Clinical Analysis of Febrile Seizures in Children with COVID-19 in the Omicron Era: a Single-Center Retrospective Observational Study (preprint)

Objectives：This study sought to investigate the characteristics of febrile seizures in children infected with the Omicron variant in Chongqing province, west of China, and underscore the importance of monitoring for potential neurological complications associated with this variant. Methods: This retrospective study enrolled a total of 84 pediatric patients with COVID-19 and FS who were admitted to Chongqing University Three Gorges Hospital between December 11th and December 26th, 2022. Demographic, clinical, laboratory, radiological and EEG data were retrospectively summarized. Results: The study enrolled 84 children, with a median age of 21.5 (15-35.5) months and a range of 6-162 months. Among these, 11.9% were of atypical age (age > 5 years). The patient population comprised of 54 (64.29%) boys and 30 (35.71%) girls. 32.14% presented with complex FS. Generalized tonic-clonic seizures occurred in 51.19%, followed by generalized tonic seizures (43.43%). 86.9% occurred within 24h after fever onset and 80.95% continued for ≤ 5min. Conclusions: Febrile seizures in children with Omicron VOC are common COVID-19 illness with a higher prevalence compared with other VOCs. They present with similar clinical manifestations and resolve spontaneously with a benign clinical outcome in line with other seasonal viruses.

A Study on the Economic Resilience of Industrial Parks

The development of globalization has brought about obvious differences in the resilience of different regions against economic crises. Regional economic resilience refers to the ability of a region's economy to resist shocks when faced with external disturbances or to break away from its existing growth model in favor of a better path, Resilience represents the region's adaptability, innovation, and sustainability. This paper describes an empirical analysis on the 60 designated industrial park developments under the Industrial Development Bureau in Taiwan. Over a period of short-term disturbances, the industrial parks are analyzed from four aspects: industrial structure, regional development foundation, enterprise competitiveness and labor conditions, and government governance and policy systems. Through discriminant analysis, we analyze the characteristics of factors that mainly affect the economic resilience of 60 industrial parks faced with shocks such as the subprime mortgage crisis in 2008, the five-day work week in 2016, and the COVID-19 outbreak in 2019. We found that industrial structure, specifically diversified industrial structure, is the major factor behind enhanced regional economic resilience. If the scale of specialized industries is large enough, they can form sufficient capacity to resist external changes and also be economically resilient. Under the negative impact, the amount of innovation can be an important part of post-disaster recovery, and stable innovation input will become a main factor for the sustainable development of industrial parks. The pressure of the uncertainty of global economic development and the transformation and upgrading of the domestic economy underscore that enterprises urgently need automation and digital transformation to enhance their competitiveness. In order to enhance economic resilience to adapt to changes in the overall environment, the industrial parks need to adjust adaptively, improve their industrial structure, and promote innovation, hoping that the regional economy will move towards a more stable and sustainable development path.

Natural evolution of SARS-CoV-2 variants in K18-ACE2 mice gives rise to more virulent virus and variant alleles associated with treatment resistance. (preprint)

Background: The continuing COVID-19 pandemic is partially due to viral evolution decreasing vaccine and treatment efficacies. Predicting viral evolution is difficult. Others have found that serial infections of the original SARS-CoV-2 isolate in non transgenic mice is accompanied with selection of alleles (such as Spike 417N, 493H and 501Y) conferring adaptation and greater binding affinity for the murine ACE2 receptor, enhanced infectivity, and lethal phenotype in mice. We designed a study to investigate long-term viral evolution's impact in K18-ACE2 mice with virus closer related to the Omicron sub-lineage. Methods: We serially infected SARS-CoV-2-naive mice with either the B.1.351 (Beta) or the B.1.617.2 (Delta) variant across twenty passages without selective pressures. We sequenced virus across passages, annotating variant alleles changing in frequency using published tools, tracking alleles suspected of decreasing vaccine/treatment efficacy. We evaluated virulence in animals infected with virus isolated at study completion and determined antibody neutralization sensitivity using sera from vaccinated individuals. Results and Conclusions: We observed variant alleles with documented roles in vaccine-elicited immunity evasion. This included the Omicron-associated mutation spike S371F that arose de-novo during our study. Passage 20 (P20) viruses were more virulent that their P0 counterpart with P20 Delta lineage being significantly more resistant to antibody neutralization. These developments occurred within two months of the study starting, suggesting that our model can rapidly emulate pandemic progression in mammals. While our model lacked selective pressures, such as pre-existing SARS-CoV-2 immunity, these conditions could readily be adapted. Such modeling could enable development of more evolution-resistant treatments.

The therapeutic monoclonal antibody bamlanivimab does not enhance SARS‑CoV-2 infection by FcR-mediated mechanisms (preprint)

Background Antibodies targeting envelope glycoproteins have been shown in some instances to enhance infection by subverting Fc receptor and complement function, or by directly inducing fusion with cellular membranes. The potential for antibody dependent enhancement (ADE) of infection raises concern that passive immunization with a therapeutic anti-viral antibody could increase risk of disease. As part of the nonclinical package characterizing the risk profile of the SARS-CoV-2 neutralizing monoclonal antibody bamlanivimab, studies were conducted to evaluate the potential for ADE of infection in vitro and in a non-human primate model of COVID-19.Methods In vitro assays were performed in primary human macrophage, Raji, or THP-1 cells exposed to SARS-CoV-2 in the presence of bamlanivimab ranging from approximately IC50 to more than 100-fold above or below the IC50. Samples were evaluated for demonstration of productive viral infection. Bamlanivimab binding to C1q and FcR were quantified, and activity was studied by cell-based assays. In vivo studies were performed in African green monkeys (AGM) infected with SARS-CoV-2 virus following sub-saturating or saturating doses of bamlanivimab or IgG control. Viral loads, clinical pathology, and histology endpoints were assessed to determine if bamlanivimab enhanced SARS-CoV-2 replication or clinical illness. Mixed model repeated measures were used to evaluate virology statistics.Results Bamlanivimab did not increase viral RNA production in FcγR-expressing cell lines, despite demonstration of effector function. No significant differences were found among the AGM groups in terms of weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Microscopic findings along with decreases in viral loads in bamlanivimab-treated animals indicated that ADE of disease was not observed in this study.Conclusions Sub-saturating doses of bamlanivimab treatment do not induce ADE of SARSCoV2 infection in either in vitro or an AGM model of infection. Findings suggest that high affinity monoclonal antibodies pose a low risk of mediating ADE in patients and further supports their safety profile as a treatment of COVID-19 disease.

Neutralization effect of plasma from vaccinated COVID-19 convalescents on SARS-CoV-2 Omicron variants

Background COVID-19 has caused a global pandemic and the death toll is increasing. With the coronavirus continuously mutating, Omicron has replaced Delta as the most widely reported variant in the world. Studies have shown that the plasma of some vaccinated people does not neutralize the Omicron variant. However, further studies are needed to determine whether plasma neutralizes Omicron after one- or two-dose vaccine in patients who have recovered from infection with the original strain. Methods The pseudovirus neutralization assays were performed on 64 plasma samples of convalescent COVID-19 patients, which were divided into pre-vaccination group, one-dose vaccinated group and two-dose vaccinated group. Results In the three groups, there were significant reductions of sera neutralizing activity from WT to Delta variant (B.1.617.2), and from WT to Omicron variant (B.1.1.529) (ps<0.001), but the difference between Delta and Omicron variants were not significant (p>0.05). The average neutralization of the Omicron variant showed a significant difference between pre-vaccination and two-dose vaccinated convalescent individuals (p<0.01). Conclusions Among the 64 plasma samples of COVID-19 convalescents, whether vaccinated or not, Omicron (B.1.1.529) escaped the neutralizing antibodies, with a significantly decreased neutralization activity compared to WT. And two-dose of vaccine could significantly raise the average neutralization of Omicron in convalescent individuals.

Effects of Home Office Order on Ambient Particulate Matters Assessed by Interrupted-Time-Series Analysis: Evidence from Shanghai, China

Coronavirus Disease 2019 (COVID-19) has caused a pandemic globally since its outbreak in 2019. As an important port city with prosperous foreign trade, Shanghai has been under severe pressure to prevent the input of COVID-19. With this in mind, solid policies and measures have always been taken in Shanghai to control the input of COVID-19 strictly. In March 2022, the SARS-CoV-2 Omicron variant swept Shanghai, and then the home office order was rapidly carried out in most of the districts. This article focuses on quantifying the changes in concentrations of PM10 and PM2.5 in Shanghai after implementing the home office order and exploring the spatial-distribution characteristics and time trend of the impact of the home office order on airborne particulate matters (PMs) through an interrupted-time-series (ITS) analysis. This study found that PM10 and PM2.5 decreased by 31.40 μg/m3 (p = 0.028) and 10.33 μg/m3 (p = 0.276), respectively, with the fastest decrease speed in the first 10 days of the home office order. Meanwhile, the changes in PM concentrations in eastern areas such as Fengxian District and Chongming District are less than those in central and western areas of Shanghai. Therefore, it can be concluded that implementing the home office order for 10 days could effectively cut down PM concentrations, and the reduction values can be affected by spatial difference and time factor.

Computer-aided Classification of Lung Nodules on CT Images with Expert Knowledge

Accurate classification of pulmonary nodules in the CT images is critical for early detection of lung cancer as well as the assessment of the effect from COVID-19. In this paper, we propose a computer-aided classification method for lung nodules using expert knowledge. We use a decoupling metric learning model to describe the deep characteristics of the nodules and then calculate the similarity between the current nodule and the nodules in the database. By analyzing the returned nodules with the diagnosis information, we obtain the expert knowledge of similar nodules, based on which we make the decision of the current nodule. The proposed method has been evaluated on the benchmark LIDC-IDRI dataset and achieved an accuracy of 95.7% and AUC of 0.9901. The proposed classification method can have a variety of applications in lung cancer detection, diagnosis and therapy.

Long-term immune persistence induced by two-dose BBIBP-CorV vaccine with different intervals, and immunogenicity and safety of a homologous booster dose in high-risk occupational population. Secondary Study Based on a Randomized Clinical Trial (preprint)

Background BBIBP-CorV vaccine with two doses and an interval of 3-4 weeks had been proved to have good immunogenicity and efficacy as well as an acceptable safety profile according to our initial research and other similar studies. Maintaining adequate neutralizing antibody levels is also necessary for long-term protection, especially in the midst of the COVID-19 pandemic. Our aim was to evaluate the immune persistence of neutralizing antibody elicited by BBIBP-CorV vaccines with day 0-14, 0-21 and 0-28 schedule, and assess the immunogenicity and safety of a homologous booster dose in the high-risk occupational population aged 18-59 years. Methods A total of 809 eligible participants, aged 18-59 years, were recruited and randomly allocated to receive BBIBP-CorV vaccine with day 0-14, 0-21 or 0-28 schedule respectively between January and May 2021 in Taiyuan City, Shanxi Province, China among the public security officers and the airport ground staff in initial study. In this secondary study, the responders (GMT [≥] 16) at day 28 after priming two-dose vaccine were followed up at months 3, 6 and 10 to evaluate the immune persistence of three two-dose schedules. At month 10, eligible participants of three two-dose schedules were received a homologous booster dose respectively (hereafter abbreviated as 0-14d-10m group, 0-21d-10m group and 0-28d-10m group), and followed up at day 28 post-booster to assess the safety and immunogenicity of the booster dose. The contents of follow-up included the blood samples, oropharyngeal/nasal swabs, and adverse reactions collection. The main outcomes of the study included geometric mean titers (GMT) of neutralizing antibody to live SARS-CoV-2, the positive rates of different criteria and the constituent ratio of GMT of neutralizing antibodies at different follow-up point. Meanwhile, we explored the kinetics of antibody levels of different vaccination regimens by generalized estimating equations (GEE) and used exponent curve model to predict the duration of maintaining protected antibody after the booster dose. We also determined predictors of maintaining protected antibody level within 10 months after the second dose by Cox proportional hazards regression model and nomogram. The trial was registered with ChiCTR.org.cn (ChiCTR2100041705, ChiCTR2100041706). Results The number of 241, 247 and 256 responders (GMT [≥] 16) at day 28 after two-dose BBIBP-CorV vaccine in 0-14d, 0-21d and 0-28d schedule were followed-up at months 3, 6, and 10 for immune persistence evaluation. At month 10, a total of 390 participants were eligible and received a booster dose with 130 participants in the 0-14d-10m, 0-21d-10m and 0-28d-10m group respectively, of whom 74.1% (289/390) were male, with a mean age of 37.1{+/-}10.3 years. The GMT of neutralizing antibody in 0-28d-10m and 0-21d-10m group were significantly higher than 0-14d-10m group at month 3 (GMT: 71.6 & 64.2 vs 46.4, P<0.0001 ), month 6 (GMT: 47.1 & 42.8 vs 30.5, P<0.0001) and month 10 (GMT: 32.4 vs 20.3, P<0.0001; 28.8 vs 20.3, P=0.0004) after the second dose. A sharply decrease by 4.85-fold (GMT: 94.4-20.3), 4.67-fold (GMT: 134.4-28.8) and 4.49-fold (GMT: 145.5-32.4) was observed from day 28 to month 10 after the second dose in 0-14d-10m, 0-21d-10m and 0-28d-10m group, respectively, and they had similar decline kinetics (P=0.67). At 28 days after booster dose, a remarkable rebound in neutralizing antibody (GMT: 246.2, 277.5 and 288.6) were observed in three groups, respectively. Notably, the GMT after booster dose was not affected by priming two-dose schedule. The predictive duration of neutralizing antibody declining to the cutoff level of positive antibody response may be 18.08 months, 18.83 months and 19.08 months after booster dose in three groups, respectively. Long-term immune persistence within 10 months after the second dose was associated with age<40, female, and history of influenza vaccination. All adverse reactions were mild after the booster injection. None of the participants were infected SARS-CoV-2 during the trial period. Conclusions The priming two-dose BBIBP-CorV vaccine with 0-28 days and 0-21 days schedule could lead a longer persistence of neutralizing antibody than 0-14 days schedule. Maintaining long-term immune persistence was also associated with age<40, female, and history of influenza vaccination. Regardless of priming two-doses vaccination regimens, a homologous booster dose led to a strong rebound in neutralizing antibody and might elicit satisfactory persistent immunity.

How social enterprises gain cognitive legitimacy in the post-pandemic period? Social welfare logic and digital transformation

Purpose>This paper aims to propose a social enterprise legitimation mechanism by combining the established logic and transformational logic to test the validity of the conceptual model.Design/methodology/approach>The authors construct the theoretical framework based on integrating organizational identity theory, attention-based view and collected 128 social enterprises data during the post-pandemic period in China. The authors applied multiple hierarchical regression analysis and mediation analysis to test the research hypothesis.Findings>The results show that strong organizational identity contributes significantly to the cognitive legitimacy of social enterprise. Besides, we found that social welfare logic and digital transformation can positively mediate the correlation between organizational identity and cognitive legitimacy.Practical implications>Social enterprises enhance legitimacy significantly by social welfare logic comparing with commercial logic, which indicates that social enterprises should allocate more internal resources and attention to present the organization's social value through various distributions. More importantly, social enterprises should embrace digital transformation to enhance transparency and efficiency, decrease transaction costs, enlarge organizational social impact to strengthen cognitive legitimacy.Originality/value>The paper first proposed and empirically tested that digital transformation is an important mechanism to enhance the social enterprise's cognitive legitimacy.

Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccine in High-Risk Occupational Population: a randomized, parallel, controlled clinical trial (preprint)

Vaccination is urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we conducted a randomized, parallel, controlled clinical trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval for high-risk occupational population. Participants were randomly assigned to receive two doses of inactivated SARS-CoV-2 vaccine (4 {micro}g per dose) at an interval of either 14 days, 21 days or 28 days. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Our results showed that the seroconversion rates (GMT [≥] 16) were all 100% in the three groups and the 0-21 and 0-28 groups elicited significantly higher SARS-CoV-2 neutralizing antibody level. All reported adverse reactions were mild. (Chinese Clinical Trial Registry: ChiCTR2100041705, ChiCTR2100041706)

Change of disease distribution in pediatric neurology inpatients during the COVID-19 outbreak in southwest China (preprint)

This study aimed to investigate the change of disease distribution in pediatric neurology inpatients during the COVID-19 outbreak in southwest China. We retrospectively extracted the demographic data and diagnosis of discharged patients registered at pediatric neurology department of Chengdu Women’s and Children’s Central Hospital from January 1 to July 31, 2019 and January 1 to July 31, 2020. Total number of inpatients decreased during COVID-19 outbreak. Children diagnosed as febrile seizure caused by infection (1799/60.7% vs 980/59%, P = 0.141), dyskinesia (31/1.0% vs 28/1.7%, P = 0.075) and benign intracranial hypertension (41/1.4% vs 21/1.3%, P = 0.791) did not change. While children diagnosed as epilepsy (304/10.3% vs 348/21%, P < 0.001), migraine (25/0.8% vs 31/1.9%, P = 0.003), mental disease (24/0.8% vs 43/2.6%, P < 0.001) and peripheral neuropathy (38/1.3% vs 43/2.6%, P = 0.001) increased in 2020. Children diagnosed as intracranial infection (535/18% vs113/6.8%, P < 0.001) and myopathy (106/3.6% in vs 22/2.0%, P = 0.003) reduced in 2020. Conclusions: We found a significant increase in the proportion of mood-related diseases, while disease caused by infection decreased. We should pay attention to children’s mental state during the public health epidemic and the management of chronic disease.

Precaution and prevention of coronavirus disease 2019 infection in the eye.

Although current studies suggested that conjunctivitis is not a common presentation of coronavirus disease 2019 (COVID-19), several studies have reported the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ocular secretions. Coronavirus had not yet been successfully cultured from tears or conjunctival swabs in humans, neither SARS-CoV-2 nor SARS-CoV. However, live feline coronavirus has been isolated from conjunctival swabs. In addition, infection of COVID-19 through unprotected eye exposure had been suspected in several articles. Reports of ophthalmologists and otolaryngologists died of COVID-19 also raised concern on ocular transmission. As a result, we strongly suggest that personal protective equipment (PPE) should cover the mouth, nose, and eyes of ophthalmologists, especially when conjunctivitis caused by SARS-CoV-2 is clinically indistinguishable from other viral follicular conjunctivitis.

A Simple Nomogram for Predicting Failure of Non-Invasive Respiratory Therapies in Adults with COVID-19: A Retrospective Multicenter Study (preprint)

Background: Non-invasive respiratory therapies (NIRTs) (high flow nasal cannula and non-invasive ventilation) are widely used in COVID-19 patients who developed acute respiratory failure. However, use of these therapies may delay initiation of invasive mechanical ventilation in some patients and hence worsen their outcome. This study set out to identify early predictors of NIRT failure and to develop a simple-to-use nomogram and an online calculator identifying patients at high risk of NIRT failure. Methods: A retrospective cohort of 652 COVID-19 patients with ARF who received NIRTs, was used to develop early predictors of NIRT failure, defined as subsequent need for invasive mechanical ventilation or death within 28 days after ICU admission. Multivariate logistic analysis was used to develop the nomogram and ten-fold cross-validation was applied to internally validate the stability of the model. Findings: The failure rate of NITRs was 63% (415/652). The ROX index (ratio of pulse oximetry oxygen saturation/fraction of inspired oxygen to respiratory rate), age, GCS score, and use of vasoprEssors on the first day of NIRTs were independent risk factors for NIRT failure (RAGE factors). Based on the multivariate analysis, the RAGE nomogram for NIRTs failure had a C-statistics of 0 . 83 (95% CI:0 . 80–0 . 87). An internal validation demonstrated that the mean C-statistic remained stable (C-statistics=0 . 84±0 . 03). Internal calibration was excellent (calibration slope=1). Interpretation: The nomogram and online calculator are relatively simple-to-use and able to predict the risk of NIRT failure in COVID-19 patients with acute respiratory failure. Funding Statement: This work was supported by Key Research and Development Plan of Jiangsu Province (BE2018743 and BE2019749) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences (2016-I2M-1-014).Declaration of Interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.Ethics Approval Statement: The study was approved by the ethics committee of Jin Yintan Hospital (KY-2020-10.02). Informed consent was waived due to the retrospective and observational nature of the study.

Anaemia is Associated with Severe Illness in COVID-19: A Retrospective Cohort Study (preprint)

Background and objective:Anaemia commonly aggravates the severity of respiratory diseases, whereas thus far, no study has elucidated the impact of anaemiaonCorona Virus Disease 2019(COVID-19). The aim of this study was to evaluate the clinical characteristics of patients with anaemia, and to further explore the relationship between anaemiaand the severity of COVID-19.METHODS:In this single-center, retrospective, observational study, a total of 222 patients were recruited, including 79 patients with anaemia and 143 patients without anaemia. Clinical characteristics, laboratory findings, disease progression and prognosis were collected and analyzed. Risk factors associated with the severe illness in COVID-19were established by univariable and multivariable logistic regression models.Result：In our cohort, compared to patients without anaemia, patients with anaemia were more likely to experience one or more comorbidities and severe COVID-19 illness, as well as higher mortality. More patients demonstrated elevated levels of C-reactive protein (CRP), procalcitonin(PCT) and creatinine in anaemia group. Levels of erythrocyte sedimentation rate(ESR), D-dimer, myoglobin, T-pro brain natriuretic peptide(T-pro-BNP) and urea nitrogen(BUN)in patients with anaemia were significantly higher than those without. In addition,the proportion of patients with dyspnoea，elevated CRP and PCT was positively associated with the severity of anaemia. The Odd Ratio (OR) of anaemia related to the severe condition of COVID-19 was 5.07 (95% CI:1.82-14.18, P=0.002) and 3.47 (95% CI:1.02-11.75, P=0.046) after adjustment for baseline date and laboratory indices, respectively.Conclusion:Anaemia is an independent risk factor associated with the severe illness of COVID-19, and healthcare professionals should be more sensitive to the haemoglobin levels of COVID-19 patients on admission. To avoid rapid deterioration, more intensive care should be given to patients with anaemia.Trial registration: Ethics committee of Wuhan University People's Hospital (wdry2020-k064)

Clinical features and the maternal and neonatal outcomes of pregnant women with coronavirus disease 2019 (preprint)

BACKGROUND There is little information about the coronavirus disease 2019 (Covid-19) during pregnancy. This study aimed to determine the clinical features and the maternal and neonatal outcomes of pregnant women with Covid-19. METHODS In this retrospective analysis from five hospitals, we included pregnant women with Covid-19 from January 1 to February 20, 2020. The primary composite endpoints were admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Secondary endpoints included the clinical severity of Covid-19, neonatal mortality, admission to neonatal intensive care unit (NICU), and the incidence of acute respiratory distress syndrome (ARDS) of pregnant women and newborns. RESULTS Thirty-three pregnant women with Covid-19 and 28 newborns were identified. One (3%) pregnant woman needed the use of mechanical ventilation. No pregnant women admitted to the ICU. There were no moralities among pregnant women or newborns. The percentages of pregnant women with mild, moderate, and severe symptoms were 13 (39.4%),19(57.6%), and 1(3%). One (3.6%) newborn developed ARDS and was admitted to the NICU. The rate of perinatal transmission of SARS-CoV-2 was 3.6%. CONCLUSIONS This report suggests that pregnant women are not at increased risk for severe illness or mortality with Covid-19 compared with the general population. The SARS-CoV-2 infection during pregnancy might not be associated with as adverse obstetrical and neonatal outcomes that are seen with the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy. (Funded by the National Key Research and Development Program.)