Lessons for preparedness and reasons for concern from the early COVID-19 epidemic in Iran

Highlights • Our phylogenetic analysis reveals the Iranian epidemic started nearly two months before when the first cases were reported. • By analysing 46 genomic samples of SARS-CoV-2 from Iran we find at least 5 independent introductions into the country in 2020. • Analyses of air travel data and registered deaths revel significant levels of under-reporting during the first and second wave. • The epidemic was likely seeded by only a few imported cases from China that belong to a high-risk group with frequent travels. • We reconstruct early transmission dynamics in Iran and predicted the relaxation of NPIs would have led to a second peak. Introduction Many countries with an early outbreak of SARS-CoV-2 struggled to gauge the size and start date of the epidemic mainly due to limited testing capacities and a large proportion of undetected asymptomatic and mild infections. Iran was among the first countries with a major outbreak outside China. Methods We constructed a globally representative sample of 802 genomes, including 46 samples from patients inside or with a travel history to Iran. We then performed a phylogenetic analysis to identify clades related to samples from Iran and estimated the start of the epidemic and early doubling times in cases. We leveraged air travel data from 36 exported cases of COVID-19 to estimate the point-prevalence and the basic reproductive number across the country. We also analysed the province-level all-cause mortality data during winter and spring 2020 to estimate under-reporting of COVID-19-related deaths. Finally, we use this information in an SEIR model to reconstruct the early outbreak dynamics and assess the effectiveness of intervention measures in Iran. Results By identifying the most basal clade that contained genomes from Iran, our phylogenetic analysis showed that the age of the root is placed on 2019-12-21 (95 % HPD: 2019-09-07 – 2020-02-14). This date coincides with our estimated epidemic start date on 2019-12-25 (95 %CI: 2019-12-11 – 2020-02-24) based air travel data from exported cases with an early doubling time of 4.0 (95 %CI: 1.4–6.7) days in cases. Our analysis of all-cause mortality showed 21.9 (95 % CI: 16.7–27.2) thousand excess deaths by the end of summer. Our model forecasted the second epidemic peak and suggested that by 2020-08-31 a total of 15.0 (95 %CI: 4.9–25.0) million individuals recovered from the disease across the country. Conclusion These findings have profound implications for assessing the stage of the epidemic in Iran despite significant levels of under-reporting. Moreover, the results shed light on the dynamics of SARS-CoV-2 transmissions in Iran and central Asia. They also suggest that in the absence of border screening, there is a high risk of introduction from travellers from areas with active outbreaks. Finally, they show both that well-informed epidemic models are able to forecast episodes of resurgence following a relaxation of interventions, and that NPIs are key to controlling ongoing epidemics.