General introduction 13 1 Figure 1.1. Epidemic curve of confirmed COVID-19 cases worldwide, by date of report and WHO region from 30 December 2019 through 30 April 2020[9] As SARS-CoV-2 spread internationally during the first months of 2020, experts looked to the characteristics of SARS-CoV-1 to make predictions about the likelihood of the outbreak to become a global pandemic. We now know, however, that several key differences between SARS-CoV-1 and -2 meant that the latter posed a far greater threat. Firstly, rapid replication of the SARS-CoV-2 in the upper respiratory tract during the incubation period results in a high viral load up to 48 hours before the onset of any symptoms[10], the pre-symptomatic phase, when an individual may continue to have close contact with others. This contrasts with SARS-CoV-1, where the viral load peaked after the onset of symptoms[11, 12], allowing individuals to be isolated before becoming most infectious. Secondly, SARS-CoV-2, unlike SARS-CoV-1, can result in very mild illness or even asymptomatic infection in a substantial proportion of the population[13]. The contribution of such mildly symptomatic and asymptomatic cases to COVID-19 transmission on a population level has been a topic of intense speculation due to its profound implications for public health policy. Evidence suggests that even those lacking (overt) symptoms may, albeit to a lesser extent, pass SARS-CoV-2 on to others[14]. Therefore, during the first months of the pandemic, when testing was generally restricted to those with severe symptoms such as fever, individuals with mild disease probably played a key role in driving largely undetected circulation of the virus. Finally, SARS-CoV-2 exhibited a shorter incubation period of COVID-19 compared to
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