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Background Since the appearance of severe acute respiratory coronavirus 2 (SARS-CoV-2) and the coronavirus disease 2019 (COVID-19) pandemic, a growing body of evidence has suggested that weather factors, particularly temperature and humidity, influence transmission. This relationship might differ for the recently emerged B.1.617.2 (delta) variant of SARS-CoV-2. Here we use data from an outbreak in Sydney, Australia that commenced in winter and time-series analysis to investigate the association between reported cases and temperature and relative humidity. Methods Between 16 June and 10 September 2021, the peak of the outbreak, there were 31,662 locally-acquired cases reported in five local health districts of Sydney, Australia. The associations between daily 9:00 am and 3:00 pm temperature (°C), relative humidity (%) and their difference, and a time series of reported daily cases were assessed using univariable and multivariable generalized additive models and a 14-day exponential moving average. Akaike information criterion (AIC) and the likelihood ratio statistic were used to compare different models and determine the best fitting model. A sensitivity analysis was performed by modifying the exponential moving average. Results During the 87-day time-series, relative humidity ranged widely (&lt; 30–98%) and temperatures were mild (approximately 11–17 °C). The best-fitting (AIC: 1,119.64) generalized additive model included 14-day exponential moving averages of 9:00 am temperature ( P  &lt; 0.001) and 9:00 am relative humidity ( P  &lt; 0.001), and the interaction between these two weather variables ( P  &lt; 0.001). Humidity was negatively associated with cases no matter whether temperature was high or low. The effect of lower relative humidity on increased cases was more pronounced below relative humidity of about 70%; below this threshold, not only were the effects of humidity pronounced but also the relationship between temperature and cases of the delta variant becomes apparent. Conclusions We suggest that the control of COVID-19 outbreaks, specifically those due to the delta variant, is particularly challenging during periods of the year with lower relative humidity and warmer temperatures. In addition to vaccination, stronger implementation of other interventions such as mask-wearing and social distancing might need to be considered during these higher risk periods. Graphical Abstract

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Challenges in the control of COVID-19 outbreaks caused by the delta variant during periods of low humidity: an observational study in Sydney, Australia