SARS-COV-2 DELTA VARIANT PATHOGENESIS IN SYRIAN HAMSTERS AND HOST RESPONSE
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SARS-CoV-2 Delta variant pathogenesis in Syrian hamsters and
host response
WHO Global Consultation of vaccine boost strategies
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
B.1.617 and its evolution to Delta Variant
❑ B.1.617 lineage variants were first Phenotypic characteristics
reported from India in October 2020
❑ Sub lineages: B.1.617.1 (Kappa), Transmissibility
B.1.617.2 (Delta), B.1.617.3
❑ Characteristic mutations in the spike
gene : D111D, L452R, D614G, P618R and
Delta Secondary
±E484Q (Cherian et al., Microorganism 2021) Hospitalizat
variant attack rate
ion risk
❑ Mutations suggest increased ACE2
binding, transmissibility and escape of
neutralization.
Reduction in
❑ Further its mutated to Delta AY.1, AY.2 neutralization
AY.3 and AY.3.1 with different
mutations. (WHO Epidemiological update, July, 2020)
Genomic analysis of COVID-19 breakthrough infections
during second wave in different states of India
• 86% of the breakthrough
infections have been caused by
the Delta variant.
• Only 9.8 % of breakthrough
required hospitalization.
• Fatality was observed in only 0.4
% of cases.
• The study found that Alpha was
predominant in the northern
region.
• Delta and Kappa mainly caused
breakthrough infections in the
southern, western, eastern and
north-western regions.
• Around 71% of these infections
were symptomatic and 29% was
asymptomatic. [Gupta N & Yadav PD et al., BiorXIv,
doi: https://doi.org/10.1101/2021.07.13.21260273]
Distribution of SARS-CoV-2 during breakthrough
(March-June, 2021)
4 distinct sub-lineages of the
Delta SARS-CoV-2 variant
observed
86.09% of the breakthrough
infections were caused by the
Delta variant (B.1.617.2)
followed by
B.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)
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 BiorXiv
doi: https://doi.org/10.1101/2021.07.24.453631
Study Design
105.5 TCID50/ml,
1
B.1, Delta, AY.1
15 hamsters/group
infection
(Euthanized 3, 7, 14 days)
Re-infection
105.5 TCID50/ml,
B.1 infected vs
2 4 hamsters/group
B.1/Delta/AY.1
(Euthanized at 7 post re-
Post 3months of 1st
infection days)
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
SARS-CoV-2 variants used in our study Delta B.1.617.3 AY.1
Body weight
105.5 TCID50/ml Reinfection
(1.4±3.34) (1.74±3.9)
(0.67±3.8)
(0.23±5.18)
(-0.3±3.05)
(-9.5±6.5)
Significant
Delta variant infected hamsters Reinfected hamsters
showed significant weight loss showed no weight loss post
reinfection
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
Delta ❑Significantly
lower gRNA and
sgRNA load in
nasal wash and
AY.1 throat swab
samples of Delta
and B.1
re-infected
hamsters.
B.1 ❑In AY.1 infected
animals no
significant
difference
observed.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 gRNA
loads 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
Post 90
days
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.Neutralizing antibody response post 105.0 TCID50/ml
infection study
B.1.617.2: 1.8 fold B.1: 1.7 fold B.1: 1.7 fold
B.1.617.3: 1.3 fold B.1.617.3: 1.1 fold B.1.617.2: 1.8 fold
B.1351: 2.3 fold B.1351: 2.5 fold B.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 awaitedLung pathology
B.1.617.2:
105 TCID50/ml
Moderate
severity (4/12)
B.1.617.3:
Moderate
severity (1/12)
105.5 TCID50/ml
AY.1:
Gross lesions
(2/10)
B.1.617.2
Gross lesions
(5/10)
B.1.617.2
Focal lesions (2/4)
Re-infection
AY.1:
Focal lesions (1/4)
B.1:
Focal lesions (1/4)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
➢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).
Yadav et al, J Travel Med, taab104, https://doi.org/10.1093/jtm/taab104Neutralization of Beta and Delta variant with sera of COVID-19
recovered cases and vaccinees of inactivated COVID-19 vaccine
BBV152/Covaxin
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.
A significant reduction in neutralization titre of
COVID-19 recovered and BBV152 vaccinee sera
against Beta and Delta in comparison B.1
Yadav et al, J Travel Med, taab104, ttps://doi.org/10.1093/jtm/taab104Neutralization of SARS-CoV-2 Delta AY.1 and Delta in individuals sera
vaccinated with BBV152 and comparison with B.1
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• 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.
Neutralization of Delta variant with sera of Covishield™ vaccinees and COVID-19recovered vaccinated individuals ❑ 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.
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-HQYou can also read
