The COVID-19 pandemic: key considerations for the epidemic and its control

The response to the ongoing COVID-19 pandemic has been characterized by draconian measures and far too many important unknowns, such as the true mortality risk, the role of children as transmitters and the development and duration of immunity in the population. More than a year into the pandemic much has been learned and insights into this novel type of pandemic and options for control are shaping up. Using a historical lens, we review what we know and still do not know about the ongoing COVID-19 pandemic. A pandemic caused by a member of the coronavirus family is a new situation following more than a century of influenza A pandemics. However, recent pandemic threats such as outbreaks of the related and novel deadly coronavirus SARS in 2003 and of MERS since 2012 had put coronaviruses on WHOs blueprint list of priority diseases. Like pandemic influenza, SARS-CoV-2 is highly transmissible (R₀ ~ 2.5). Furthermore, it can fly under the radar due to a broad clinical spectrum where asymptomatic and pre-symptomatic infected persons also transmit the virus-including children. COVID-19 is far more deadly than seasonal influenza; initial data from China suggested a case fatality rate of 2.3%-which would have been on par with the deadly 1918 Spanish influenza. But, while the Spanish influenza killed young, otherwise healthy adults, it is the elderly who are at extreme risk of dying of COVID-19. We review available seroepidemiological evidence of infection rates and compute infection fatality rates (IFR) for Denmark (0.5%), Spain (0.85%), and Iceland (0.3%). We also deduce that population age structure is key. SARS-CoV-2 is characterized by superspreading, so that ~10% of infected individuals yield 80% of new infections. This phenomenon turns out to be an Achilles heel of the virus that may explain our ability to effectively mitigate outbreaks so far. How will this pandemic come to an end? Herd immunity has not been achieved in Europe due to intense mitigation by non-pharmaceutical interventions; for example, only ~8% of Danes were infected across the 1^st and 2^nd wave. Luckily, we now have several safe and effective vaccines. Global vaccine control of the pandemic depends in great measure on our ability to keep up with current and future immune escape variants of the virus. We should thus be prepared for a race between vaccine updates and mutations of the virus. A permanent reopening of society highly depends on winning that race.