Chairman of Apex Level Advisory Committee to Government of J&K for COVID-19 and member of governing body SKIMS, Dr Sultan Khuroo in conversation with news agency KNO
KNO: Can you educate our readers about Virus and its latest Omicron Variant?
SARS-CoV-2, the virus responsible for COVID-19, is a single-stranded positive-sense RNA, 30 kb, and made up of around 30,000 nucleotides arranged in sequence. SARS-CoV-2 as other RNA viruses show mutations during virus replication (making copies of its genome) or under the effect of mutagens or stress from therapeutic interventions like plasma therapy, use of monoclonal antibodies, etc. The mutations can occur in many parts of the genome, however, mutations in Spike protein are crucial as this protein attaches to ACE2 receptors present at the cell surface and enter cells to replicate and cause cell damage. The dictum of the mutation is that the more the viruses circulate, the more the virus will change and mutate.
A variant is a virus that has changed in the viral genome through these mutations, leading to changed adaptation to the environment as compared to wild strain. ‘Variant of Concern’ means that the virus has one or more of the three characteristics namely increased transmissibility (more efficient transmission), more severe diseases or immune evasion (can cause reinfections or breakthrough infections in those vaccinated or with previous infections or those who have received monoclonal antibodies).
Up till now 13 variants of the virus have been detected which are named by WHO after letters of Greek Alphabets from Alpha to Omicron. Of these, five variants have been designated as ‘variants of concern’ based on the one of the above three mentioned characteristics (Alpha, Beta, Gamma, Delta, and Omicron), while others have been designated as ‘Variants of Interest’ as they have none of the above three characteristics.
Of the three major waves in India and many other countries, the first wave was caused by wild strain of the virus variant which spread out of Yuhan, China (with major D614G mutation), second wave by Delta variant and the third wave by Omicron. Omicron has been exceptional in its mutations (total 50 mutations with 32 mutations in spike protein) as it has acquired nearly all the mutations of other Variants of Concern and many other new mutations. Because of these mutations selectively targeting Spike protein, the virus has some of the unique characteristics in its transmissibility, attachment to ACE2 receptors and immune evasion.
KNO: Is the third wave in J&K caused exclusively by the new Omicron variant?
In J&K, an Omicron-driven wave was introduced in late December 2021. Genomic sequencing of samples taken in the first week of January 2022 showed that Omicron was the cause of 40 percent of infections and remaining patients had Delta infection. As expected, Omicron has quickly displaced Delta and by now this is the dominant variant causing COVID-19 infections. Of course, a small percentage of infections caused by Delta will stay in the community and may lead to more severe disease-causing pneumonias.
KNO: Can the Omicron variant which is causing current Covid-19 infection be called Flu. And do we need to do any preventive measures?
Khuroo: To answer this question, we must understand what flu is and how it behaves. Flu is caused by influenza viruses that infect the nose, throat, and lungs. These viruses spread through droplets when an infected person coughs, sneezes or talks. Flu lasts for a few days with fever, chills, muscle aches, running nose, headaches, and cough. This innocuous disease in young healthy persons can cause severe pneumonia in high-risk groups, which needs hospitalizations, intensive care treatment and can be fatal.
The disease is endemic and has seasonal occurrence especially at onset of or during winters when cases show mild surge. Each seasonal surge of flu is caused by a new Influenza virus which has evolved through antigen drift. A flu shot (vaccine) made for the suspected new antigenic drifted-strain introduced each year in autumn is protective.
To compare Omicron Covid-19 third wave to flu at this moment is wrong. This is not seasonal disease as flu is, but a distinct massive wave resembling first, and second COVID-19 wave and with much sharper upsurge. The numbers of cases are exceptionally high and there is every possibility that healthcare can come under pressure if measures are not taken to control the spread of disease. Also, deaths in unvaccinated persons and those with high-risk groups is a matter of concern and we must take all measures including masking, social distancing, avoid gathering, use hand sanitizers and vaccinations to protect loved ones.
KNO: What are characteristics of Omicron Covid-19 disease which made the infection distinctive from other variants?
Khuroo: Based on the exceptional mutations in Spike protein of Omicron as mentioned above, the disease caused by this infection has three characteristics:
First, Omicron is highly transmissible and spreads four times faster than the Delta variant from one person to another. The reason for this phenomenon is related to the fact that Omicron spike protein, with 32 mutations, has higher affinity to ACE2 receptors on the cell membrane as well as increased efficiency to enter the cells.
The infectivity of an infectious agent is estimated by calculating R0 (read as R naught, Reproduction number; average number of people who will contract a contagious disease from one person with that disease in a population of people who were previously free of infection and haven’t been vaccinated.) and the generation time (time between getting infected and infecting someone else). Higher R0 and shorter Generation time make an agent more infectious and spread faster from one person to another. Till now, the most infectious disease known has been measles (R0 15-18) followed by Mumps (R0 10). Estimated R0 of SARS-CoV-2 has been calculated as follows: Wild strain (Original strain) 1.5-3; Delta 5-8 and Omicron 8-15. Thus, Omicron has the second highest R0, only second to measles and ahead of mumps.
Next, Generation time for Measles is 11-12 days while Omicron has generation time of three days and Delta and other variants five days. Based on these two characteristics Omicron spreads faster than measles and as of today is the fastest spreading infectious agent known to mankind for over 100 years.
Second, Omicron has been reported to cause milder (not mild) disease severity than Delta. Omicron infections are 70 percent less likely to develop severe disease and 80% less likely to be hospitalized than those with delta variant.
Similarly, hospital admissions with Omicron are about one third of that for the delta variant and need for emergency care is about half of that for delta. This may be good news. However, the benefits of this are likely to be and/or can be nullified by the much larger number of infections and healthcare services can come under stress at the peak of the wave.
The pathogenesis of reduced severity of Omicron has been explained by the mechanism this variant attaches to and enters the cells. Omicron, in contrast to Delta, selectively attaches to the throat and attachment to lungs is much less in intensity and severity.
Thus, lung infections with consequent pneumonias are seen much less with Omicron and most of the symptoms are related to the upper respiratory tract. SARS-CoV-2 virus uses spike proteins to attach to the ACE2 receptors and after attachment uses either classical mechanism (Furin/TMPRSS2 cleavage followed by fusion mechanism) or alternative mechanism (Endocytosis followed by Cathepsin L cleavage).
Omicron based on mutations in the spike protein selectively uses the alternative mechanism to attach and enter the cells. Thus, the role of TMPRSS2, most prevalent in lungs, is markedly diminished in Omicron infections. Cathepsin L dependent mechanism happens more often in the throat, and this explains selective involvement of the throat and relative sparing of the lungs by Omicron.
The third characteristic of Omicron is its ‘immune evasion’ behavior. Omicron can cause reinfections in persons who have been vaccinated (one or 2 doses) or who had COVID-19 disease by other variants namely Delta or Wild (original) strain. Thus, re-infections and breakthrough infections are very common with Omicron. People who have received two doses of a potent mRNA vaccine had over 90-95 percent efficacy with existing variants of the virus. This drops to around 20-40 percent with Omicron. If a booster dose of the same vaccine is given, the efficacy against Omicron can be raised up to 80 percent. However, while vaccinated persons can be often re-infect with Omicron, the disease severity is much less than in unvaccinated people and reduced severity of Omicron may partly reflect global vaccination strategy.
KNO: How long will the pandemic last?
About the pandemic the situation is not well defined. There are three distinct possibilities:
Omicron may be the ‘Beginning of the End’. This is based on the assumption that Omicron will infect the majority of the population and if the immune response to the infection is long lasting and protective, the pandemic may come to an end, a big relief to humanity!
More Waves of pandemic in the offering. As virus is circulating in the populations with consequent replications, mutations are apt to occur. New variants may emerge which can lead to new COVID-19 waves. However, the next variant has to have significant characteristics before it can cause further waves. The variant should possess such mutations which make it move faster in the community to displace Omicron. As of today, there are few new variants described, however, the characteristics and behavior of such variants is not known yet. The world community is watching closely on this aspect of the COVID-19 pandemic.
We may have to live with it and COVID-19 may become an endemic disease. Because there has been a massive global use of vaccines and substantial exposure of population to 3 massive COVID-19 waves, the virus in any form may not be able to cause disease waves. So, disease will exist in the community and show seasonal surge with either existing or new variants. This will be akin to influenza virus, which after the pandemic has become endemic. The virus based on yearly “antigenic drift” shows small changes in the gene leading to changes in the surface proteins of the virus [HA (hemagglutinin) and NA (neuraminidase)] and this new variant causes yearly seasonal disease surge. Most believe that this is the most likely possibility to happen, maybe after this wave or another wave.
KNO: Can lockdown curb the virus?
Lockdown, though so unpleasant, is used as a temporary measure to flatten the epidemic curve and prevent healthcare from coming under pressure. This will help better management of patients admitted to the hospitals efficiently to reduce mortality. I believe as lockdown has many economic and social ramifications, it should be done selectively, and its need and impact reviewed frequently.
KNO: What advice will you give to people to fight the wave?
Always follow Standard Operating Procedures so well circulated in the public by healthcare authorities. Broadly it included proper masking, maintaining social distancing, avoiding gathering in closed rooms and hygienic measures to frequently clean hands with either soap or water (20 seconds) or 70 percent alcohol.
Be very strict to keep your vaccination protocol meticulous. If not vaccinated, be sure to get the dose. For medical professionals and high-risk groups, take a booster dose as recommended by authorities. Protect your children (15-17 years) by vaccination programs authorized and in vogue.
If you have been infected, seek medical advice. It starts with a test and if positive, follow the advice given depending upon your risk factors, severity of disease and frequently taken parameters. Of course isolation is mandatory to safeguard your loved ones
