2 min read
Pandemic Updates

1. Introduction 

2. Data Science and COVID Data Introduction (30th October)

4 . Immunology 1.01










Pre-2022

With the initial pandemic waves largely behind us we recall that Summer 2021 was dominated by SARS-CoV2 Delta variant infection.

Current estimates suggest that BA.2 variants have replication rates at least 30% greater than BA.1 variants with higher re-infection rates.

2 variants, BA.4 and BA.5 in Europe, were also recently identified as strains to monitor by the World Health Organization that became dominant throughout 2022 diversifying in September 2022 into current circulating XBB and BQ1. 

lllustrations show genetic diversity so far within omicron around the world, sequences available on nextstrain.org site as below. 

But what does this really mean in terms of longer term immunity to infection?

Presently L452R and F486V mutations are under investigation amongst others. Earlier pandemic waves indicated that these could pose a risk to long term immunity. Recent findings in 2021 detailed by Motozono et al in Cell Host and Microbe suggest that the L452R substitution increases the binding affinity of the SARS-CoV-2 RBD toward human ACE2, protein stability, and viral infectivity. 

Although the L452 residue is not directly located at the binding interface, structural analysis and in silico mutagenesis suggest that the L452R substitution promotes electrostatic complementarity. because it is located in close proximity to a negatively charged patch of ACE2 residues (E35, E37, and D38), the increase in viral infectivity caused by the L452R substitution can be attributed to an increase in electrostatic interaction with ACE2.

Trevor Bedford's group (source below) produced this interesting graph showing the drift comparison between recent strains of influenza v SARS-COV2 showing the difference between the 2 types of virus in terms of what we can antigenic drift. Each year influenza regularly has different variants, some are of little concern whilst others are.  

The "Delta" (L452R) mutation found in both the BA.2.12.1 and BA.4/BA.5 variants is key to both immune escape and enhanced cell fusion (not present in BA.1 or BA.2). Some with prior  Delta infections have better neutralization to these variants