Can public emergencies force farmers to improve Automation level? (preprint)

The frequent occurrence of public emergencies seriously affects the healthy development of the farming industry, and it is important to improve the level of farming automation to cope with the impact of public emergencies and improve farming efficiency and the healthy development of the farming industry. Based on the dual impact of African swine fever and COVID-19, the article empirically analyzes the impact of unexpected public events on the level of farming automation using primary research data and an Ordered Logit model. It is found that: 1) both direct and indirect shocks of public emergencies will force farming entities to improve their automation levels; 2) there are differences in the impact of public emergencies on different scale farming entities to improve their automation levels. For conventional farmers, the direct impact of public emergencies on the improvement of farming automation level changes from negative to positive with the introduction of control variables. For non-regulated farmers, both direct and indirect shocks from public emergencies increase the probability of increasing automation level. Accordingly, the article proposes suggestions in terms of increasing the investment in automation facilities, investment in disease prevention and control, and consideration of scale differences to help farmers better cope with the shocks of unexpected public events and thus stabilize production.

Optimization and deoptimization of codons in SARS-CoV-2 and the implications for vaccine development (preprint)

ABSTRACT The spread of Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has progressed into a global pandemic. To date, thousands of genetic variants have been identified across SARS-CoV-2 isolates from patients. Sequence analysis reveals that the codon usage of viral sequences decreased over time but fluctuated from time to time. In this study, through evolution modeling, we found that this phenomenon might result from the virus’ preference for mutations during transmission. Using dual luciferase assays, we further discovered that the deoptimization of codons on viruses might weaken protein expression during the virus evolution, indicating that the choice of codon usage might play important role in virus fitness. Finally, given the importance of codon usage in protein expression and particularly for mRNA vaccine, we designed several omicron BA.2.12.1 and BA.4/5 spike mRNA vaccine candidates based on codon optimization, and experimentally validated their high levels of expression. Our study highlights the importance of codon usage in virus evolution and mRNA vaccine development.

The runaway evolution of SARS-CoV-2 leading to the highly evolved Delta strain (preprint)

In new epidemics after the host shift, the pathogens may experience accelerated evolution driven by novel selective pressures. When the accelerated evolution enters a positive feedback loop with the expanding epidemics, the pathogen's runaway evolution may be triggered. To test this possibility in COVID-19, we analyze the extensive databases and identify 5 major waves of strains, one replacing the previous one in 2020-2021. The mutations differ entirely between waves and the number of mutations continues to increase, from 3-4 to 21-31. The latest wave is the Delta strain which accrues 31 new mutations to become highly prevalent. Interestingly, these new mutations in Delta strain emerge in multiple stages with each stage driven by 6-12 coding mutations that form a fitness group. In short, the evolution of SARS-CoV-2 from the oldest to the youngest wave, and from the earlier to the later stages of the Delta wave, is a process of acceleration with more and more mutations. The global increase in the viral population size (M(t), at time t) and the mutation accumulation (R(t)) may have indeed triggered the runaway evolution in late 2020, leading to the highly evolved Alpha and then Delta strain. To suppress the pandemic, it is crucial to break the positive feedback loop between M(t) and R(t), neither of which has yet to be effectively dampened by late 2021. New waves beyond Delta, hence, should not be surprising.

One viral sequence for each host? - The neglected within-host diversity as the main stage of SARS-CoV-2 evolution (preprint)

The standard practice of presenting one viral sequence for each infected individual implicitly assumes low within-host genetic diversity. It places the emphasis on the viral evolution between, rather than within, hosts. To determine this diversity, we collect SARS-CoV-2 samples from the same patient multiple times. Our own data in conjunction with previous reports show that two viral samples collected from the same individual are often very different due to the substantial within-host diversity. Each sample captures only a small part of the total diversity that is transiently and locally released from infected cells. Hence, the global SARS-CoV-2 population is a meta-population consisting of the viruses in all the infected hosts, each of which harboring a genetically diverse sub-population. Advantageous mutations must be present first as the within-host diversity before they are revealed as between-host polymorphism. The early detection of such diversity in multiple hosts could be an alarm for potentially dangerous mutations. In conclusion, the main forces of viral evolution, i.e., mutation, drift, recombination and selection, all operate within hosts and should be studied accordingly. Several significant implications are discussed.

Worldwide tracing of mutations and the evolutionary dynamics of SARS-CoV-2 (preprint)

Understanding the mutational and evolutionary dynamics of SARS-CoV-2 is essential for treating COVID-19 and the development of a vaccine. Here, we analyzed publicly available 15,818 assembled SARS-CoV-2 genome sequences, along with 2,350 raw sequence datasets sampled worldwide. We investigated the distribution of inter-host single nucleotide polymorphisms (inter-host SNPs) and intra-host single nucleotide variations (iSNVs). Mutations have been observed at 35.6% (10,649/29,903) of the bases in the genome. The substitution rate in some protein coding regions is higher than the average in SARS-CoV-2 viruses, and the high substitution rate in some regions might be driven to escape immune recognition by diversifying selection. Both recurrent mutations and human-to-human transmission are mechanisms that generate fitness advantageous mutations. Furthermore, the frequency of three mutations (S protein, F400L; ORF3a protein, T164I; and ORF1a protein, Q6383H) has gradual increased over time on lineages, which provides new clues for the early detection of fitness advantageous mutations. Our study provides theoretical support for vaccine development and the optimization of treatment for COVID-19. We call researchers to submit raw sequence data to public databases.

The Way a General Hospital Treated COVID-19 in Shenzhen, China & the Epidemiological and Clinical Characteristics of its Confirmed Patients (preprint)

Objectives: To discuss the prevention and containment of COVID-19 at a general hospital in Shenzhen China; to analyze the epidemiological and clinical characteristics of its confirmed patients, which is intended to provide a model for other hospitals in COVID-19 management.Methods: The General Hospital of Shenzhen University sets up 4 medical zones relative to the COVID-19 prevention and containment. In so doing, the suspected patients classified into different kind of ward receive different treatment (Classified and Separated Treatment). The epidemiological distribution and clinical characteristics of 28 confirmed cases in the hospital were analyzed.Results: There are no medical personnel infected cases, no cross-infection among the patients in the hospital, and no misdiagnosis or missed diagnosis of COVID-19. The majority of cases in the group is from 15 to 60 years old, 25 cases had a definite travel history or close contact history in the epidemic area, and parents and spouses of the confirmed patients are the main contact groups. Fever and respiratory symptoms have a high proportion, 4 diarrhea and 4 asymptomatic cases. Additionally, the decrease of lymphocyte is observed in 8 cases. Chest CT scan shows viral pneumonia in 14 cases，All patients were confirmed by nucleic acid tests.Conclusions: Classified and Separated Treatment facilitates management of COVID-19 in the general hospital. Relative to suspected patients in the general hospital, diagnosis matters more than treatment. Epidemiological history, lymphocyte count, and chest CT scan play an important role as the indicator in early diagnosis of COVID-19.

A New, Simple Projection Model for COVID-19 Pandemic (preprint)

With the worldwide outbreak of COVID-19, an accurate model to predict how the coronavirus pandemic will evolve becomes important and urgent to help policy makers in different countries address the epidemic outbreak and determine policies to control spread more efficiently and effectively. Unlike the classic public health and virus propagation models, this new projection model takes government intervention and public response into account to make reliable projections of the outbreak 10 days to 2 weeks in advance.