n = 185) and pediatric patients (n = 80)] in the Fujian haemophilia therapeutic center (Fuzhou City, China) during the COVID-19 pandemic, and data were collected between January 2022 and January 2023. The impacts of SARS-CoV-2 infection on haemophilia symptoms, drug use, and social intercourse of these patients were investigated, and the association between the recovery time and disease conditions was explored in infected patients. Results: During the COVID-19 pandemic, compared with adult patients, pediatric patients had reduced social intercourse and outdoor activities because of the fear of contracting COVID-19 (85.0% vs. 66.5%; P = 0.002). Bleeding events were also significantly fewer in children than in adults (61.2% vs. 81.1%; P = 0.001). The SARS-CoV-2 infection rate was significantly higher in patients living in urban areas than in those living in rural areas (74.3% vs. 53.6%; P < 0.001). The duration of achieving symptomatic recovery from COVID-19 was not significantly associated with hemorrhage, type and classification of haemophilia, presence of inhibitors, complications, and vaccination status. Conclusion: Having COVID-19 infection did not significantly influence the symptoms and treatments in patients with haemophilia. Compared with adults, pediatric patients had significantly fewer bleeding events.

Host-Microbe Multiomic Profiling Reveals Age-Dependent COVID-19 Immunopathology (preprint)

Age is a major risk factor for severe coronavirus disease-2019 (COVID-19), yet the mechanisms responsible for this relationship have remained incompletely understood. To address this, we evaluated the impact of aging on host and viral dynamics in a prospective, multicenter cohort of 1,031 patients hospitalized for COVID-19, ranging from 18 to 96 years of age. We performed blood transcriptomics and nasal metatranscriptomics, and measured peripheral blood immune cell populations, inflammatory protein expression, anti-SARS-CoV-2 antibodies, and anti-interferon (IFN) autoantibodies. We found that older age correlated with an increased SARS-CoV-2 viral load at the time of admission, and with delayed viral clearance over 28 days. This contributed to an age-dependent increase in type I IFN gene expression in both the respiratory tract and blood. We also observed age-dependent transcriptional increases in peripheral blood IFN-(, neutrophil degranulation, and Toll like receptor (TLR) signaling pathways, and decreases in T cell receptor (TCR) and B cell receptor signaling pathways. Over time, older adults exhibited a remarkably sustained induction of proinflammatory genes (e.g., CXCL6) and serum chemokines (e.g., CXCL9) compared to younger individuals, highlighting a striking age-dependent impairment in inflammation resolution. Augmented inflammatory signaling also involved the upper airway, where aging was associated with upregulation of TLR, IL17, type I IFN and IL1 pathways, and downregulation TCR and PD-1 signaling pathways. Metatranscriptomics revealed that the oldest adults exhibited disproportionate reactivation of herpes simplex virus and cytomegalovirus in the upper airway following hospitalization. Mass cytometry demonstrated that aging correlated with reduced naive T and B cell populations, and increased monocytes and exhausted natural killer cells. Transcriptional and protein biomarkers of disease severity markedly differed with age, with the oldest adults exhibiting greater expression of TLR and inflammasome signaling genes, as well as proinflammatory proteins (e.g., IL6, CXCL8), in severe COVID-19 compared to mild/moderate disease. Anti-IFN autoantibody prevalence correlated with both age and disease severity. Taken together, this work profiles both host and microbe in the blood and airway to provide fresh insights into aging-related immune changes in a large cohort of vaccine-naive COVID-19 patients. We observed age-dependent immune dysregulation at the transcriptional, protein and cellular levels, manifesting in an imbalance of inflammatory responses over the course of hospitalization, and suggesting potential new therapeutic targets. One sentence summaryWe observed age-dependent immune dysregulation at the transcriptional, protein and cellular levels, manifesting in an imbalance of inflammatory responses over the course of hospitalization, and suggesting potential new therapeutic targets.

Exploring the Intersection of Complex Aesthetics and Generative AI for Promoting Cultural Creativity in Rural China after the Post-Pandemic Era (preprint)

This paper explores using generative AI and aesthetics to promote cultural creativity in rural China amidst COVID-19's impact. Through literature reviews, case studies, surveys, and text analysis, it examines art and technology applications in rural contexts and identifies key challenges. The study finds artworks often fail to resonate locally, while reliance on external artists limits sustainability. Hence, nurturing grassroots "artist villagers" through AI is proposed. Our approach involves training machine learning on subjective aesthetics to generate culturally relevant content. Interactive AI media can also boost tourism while preserving heritage. This pioneering research puts forth original perspectives on the intersection of AI and aesthetics to invigorate rural culture. It advocates holistic integration of technology and emphasizes AI's potential as a creative enabler versus replacement. Ultimately, it lays the groundwork for further exploration of leveraging AI innovations to empower rural communities. This timely study contributes to growing interest in emerging technologies to address critical issues facing rural China.

Effectiveness of Xiangsha Liujun pills on decreased digestive function in convalescent patients of coronavirus disease 2019: a randomized, double blind, placebo controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness and safety of Xiangsha Liujun pills on the decreased digestive function in patients in the recovery phase of the Coronavirus disease 2019 (COVID-19). METHODS: A randomized, double blind, placebo controlled clinical trial was conducted. A total of 200 COVID-19 patients in the recovery phase were included in our study in Ezhou Hospital of Traditional Chinese Medicine. Totally 200 subjects were randomly divided into a treatment group (Xiangsha Liujun pills) and a control group (placebo), with 100 in each group. Subjects took Xiangsha Liujun pills or placebo orally three times a day for two weeks. Three visits were scheduled at week 0 (baseline), week 1 (the middle of the intervention) and week 2 (the end of the intervention) for each eligible patient. The total efficacy rates for improving the Traditional Chinese Medicine (TCM) symptoms (fatigue, poor appetite, abdominal distension and loose stools) and the disappearance rates of symptoms were observed and compared in the treatment and control groups. Adverse events were recorded during the study period. SAS 9.4 was used to analyze the data. RESULTS: A total of 200 patients were included in this study, among which 4 participants withdrew because the drugs did not work. Three patients were excluded for age. Before the treatment, there was no significant difference between the TCM symptoms scores of subjects. After 1 week of treatment, the full analysis set (FAS) showed that the efficacy rates for abdominal distension and loose stools in the treatment group were significantly higher than the control group ( 0.05). There were no significant differences in the efficacy rates for fatigue and poor appetite between the two groups (0.05). In addition, the disappearance rate of fatigue in the treatment group was significantly higher than the control group (0.05); there were no significant differences between the two groups after treatment in the rates of poor appetite, abdominal distension, and loose stools (>0.05). After 2 weeks of treatment, the efficacy rates for fatigue, poor appetite, abdominal distension, and loose stools in the treatment group were significantly higher than the control group (0.05). The disappearance rate of loose stools in the treatment group was significantly higher than the control group ( 0.05). However, there were no significant differences in the disappearance rates of fatigue, poor appetite, and abdominal distension between the two groups ( 0.05). No severe adverse events were reported by subjects during the study. CONCLUSIONS: This clinical study confirmed that Xiangsha Liujun pills can effectively improve the symptoms related to the decreased digestive function in COVID-19 convalescent patients.

COVID-19 Infection and Dementia: Analyses of time-varying risk, subtypes, and subpopulations from the UK Biobank (preprint)

Background Although COVID-19 patients were suggested to experience worse cognitive outcomes, there is a paucity of evidence on time-varying risk of dementia, especially the subtypes, as well as among critical subpopulations.Methods Out of over 50000 individuals from general population in the UK Biobank, SARS-COV-2 infected patients between March 1, 2020, and July 31, 2021 and maximally 5:1 propensity score matched contemporary non-infected individuals were selected, with baseline dementia excluded. Matching was done on demographic characteristics, lifestyle, and comorbidities. Dementia was captured according to primary care, inpatient records, and death registry, with the follow-up ending at the earliest of outcome occurrence, death, or August 31, 2021. Associations were evaluated using time-varying hazard ratios (HRs) and odds ratios (ORs).Results With a mean age of 64.5 years for 18032 COVID-19 patients and 83,008 controls, participants were followed for a median of 247 (IQR: 204–305) days and 255 dementia cases occurred, including 90 Alzheimer’s disease (AD) cases and 42 vascular dementia (VaD) cases. Compared with matched controls, dementia risk declined drastically after COVID-19 infection and sustained for all-cause dementia, VaD, and other dementia. During the acute phase (first 30 days), COVID-19 infection was associated with increased risks of dementia, with HRs (95% CIs) being 12.77 (6.77, 24.08) for all-cause dementia, 9.21 (2.77, 30.59) for AD, 5.53 (1.69, 18.11) for VaD, and 25.35 (8.74, 73.56) for other dementia. Among those not hospitalized within 30 days of enrollment, elevated dementia risk remained for all-cause dementia, VaD, and other dementia, with ORs being 1.82, 4.55, and 1.64, respectively. Among most of the subpopulations classified by demographic characteristics, APOE genotype, and comorbidities (except for those with chronic obstructive pulmonary diseases at enrollment), COVID-19 infection was associated with an elevated all-cause dementia risk and no modification effect was detected.Conclusions Declined yet sustained elevated dementia risk since COVID-19 infection was found and vascular risk factors may need extra attention during the long-term follow-up. Increased dementia risk from COVID-19 infection also applied for the non-hospitalized during the acute phase and most subpopulations. The potential dementia risk associated with Omicron and newer variants warrants further evaluation.

COVID-19 Infection and Dementia: A Prospective Analysis of Time-Varying Risk, Subtypes, and Subpopulations from the UK Biobank (preprint)

Background: Although COVID-19 patients were suggested to experience worse cognitive outcomes, there is a paucity of evidence on time-varying risk of dementia, especially the subtypes, as well as among critical subpopulations. Methods: Out of over 50000 individuals from general population in the UK Biobank, SARS-COV-2 infected patients between March 1, 2020, and July 31, 2021 and maximally 5:1 propensity score matched contemporary non-infected individuals were selected, with baseline dementia excluded. Matching was done on demographic characteristics, lifestyle, and comorbidities. Dementia was captured according to primary care, inpatient records, and death registry, with the follow-up ending at the earliest of outcome occurrence, death, or August 31, 2021. Associations were evaluated using time-varying hazard ratios (HRs) and odds ratios (ORs). Results: With a mean age of 64.5 years for 18032 COVID-19 patients and 83,008 controls, participants were followed for a median of 247 (IQR: 204–305) days and 255 dementia cases occurred, including 90 Alzheimer’s disease (AD) cases and 42 vascular dementia (VaD) cases. Compared with matched controls, dementia risk declined drastically after COVID-19 infection and sustained for all-cause dementia, VaD, and other dementia. During the acute phase (first 30 days), COVID-19 infection was associated with increased risks of dementia, with HRs (95% CIs) being 12.77 (6.77, 24.08) for all-cause dementia, 9.21 (2.77, 30.59) for AD, 5.53 (1.69, 18.11) for VaD, and 25.35 (8.74, 73.56) for other dementia. Among those not hospitalized within 30 days of enrollment, elevated dementia risk remained for all-cause dementia, VaD, and other dementia, with ORs being 1.82, 4.55, and 1.64, respectively. Among most of the subpopulations classified by demographic characteristics, APOE genotype, and comorbidities (except for those with chronic obstructive pulmonary diseases at enrollment), COVID-19 infection was associated with an elevated all-cause dementia risk and no modification effect was detected. Conclusion: Declined yet sustained elevated dementia risk since COVID-19 infection was found and vascular risk factors may need extra attention during the long-term follow-up. Increased dementia risk from COVID-19 infection also applied for the non-hospitalized during the acute phase and most subpopulations. The potential dementia risk associated with Omicron and newer variants warrants further evaluation.

Source tracing of the COVID-19 infection case in Guangxi, China

The study describing the process of discovery and source tracing of a native case of coronavirus disease 2019 (COVID-19) infection on Jan 2021, in Guangxi, China, to provide methodology for source investigation better in the future. Following the Epidemiological Investigation Plan for COVID-19 (version 7), information of the native COVID-19 case and related close contacts were collected. Real time reverse transcription-quantitative polymerase chain reaction was performed to detect the nucleic acids of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in samples collected from the infection case, related close contacts, and the environment, combined with serum specific antibody detection. The positive nucleic acid samples were undergone whole genome sequencing, phylogenetic analysis and analyses of variation of amino acids. The whole genome sequence from the native case and the imported asymptomatic infected case from Indonesia containing 25 nucleotide mutation sites belong to L-Lineage European Branch II. 3. The imported asymptomatic case was the source of infection of this native case. The possible route of infection was that native case was exposed to contaminated environment by imported case, due to improper personal protective equipment. A focus on local outbreaks of COVID-19 caused by SARS-CoV-2-infected people from outside China is needed.

Immune response of primary and booster immunity of SARS-CoV-2 vaccination among patients with chronic liver disease: a real-world study (preprint)

Aim: The present study discussed the humoral immune response and antibody dynamics after primary and booster immunity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic liver disease (CLD) in the real world. Thus, it provided data to develop SARS-CoV-2 vaccination strategy. Methods: Patients with confirmed CLD and completed primary or booster immunity of SARS-CoV-2 vaccines were enrolled. Serological specimens were collected after primary or booster immunity of SARS-CoV-2 vaccines to detect novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD). Thus, we could evaluate the humoral immune response and antibody dynamics after primary and booster immunity of SARS-CoV-2 vaccines among patients with CLD. Simultaneously, baseline demographics, liver disease-related situations, comorbidity-related situations, SARS-CoV-2 vaccination information, and laboratory examination-related indicators of patients were collected. Results: A total of 315 patients received SARS-CoV-2 vaccines, including 223 patients who completed the primary immunity of SARS-CoV-2 vaccines, 114 patients who completed booster immunity of SARS-CoV-2 vaccines, and 22 patients who underwent the antibody detection of SARS-CoV-2 vaccines after both primary and booster immunities. The positive rate of nCoV NTAb was 59.64% in Primary and 87.72% in Booster (P<0.001). The median level of nCoV NTAb was 11.53 AU/mL in Primary and 31.98 AU/mL in Booster (P<0.001). The positive rate of nCoV S-RBD was 69.06% in Primary and 91.23% in Booster (P<0.001). The median level of nCoV S-RBD was 21.60AU/mL in Primary and 112.65 AU/mL in Booster (P<0.001). After booster immunity of SARS-CoV-2 vaccines in 22 patients, the positive rate of nCoV NTAb increased from 59.09% to 86.36%, and that of nCoV S-RBD increased from 68.18% to 90.91%. The median level of nCoV NTAb increased from 11.24 AU /mL to 59.14 AU /mL after booster immunity. The median level of nCoV S-RBD increased from 27.28 AU/mL to 219.10 AU/mL. Compared to the antibody level of primary immunity, the median level of nCoV NTAb and nCoV S-RBD in 22 patients was increased by 5.26 and 8.03 times, respectively. Among 22 patients, 9 were negative for nCoV NTAb after primary immunity, while 6 were transformed positive after booster immunity, and the positive conversion rate of nCoV NTAb was 66.7%. On the other hand, 7 patients were negative for nCoV S-RBD after primary immunity, while 5 were transformed positive after booster immunity, and the positive conversion rate of nCoV S-RBD was 71.4%. Conclusion: Patients with CLD show improved humoral immune response after completing primary and booster immunity of SARS-CoV-2 vaccines, while booster immunity further improves the positive rate and antibody level of patients with CLD. Finally, the positive conversion rate among patients with primary immunity failure also can be improved after booster immunity. Keywords: immune response; primary and booster immunity; SARS-CoV-2 vaccination; chronic liver disease

The Spatial Variation of the Influence of Lockdown on Air Quality across China and Its Major Influencing Factors during COVID-19

China has experienced a series of COVID-19 recurrences in different cities across the country since 2020, and relatively strict (full lockdown) or lenient closure (semi-lockdown) strategies have been employed accordingly in each city. The differences in detailed transmission control measures during lockdown periods led to distinct effects on air quality, which has rarely been studied. To fill this gap, we examined the effects of semi-lockdown and full lockdown on six major airborne pollutants, based on 55 lockdown cases. For all lockdown cases, the concentrations of PM2.5, PM10, SO2, NO2 and CO were much lower than in previous years. Specifically, due to the stricter transmission control, the concentration of the five airborne pollutants experienced a much sharper decline during full lockdown. However, O3 presented a different variation pattern during lockdown periods. Generally, O3 concentrations presented a slight increase in semi-lockdown cases and a notable increase in full lockdown cases. Meanwhile, O3 increased notably in northern China, particularly in the Beijing–Tianjin–Hebei region, while O3 had a slight variation in southern China. The unique variation of O3 across regions and lockdown types was mainly attributed to the spatial heterogeneity of O3 formation regimes, especially the VOCs-controlled O3 formation in northern China. Based on Geographical Detector, we examined the spatial continuity of natural and socio-economic factors on the variation of airborne pollutants during lockdown. In terms of meteorological factors, humidity and precipitation were the dominant factors for PM2.5 and PM10, respectively, while humidity and temperature were the dominant factors for O3. In terms of socio-economic factors, the numbers of taxis and private cars were the dominant factors for PM2.5 and O3 variations during lockdown. GD also revealed that the combination of natural and socio-economic factors had a significantly enhanced effect on airborne pollutants during lockdown. The combination of relative humidity and total area of urban built-up areas exerted the strongest interactive effects on both PM2.5 and O3. This research highlighted the challenge for urban O3 management, and suggested the control of VOCs emissions should be preferably considered, especially in northern China.

Immunogenicity profiling and distinct immune response in liver transplant recipients vaccinated with SARS-CoV-2 inactivated vaccines

SARS-CoV-2 vaccination has been recommended for liver transplant (LT) recipients. However, our understanding of inactivated vaccine stimulation of the immune system in regulating humoral and cellular immunity among LT recipients is inadequate. Forty-six LT recipients who received two-dose inactivated vaccines according to the national vaccination schedule were enrolled. The clinical characteristics, antibody responses, single-cell peripheral immune profiling, and plasma cytokine/chemokine/growth factor levels were recorded. Sixteen (34.78%) LT recipients with positive neutralizing antibody (nAb) were present in the Type 1 group. Fourteen and 16 LT recipients with undetected nAb were present in the Type 2 and Type 3 groups, respectively. Time from transplant and lymphocyte count were different among the three groups. The levels of anti-RBD and anti-S1S2 decreased with decreasing neutralizing inhibition rates. Compared to the Type 2 and Type 3 groups, the Type 1 group had an enhanced innate immune response. The proportions of B, DNT, and CD3+CD19+ cells were increased in the Type 1 group, whereas monocytes and CD4+ T cells were decreased. High CD19, high CD8+CD45RA+ cells, and low effector memory CD4+/naïve CD4+ cells of the T-cell populations were present in the Type 1 group. The Type 1 group had higher concentrations of plasma CXCL10, MIP-1 beta, and TNF-alpha. No severe adverse events were reported in all LT recipients. We identified the immune responses induced by inactivated vaccines among LT recipients and provided insights into the identification of immunotypes associated with the responders.

Development of Clinical Risk Scores for Detection of COVID-19 in Suspected Patients During a Local Outbreak in China: A Retrospective Cohort Study

Objectives: To develop and internally validate two clinical risk scores to detect coronavirus disease 2019 (COVID-19) during local outbreaks. Methods: Medical records were extracted for a retrospective cohort of 336 suspected patients admitted to Baodi hospital between 27 January to 20 February 2020. Multivariate logistic regression was applied to develop the risk-scoring models, which were internally validated using a 5-fold cross-validation method and Hosmer-Lemeshow (H-L) tests. Results: Fifty-six cases were diagnosed from the cohort. The first model was developed based on seven significant predictors, including age, close contact with confirmed/suspected cases, same location of exposure, temperature, leukocyte counts, radiological findings of pneumonia and bilateral involvement (the mean area under the receiver operating characteristic curve [AUC]:0.88, 95% CI: 0.84–0.93). The second model had the same predictors except leukocyte and radiological findings (AUC: 0.84, 95% CI: 0.78–0.89, Z = 2.56, p = 0.01). Both were internally validated using H-L tests and showed good calibration (both p > 0.10). Conclusion: Two clinical risk scores to detect COVID-19 in local outbreaks were developed with excellent predictive performances, using commonly measured clinical variables. Further external validations in new outbreaks are warranted.

Quantitative Analysis of the Impact of Ecological Industry and Ecological Investment on the Economy: A Case Study of Beijing, China

As China attaches increasing importance to its ecological environment, ecology-related industries have become essential to China’s national economy. However, in the current national economic accounting practice, the ecological industry (eco-industry) is not independent, and the ecological service value ecology creates is currently not within the scope of national economic accounting. To clarify the impact of the development of the eco-industry on the whole regional economy, this paper takes Beijing as the study area. For the first time, the input–output analysis method is adopted to differentiate the eco-industry as an independent sector. Moreover, the ecosystem services value is integrated into the eco-industry, and each coefficient is quantitatively analyzed from an industrial-chain perspective. The results show that the eco-industry exerts a good pulling effect on the regional economy. The inputs and outputs of the eco-industry clearly tend to focus on eco-environmental and public-service-related industries, followed by industries for which ecological development can create value. Judging from the entire regional economy, ecological investment significantly impacts both the education and financial industries. Ecological investment can promote socio-economic development, achieving a 1.318 increase in regional GDP per unit of eco-investment. The results imply that the development of the eco-industry in China should be boosted further and social capital investment should be attracted. Finally, this paper provides a scientific basis for policymakers to better understand the overall situation of both the eco-industry and industry linkages and guide them to develop relevant ecological investment strategies.

Research progress on immunological features and immunotherapy strategies of coronavirus disease 2019

Since December 2019, there had been an outbreak of coronavirus disease 2019 (COVID-19) epidemic caused by severe-acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China. Immunological features of COVID-19 have a potential value for clinical diagnosis and treatment. This review discussed the importance of immune homeostasis in COV1D-19, and provided several suggestions on immunoprophykxis and immunotherapy for COVID-19.

A Multicentre Study on the Prevalence of Respiratory Viruses in Children with Community Acquired Pneumonia Requiring Hospitalization in the Setting of the Zero-COVID Policy in China (preprint)

Stringent nonpharmaceutical interventions (NPIs) have been implemented worldwide to combat the COVID-19 pandemic, and the circulation and seasonality of common respiratory viruses have subsequently changed. Multicentre studies and comparisons of the prevalence of respiratory viruses accounting for community-acquired pneumonia (CAP) in hospitalized children between the pre-COVID period and the period after community and school reopening in the setting of the zero-COVID policy are rare. In this study, we included 1543 children with CAP who required hospitalization from November 1st, 2020 to April 30th, 2021 (Period 1) and 629 children with the same conditions from November 1st, 2018 to April 30th, 2019 (Period 2) in our study. All respiratory samples from the included patients were screened for six respiratory viruses (respiratory syncytial virus [RSV], adenovirus [ADV], influenza A virus [Flu A], influenza B virus [Flu B], parainfluenza virus type 1 [PIV1], and parainfluenza virus type 3 [PIV3]) using a multiplex real-time PCR assay. The median ages of enrolled patients at the time of diagnosis were 1.5 years and 1.0 years for period 1 and period 2, respectively. In period 1, viral pathogens were detected in 50.3% (776/1543) of enrolled patients. The most frequently identified viral pathogen was RSV (35.9%, 554/1543), followed by PIV3 (9.6%, 148/1543), PIV1 (3.6%, 56/1543), ADV (3.4%, 52/1543), Flu A (1.0%, 16/1543) and Flu B (0.8%, 13/1543). The total detection rates of these six viruses in the peak season of CAP were at the pre-COVID level. The prevalence of Flu A decreased dramatically and circulation activity was low compared to pre-COVID levels, while the incidence of PIV3 increased significantly. There were no significant differences in the detection rates of RSV, ADV, Flu B and PIV1 between the two periods. Our results showed that respiratory viruses accounted for CAP in hospitalized children at pre-COVID levels as communities and schools reopened within the zero-COVID policy, although the prevalence aetiology spectrum varied.