EV-D68 has been reported in many countries, including the USA, Canada, European countries, and parts of Asia. The frequency and intensity of outbreaks may vary from year to year and between regions [16–25]. EV-D68 infections primarily occur during late summer and fall, typically peaking between August and October in the Northern Hemisphere. However, sporadic cases can be reported throughout the year [23, 26]. EV-D68 infections predominantly affect children, particularly those between the ages of 4 and 12 years. This age group is more susceptible to the virus, possibly due to lower pre-existing immunity [23, 26, 27].
Since 2014, EV-D68 continues to circulate, and sporadic outbreaks have been reported in various countries. However, the frequency and intensity of outbreaks can vary from year to year. It is important to note that while EV-D68 can cause severe respiratory illness, most individuals who contract the virus experience mild symptoms and recover without complications [5, 7, 10].
The exact mortality rate associated with EV-D68 is challenging to determine as it varies depending on factors such as population demographics, healthcare access, and the availability of supportive care. Additionally, not all cases of EV-D68 infection are reported, which can affect the accuracy of mortality data. In a meta-analysis, was identified the highest EV-D68 prevalence’s were in hospital outbreaks, in developed countries, in children under 5, and in patients with acute flaccid myelitis and asthma-related diseases. Sporadic deaths linked can occur associated with severe respiratory EV-D68 infections. EV-D68 shows a low prevalence of current as opposed to the existence of EV-D68 antibodies in almost all children. Therefore, highlight the need to implement and/or strengthen continuous surveillance of EV-D68 infections in hospitals and in the community for the anticipation of the response to future epidemics [5, 16].
The evolutionary dynamics of EV-D68 are complex and influenced by various factors, including immune pressure, viral fitness, host range, and population immunity. Evolutionary changes can occur through genetic mutations, recombination events, and selection pressures, leading to the emergence of new strains or variants over time [6, 9, 28–31]. Molecular analysis has shown that different EV-D68 clades have circulated globally, with some clades being more prevalent in certain regions or during specific outbreak periods. Genomic surveillance helps track the spread of different clades and understand their geographic distribution [27–29, 31]. In the present study, we performed Bayesian analysis to estimate the molecular evolution of EV-D68. The results shown that this virus was originated in Canada in 1995, later it was disseminated in France in 1997, the USA in 1999, Taiwan in 2008, Tanzania in 2008, China in 2008, Philippines in 2008, Vietnam in 2009, the Netherlands in 2009, New Zealand in 2010, Japan in 2010, Hong Kong in 2012, Mexico in 2014, Kenya in 2015, Sweden in 2016, India in 2017, Switzerland in 2018, Spain in 2018, Belgium in 2018, Australia in 2018, and Denmark in 2019. Recently, in 2022 this virus circulated in the USA.
The present study has some limitations: i) The evaluated WGS were obtained from databases such as GISAID and GenBank, so we did not sequence from South America; ii) Due to the smaller amount of WGS available from the databases used for phylogenetic analysis, the African continent was underrepresented which could impact statistical reliability of the findings. iii) The characterization of EV-D68 clades mutations has not been specifically evaluated. These results could add to the molecular knowledge of EV-D68, and hypothetically influence potential treatments that could be implemented, as well as vaccination. However, the present study is different from previous studies, as it presents an evolutionary reconstruction of the four main EV-D68 clades, considering 976 WGS worldwide. In this sense, given the current knowledge, there are no studies that evaluated a sample number of WGS similar to this one in the literature, as well as that addressed the four main clades of EV-D68. Furthermore, the fact that we evaluated more than 950 WGS and not just partially sequenced genomic regions of EV-D68, provides greater reliability of the phylogenetic inferences shown in this study. Associated with this, we adopted consolidated statistical criteria in the phylogenetic analyses, generating robustness in the conclusions of the tMRCA and HPD95% values, as well as the EV-D68 transmission routes statistically supported by the BF values. This study shows new information, based on a robust sample, which will substantially contribute to the literature on the molecular epidemiology of EV-D68, serving as an important theoretical reference in the formulation of future scientific hypotheses aimed at the molecular characterization of this virus.
In conclusion, EV-D68 has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of EV-D68 clades, showed the origins of clades A1, A2, B, B1, B2, B3, and C (A1 in 2005-04-17 in the USA, A2 in China in 2003-07-06, B1 in 2010-03-21 in Vietnam, B2 in 2006-11-25 in Vietnam, B3 in 2011-01-15 in China, and C in 2000-06-27 in the USA). EV-D68 was originated in Canada in 1995 and spread to Europe, Asia, Oceania, Latin America, and Africa. Recently, in 2022 this virus circulated mainly in the USA. Finally, urgent actions are necessary to control dengue, which is expanding, where it is possible to generate innovative and effective tools in vector control in urban populations, mainly protecting high-risk areas. Also, it is important to note that the molecular evolution of EV-D68 is an ongoing field of study, and new findings may emerge as research progresses. Continued surveillance and genetic analysis are essential for monitoring the virus's evolutionary changes and informing public health interventions.