General introduction 15 1 approximately one week after illness onset, presenting with dyspnoea and hypoxaemia secondary to acute respiratory distress syndrome (ARDS)[25]. Histopathological studies have demonstrated alveolar damage and fibrin formation in the lungs of hospitalised COVID-19 patients[26]. In addition, severe COVID-19 is characterised by a cytokine storm which may present with thromboembolic complications (such as a stroke or pulmonary embolism) due to microthrombi formation, septic shock and respiratory failure[27]. Due to limited testing during the first months of the pandemic, however, it was difficult to estimate exactly what proportion of infections resulted in severe disease. Initial crude estimates of the case fatality rate (CFR) of COVID-19 were also hampered by delayed reporting of deaths[28] and a case definition that was – due to overreliance on existing knowledge of SARS-CoV-1 – biased towards capturing those with more severe disease. Most initial estimates suggested that, in a fully-susceptible population, the CFR of SARS-CoV-2 infection was lower than that of SARS-CoV-1 and MERS-CoV, but higher than that of seasonal influenza[29]. These estimates have since been influenced by natural and vaccine-derived immunity and viral evolution. Risk factors for COVID-19 hospitalisation and mortality are most notably increased age, cardiovascular comorbidities, obesity, and pregnancy[30, 31]. Figure 1.2. Disease severity pyramid of COVID-19 in 2020[23]* * This figure shows estimated disease severity proportions of the COVID-19 wild-type (Wuhan) variant, prior to the acquirement of natural or vaccine-derived population immunity, and emergence of other variants of concern (VoCs).
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