The zoonotic coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), which causes COVID-19 (coronavirus disease-2019), has resulted in a pandemic. This has led to an urgent need to understand the molecular determinants of SARS-CoV-2 infection, factors associated with COVID-19 heterogeneity and severity, and therapeutic options for these patients. In this review, we discuss the role of host factors in SARS-CoV-2 infection and describe variations in host factor expression as mechanisms underlying the symptoms and severity of COVID-19. We focus on two host factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), implicated in SARS-CoV-2 infection. We also discuss genetic variants associated with COVID-19 severity revealed in selected patients and based on genome-wide association studies (GWASs). Furthermore, we highlight important advances in cell and chromatin biology, such as single-cell RNA and chromatin sequencing and chromosomal conformation assays, as methods that may aid in the discovery of viral–host interactions in COVID-19. Understanding how regulation of host factor genes varies in physiological and pathological states might explain the heterogeneity observed in SARS-CoV-2 infection, help identify pathways for therapeutic development, and identify patients most likely to progress to severe COVID-19. SARS-CoV-2: More virus-host interaction studies needed Aberrant host immune responses probably influence the severity of COVID-19 more than viral activity itself, but more research is needed to understand how the virus and host interact. The effects of SARS-CoV-2 infection vary widely in severity, from asymptomatic cases to multiple organ failure. Simon Biddie at the University of Edinburgh, UK, and co-workers reviewed current knowledge of host factors in SARS-CoV-2 infection. They focused on host enzymes called ACE2 and TMPRSS2, which facilitate viral entry and replication. High expression levels of these enzymes in certain organs may influence disease severity, and genetic variations influencing their expression should be explored. The researchers believe that pathways involving proinflammatory factors also play wide-ranging roles in COVID-19. Advances in sequencing technologies, high-throughput assays and single-cell methodologies will aid exploration of virus-host interactions.
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