COVID-19 is an acute respiratory infectious disease caused by SARS-CoV-2. It was first reported in Wuhan, China in December 2019 and rapidly spread globally in early 2020, triggering a global pandemic. In December 2022, China adjusted the dynamic COVID-zero strategy that lasted for three years. The number of positive cases in China increased rapidly in the short term. Weihai was also affected during this period. We conducted genomic surveillance of SARS-CoV-2 variants in Weihai during this period, hoping to understand the changes in the genomic characteristics of SARS-CoV-2 before and after the adjustment of the epidemic policy. In this study,we collected SARS-CoV-2 positive samples from March 2022 to March 2023 in Weihai and performed SARS-CoV-2 whole genome sequencing on these samples using next-generation sequencing technology. we obtained a total of 704 SARS-CoV-2 whole genome sequences, and selected 581 high-quality sequences for further analysis. The analysis results showed that from March 2022 to November 2022, before the adjustment of epidemic policy, the COVID-19 cases in Weihai were mainly from four local clusters,which were caused by four variants, including BA.2,BA.1.1,P.1.15 and BA.5.2.1. Phylogenetic analysis showed that: In the same cluster,the sequences between each other were highly homologous, and the whole genome sequence were almost identical. After December 2022, the epidemic policy was adjusted, BF.7 and BA.5.2 became the dominant variants in Weihai, consistent with the main domestic strains in China during the same period. Phylodynamic analysis showed that BF.7 and BA.5.2 had a large amount of genetic diversities in December, and the effective population size of BF.7 and BA.5.2 also showed explosive growth in December. In conclusion, we reported the composition and dynamic trend of SARS-CoV-2 variants in Weihai from March 2022 to March 2023. We found that there have been significant changes in the variants and expansion patterns of SARS-CoV-2 before and after the adjustment of epidemic policies. But the dominant variants in Weihai were the same as the SARS-CoV-2 variants circulating globally at the same time and we found no persistently dominant variants or new lineages during this period.

Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.

The contamination status of H5 avian influenza viruses and distribution of subtypes of H5N1 and H5N6 in poultry-related environment of Hubei areas were investigated. Urban and rural live poultry markets, poultry farms, intensive livestock farms and other monitoring types of 103 counties in 17 cities were selected in Hubei. Wiping samples from cage surface, wiping samples from chopping board, fecal specimens and other environmental samples were collected and tested by real-time RT-PCR using primers and probes of influenza A, avian influenza of H5, N1 and N6 from December 2017 to March 2018. The avian influenza virus positive rate was compared among different monitoring sites, samples, time and regions. Totally, 7132 environmental samples were collected in 1634 monitoring points with a positive rate of 2.24%. The positive rate of H5 avian influenza virus was the highest in urban and rural live poultry markets (3.44%, χ2=61.329, P<0.05) in 6 monitoring sites and wiping samples from chopping board (5.46%, χ2=67.072, P<0.05) in 6 sample types. H5N6 avian influenza viruses were detected more in eastern than western Hubei, and H5N6 avian influenza viruses were detected only in Xiangyang city of western Hubei. There were important high-risk places of human infection with H5 avian influenza virus in urban and rural live poultry markets and the poultry slaughtering plants. H5N6 has been the predominant subtype of H5 avian influenza viruses in the eastern and western Hubei and H5N6 avian influenza viruses were still present in a few areas of Hubei. Outbreaks of human H5N1 and H5N6 avian influenza remain at risk in Hubei province.

Objective To analyze the genetic characteristics of norovirus( NoV) in Jilin province from 2014 to 2016. Methods Stool samples from children under 5 years of age with diarrhea were collected from Changchun Children's Hospital. Samples were amplified by RT-PCR. The polymerase and capsid gene of the positive specimens were amplified. Sequences were analyzed by homologous comparison and phylogenetic analysis. Results A total of 1335 samples were detected,177 were positive for NoV, and positive rate was 13. 26％. The positive rate was 11. 83％ in 2014, 12. 53％ in 2015 and 15. 75％ in 2016. Genotyping of polymerase region revealed GII. P12 types dominated in 2014 and GII. Pe types dominated in 2015 and 2016. Genotyping of polymerase region revealed that GII. 3 types dominated in 2014 and GII. 4 Sydney2012 types dominated in 2015 and 2016. The types of both regions included GII.P17/GII.17, GII.Pe/GII.4 Sydney2012, GII. P12/GII. 3, GII. Pe/GII. 3、GII. P16/GII. 2 and GII. P7/GII. 6. Conclusions Genotypes of NoV infection are diverse in Jilin province. Most of them are recombinant strains. The main epidemic strains changed from GII.P12/GII.3 in 2014 to GII.Pe/GII.4 Sydney2012 in 2015 and 2016.

Influenza A H1N1pdm09 Virus; Chicken embryo; Phylogenetic tree; Egg-adaptation; Antigenic site; Drug-resistance site; Abstract: To investigate egg-adapted mutation in influenza A H1N1pdm09 viruses isolated from the Hubei influenza surveillance network, a comparative analysis was performed of three influenza A H1N1pdm09 viruses isolated in chicken embryo and the corresponding MDCK cell-derived viruses. Analyses included examination of the phylogenetic tree, evolutionary rates, amino acid substitutions, egg-adapted mutation and homology modeling. We found differences between the egg-adapted viruses and MDCK cell-derived viruses based on phylogenetic trees and evolutionary rates; the viruses showed a trend of " NA>HA>MP". Four amino acid substitutions(Q223R,V527 I,M19Iand H275Y)were found in three egg-adapted viruses.Q223 Rand V527Iwere present in the haemagglutinin protein, while M19I and H275Y were detected in neuraminidase.The Q223R mutation changed the structure of antigenic sites between Sb and Ca2. H275Y is a classic neuraminidase resistance mutation. The results suggest that the egg-adapted mutations were introduced when influenza viruses were isolated in chicken embryos from the Hubei influenza surveillance network. These mutations may affect the selection of vaccine candidates and vaccine efficacy; therefore, monitoring of egg-adapted mutations should be strengthened in the influenza surveillance network.