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The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease., Competing Interests: Competing Interests AuthorCompeting InterestsLast ReviewedHalie M. RandoNone2021-01-20Adam L. MacLeanNone2021-02-23Alexandra J. LeeNone2020-11-09Ronan LordanNone2020-11-03Sandipan RayNone2020-11-11Vikas BansalNone2021-01-25Ashwin N. SkellyNone2020-11-11Elizabeth SellNone2020-11-11John J. DziakNone2020-11-11Lamonica ShinholsterNone2020-11-11Lucy D’Agostino McGowanReceived consulting fees from Acelity and Sanofi in the past five years2020-11-10Marouen Ben GuebilaNone2021-08-02Nils WellhausenNone2020-11-03Sergey KnyazevNone2020-11-11Simina M. BocaCurrently an employee at AstraZeneca, Gaithersburg, MD, USA, may own stock or stock options.2021-07-01Stephen CaponeNone2020-11-11Yanjun QiNone2020-07-09YoSon ParkYoSon Park is affiliated with Pfizer Worldwide Research. The author has no financial interests to declare and contributed as an author prior to joining Pfizer, and the work was not part of a Pfizer collaboration nor was it funded by Pfizer.2020-01-22Yuchen SunNone2020-11-11David MaiNone2021-01-08Joel D BoerckelNone2021-03-26Christian BruefferEmployee and shareholder of SAGA Diagnostics AB.2020-11-11James Brian ByrdFunded by FastGrants to conduct a COVID-19-related clinical trial2020-11-12Jeremy P. KamilTBD2021-04-30Jinhui WangNone2021-01-21Ryan VelazquezNone2020-11-10Gregory L SzetoNone2020-11-16John P. BartonNone2020-11-11Rishi Raj GoelNone2021-01-20Serghei MangulNone2020-11-11Tiago LubianaNone2020-11-11COVID-19 Review ConsortiumNone2021-01-16Anthony GitterFiled a patent application with the Wisconsin Alumni Research Foundation related to classifying activated T cells2020-11-10Casey S. GreeneNone2021-01-20