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Re-visiting the basics of the ‘crown bug’
In the face of the rapidly-spreading Omicron, the Sunday Times takes a re-look at variants and immunity with Consultant Microbiologist Dr. Mahen Kothalawala who is attached to the National Hospital of Sri Lanka.
What is the distinction between ‘infection’ and ‘disease’, he asks before explaining that it is very important to understand the dynamics of the current outbreak. An ‘infection’ is when a ‘pathogen’ (an organism that causes disease) gains entry to the body. A ‘disease’, meanwhile, is when the pathogen gains entry, overcomes the body’s defences and causes a ‘symptomatic illness’. The mere entry of pathogens into a person’s body is not sufficient to produce disease.
Dr. Mahen Kothalawala
A disease is a symptomatic infection, but some of the infected may remain symptomless (asymptomatic or without symptoms) throughout, says Dr. Kothalawala, going onto look at the ‘coronavirus disease of 2019’.
He says: “COVID-19 is the symptomatic infection produced by SARS-CoV-2. The term ‘COVID-19’ naturally excludes asymptomatic infection. However, asymptomatics are important when studying the transmission kinetics of the virus. For every symptomatic COVID case found, there may be at least 3 to 4 times more asymptomatic cases.
“The natural history of the disease is the progression of a disease process over time in the absence of treatment. Four distinct entities have been described based on the natural history of COVID-19.”
These groups are:
- Acute COVID-19 cases – within four weeks (a month) of symptomatic onset
- Post-acute COVID-19 cases – symptoms beyond four weeks (beyond a month)
- Ongoing or sub-acute COVID-19 – symptoms up to 12 weeks (up to 3 months)
- Chronic, Post or Long-COVID-19 – symptoms beyond 12 weeks (beyond 3 months)
According to Dr. Kothalawala most acute cases present with mild to moderate symptoms and will recover with minimal or no post-viral symptoms. Some, however, will end up with ‘Post COVID-19 Syndromes’ – a broad-spectrum clinical manifestation associated with the involvement of multiple organs.
Looking at the viral structure and genome, Dr. Kothalawala says that SARS-CoV-2 shares many similarities to other coronaviruses. The pandemic potential and pathogenesis of SARS-CoV-2 are closely associated with its structure.
- The virus has a single stranded RNA molecule, a lipid envelope and several associated proteins
- The Spike protein (S-protein) mediates in selective binding to the host cell and also mediates in the entry to the cells
- Once within the cell, the virus functionally ‘hijacks the host systems’ and multiplies
- The ‘S protein’ plays a central role in the pathogenesis of COVID-19
- If the ‘S protein’ can be neutralized before it binds to the host receptors, the chances of getting the disease become very unlikely
Focusing on virus multiplication and generation of variants, he says that the SARS-CoV-2 genome consists of 30,000 base pairs. It codes for around 30 essential proteins which help the virus survive and propagate. These proteins mediate in all viral activities within cells. The ‘Spike protein’, as mentioned before, mediates in the virus’s entry to host cells.
Once within the cell, the virus will produce millions and millions of copies of viruses within a very short time.
The aim of this process is to enhance the virus spread and survival. The virus multiplication is preceded by RNA replication and the RNA replicatory mechanism is a process that is highly error-prone. This results in groups of virus progeny with different ‘genetic make-ups’. These changes are known as ‘mutations’. The changed viruses are called variants, he says, pointing out that such a variant could have one or more mutation in its RNA molecule. These mutations could produce structural and functional changes in the viral components, giving the virus many new properties.
As a result, some variants could acquire new characteristics such as improved survival fitness, immune evasion and transmissibility, it is understood. Depending on perceived public health significance, these variants can be classified under one of four threat levels:
- Variant of Interest (VOI) – may drive surges and may be contagious, with possible immune evasion
- Variant of Concern (VOC) – may drive surges and can cause more severe disease. May be contagious with possible immune evasion
- Variant Being Monitored (VBM) – previously identified VOIs or VOCs being followed up
- Variant of High Consequence (VOHC) – definitively drives surges and is contagious with high virulency and also evades immunity
Dr. Kothalawala says that some of these variants show high survival fitness than others. With time, the fittest variant can replace other non-fit variants from circulation. To date, no VOHC has been identified anywhere in the world.
Data from many countries have shown that the Omicron variant has a clear “fitness advantage” over other variants. As a consequence, Omicron has already replaced other variants and has emerged as the dominant variant in many countries, he adds.
(Next: Immunity and vaccination)
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