How deadly is the COVID-19 pandemic? What is the theoretical effect of ”super spreader events” on transmission and control? What is the consequence of different control strategies from an epidemic perspective? How will the COVID-19 pandemic end? What is the post-pandemic dynamic after herd immunity? Have we seen a coronavirus pandemic before? Professor Lone Simonsen focuses on these issues and many more in the Semper Ardens project ”Pandemic X”. By Lone Simonsen, professor, PhD, Department of Science and Environment, Roskilde University Measuring the deadliness of the respiratory virus COVID-19 is complicated at the start of the epidemic because there is an unknown delay in deaths relative to sickness, and because many cases are going undetected because the disease often can be asymptomatic or so mild that no testing is done. It also does not help that the cause of death is often stated as an underlying chronic disease, and that not all those who get sick with or die from COVID-19 are tested for an active infection. Consequently, later in the epidemic we are using statistical models to measure the excess mortality in the population against a baseline. In the case of the historical influenza pandemics of 1918, 1957, 1968 and 2009, there was a shift towards younger mortality compared to seasonal influenza, while the number of global deaths varied from catastrophic (1918 Spanish flu, 20–50 million deaths) to low (2009 swine flu, 0.5 million deaths). SARS-CoV-2 is closely related to SARS-CoV However, in both these latter pandemics, 95% of deaths were in the under-65 age group because the elderly had protective antibodies from similar viruses in childhood. In the middle of these two pandemics came the moderate pandemics of 1957 and 1968, which showed only a modest age-related shift (Miller et al., NEJM, 2009). Pandemics put into mathematical formulas COVID-19 – a brand-new type of pandemic. The COVID-19 pandemic – the first coronavirus pandemic – has a unique ”signature”, which we are working to map. We are seeing no sign of excess mortality in the younger age groups; it is the elderly who are dying, especially the very old. Only approximately 3% of COVID-19 deaths are in the under-65 group. Together with colleagues in the USA, we have modelled the excess mortality data from there, and the Washington Post is publishing updated data weekly (Weinberger, 2020). We have looked at European data from the unique weekly EuroMoMo monitoring system, but as mortality is only presented relatively, we cannot use the model on this data. We can, however, see that some countries already have high covid-related mortality, relative to seasonal influenza. Why did SARS-CoV-2 cause a pandemic when SARS-CoV was stopped in 2003? SARS-CoV-2 is closely related to SARS-CoV, and both have a transmission potential (R0 = 2.5) that is just as high as the 1918 influenza pandemic, which spread globally in just a few months. So what are the reasons why SARS was eradicated in 2003 and the COVID-19 pandemic can be controlled effectively with social distancing and quarantine? We look at a number of factors, including SARS-CoV-2’s ability to spread under the radar given that many people have mild symptoms or are asymptomatic and do not visit a doctor. But we also look at the mathematics of the effect of ”super spreaders”, i.e. a minority of infected people who infect far more effectively than others (Sneppen et al., preprint). In a review, we have compared features of SARS and Covid-19 with the 1918 and 2009 pandemics (Petersen et al., Lancet Inf Dis). The pandemic response has been draconian – and highly effective In Denmark and other European countries, the fear of an uncontrollable COVID-19 pandemic and impact such as the deadly wave that occurred in Northern Italy have led to draconian control methods, including quarantine and border closures, which we have not deployed since the plague. The ”green wave” strategy aims to reduce infection so that hospitals are not overloaded while immunity is built up in the population. Two months after the initial unlocking, we saw no sign of any real increase in transmission The lockdown of Denmark has been amazingly effective; two weeks after the initial unlocking, we saw no sign of any real increase in transmission. The epidemic almost came to a standstill following a decline from approximately 100 to approximately 10 daily hospital admissions, with less than 50 intensive care beds in use. From serological studies of blood donors, we can see that only very few people have been infected and are possibly immune. But the unlocking of society was necessary. We modelled alternative scenarios transitioning from the green wave to keeping the infection rate close to zero with testing and contact tracing to eliminate infection chains and thereby achieve a significant degree of freedom to unlock society (Videnskab. dk, 2020). An effective vaccine is still a long way down the road (one to two years in the most optimistic scenario), and herd immunity is also one to two years away.