key: cord-0750172-k3db0zlk authors: Most, Zachary M; Holcomb, Michael; Jamieson, Andrew R; Perl, Trish M title: A Silver Lining? Fewer non-SARS-CoV-2 Respiratory Viruses during the COVID-19 Pandemic date: 2021-04-08 journal: J Infect Dis DOI: 10.1093/infdis/jiab191 sha: b8eb2ff8a21794a9606861de931bacc525df1a7a doc_id: 750172 cord_uid: k3db0zlk Non-pharmaceutical interventions (NPIs) have “flattened the curve” of the COVID-19 pandemic, however the effect of these interventions on other respiratory viruses is unknown. We used aggregate level case count data for eight respiratory viruses and compared the institutional and statewide case counts before and during the period that NPIs were active. We observed a 61% (IRR 0.39, 95% CI 0.37 to 0.41, P < 0.0001) decrease in non-SARS-CoV-2 respiratory viral infections when NPIs were implemented. This finding, if further verified, should guide future public health initiatives to mitigate viral epidemics. Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has led to a pandemic with morbidity and mortality not experienced in recent memory. As of December 3, 2020 there are over 64 million confirmed cases and over 1.5 million deaths attributed to COVID-19 worldwide [1] . To reduce transmission of SARS-CoV-2, in addition to rigorous contact tracing and isolation, several non-pharmaceutical interventions (NPI) have been enacted in various geographic regions. These include school closures, shelter-in-place orders, voluntary and mandatory mask wearing policies, and physical distancing. Evidence is mounting that these interventions have led to a "flattened curve" and have effectively reduced transmission of SARS-CoV-2 [2] [3] [4] . The NPIs are generic interventions that are not specific for SARS-CoV-2. Hence, their widespread implementation should reduce transmission of other respiratory viruses that disseminate similarly. Reduction in transmission of these respiratory viruses is a long-term public health priority. For instance, seasonal influenza infections cause an average of nearly 40,000 deaths per year in the US [5] , and other respiratory viruses are known to cause morbidity in pediatric and immunocompromised patients, along with economic losses from missed school and work [6] [7] [8] . While the transmission dynamics of respiratory viruses vary and are not completely elucidated, there is evidence that children in school and day care play an important role in transmission [8, 9] . Several recent studies have highlighted reduced influenza and other respiratory virus incident infections during the COVID-19 pandemic [10] [11] [12] [13] . However, the effect of NPIs on non-SARS-CoV-2 viral transmission has not been quantified. We hypothesized that the incidence of non-SARS-CoV-2 respiratory viruses has decreased during A c c e p t e d M a n u s c r i p t 4 the COVID-19 pandemic compared to previous years as a result of the rigorous implementation of NPIs in our community. Our objective was to quantify the magnitude of this effect. We conducted an observational ecological comparison of the incidence of respiratory viral infections from January 1, 2014 through February 21, 2021 at one large pediatric health system in Dallas, Texas. variables. This allowed the model to control for seasonal variation in respiratory viral incidence and the number of tests ordered. Then, an additional explanatory variable was added to the model that took the value of 0 prior to the implementation of NPIs, and the value of 1 from March 15, 2020 to February 21, 2021. This allowed the model to account for a shift in the incidence for all viruses when the NPIs were initiated locally. We labeled the coefficient for this variable the global effect factor. Finally, a model was built removing the global effect factor and instead using pathogen specific effect factors for the eight viruses studied. The methods were the same for the statewide data, except that weekly incidence was used rather than daily incidence (see Supplementary Methods). The quality of each model was measured using the Akaike information criterion (AIC) which accounts for both the goodness of fit to the observed data, and the model"s simplicity. A lower AIC indicates a higher quality model. In each model, the exponentiation of the coefficient for the effect factor A c c e p t e d M a n u s c r i p t 6 equals the incidence rate ratio (IRR) for the implementation of NPIs. These were tested against the null hypothesis that the incidence rate ratio equals one and does not change the incidence. Ninety-five percent confidence intervals (95% CI) for the IRR estimates were calculated from the model. A two-sided type I error rate of 0.05 was used for statistical significance with a Holm-Sidak correction for multiple comparisons. Dallas County, Texas implemented several NPIs throughout the study period beginning with a local health emergency declared on March 12, 2020. All schools in the county were closed on March 17, 2020 and reopened for hybrid learning in the fall. In addition, local health authorities encouraged maintaining a physical distance of at least six feet in public, limiting gathering size, minimizing non-essential travel, and wearing masks in public. A shelter-in-place order was enforced for non-essential workers between March 30, 2020 and April 29, 2020 and a statewide order to wear masks in public went into effect on July 3, 2020 (see Supplemental Figure 1 ). This study was determined to be exempt from review by the local Institutional Review Board. Table 2 and Supplemental Figure 2 ). The statewide data followed a similar pattern to the local data. Inclusion of the global effect factor improved the parsimony of the model (AIC reduced by 11,506). The period of active NPIs since CDC week 12 in 2020 was associated with a 68% reduction in the incidence of all respiratory viruses (IRR 0.32, 95% CI 0.31 to 0.33, P < 0.0001). Replacing the global effect factor with pathogen specific effects (Figure 1 ) further improved model parsimony (AIC reduced by an additional 6,938). The predicted counts from the model were much lower for 2020 than for previous years due to fewer tests being performed. Using the pathogen specific model, the period of active NPIs was associated with a significant reduction in the incidence of all eight viruses (Figure 2 , see Supplemental Table 3 and Supplemental Figure 2) . Using aggregated data from respiratory viral testing in a large Children"s Hospital and statewide in Texas, we found that the observed number of respiratory viral infections decreased while several NPIs were in place during the COVID-19 pandemic. The reduced incidence was most notable for RSV, influenza A and B, parainfluenza virus, and seasonal human coronaviruses. It is not clear why the effect of the NPIs on rhinovirus/enterovirus and adenovirus infections was weaker. These viruses have little if any seasonality and are always endemic in the population. Both of these viruses saw reduced incidence early after the initial NPIs were implemented but they returned to normal levels by the summer. This could be due to virusspecific differences in effective transmission contact that respond differently to specific NPIs. For instance, rhinovirus/enterovirus and adenovirus may have been more sensitive to school closure and reopening. Human metapneumovirus counts were strongly affected by a local outbreak in March 2020 that started prior to the implementation of NPIs. A strength of this study is that we used a large dataset in a particular geographic region to evaluate the incidence of viral infections during the period of NPIs. Therefore, we reduced the effect of variable geographic implementation of NPIs over time. When expanding our analysis to data from the entire state that included both children and adults, we found a similar effect size, which supports the robustness of this finding. In addition, our results are concordant with dramatic decreases in influenza infection incidence rates associated with the implementation of NPIs reported by other investigators [10] [11] [12] . However, this study has several weaknesses. Not all positive PCR tests represent acute infections. We only had access to aggregate data which limited the comparisons we could make and this type of ecological analysis cannot show causation. There are alternate A c c e p t e d M a n u s c r i p t 9 explanations (such as viral interference [14] with SARS-CoV-2 or random chance) but none are as plausible as an effect of NPIs. Changes in the indication for PCR testing over time may have contributed to the reduction in percent positivity observed locally. However, the state (which saw a reduction in PCR testing) and the local hospital (which saw an increase in PCR testing) had similar estimates for the effect size, so it is unlikely that changes in testing strategy substantially confounded the results. Finally, in this observational study we could not isolate the impact of any specific NPIs or other factors. For instance, we cannot say whether school closure, mask wearing, or increased lay awareness of viral transmission dynamics played a role. These results suggest that the children in Dallas and the population of Texas had far fewer respiratory viral infections in 2020 compared to usual years. This study helps to quantify the potential protective effect of enacting NPIs during other, non-SARS-CoV-2, respiratory virus epidemics. This could help public health and governmental planning to strategize future implementation of NPIs during high incidence epidemics for respiratory viruses. In conclusion, we have identified a large decrease in the incidence of non-SARS-CoV-2 respiratory viral infections during the COVID-19 pandemic that may be due to the implementation of NPIs. This information should be used by local and national health authorities for resource preparation for upcoming viral epidemics. Additional surveillance of respiratory viral infections will be crucial to understanding the short-and long-term effects of this period. 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