Opinion: Comparing Coronaviruses
Opinion: Comparing Coronaviruses

Opinion: Comparing Coronaviruses

In addition to continued scruitiny of the SARS-CoV-2 virus, research on similar pathogens could aid in the fight against the COVID-19 pandemic and future disease outbreaks.

Nicola Petrosillo
Jun 1, 2021

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COVID-19 is not humanity’s first brush with a coronavirus outbreak. A related pathogen, SARS-CoV, first emerged in Foshan, China, in November 2002. In February 2003 the virus was transported to Hong Kong, and from there, severe acute respiratory syndrome (SARS), the disease it causes, spread globally. By May 2004, that epidemic was quelled. Almost a decade later, in April 2012, the first cases of Middle East respiratory syndrome (MERS) occurred in Jordan. Countries in the region hosted persistent epidemics, and cases of MERS popped up in countries outside the Middle East. We can learn a lot about SARS-CoV-2 by comparing and studying the characteristics of these similar coronaviruses and the outbreaks they fueled.

SARS-CoV-2 belongs to the diverse family of coronaviruses that are enveloped, single-stranded RNA viruses. Among the four genera (alpha, beta, gamma, and delta), alpha and beta coronaviruses are the most relevant to public health due to their propensity to cross animal-human barriers, thus becoming human pathogens. SARS-CoV, SARS-CoV-2, and MERS-CoV are all beta coronaviruses with high morbidity, mortality, and transmissibility. Other human coronaviruses, of both the alpha and beta variety, are responsible for up to one-third of common cold cases and sometimes cause gastroenteritis. 

SARS-CoV, SARS-CoV-2, and MERS-CoV all consist of nonstructural replicase proteins and four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. The N protein stabilizes the RNA genome, and the S, E, and M proteins together create the viral envelope. Phylogenetic analysis shows that SARS-CoV-2 belongs, together with SARS-CoV and SARS-like coronaviruses isolated in China from horseshoe bats between 2015 and 2018, to a different clade from MERS-CoV, and it is more closely related to the bat SARS-like coronaviruses than to SARS-CoV.

SARS-CoV-2 belongs to a family of viruses that includes pathogens responsible for recent and ongoing epidemics.

Accumulating evidence based on genomic analyses suggests that SARS-CoV-2 shares with SARS-CoV the same human cell receptor, angiotensin-converting enzyme 2 (ACE2)—analysis of receptor affinity shows that SARS-CoV-2 binds ACE2 more efficiently than SARS-CoV does—while MERS-CoV uses dipeptidyl peptidase 4 (DPP4) to enter host cells. But pathogenicity is different among the three viruses. The pathogenesis of SARS-CoV-2 and SARS-CoV is related to an immune system phenomenon involving a sharp increase in inflammatory proteins called a cytokine storm, whereas MERS-CoV’s proteins target host interferons to inactivate natural killer cells. In addition to initiating cytokine storms, SARS-CoV-2 promotes various cell death programs, such as pyroptosis, apoptosis, and necrosis, which may contribute to COVID-19 pathogenesis. In the immediate future, an in-depth study of these peculiarities of SARS-CoV-2 requires novel approaches—i.e., omnigenetics,  network immunological and biological approaches, etc.—to identify intrinsic factors (genetic risks, immune response kinetics, and other determinants) and biomarkers associated with COVID-19 severity.

Although it changes rapidly, as per an August 2020 paper, the COVID-19 case fatality rate was 4.4 percent, compared with 9.5 percent and 34.4 percent for SARS and MERS, respectively. This can be partly explained by the fact that the case fatality rates for both MERS-CoV and SARS-CoV infections may be overestimates of the true mortality rates, as mild cases of SARS and especially MERS may have been missed by surveillance systems at the time. 

Regarding differences in transmissibility, a metric used to describe this spread is the basic reproductive rate (R0), defined as the average number of secondary transmissions from one infected person. According to a paper published last year, the R0 estimates for SARS-CoV-2, SARS-CoV, and MERS-CoV are on average 2.5, 2.4, and 0.69, respectively. The incubation periods range from 4 to 11, 2 to 7, and 2 to 14 days for SARS-CoV-2, SARS-CoV and MERS-CoV, respectively.

Unlike SARS-CoV and MERS-CoV, SARS-CoV-2 uses multiple modes of transmission, and its structure is optimized for different environmental conditions. During the course of the pandemic, SARS-CoV-2 has undergone genomic rearrangements, resulting in the new variants that have appeared in patients around the world—an important means of immunological escape. 

For the past year and a half, much scientific research has been devoted to COVID-19, but many questions remain unanswered: Why is COVID-19 transmitted so quickly? Do some specific features of SARS-CoV-2’s structure play a role in its rapid spread? Are any host or environmental factors responsible for the different course of COVID-19 compared to other coronavirus diseases? Has the knowledge accumulated during the pandemic advanced our efforts to fight COVID-19? Researchers can answer these crucial questions by continuing to study the intricacies of SARS-CoV-2. But scientists should also consider the structure and behavior of the virus’s deadly cousins and the outbreaks they sparked.

Already, the emergence of SARS-CoV-2 variants has increased transmissibility of the virus up to 50 percent above that of the original strain that emerged in Wuhan. Concurrently, hospitalizations and death rates associated with these variants have risen across all age groups, particularly in older patients with comorbidities. A revised R0 estimate for these variants has increased to around 3.5. 

Intensively studying SARS-CoV-2 is crucial, especially in light of the fact that the virus continues to change and adapt as it lingers in human populations around the globe. But scientists should keep in mind that SARS-CoV-2 belongs to a family of viruses that includes pathogens responsible for recent and ongoing epidemics. Understanding the evolutionary, structural, and functional relationships among coronaviruses can facilitate the prevention or mitigation of the next pathogen poised to cross over from animals to humans. 

Nicola Petrosillo is director of the clinical and research department at Italy’s Lazzaro Spallanzani National Institute for Infectious Diseases in Rome. Reach out to him at nicola.petrosillo@inmi.it