The pandemic of coronavirus disease 2019 (COVID-19) is spreading rapidly. Although the cause was quickly identified as a new coronavirus named SARS-CoV-2, our knowledge of this novel virus remains very limited. High infectivity of the virus, lack of effective antivirals and vaccines, and potentially large asymptomatic populations, have made management of COVID-19 extremely challenging. In addition to rapid medical responses, continuous efforts to better understand the pathogenesis of this disease will undoubtedly enlighten the optimal management of the growing pandemic.

SARS-CoV-2 belongs to the β-coronavirus family, and is partially related with the known SARS-CoV (~ 79% similarity) and MERS-CoV (~ 50% similarity) according to genome sequencing. 1 Same as SARS-CoV, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as its main receptor, which is broadly expressed in vascular endothelium, respiratory epithelium, alveolar monocytes, and macrophages. 1 The main transmission route is through direct or indirect respiratory tract exposure. Of note, SARS-CoV-2 is capable of active replication in the upper respiratory tissues, 1, 2 as demonstrated by successful live virus isolation from throat swabs and detection of viral subgenomic messenger RNA (sgRNA) in cells of upper respiratory tract. 2 Tropism of the upper respiratory tissue probably explains continuous pharyngeal shedding of the virus and a more efficient transmission of SARS-CoV-2 than SARS-CoV when symptoms are still minimal and restricted to the upper respiratory tract. Later in the disease course, COVID-19 resembles SARS in terms of viral replication in the lower respiratory tract, and generates secondary viremia, followed by extensive attack against target organs that express ACE2, such as heart, kidney, gastrointestinal tract and vast distal vasculature. This process of viral spreading correlates with the clinical deterioration, mainly taking place around the second week following disease onset. However, it has been generally recognized that disease exaggeration till the late stage is not only attributed to direct viral damage, but also a consequence of immune-mediated injury induced by SARS-CoV-2. Of note, two distinctive features have been noticed in severe and critical patients with COVID-19, progressive increase of inflammation and an unusual trend of hypercoagulation. Although the concept of inflammatory storm remains controversial, there is no doubt that immune-mediated inflammation plays an important role in the pathogenesis of COVID-19, just as it did in SARS. The progression of COVID-19 was associated with a continuous decrease in lymphocyte count and significant elevation of neutrophils. Meanwhile, inflammatory markers were markedly elevated including C-reactive protein, ferritin, interleukin