CME INDIA Presentation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh, India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.

Arrives the most heavily mutated version of the Coronavirus – How much to panic? What are the ways ahead?

“I would not be surprised if it is [in the US], we have not detected it yet, but when you have a virus that is showing this degree of transmissibility and you’re having travel-related cases they’ve noted in other places already, when you have a virus like this, it almost invariably is going to go all over.” – Fauci, the CDC director

“Early evidence suggests the Omicron variant, first identified in South Africa, could pose an increased risk of reinfection.” – World Health Organization (WHO)

“More research is needed to determine whether the variant is more contagious, whether it causes more severe disease, and whether these mutations have some worrying characteristics.” – Maria Van Kerkhove, WHO’s technical lead

At present, relatively little is known about Omicron. It has the heaviest mutations till date. Scientists fear that this could make it more infectious and less susceptible to vaccines. It is also unclear whether the variant is more transmissible than Delta? But worth pondering — neither of these effects is yet established. All we know comes from hints from computer modelling that B.1.1.529 could dodge immunity conferred by another component of the immune system called T cells.

Most confirmed cases of the variant are contained to southern African countries. But worries that Omicron could have spread more widely before scientists discovered it, is a genuine one.

Timeline

When was it first detected?

• The first known confirmed B.1.1.529 infection was from a specimen collected on 9th November 2021.
• According to an international database of variants, Omicron first came to light in Botswana. So far, six people have tested positive for omicron there. Around the same time, researchers in South Africa stumbled across omicron in a cluster of cases in the Gauteng province, which includes Johannesburg and Pretoria, and now omicron may already be present in most provinces of South Africa.
• The epidemiological situation in South Africa has been characterized by three distinct peaks in reported cases, 2nd Peak was by Beta variant and 3rd peak was predominantly the Delta variant. Lately, South Africa has reported a four-fold increase in new cases over the last two weeks, coinciding with the emergence of B.1.1.529.

What are the mutations that characterize this variant?

B.1.1.529 has “very unusual constellations of 32 mutations.” These are:

1. Cluster of mutations, known as H655Y + N679K + P681H, (spike protein) is associated with more efficient cell entry, indicating enhanced transmissibility.
2. There is also a deletion, nsp6, which is similar to a deletion in the Alpha, Beta, Gamma, and Lambda variants. This may be associated with evasion of innate immunity, and could enhance transmissibility.
3. New variant carries the mutations R203K+G204R — also seen in Alpha, Gamma and Lambda — and which are associated with increased infectivity.
4. Mutations on a part of the virus known as the furin cleavage site are similar to those seen in the alpha and delta variants, which could help the variant spread more easily.

Parameters of a deadly variant and where does Omicron fit into these parameters?

1. Diagnostic Escape:

Currently available tests (RTPCR) continue to detect the new variant. However, there is S Gene deletion in this variant. While large number of Diagnostic kits in India detect N gene and RdRp gene. Some test kits across the world additionally detect S gene which if not detected can serve as crude test indicative of Omicron infection. Rapid Antigen tests detect S gene so it may not be able to detect the new variant.

2. Therapeutic Escape:

Though there are not many drugs effective against the coronavirus but currently available Experimental antiviral pills – such as Pfizer Inc’s (PFE.N) Paxlovid and Merck & Co Inc’s (MRK.N) molnupiravir – target parts of the virus that are not changed in Omicron. Rather these drugs could become even more important if vaccine-induced and natural immunity are threatened.

3. Immune Escape:

The new variant has over 30 mutations in Spike proteins of the virus. Most present vaccines namely Covishield and mRNA Vaccines target spike proteins. It is possible that changing spike proteins might override the immunity provided by these vaccines. However, killed virus vaccines as Covaxin target additional genes like N Gene which is not affected by present mutations. In addition, all Covid vaccines stimulate Cell Mediated Immunity which should remain functional.

It is noteworthy what the mutations would mean

It is all theoretical and based on experience of past mutations of SARS-CoV-2 rather than actual lab tests. (Re)infection by overriding the immunity of past natural SARS-CoV-2 infection or following Covid vaccination is yet to be established for Omicron. And it may take several weeks to find the same. However, Omicron’s mutations may render certain monoclonal COVID-19 treatments e.g., Regenron – ineffective.

4. Transmissibility:

Omicron is suspected to be highly transmissible It is suspected of driving a spike in new infections in South Africa. Number of cases of this variant appears to be increasing in almost all provinces in South Africa.

5. Severity:

“No unusual symptoms” have been reported following infection with the B.1.1.529 variant. It has highlighted that, as with other infectious variants such as Delta, some individuals are also asymptomatic.

Why WHO classified it as VOC so early?

• Because it has been identified as causing significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence to suggest an emerging risk to global public health.
• In South Africa, national daily cases have gone from 274 on 11th November to 1000, a fortnight later. While the rate of growth has been fast, absolute numbers are still relatively low compared with the UK, which saw 50,000 cases on 26th November. However, no cases of omicron have been detected in the UK yet.

How far has it spread?

• Genomic sequencing has found the variant in South Africa, Botswana and Hong Kong. There are also reported cases in Israel, apparently originating from a traveler from Malawi, and in Belgium, from someone who had travelled from Egypt. It is “highly likely” that the variant has spread to other countries.

How Countries have responded?

• The UK and EU have imposed restrictions on people travelling from countries in southern Africa. Countries, including India, Australia, Japan and the UK, have voiced concern.
• India has started monitoring flights from affected countries. Quarantine remains the key presently.

Variant B.1.1.529: Real threat or just panic?

Why New variants are coming from Africa?

• Mutations occur when the virus gets a chance to multiply in a weak immunocompromised host.
• Vaccination figures of Africa show that it has poor vaccination records.
• Inequality in vaccination is likely to drive the further course of pandemic.
• Out of more than 8 billion doses of vaccines used worldwide only 10% have gone to Africa. Less than 7%of Africa’s population is fully vaccinated.
• Rich nations need to divert vaccination ships to Africa. World is not a safe place even if one person on earth remains vulnerable.

Real threat of B.1.1.529 or just Panic?

• We are being made to live a state of fear and phobia by those in driving seat.
• Possibly World watchdogs press the panic button as part of their duty driven by abundance of caution. 
• Initially it was fear of Third wave. In between came the Fear of Delta Plus and then AY.4.2
• These Variants in past too caused panic but failed to rise to dreadful scales. Now it is B.1.1.529 which too should pass peacefully.
• Total of less than 100 cases of B.1.1.529 in the World out of which 80% are confined to Gauteng province.
• However, now markets are opening up, use of masks have decreased, social distancing is no more a norm, sanitizers no longer popular, the virus might find it easier to spread and if so happens, third wave may not be far. But all this still remains a theory.

Do number of mutations make a variant more deadly?

• No. Number of mutations doesn’t matter as long as they don’t cause severe disease. So, there is nothing to fear from 32 mutations as new Variant.

What can I do to protect myself?

1. Get fully vaccinated.
2. Motivate others for vaccination.
3. Follow Covid Appropriate Behavior.
4. Mask, Social Distancing and Hand Sanitization.

What can Governments do?

• Send vaccines to Africa.
• Monitor flights from affected nations.
• Quarantine people from affected countries.
• Enhance Genomic Surveillance.
• Educate people.
• Enforce Laws to ensure Covid Appropriate Behavior.

Variants will keep knocking, it is for people to permit them entry or not.

• Stay alert but not in Panic.

CME INDIA Important Highlights

S-gene target failure (SGTF) testing / algorithm (WHO)

• For countries with access to diagnostic tests in which at least one gene target contains the S gene target:
  1. Prioritize specimens with S Gene target failure (no detection for S gene and detection for other gene targets) for sequencing confirmation of the Omicron.
  2. A sudden increase in S gene target failures may be indicative of circulation of the Omicron in light with reducing prevalence of Alpha variant, however, confirmation by sequencing is recommended.
• For countries without access to diagnostic tests with S gene target:
  1. Enhanced surveillance and sequencing is recommended to characterize the circulating SARS-CoV-2 variants.

Vaccination (WHO)

• The presence of multiple mutations of the spike protein in the receptor-binding domain indicates that the Omicron have a high likelihood of immune escape from antibody-mediated protection.
• However, immune escape potential from cell-mediated immunity is more difficult to predict.
• Overall, there are still considerable uncertainties in the magnitude of immune escape potential of the Omicron.
• Further research studies are needed to better understand the escape potential against vaccine- and infection-induced immunity.
• Research efforts are ongoing, and the data are expected to be available within two to three weeks.
• Despite uncertainties, it is legitimate to consider that currently available vaccines may offer some level of protection against hospitalization and death.
• Meanwhile, efforts should be intensified to accelerate the vaccination coverage, especially among priority populations initially targeted for COVID-19 vaccination who remain unvaccinated or not yet fully vaccinated.
• Increasing COVID-19 vaccination coverage in all eligible age groups, but particularly in the old adults, health care workers and others with high risks of severe diseases should be prioritized by public health authorities.

CME INDIA Tail Piece

1:

2:

World Health Organisation (WHO) identified the variant of concern, found in South Africa, as Omicron. The virus is feared to be more dangerous and has been seen to show more mutations.

“It presents mild disease with symptoms being sore muscles and tiredness for a day or two not feeling well. So far, we have detected that those infected do not suffer loss of taste or smell. They might have a slight cough. There are no prominent symptoms. Of those infected some are currently being treated at home,” – Angelique Coetzee, chairwoman of South African Medical Association (SAMA).

South Africa on Sunday said that it was being punished for reporting the virus.

3:

Omicron variant is causing mild disease. South African Medical Association slams this hype.

References:

1. WHO. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2- variant-of-concern
2. European Centre for Disease Prevention and Control. Threat Assessment Brief: Implications of the emergence and spread of the SARS-CoV-2 B.1.1. 529 variant of concern (Omicron) for the EU/EEA. https://www.ecdc.europa.eu/en/publications-data/threat-assessment-brief-emergence-sars-cov-2- variant-b.1.1.529
3. Nature,doi: https://doi.org/10.1038/d41586-021-03552-w
4. Technical Brief: Enhancing Readiness for Omicron (B.1.1.529) in the WHO South-East Asia Region WHO Regional Office for South-East Asia 27 November 2021

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