Author: Saila Ismail (Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia).
In late 2019, a new coronavirus emerged and rapidly changed the world. Within months, SARS-CoV-2, the virus responsible for COVID-19, spread across continents and became the first coronavirus to cause a global pandemic.
Schools closed, healthcare systems faced unprecedented challenges, and communities worldwide experienced disruptions unlike anything seen in modern times.
But an important question remains: Why did SARS-CoV-2 spread globally while previous coronaviruses, such as SARS-CoV-1 and MERS-CoV, did not?
The answer lies in the biology of the virus: how it enters human cells, where it replicates, and most importantly, how it spreads before people realise they are infected.
COVID-19 did not become a pandemic because SARS-CoV-2 was the deadliest coronavirus. In fact, SARS-CoV-1, responsible for the 2003 SARS outbreak, caused more severe disease and had a higher fatality rate. However, SARS-CoV-2 possessed a unique combination of characteristics that allowed it to spread much more efficiently among humans (Peiris et al., 2003; He et al., 2020).
One of the greatest challenges of COVID-19 was silent transmission. Many infectious diseases are easier to control because infected individuals develop noticeable symptoms before they become highly infectious. Once people become sick, they are more likely to seek medical attention and reduce contact with others. However, SARS-CoV-2 demonstrated a different pattern.
Many infected individuals experienced mild symptoms or no symptoms at all. While they appeared healthy, the virus was already multiplying in their respiratory tract and could be transmitted to others (Oran & Topol, 2021).
A person could spread the virus through normal activities such as talking, coughing, or sneezing without knowing they were infected. This silent transmission allowed SARS-CoV-2 to spread through communities before outbreaks were detected.
Whiles SARS-CoV-1 and SARS-CoV-2 are closely related coronaviruses, (both use their spike (S) protein to attach to the ACE2 receptor on human cells, allowing viral entry (Zhou et al., 2020)), differences in their spike proteins and infection patterns gave SARS-CoV-2 a major advantage in transmission. These differences are outlined below.
Spike protein features of SARS-CoV-2
The spike protein is the structure on the surface of coronavirus particles that allows the virus to enter human cells. A region of the spike protein called the receptor-binding domain (RBD) interacts with the ACE2 receptor found on human respiratory cells.
Structural studies have showed that SARS-CoV-2 spike protein contains features that allow efficient interaction with human ACE2, supporting effective infection of respiratory cells (Wrapp et al., 2020; Shang et al., 2020).
However, successful transmission depends on more than ACE2 interaction alone. The ability of the virus to enter cells, replicate efficiently, and spread between individuals is determined by multiple viral and host factors.
SARS-CoV-2 contains a furin cleavage site
One important difference between SARS-CoV-2 and SARS-CoV-1 is the presence of a polybasic furin cleavage site in the SARS-CoV-2 spike protein. Before coronavirus particles can enter cells, the spike protein must be activated by host enzymes.
The furin cleavage site allows SARS-CoV-2 spike activation by widely expressed human enzymes, improving viral entry into host cells (Hoffmann et al., 2020). This feature may contribute to the ability of SARS-CoV-2 to efficiently infect respiratory tissues.
SARS-CoV-2 replicated efficiently in the upper respiratory tract
Another major difference between SARS-CoV-1 and SARS-CoV-2 was where the viruses replicated. SARS-CoV-1 primarily infected the lower respiratory tract, especially the lungs. Patients commonly developed noticeable symptoms such as fever and pneumonia before significant transmission occurred (Peiris et al., 2003).
In contrast, SARS-CoV-2 can replicate efficiently in the upper respiratory tract, including the nose and throat (Hou et al., 2020). This provided a major transmission advantage because viruses in these locations can easily spread through breathing, talking, coughing, sneezing, and close contact.
A virus replicating in the nose and throat can spread effectively before causing severe disease.
The differences between SARS-CoV-1 and SARS-CoV-2 can be summarised below:
| Feature | SARS-CoV-1 (SARS, 2003) | SARS-CoV-2 (COVID-19) |
| Main replication site | Mainly lower respiratory tract | Upper and lower respiratory tract |
| Spike protein | Uses ACE2 for entry | Spike contains structural features supporting efficient entry |
| Furin cleavage site | Absent | Present, improves spike activation |
| Viral shedding | Mainly after symptom development | Around or before symptoms |
| Silent transmission | Limited | Common |
Why SARS-CoV-2 caused the Pandemic
SARS-CoV-2 caused the COVID-19 pandemic because it combined several transmission advantages, including: efficient infection of human respiratory cells, replication in the upper airway, transmission before symptoms appeared, and frequent mild or asymptomatic infections.
The pandemic demonstrated that the most successful viruses are not always the ones that cause the most severe disease. A virus that can spread efficiently while remaining hidden can have a much greater global impact.
References
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