A systematic review and meta-analysis of canine enteric coronavirus prevalence in dogs of mainland China

The study aims to evaluate the overall prevalence of CECoV in mainland China and identify potential factors associated with infection variability. As CECoV remains a commonly encountered infectious disease in dogs, characterized by transient symptoms and limited vaccine availability, understanding its prevalence dynamics is crucial. Recent reports underscore the emergence of mutated and recombinant CECoV strains globally, posing significant threats to both animal and human health [5]. In light of the growing demand for vaccine development and the necessity for preventive and control measures, an updated systematic review is imperative to provide comprehensive insights.

This study conducted a systematic review and meta-analysis of CECoV epidemiological studies conducted between 1996 and 2022, focusing on dogs in mainland China. Analysis of 27 included studies revealed an overall CECoV prevalence of 0.30 (95% CI: 0.24, 0.37), indicating a significant prevalence within mainland China. This underscores concerns regarding the emergence of new CECoV strains and their potential impact on public health security. Our findings closely align with a previous analysis by Dong Bo et al. [12], although some differences exist in inclusion criteria, such as the exclusion of literature due to issues such as unclear study periods and data overlap. Compared to the previous approach employed by Dong Bo et al., this study's search strategy yielded a lower number of hits (414 versus 972). The discrepancy was partially attributed to the omission of Google Scholar, Cochrane Library, and clinical trials databases, which typically produce overlapping results with PubMed. However, the number of screened and included studies was substantially higher in this study (27 versus 15).

Dogs infected with CECoV may experience mild diarrhea, but when accompanied by other pathogens such as CPV, it can result in severe symptoms and possibly death, particularly in young puppies. A key question of interest is whether diseased dogs are more likely to test positive for CECoV. Our subgroup data indicated a higher prevalence of CECoV in healthy than diseased dogs, consistent with the findings of the study conducted by Shanshan Wu et al. during 2020–2021 in Chengdu, China [16]. This may be attributed to healthy dogs being more active and potentially transmitting the virus through social movement. Conversely, environments with more than one dog are associated with a higher positivity rate compared to only one dog.

Given the association between health and multi-dog household with elevated CECoV infection rates, it is imperative to examine the infection rates specifically in healthy dogs residing in multi-dog environments. Our results highlight the potential for increased CECoV prevalence in multi-dog environments and emphasize the importance of regular monitoring for all dogs in such settings. However, it's worth noting that the subset of healthy dogs residing in multi-dog environments is based on only two studies conducted prior to 2003, and the limited data available may impact the reliability of the results. Further research with larger sample sizes and more recent data is warranted to validate these findings.

Dogs of any age can be infected with CECoV, and previous studies have indicated that puppies younger than 6 months of age are at greater risk of infection. Our subgroup analysis investigated the relationship between age and CECoV prevalence, revealing that younger animals have a higher prevalence of infection. While maternal antibodies may offer some protection to puppies, our data suggest that this protection may be limited, and circulating antibodies may not provide sufficient immunity against CECoV infection. However, systematic investigations are needed to assess the effectiveness of circulating antibodies induced by vaccine, although there is currently limited published information on such studies.

For investigating the influence of genetic factors on the likelihood of CECoV infection across different dog breeds. various canine breeds into four categories: large, medium, small, and mongrel dogs. The small breed category includes Chihuahua, Poodle, Pug, Corgi, Shih Tzu, and Bichon Frise. The medium breed category encompasses Border Collie, Huskie, Shiba Inu, Samoyed, and Chow Chow. The large breed category includes German Shepherd, Alaskan Malamute, Golden Retriever, Akita, Great Pyrenee, and Labrador Retriever. Subgroup analysis revealed that the prevalence among medium-sized, small, and mongrel dogs was relatively low, but environmental factors during growth could not be ruled out. Additionally, our analysis found no significant difference in CECoV positivity rates between genders, consistent with previous research findings [16].

This study presents the first analysis of CECoV prevalence distribution over time, revealing two peaks in prevalence in 2003 and 2016–2017, followed by a decline. The decrease in prevalence post-peak could be attributed to various factors, including public health interventions, increased awareness, and advancements in healthcare infrastructure. However, the possibility of episodic events influencing these fluctuations cannot be overlooked. Certain variations in infection rates at different time points may also stem from non-random sample collection practices. For instance, a higher proportion of sick animals or sampling from infected colonies could inflate infection rates. Conversely, research by Zhang Yue on conventional Beagle dog colonies during 2021–2022 reported notably lower infection rates [15]. The excessively low prevalence may also be due to the inapplicability of the assay to emerging mutant viruses.

The diverse climatic conditions across various regions in China likely impact the survival and transmission of CECoV. Previous studies conducted in China have reported varying rates of CECoV infection in different regions. For instance, Tianjin in the north exhibited the highest rate at 60%, followed by Gansu in the northwest at 43%, Shandong in the east at 42%, Beijing in the north at 38%, Heilongjiang in the northeast at 28%, Henan in central China at 24%, Jiangsu in the east at 23%, and Jilin in the northeast at 20% [12]. In our meta-analysis, employing stringent inclusion criteria, the highest prevalence of CECoV was observed in southwest China at 44%, while northern China had a prevalence rate of 20%. However, the limited number of studies available for certain regions, such as south China, may have influenced the results of this study. Despite variations in CECoV prevalence across different regions, no significant difference was observed among these regions.

The climate in China is characterized by continental monsoon patterns, featuring cold winters and hot summers. While no significant regional variations in CECoV prevalence were observed in China, further investigation into potential differences among seasons is essential. Previous surveys conducted in Chengdu revealed that summer had the lowest positive rate (16.0%). However, a systematic review of CECoV infection in Chinese domestic dogs indicated no significant difference between seasons. In our study, no significant difference was found in CECoV prevalence between seasons, and the summer was confirmed to have the lowest prevalence.

Despite these insights, our study encountered significant heterogeneity and publication bias, highlighting the need for cautious interpretation of results. Sensitivity analysis confirmed robustness to outliers, while publication bias may arise from the inclusion of published papers and the diagnostic method. The coronavirus pandemic in the human population has likely sparked heightened interest in researching CECoV epidemiology. However, China currently lacks an official plan for CECoV epidemiology, which may lead to randomized study distribution across different regions and years. While RT-PCR detection was utilized in most studies, it should be noted that certain primer pairs may fail to match the latest CECoV variant, resulting in an underestimation of the positive rate. These circumstances may increase heterogeneity in meta-analyses. Furthermore, the limited number of studies reporting prevalence among healthy dogs underscores the need for further research to understand the full spectrum of CECoV infection.

Limitations of this review

Firstly, there were variations in sampling time, location, specific dog breeds, sensitivity of the detection methods and housing conditions among the included studies, which may have influenced the results. Pooling the data from these studies regardless of these differences may not fully capture the true variability across different settings. Secondly, the sample sizes in some subgroup analyses were relatively small, which could limit the statistical power to detect significant differences or associations. Thirdly, the use of a single-group analysis in this study may contribute to substantial heterogeneity, as it does not account for potential confounding factors or other sources of variability. Finally, this study did not investigate the impact of immunological and non-immunized factors on the CECoV infection, as most of literatures did not specify the type of vaccine utilized, making it impossible to determine whether the animals were vaccinated against CECoV.

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