With input from Dr Monica Vasudev

1241:   A second wave in Pakistan: Pakistan’s COVID-19 positivity rate has increased up to  of tests administered in recent weeks from only 2% in October, thus inciting a plea from health experts and doctors in Karachi for the government to impose strict nationwide lockdown. (nytimes.com)

1242: Health authorities in Thailand announced the country’s biggest outbreak to date: In all, 689 infections, linked to a shrimp market not far from Bangkok were reported. A two-week lockdown has been imposed in Samut Sakhon, the coastal province where the market is located. Migrant workers have been barred from leaving and most stores have been closed except for food takeout. Cases connected to the market are now surfacing all across the country, raising the fears that the virus has already spread widely. The first case linked to the shrimp market was confirmed only a week ago. (nytimes.com)

1243:  What to look for when a new virus strain arises?

1. Transmissibility
2. Pathogenicity
3. Immunogenicity

501 variants are more transmissible. It is yet to be proved whether they are more pathologic.

1. Another thing to look for is antigenic drift (minor mutation) or antigenic shift (major mutation). 614 mutation was a single gene mutation and 501 variants are three genes mutation.

Antigenic Drift

One way viruses change is called “antigenic drift.” These are small changes (or mutations) in the genes of the viruses that can cause changes in the surface proteins of the virus. The surface proteins are “antigens,” and are recognized by the immune system and trigger an immune response, including production of antibodies that can curb the infection. The changes associated with antigenic drift happen continuously as the virus replicates. Most vaccines target the spike proteins.

The small changes that occur as a result of antigenic drift usually produce viruses that are closely related to each other, which can be shown by their location close together on a phylogenetic tree.

For example influenza viruses that are closely related to each other usually have similar antigenic properties. The antibodies that the immune system creates against one influenza virus will likely recognize and respond to antigenically similar influenza viruses. This is termed as cross-protection.

The small changes associated with antigenic drift  accumulate over time resulting in viruses that are antigenically different (further away on the phylogenetic tree).

It is possible that a single (or small) change, in a particularly important location on the protein, may result in antigenic drift. When there is an antigenic drift, the body’s immune system may not be able to recognize and prevent sickness caused by the newer viruses. An individual thus becomes susceptible to infection again, because the antigenic drift changes the virus enough that a person’s existing antibodies fail to recognize and neutralize the newer viruses.

In the case of flu, antigenic drift is the key reason why people get the flu more than one time, and it’s also a primary reason why the flu vaccine composition must be reviewed and updated every year (as needed) to keep up with evolving influenza viruses.

Three major antigenic drifts in COVID-19:

1. D 614 G

Amino acid 614 on spike protein RBD part now contains G (Glycine) in place of aspartic acid (D)

2. UK Strain: Multiple gene mutations also called VUI 2020-12/01

N501Y: Amino acid N (asparagine) replaced with Y tyrosine in this amino acid on spike RBD location

Deleted His69  Histidine at 69 location

Deleted Val70 Valine at 70 location

Deletion 144

A570D

D614G

P681H

T716I

S982A

D1118H

as well as mutations in other genomic regions.

3. South Africa drift: also 3 gene mutation

N501Y: Amino acid N (asparagine) replaced with Y tyrosine in this amino acid on spike RBD location

Plus two other gene mutations

Antigenic Shift

The other type of change is called “antigenic shift.” This is an abrupt, major change in a virus, giving rise to new proteins in viruses that infect humans. The shift can lead to a virus subtype in humans.

One way shift can happen is when a virus from an animal population develops the ability to infect humans. The animal-origin viruses can contain a protein which is extremely different from the same subtype in humans and most people do not have immunity to the new (e.g., novel) virus.

Such a shift was seen in the spring of 2009, when an H1N1 virus with genes from North American Swine, Eurasian Swine, humans and birds emerged to infect people and quickly spread, resulting in a pandemic. When shift happens, most people have little or no immunity against the new virus.

While influenza viruses change frequently due to antigenic drift, antigenic shift is less common. Influenza pandemics occur very rarely; there have been four pandemics in the past 100 years. Type A influenza viruses undergo both antigenic drift and shift and are the only influenza viruses known to cause pandemics, while influenza type B viruses change only by the process of antigenic drift. (CDC)

1244:  SARS-CoV-2 variant with multiple spike protein mutations in UK

1. A novel SARS-CoV-2 variant has been identified in the United Kingdom.
2. As per preliminary analysis, the variant appears to be significantly more transmissible than previously circulating variants, according to a Threat Assessment Brief issued by the European Centre for Disease Prevention and Control.
3. The new variant, SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01), seems to have an estimated potential to increase the reproductive number (R) by ≥0.4, and increased transmissibility of up to 70%.
4. There is no indication, so far, of increased infection severity associated with the new variant.
5. SARS-CoV-2 VUI 202012/01 is defined by multiple spike protein mutations (deletion 69-70, deletion 144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H), and mutations in other genomic regions.
6. The most affected region was in Kent/South East England, where there was a rise in the 14-day case notification rate from 100 cases per 100,000 population in week 41 of 2020 to more than 400 per 100,000 in week 50 of 2020.
7. Analysis using viral genome sequence data identified that a large proportion (>50%) of cases belonged to novel variant. As of December 13, 2020, 1,108 individuals had been identified with the novel variant in England, with the earliest case identified on September 20, 2020.
8. It has also been seen in other countries, including Denmark and the Netherlands.
9. European Centre for Disease Prevention and Control is recommending the following:

• Public health authorities and laboratories have been urged to analyze and sequence virus isolates to detect cases of the new variant.
• Individuals with an epidemiological link to cases with the new variant or travel history to areas affected should be identified immediately to test, isolate and follow-up their contacts to curb the spread of the new variant.
• If cases infected with this new variant or other new SARS-CoV-2 variants of potential concern are identified, countries must notify through the Early Warning and Response System of the European Union.
• Communicate the significance of strict adherence to non-pharmaceutical interventions according to national policies to the public, and in particular guidance on the avoidance of non-essential travel and social activities should be emphasized.
• Laboratories must review the PCR performance and drop-out of the S-gene. PCR could be used as an indicator for cases with the new variant for further sequencing and investigation.
• Suspected cases of COVID-19 reinfection should be followed-up, closely accompanied by sequencing respective virus isolates from these cases. Cases with treatment failures using convalescent plasma or monoclonal antibodies should be assessed further.
• With the implementation of vaccination, close monitoring of COVID-19-vaccinated individuals must be ensured to identify possible vaccination failure and breakthrough infections. Virus isolates from these cases need to be sequenced and characterized genetically and antigenically.

The United Kingdom has an established SARS-CoV-2 genome sequencing consortium known as COG-UK.

It includes the national public health institutes, National Health Service organisations, academic institutions, and the Wellcome Sanger Institute. They are working towards keeping the sequencing coverage high and geographically representative and to keep turnaround times low. This initiative raises the odds that emerging variants are identified and can be timely assessed.

(Source: DG Alerts; https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spike-protein-mutations-United-Kingdom.pdf)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA