Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract — severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

Introduction

The first cases of coronavirus disease 2019 (COVID-19) likely occurred from a zoonotic transmission in China in December 2019, linked to a large seafood market that also traded in live wild animals. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is capable of human-to-human transmission and spread rapidly to other parts of China and then to other locations. By 24 March 2020, SARS-CoV-2 had infected more than 381,000 people across 195 countries/regions and killed more than 16,000: a pandemic as declared by the World Health Organization¹. Daily reports of sharp rises in the number of new cases continue to emerge from many countries/regions, but efforts to overcome the virus are hampered by a lack of knowledge of several important aspects of SARS-CoV-2 infection, ranging from pathogen biology to host response and treatment options. Therefore, there is an urgent need to better understand the host–pathogen biology of COVID-19 as this will offer important insights into treatment and management of the disease, including identification of new therapies. Here, we review the literature on SARS-CoV-2 pathophysiology, its interaction with target cells and the immune response to the virus, including the contribution of dysfunctional immune responses to disease progression. Specifically, we highlight the implications of specific features of the infection for promising therapeutic interventions that could target the virus or the dysfunctional immune response. Moreover, we discuss how studies focused on the adaptive immune response will be crucial in informing the development of vaccines and therapeutic monoclonal antibodies.