Dr. Pragya D Yadav,
Scientist E & In-charge Maximum Containment
Facility, ICMR-NIV, Pune Department of Health
Research, Ministry of Health & Family Welfare,
Government of India
SARS-CoV-2 Delta variant pathogenesis in Syrian hamsters and host response
WHO Global Consultation of vaccine boost strategies
B.1.617 and its evolution to Delta Variant
❑ B.1.617 lineage variants were firstreported from India in October 2020
❑ Sub lineages: B.1.617.1 (Kappa),B.1.617.2 (Delta), B.1.617.3
❑ Characteristic mutations in the spikegene : D111D, L452R, D614G, P618R and±E484Q (Cherian et al., Microorganism 2021)
❑ Mutations suggest increased ACE2binding, transmissibility and escape ofneutralization.
❑ Further its mutated to Delta AY.1, AY.2AY.3 and AY.3.1 with differentmutations.
Delta variant
Transmissibility
Secondary attack rate
Reduction in neutralization
Hospitalization risk
Phenotypic characteristics
(WHO Epidemiological update, July, 2020)
• 86% of the breakthroughinfections have been caused bythe Delta variant.
• Only 9.8 % of breakthroughrequired hospitalization.
• Fatality was observed in only 0.4% of cases.
• The study found that Alpha waspredominant in the northernregion.
• Delta and Kappa mainly causedbreakthrough infections in thesouthern, western, eastern andnorth-western regions.
• Around 71% of these infectionswere symptomatic and 29% wasasymptomatic. [Gupta N & Yadav PD et al., BiorXIv,
doi: https://doi.org/10.1101/2021.07.13.21260273]
Genomic analysis of COVID-19 breakthrough infections during second wave in different states of India
Distribution of SARS-CoV-2 during breakthrough (March-June, 2021)
86.09% of the breakthroughinfections were caused by theDelta variant (B.1.617.2)followed byB.1.1.7 (n=28).B.1.617.1(n=22),B.1.617.3 (n=2),B (n=1),B.1.36 (n=5), B.1.1.294 (n=1),B.1.36.16 (n=1), B.1.1.306 (n=1), and Delta AY.2 (n=1)
4 distinct sub-lineages of the Delta SARS-CoV-2 variant
observed
Summary of Delta variant pathogenicity study in hamsters using 104 TCID50
• Virus shedding: No significantly high viral shedding observed
• Body weight loss: No significant body weight loss observed, least gain was observed
in case of Delta
• Viral load in respiratory organs: Longer persistence of sgRNA in the nasal
turbinates and lungs (14 post infection day)
• Lung pathology: Lung disease with moderate severe lesions were observed in case
of 35% of Delta infected hamsters Mohandas S et BiorXivdoi: https://doi.org/10.1101/2021.07.24.453631
Study Design
105.5 TCID50/ml, 15 hamsters/group (Euthanized 3, 7, 14 days)
B.1, Delta, AY.1 infection
105.5 TCID50/ml, 4 hamsters/group (Euthanized at 7 post re-infection days)
Re-infectionB.1 infected vsB.1/Delta/AY.1
Post 3months of 1st
infection Intranasal, 0.1 ml volume Euthanasia and sample collection
❑Virus shedding Nasal wash, throat swab and fecal samples alternate day❑Pathogenicity Weight loss, viral load, antibody response, lung pathology
1
2
SARS-CoV-2 variants used in our study
Delta
AY.1
B.1.617.3
Body weight
(-9.5±6.5)
(0.23±5.18)
(1.4±3.34)
105.5 TCID50/ml
Delta variant infected hamsters showed significant weight loss
(0.67±3.8)
(-0.3±3.05)
(1.74±3.9)
Reinfection
Reinfected hamsters showed no weight loss post reinfection
Significant
Virus shedding (gRNA and sgRNA level)
• Significantly high gRNA load and longer shedding was observed in Delta variant infected hamsters in throat and nasal wash.
• Significantly high gRNA load was observed in nasal wash of Delta variant infected hamsters on 8 and 10 DPI.
Re-infection (gRNA and sgRNA level)Post 3 months and 1st infection samples comparison
❑Significantly
lower gRNA and
sgRNA load in
nasal wash and
throat swab
samples of Delta
and B.1
re-infected
hamsters.
❑In AY.1 infected
animals no
significant
difference
observed.
Delta
AY.1
B.1
Viral load in respiratory tract(gRNA and sgRNA level)
gRNA
sgRNA
• Significantly high sgRNA loads were observed in nasal turbinates of Delta variant infected hamsters on14 DPI.
Re-infection (gRNA and sgRNA load in respiratory organs)
• A reduction in lung and nasal turbinate viral gRNAloads was observed in case of Delta, although not statistically significant
• Lung viral load reduction in case of B.1 infected hamsters was significant.
IgG response in hamsters post infection
105.5 TCID50/ml Re-infection
• Anti-IgG response could be observed post 90 days in B.1 infected hamsters.
• Antibody levels were increased post reinfection irrespective of variant infected.
Post 90 days
infection
Neutralizing antibody response post 105.0 TCID50/mlinfection study
B.1.617.2: 1.8 foldB.1.617.3: 1.3 foldB.1351: 2.3 fold
B.1: 1.7 foldB.1.617.3: 1.1 foldB.1351: 2.5 fold
B.1: 1.7 foldB.1.617.2: 1.8 foldB.1.351: 2.9 fold
• Significant neutralizing antibody reduction against B.1.351 was observed in all infected hamsters
Delta (High dose) and re-infection experiment data is awaited
Lung pathology
B.1.617.2: Moderate
severity (4/12)
B.1.617.3: Moderate
severity (1/12)
AY.1:Gross lesions
(2/10)
B.1.617.2Gross lesions
(5/10)
B.1.617.2Focal lesions (2/4)
AY.1:Focal lesions (1/4)
B.1:Focal lesions (1/4)
10
5T
CID
50
/m
l1
05
.5T
CID
50
/m
lR
e-i
nfe
ctio
n
Lung pathology
• Compared to our earlier study, more severe gross lung lesions were observed with 105.5 TCID50/ ml in Delta infected animals.
• In case of reinfected hamsters, only focal lung lesions were observed.
Conclusions
• Delta and Delta AY1. lineage variants showed pathogenicity in hamsters.
• Disease severity & virus shedding proportional to the virus dose in case
of Delta Variant
• Longer persistence of sgRNA in the upper respiratory tract for Delta
infected animals could be an indicator for transmissibility, transmission
experiments should be performed further.
• Lung disease with severe lesions and body weight loss was observed in
case of Delta variant infected hamsters, indicating the potential of the
variant to cause severe disease in hamster model
• Significant neutralizing antibody reduction against Beta variant in case of
B.1/ Delta /B.1.617.3 infected variants
• Reinfection with Delta and B.1 caused reduced nasal shedding
• Reinfection with Delta, B.1 and AY.1 prevented body weight loss, gross
pneumonic changes in B.1 infection recovered hamsters.
Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine
BBV152/Covaxin
Yadav et al, J Travel Med, taab104, https://doi.org/10.1093/jtm/taab104
➢The neutralization potential of the BBV152 has been already studied with the B.1, Alpha, Zeta and Kappa found to be effective against these variants.
➢COVID-19 recovered cases (n = 20) post 5–20 weeks of infection and vaccinees 28 days after two doses of BBV152 (n = 17) against Beta, Delta variants and compared with prototype B.1 (D614G).
➢The recovered cases were infected with B.1 (n = 17) and B.1.617.1 lineage (n = 3).
Neutralization of Beta and Delta variant with sera of COVID-19 recovered cases and vaccinees of inactivated COVID-19 vaccine
BBV152/Covaxin
Yadav et al, J Travel Med, taab104, ttps://doi.org/10.1093/jtm/taab104
A significant reduction in neutralization titre of COVID-19 recovered and BBV152 vaccinee sera
against Beta and Delta in comparison B.1
The GMT ratio of vaccinees
sera B.1 to Beta and Delta
variants was 3.0 and 2.7 .
The GMT ratio of sera of
recovered cases B.1 to
Beta and Delta variants
was 3.3 and 4.6.
Delta Delta AY.1
Sera of Covid naïve vaccinees 1.3-fold 1.5-fold
Recovered cases with full vaccination 2.5-fold 3.5,-fold
breakthrough cases 1.9-fold 2.8-fold
Neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera vaccinated with BBV152 and comparison with B.1
• However, with the observed high titers, the sera of individuals belonging to all the aforementioned groups they would still neutralize the Delta, Delta AY.1 and B.1.617.3 variants effectively.
Neutralization of Delta variant with sera of Covishield™ vaccinees and COVID-19 recovered vaccinated individuals
Covishield™ vaccinated individuals’ (n=116) sera in different categories was tested against prototype strain B.1 (D614G) and Delta variant. All the sera were collected four weeks post-vaccination for category I-IV participants Sera under five categories:
I. one dose (n=31),II. Two doses (n=31),III. COVID-19 recovered plus one dose (n=15), infected with B.1 lineage IV. COVID-19 recovered plus two doses (n=19) and infected with B.1 lineage V. breakthrough COVID-19 cases (n=20). infected with Kappa and Delta variants
All the sera were collected four weeks post-vaccination for category I-IV participants.
❑ NAb against B.1 were not observed in 11/31 (35.5%) participants in category I.
❑ Similarly, NAb against the Delta were not observed in 18/31 (58.1%) and 5/31 (16.1%) participants of categories I and II respectively.
❑ Participants in one dose (4.5 fold) and 2 dose (3.2 fold) showed reductions in NAb titers against Delta variants as compared to B.1 lineage.
❑ We observed significantly lower NAb titers (3.2-4.5-fold) for the Delta relative to B.1 variant.
❑ However, NAbs in breakthrough participants and the COVID-19 recovered individuals with one or two-dose vaccination had relatively higher protection against Delta in comparison to the vaccinees with one or two dose vaccination.
Neutralization of Delta variant with sera of Covishield™ vaccinees and COVID-19recovered vaccinated individuals
Acknowledgements
ICMR –NIV, Pune team
❖ Dr. Priya Abraham, Director
❖ Dr Sreelekshmy Mohandas, Scientist B,
❖ Dr Anita Shete, Scientist D,
❖ Dr Gajanan Sapkal, Scientist E
❖ Dr. Gururaj Deshpande , Scientist B
ICMR-HQ
❖ Dr. Prof Balaram Bhargava, Sec DHR and DG,
❖ Dr. Samiran Panda, ECD Chief , ICMR
❖ Dr. Nivedita Gupta, Virology Chief, ECD, ICMR-HQ
