Epidemiological investigation of canine coronavirus infection in Chinese domestic dogs: A systematic review and data synthesis.

Canine enteric coronavirus (CCoV) is a pathogenic virus that infects dogs worldwide, causing enteric issues and causing harm to the dog industry and dogs. Although CCoV is not recognized as a highly lethal canine intestinal pathogen, it has been reported that CCoV is significantly associated with canine diarrhea in dogs. CCoV is a common health problem in dogs, attracting major concern from veterinarians and dog owners across China. In this study, we summarized the prevalence and epidemiological characteristics of CCoV in dogs in mainland China. The study revealed that the pooled prevalence of CCoV infection was 33%, and which associated with age, but not with sex, season and immunization status. In addition, the study also further suggested that CCoV-II was the predominant CCoV subtype in Chinese dogs. This study will provide valuable information for CCoV infections across China and other countries. Furthermore, this study also suggested that continuous surveillance and epidemiological studies of CCoV are necessary.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.

COVID-19 lung infection segmentation with a novel two-stage cross-domain transfer learning framework.

With the global outbreak of COVID-19 in early 2020, rapid diagnosis of COVID-19 has become the urgent need to control the spread of the epidemic. In clinical settings, lung infection segmentation from computed tomography (CT) images can provide vital information for the quantification and diagnosis of COVID-19. However, accurate infection segmentation is a challenging task due to (i) the low boundary contrast between infections and the surroundings, (ii) large variations of infection regions, and, most importantly, (iii) the shortage of large-scale annotated data. To address these issues, we propose a novel two-stage cross-domain transfer learning framework for the accurate segmentation of COVID-19 lung infections from CT images. Our framework consists of two major technical innovations, including an effective infection segmentation deep learning model, called nCoVSegNet, and a novel two-stage transfer learning strategy. Specifically, our nCoVSegNet conducts effective infection segmentation by taking advantage of attention-aware feature fusion and large receptive fields, aiming to resolve the issues related to low boundary contrast and large infection variations. To alleviate the shortage of the data, the nCoVSegNet is pre-trained using a two-stage cross-domain transfer learning strategy, which makes full use of the knowledge from natural images (i.e., ImageNet) and medical images (i.e., LIDC-IDRI) to boost the final training on CT images with COVID-19 infections. Extensive experiments demonstrate that our framework achieves superior segmentation accuracy and outperforms the cutting-edge models, both quantitatively and qualitatively.

Genetic characteristics and genetic evolution of porcine epidemicdiarrhea virus strain FJLY1703 in western Fujian province

In order to clarify the recombination and genetic evolution of porcine epidemic diarrhea virus (PEDV) isolates inwestern Fujian, a PEDV strain (FILY1703) was isolated from PEDV infected piglet samples in western Fujian, and its N, E, M and Sgenes were amplified by PCR and further sequenced and analyzed by bioinformatics software in this study. The homology andevolutionary analysis results showed that FJLY1703 had low homology and distant relationship with classical strains such as CV777, but high homology and close evolutionary relationship with the prevalent variants isolated in domestic after 2010. The amino acidsequence analysis showed the COE of FJLY1703 strain S protein had 8 mutations that were similar to prevalent variants in Chinaafter 2010 in comparison with the vaccine strain CV777. Further more, the amino acid sequence of FJLY1703 strain E, M and N genes had 1, 3 and 12 mutation sites respectively, which were the same as the prevalent variants in China. Recombination analysis ofS gene showed that FJLY1703 was a recombination strain of classical strain CV777 and mutant strain that prevalent variants after2010, and suggested the need to develop a vaccine against PEDV epidemic strains to control the infection of PEDV. This studyprovided data support for the epidemiological study of PEDV in China.

Heightened innate immune responses in the respiratory tract of COVID-19 2 patients

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV44 2 infection has posed a severe threat to global public health. It is unclear how the human 45 immune system responds to this infection. Here, we used metatranscriptomic 46 sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight 47 COVID-19 cases. The expression of proinflammatory genes, especially chemokines, 48 was markedly elevated in COVID-19 cases compared to community-acquired 49 pneumonia patients and healthy controls,suggesting that SARS-CoV-2 infection causes 50 hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate 51 interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous 52 IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potential, with 53 overrepresentation of genes involved in inflammation. The transcriptome data was also 54 used to estimate immune cell populations, revealing increases in activated dendritic 55 cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection 3 56 could further our understanding of disease pathogenesis and point towards antiviral 57 strategies.

Epidemic prevention and control measures in China significantly curbed the epidemic of COVID-19 and influenza (preprint)

At the end of 2019, an outbreak of unknown pathogen pneumonia occurred in China, then it was named corona virus disease 2019 (COVID-19). With the rapid spread of COVID-19, a series of strict prevention and control measures were implemented to cut the spread of the epidemic. Influenza as a respiratory tract infection disease as COVID-19 might also be controlled. To assess the effects, we used the total passenger numbers sent in mainland China from 2018 to 2020 and the daily number of railway passenger (DNRP) flow in 2020 during Spring Festival travel rush to reflect the population movement and further to analyze newly and cumulative confirmed COVID-19 and influenza. We found that with implementing the series measures on COVID-19, not only COVID-19, but also influenza mitigated in China. The prevention and control measures for COVID-19 might be used in controlling respiratory tract diseases, and reducing the national health economic burden. When other countries issue measures on COVID-19 and influenza, they should consider adopting more aggressive epidemic prevention and control strategies.