ERS | monograph Preface Anh Tuan Dinh-Xuan Even though SARS-CoV-2 can theoretically infect a variety of organs after binding to the ubiquitous ACE2 cell membrane receptor, the respiratory system is still the most frequently impacted due to the airborne nature of the infective agent. The clinical picture is very heterogeneous, but the potential for severe life-threatening conditions in adults comes from lung injury, as inflammatory processes causing airways, alveolar and vascular dysfunction and damage can lead to rapidly progressive acute hypoxaemic respiratory failure. Since its appearance in December 2019, it has become rapidly apparent that this new disease behaves very differently from previously known viral pneumonias in terms of risk factors and clinical, radiological and biological presentations. It has challenged, and continues to challenge, our knowledge whilst also urging in-depth basic research and rapidly evolving clinical guidance, both of which are mandatory to improve patient care and support public health decisions. Adaptive mutations of the SARS-CoV-2 genome alter its pathogenic potential, which in turn increases the already significant obstacles to drug and vaccine development. As with other RNA viruses, the rate of nucleotide substitution in the SARS-CoV-2 genome is fast, and this rapid evolution is mainly shaped by natural selection. Despite the extraordinary speed of vaccine development against COVID-19 and 8 billion vaccine doses administered to date, the very recent emergence of omicron, yet another variant of concern which threatens to supersede the already dreadful delta variant, highlights the ongoing difficulties of achieving global control of the pandemic. Nevertheless, at the time of writing in December 2021, 2 years after the pandemic outbreak, we can state that much has been learned about the pathogenesis, epidemiology and clinical management of COVID-19. No other medical condition has ever had such a “high speed” dynamic in the emergence of medical knowledge, as reflected by the unprecedented exponential rise in scientific publications over the past 2 years. Copyright ©ERS 2021. Print ISBN: 978-1-84984-148-1. Online ISBN: 978-1-84984-149-8. Print ISSN: 2312-508X. Online ISSN: 2312-5098. https://doi.org/10.1183/2312508X.10021321 v