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Background:  Several recent studies reported a positive (statistical) association between ambient nitrogen dioxide (NO 2 ) and COVID-19 transmissibility. However, considering the intensive transportation restriction due to lockdown measures that would lead to declines in both ambient NO 2  concentration and COVID-19 spread, the crude or insufficiently adjusted associations between NO 2  and COVID-19 transmissibility might be confounded. This study aimed to investigate whether transportation restriction confounded, mediated, or modified the association between ambient NO 2  and COVID-19 transmissibility.   Methods:  The time-varying reproduction number ( R   t  ) was calculated to quantify the instantaneous COVID-19 transmissibility in 31 Chinese cities from January 1, 2020, to February 29, 2020. For each city, we evaluated the relationships between ambient NO 2 , transportation restriction, and COVID-19 transmission under three scenarios, including simple linear regression, mediation analysis, and adjusting transportation restriction as a confounder. The statistical significance ( p -value &lt; 0.05) of the three scenarios in 31 cities was summarized.   Results:  We repeated the crude correlational analysis, and also found the significantly positive association between NO 2  and COVID-19 transmissibility. We found that little evidence supported NO 2  as a mediator between transportation restriction and COVID-19 transmissibility. The association between NO 2  and COVID-19 transmissibility appears less likely after adjusting the effects of transportation restriction.   Conclusions:  Our findings suggest that the crude association between NO 2  and COVID-19 transmissibility is likely confounded by the transportation restriction in the early COVID-19 outbreak. After adjusting the confounders, the association between NO 2  and COVID-19 transmissibility appears unlikely. Further studies are warranted to validate the findings in other regions.

How Transportation Restriction Shapes the Relationship Between Ambient Nitrogen Dioxide and COVID-19 Transmissibility: An Exploratory Analysis