Page 102 - Annual report 2021-22

Annual Report 2021-22 |

Rajesh Pandey

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Rajesh Pandey’s lab has been at the forefront of SARS-CoV2 genomic surveillance in India. By
partnering with relevant agencies such as National Centre for Disease Control (NCDC), India the Indian-
state specific Integrated Disease Surveillance Programme (IDSP), their efforts have led to highlighting
the penetrance of the B.1.1.617 and its sub-lineages of B.1.1.617.1/B.1.1.617.2 and B.1.1.617.3 across
different states and Union Territories (UT) of India. Before the B.1.1.617 prominence in India, the same
strategy of pro-active genomic surveillance helped tracking of the B.1.1.7 lineage in India. Their lab’s
goal has been to identify mutations underlying the SARS-CoV-2 genomes which will have possible
functional role in evolving variants of concern (VOC) and variant of interest (VOI). To achieve this goal,
penetration of genomics technologies to far and remote locales would be important. The concept of
MicroLabs, based on the pillars of 3S plus Sample cost (4S = Scale, Speed, Sensitivity, Sample cost) was
set up as a target for Pandemic Preparedness. Pilot project towards mobile sequencing was
successfully implemented at the Delhi Airport wherein it was used for Variants of Concern (VOC)
screening for the RT-PCR positive international travellers. Three MicroLabs were set up with focus on,
Rural population of Haryana, MDU-Rohtak, Biggest swath of population in the biggest state of India,
Uttar Pradesh, CSIR-CDRI, North-eastern region of India, Assam, CSIR-NEIST. Of the current goal of
sequencing 3000 samples, the MicroLabs have been functional now at all the 3 sites after sequencing
and Genomics training of the requisite manpower to implement the genomic surveillance, aligning
with the global standards. The inherent in this is the data sharing of the SARS-CoV-2 sequences in the
global repository, GISAID. To take this forward, the networking with the clinical partners and public
health officials is critical. This has been done by all the MicroLab partners and the samples are flowing
to these labs for priority sequencing.
Emergence of SARS-CoV-2 VOCs at different time points through COVID-19 pandemic raised concern
for increased transmissibility, infectivity and vaccination breakthroughs. 1567 international travellers
plus community transmission COVID-19 cases were analysed for mutational profile of VOCS, that led
to notable waves in India, namely Alpha, Delta, and Omicron. Spike mutations in Linkage
Disequilibrium were investigated for potential impact on structural and functional changes of Spike-
ACE2. ORF1ab and spike harboured diverse mutational signatures for each lineage. B.1.617.2 and AY.
* demonstrated comparable profile, yet non-clade defining mutations were majorly unique between
international vs community samples. Contrarily, Omicron lineages showed substantial overlap in non-
clade defining mutations, signifying the early phase of transmission and evolution within the Indian
community. Mutations in LD for Alpha [N501Y, A570D, D1118H, S982A], Delta [P681R, L452R, EFR:156-
158G, D950N, G142D] and Omicron [P681H, D796Y, N764K, N969K, N501Y, S375F] resulted in
decreased binding affinity of Spike-ACE2 for Alpha and BA.1 whereas Delta, Omicron and BA.2
demonstrated strong binding. Genomic surveillance tracked spread of VOCs in international travellers'
vs community transmission. Behavioural transmission patterns of variants, based on selective
advantage incurred by spike mutations, led us to predict sudden takeover of Delta over Alpha and
BA.2 over BA.1 in India.
His lab is focussing on clinic-genomic analysis aims to identify mutations associated with disease
severity and outcome. The Single Cell Genomics based approach in clinically defined COVID-19