Introduction

One explanation for the 2022 Tripledemic and respiratory syncytial virus (RSV) surge is that prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have affected immune function, increasing susceptibility to other respiratory viruses. This type of viral-viral interaction may have contributed to the unusually high burden of RSV and influenza seen during that period, especially when combined with immunity gaps and changes in viral circulation following the coronavirus disease 2019 pandemic.

This leads us to explore the hypothesis that prior acute respiratory infection with coronavirus 2 was associated with a greater risk of subsequent respiratory viral infection in children.

Methods

We conducted a retrospective cohort study using electronic health record data from 8 pediatric emergency rooms in a health care system in Michigan. We included children under the age of 18 years, diagnosed with a viral upper respiratory infection between January 1st, 2021, and December 31st, 2023. The comparison groups were children with (a) SARS-CoV-2 alone, (b) SARS-CoV-2 and another respiratory virus, and (c) with other Non-SARS-CoV-2 infections. The primary outcome was viral re-infection in the subsequent 15 to 120 days. The secondary outcomes were the frequency of concurrent viral infections as well as clinical outcomes (i.e., oxygen use, length of stay, etc.).

Results

We included data from 37,116 patients. The cohorts consisted of 4,004 with SARS-CoV-2 alone, 1,678 with SARS-CoV-2 + another virus, and 31,434 with non-SARS-Cov-2 viruses.

In the group with SARS-CoV-2 the odds of subsequent infections was lower when compared to the other two groups (OR = 0.71). In the group with lab confirmed SARS-CoV-2 the odds of subsequent infections was also lower when compared to the other two groups (OR = 0.694) with a re-infection rate on confirmatory laboratory testing of 2% compared to 2.8% in the other groups.

Mean time to re-infection and length of stay were also higher for the SARS-Cov-2 only group, while oxygen use rate was higher in the non-SARS-CoV-2 viral group.

Overall, the most common viruses seen in re-infection in all three groups were RSV, SARS-CoV-2, and Influenza. In group A these made up 37.7% (n=26), 33.3%(n=23), and 23.2% (n=16) respectively. In groups B and C respectively, they made up 29.3% (n=12), 39.0% (n=16), 29.3%(n=12) and 32.4% (n=231), 29.2% (n=208), and 26.6% (n=190).

Conclusions

Children with SARS-CoV-2 alone at the index encounter had a significantly lower viral reinfection rate within 4 months and were less likely to have a concurrent infection with another respiratory virus than those without SARS-CoV-2, suggesting possible viral interference or differences in host response. The longer time to in the SARS-CoV-2-only group might suggest delayed susceptibility, although the group being older, age may have contributed to differences in infection patterns and clinical outcomes.

In summary, these findings suggest that prior SARS-CoV-2 infection may have influenced subsequent respiratory viral patterns in children, although the observed differences were likely multifactorial.

There is need for more studies especially in younger ages to see if age played a role in the findings.