Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48 (preprint)

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+ cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features.

Understanding spatiotemporal symptom onset risk of Omicron BA.1, BA.2 and hamster-related Delta AY.127

Purpose Investigation of the community-level symptomatic onset risk regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, is crucial to the pandemic control in the new normal. Methods Investigated in this study is the spatiotemporal symptom onset risk with Omicron BA.1, BA.2, and hamster-related Delta AY.127 by a joint analysis of community-based human mobility, virus genomes, and vaccinations in Hong Kong. Results The spatial spread of Omicron BA.2 was found to be 2.91 times and 2.56 times faster than that of Omicron BA.1 and Delta AY.127. Identified has been an early spatial invasion process in which spatiotemporal symptom onset risk was associated with intercommunity and cross-community human mobility of a dominant source location, especially regarding enhancement of the effects of the increased intrinsic transmissibility of Omicron BA.2. Further explored is the spread of Omicron BA.1, BA.2, and Delta AY.127 under different full and booster vaccination rate levels. An increase in full vaccination rates has primarily contributed to the reduction in areas within lower onset risk. An increase in the booster vaccination rate can promote a reduction in those areas within higher onset risk. Conclusions This study has provided a comprehensive investigation concerning the spatiotemporal symptom onset risk of Omicron BA.1, BA.2, and hamster-related Delta AY.127, and as such can contribute some help to countries and regions regarding the prevention of the emergence of such as these variants, on a strategic basis. Moreover, this study provides scientifically derived findings on the impact of full and booster vaccination campaigns working in the area of the reduction of symptomatic infections.

TBR-NER: Research on COVID-19 Text Information Extraction Based on Joint Learning of Topic Recognition and Named Entity Recognition

There is a centralization of the core content in the text information of the new crown epidemic notification. This paper proposes a joint learning text information extraction method: TBR-NER (topic-based recognition named entity recognition) based on topic recognition and named entity recognition to predict the labeled risk areas and epidemic trajectory information in text information. Transfer learning and data augmentation are used to solve the problem of data scarcity caused by the initial local outbreak of the epidemic, and mutual understanding is achieved by topic self-labeling without introducing additional labeled data. Taking the epidemic cases in Hebei and Jilin provinces as examples, the reliability and effectiveness of the method are verified by five types of topic recognition and 15 types of entity information extraction. The experimental results show that, compared with the four existing NER methods, this method can achieve optimality faster through the mutual learning of each task at the early stage of training. The optimal accuracy in the independent test set can be improved by more than 20%, and the minimum loss value is significantly reduced. This also proves that the joint learning algorithm (TBR-NER) mentioned in this paper performs better in such tasks. The TBR-NER model has specific sociality and applicability and can help in epidemic prediction, prevention, and control.

Extreme co-movements between infectious disease events and crude oil futures prices: From extreme value analysis perspective

This paper examines the extreme co-movements between infectious disease events and crude oil futures through extreme value analyses. We contribute to the literature by providing a novel framework of tail risk early warning and considering infectious diseases as a systemic risk factor for crude oil futures. The results provide evidence that: (1) when an extreme event occurs, the tail index of the infectious disease reaches its empirical lower threshold, which is approximately 2.30;(2) when a jump in volatility corresponding to the severeness of the epidemic is observed, the tail index reaches the lower bound, but not reversely;(3) both upside and downside extreme co-movements exist, whereas they are asymmetric;and (4) each tail quotient correlation coefficient keeps rising and reaches a peak before crises and fall sharply with the collapse of crude oil markets. The findings can offer implications for government officials, investors, portfolio managers, and policymakers, respectively.

Rational development of a combined mRNA vaccine against COVID-19 and influenza (preprint)

As the world continues to experience the COVID-19 pandemic, seasonal influenza remain a cause of severe morbidity and mortality globally. Worse yet, coinfection with SARS-CoV-2 and influenza A virus (IAV) leads to more severe clinical outcomes. The development of a combined vaccine against both COVID-19 and influenza is thus of high priority. Based on our established lipid nanoparticle (LNP)-encapsulated mRNA vaccine platform, we developed and characterized a novel mRNA vaccine encoding the HA antigen of influenza A (H1N1) virus, termed ARIAV. Then, ARIAV was combined with our COVID-19 mRNA vaccine ARCoV, which encodes the receptor binding domain (RBD) of the SARS-CoV-2 S protein, to formulate the final combined vaccine, AR-CoV/IAV. Further characterization demonstrated that immunization with two doses of AR-CoV/IAV elicited robust protective antibodies as well as antigen-specific cellular immune responses against SARS-CoV-2 and IAV. More importantly, AR-CoV/IAV immunization protected mice from coinfection with IAV and the SARS-CoV-2 Alpha and Delta variants. Our results highlight the potential of the LNP-mRNA vaccine platform in preventing COVID-19 and influenza, as well as other respiratory diseases.

Increased Occurrence of PTSD Symptoms in Adolescents with Major Depressive Disorder Soon After the Start of the COVID-19 Outbreak in China: a Cross-Sectional Survey (preprint)

ObjectiveThe Coronavirus Disease 2019 (COVID-19) pandemic continues to threaten the physical and mental health of people across the world. This study aimed to understand the psychological impact of this disease on adolescents with major depressive disorder (MDD) at one month after the start of the outbreak in China.MethodsUsing the Children's Impact of Event Scale (CRIES-13) questionnaire, we investigated the occurrence of posttraumatic stress disorder (PTSD) in two groups of adolescents: MDD patients who were in stable condition with antidepressant therapy and healthy controls. Total scores and factor subscores were compared between the two groups and subgroups stratified by sex and school grade. Logistic regression was used to identify variables associated with high total CRIES-13 scores.ResultsCompared to controls (n = 107), the MDD group (n = 90) had higher total CRIES-13 scores and a higher proportion with a total score ≥ 30. They also had a lower intrusion subscore and a higher arousal subscore. In the MDD group, males and females did not differ significantly in total CRIES-13 scores or factor subscores, but junior high school students had higher avoidance subscores than senior high school students. Logistic regression showed high total CRIES-13 scores to be associated with MDD and the experience of “flashbacks” or avoidance of traumatic memories associated with COVID-19.ConclusionsIt is crucial to understand the psychological impact of COVID-19 on adolescents with MDD in China, especially females and junior high school students. Long-term monitoring of adolescents with a history of mental illness is required to further understand these impacts.Trial registrationChiCTR, ChiCTR2000033402, Registered 31 May 2020, http://www.chictr.org.cn/index.aspx

Increased Symptoms of Posttraumatic Stress in School Students Soon After the Start of the COVID-19 Outbreak in China (preprint)

Background: The outbreak of Coronavirus Disease 2019(COVID-19) caused psychological stress in Chinese adults population. But we are unaware of whether the pandemic causes psychological stress on children.Methods: We used the Children’s Impact of Event Scale questionnaire (CRIES-13) to investigate the degree of Post-traumatic Stress (PTSD) symptoms caused by the pandemic in students selected from schools in Sichuan, Jiangsu, Henan, Yunnan, and Chongqing provinces of China.Results: A total of 7769 students(3692 male and 4077 female), aged 8-18 years, were enrolled in the study, comprising 1214 in primary schools, 2799 in junior high schools and 3756 in senior high schools. A total of 1639 students (21.1%) had severe psychological stress reactions. A large proportion of senior high school students (23.3%) experienced severe psychological stress, and they had the highest median total CRIES-13 score. Female students were more likely to experience severe psychological stress and had higher median CRIES-13 total scores than males. Conclusion: COVID-19 has placed psychological stresses on primary and secondary school students in China. These stresses are more likely to reach severe levels among female students and senior high school students. 

Retropharyngeal Abscess in an adult with Pneumonia during COVID-19 Outbreak in China (preprint)

Background: Retropharyngeal abscesses are rarely reported in adults and occur mostly in patients with immunocompromise or as a foreign body complication. Admittedly, the treatment of retropharyngeal abscesses frequently involves surgical drainage to achieve the best results. However, when retropharyngeal abscesses occurred in a highly suspected patient with COVID-19, the managements and treatments should be caution in order to prevent the spread of the virus. Case presentation: On Feb. 13, a 40-year-old male with retropharyngeal abscesses turned to our department complaining dyspnea and dysphagia. In addition, his chest CT scan shows a suspected COVID-19 infection, thus making out Multiple Disciplinary Team (MDT) determine to perform percutaneous drainage and catheterization through left anterior cervical approach under the guidance of B-ultrasound. Finally, the patient recovered and was discharged from the hospital on Feb. 27 after 14 days of isolation. There was no recurrence after half a year follow-up. Conclusions: By presenting this case, we aim at raising awareness of different surgical drainage methods and summarizing our experience in the management of retropharyngeal abscesses during the outbreak of COVID-19. 

The COVID-19 outbreak in Sichuan, China: epidemiology and impact of interventions (preprint)

In January 2020, a COVID19 outbreak was detected in Sichuan Province of China. The aim of this work is to characterize the epidemiology of the Sichuan outbreak and estimate the impact of the performed interventions. We analyzed patient records for all laboratory confirmed cases reported in the province for the period of January 21 to March 16, 2020. To estimate the basic and daily reproduction numbers, we used a Bayesian framework. In addition, we estimate the number of cases averted by the implemented control strategies. The outbreak resulted in 539 confirmed cases, lasted less than two months, and no further local transmission was detected after February 27. The median age of local cases was 8 years older than that of imported cases. Severity of symptoms increased with age. We estimated R0 at 2.4 (95% CI: 1.6-3.7). The epidemic was self sustained for about 3 weeks before going below the epidemic threshold 3 days after the declaration of a public health emergency by Sichuan authorities. Our findings indicate that, were the control measures be adopted four weeks later, the epidemic could have lasted 49 days longer (95%CI: 31-68 days), causing 9,216 (95%CI: 1,317-25,545) more cases and possibly overwhelming Sichuan healthcare system.

Contextualizing covid-19 spread: a county level analysis, urban versus rural, and implications for preparing for the next wave (preprint)

Paraphrasing [Morano and Holt, 2017], contextual determinants of health including social, environmental, healthcare and others, are a so-called deck of cards one is dealt. The ability to modify health outcomes varies then based upon how one's hand is played. It is thus of great interest to understand how these determinants associate with the emerging pandemic covid-19. To this end, we conducted a deep-dive analysis into this problem using a recently curated public dataset on covid-19 that connects infection spread over time to a rich collection of contextual determinants for all counties of the U.S and Washington, D.C. Using random forest machine learning methodology, we identified a relevant constellation of contextual factors of disease spread which manifest differently for urban and rural counties. The findings also have clear implications for better preparing for the next wave of disease.

Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver (preprint)

RNA knockdown in vivo carries significant potential for disease modelings and therapies. Despite the emerging approaches of CRISPR/Cas9-mediated permanent knock out of targeted genes, strategies targeting RNA for disruption are advantageous in the treatment of acquired metabolic disorders when permanent modification of the genome DNA is not appropriate, and RNA virus infection diseases when pathogenic DNA is not available (such as SARS-Cov-2 and MERS infections). Recently, Cas13d, a family of RNA-targeting CRISPR effectors, has been shown to accomplish robust down-regulation of cellular RNAs in mammalian cells in vitro . Among the various Cas13d subtypes, CasRx (RfxCas13d) showed the most potent RNA knockdown efficiency in HEK293T cells. However, the RNA-targeting activity of Cas13d still needs to be verified in vivo . In this study, the CasRx system was demonstrated to efficiently and functionally knock down genes related to metabolism functions, including Pten, Pcsk9 and lncLstr , in mouse hepatocytes. CasRx-mediated simultaneous knockdown of multiple genes was also achieved by sgRNA arrays, providing a useful strategy to modulate complex metabolism networks. Moreover, the AAV (adeno-associated virus)-mediated delivery of CasRx and Pcsk9 sgRNAs into mouse liver successfully decreased serum PCSK9, resulting in significant reduction of serum cholesterol levels. Importantly, CasRx-mediated knockdown of Pcsk9 is reversible and Pcsk9 could be repeatedly down-regulated, providing an effective strategy to reversibly modulate metabolic genes. The present work supplies a successful proof-of-concept trial that suggests efficient and regulatory knockdown of target metabolic genes for a designed metabolism modulation in the liver.