Virus-virus interactions of different serotypes and impact of COVID-19
Increasing evidence suggests that virus–virus interactions are common and may be critical to understanding viral pathogenesis in natural hosts. Currently, CVA6 and CVA16 are the major causative agents circulating in Nanchang, while these two viruses demonstrated a staggered prevalence pattern during 2019-2022 as shown in figure 6A, the spearman correlation analysis showed that monthly cases of CVA6 and CVA16 were negatively correlated (r =-0.459, p =0.001). To further determine this hypothesis, we conducted a pair correlation analysis for CVA16, CVA6 and EV-A71 before the COVID-19 epidemic. As expected, CVA6 versus CVA6 was negatively interacted (r =-0.578,p <0.001) during 2013-2019 and similar prevalence pattern was observed year by year (figure 6B). As EV-A71 vaccination initiated since mid-2016 and EV-A71 was no longer detected via laboratory-based surveillance after 2018, correlations of EV-A71 versus CVA16 and EV-A71 versus CVA6 during 2010-2016 and 2013-2016 were respectively analyzed to rule out the interference of EV-A71 vaccination. It’s found that EV-A71 and CVA16 displayed a strong positive interaction (r =0.644, p <0.001) (figure 6C), while EV-A71 and CVA6 were negatively interacted (r =-0.609,p <0.001) (figure 6D). However, the negative correlation between CVA6 and CVA16 was interfered by three local COVID-19 outbreaks occurred in 2020 and 2022 (r 2020=-0.400,p =0.196; r 2022=-0.178, p =0.574), while in 2019 (pre-COVID-19) and 2021 (without local COVID-19 cases), these two viruses were negatively correlated (r 2019=-0.747, p =0.007;r 2021=-0.734, p =0.009) (Figure 7A-D). These results indicated that infection exclusion type of negative interaction between CVA6 and CVA16 might exist, and NPIs for combating COVID-19, to some degree, mitigated their transmission as ARIMA forecasting indicated (Figure 7E-F). Taken together, in the absence of intervention from NPIs, the peak-shifting epidemic characteristics of CVA6, CVA16 and EVA71 sustained their seasonal regularities year by year, while the interactions might be shortly broken by strict prevention measures during COVID-19 pandemic. In addition, EV-A71 vaccination did not interfere prevalence of CVA6 and CVA16 and their interactions as figure 6B indicated.