Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters
Abstract
Delta variant has evolved to become dominant SARS-CoV-2 lineage worldwide and there are reports of secondary infections with varying severity in vaccinated and unvaccinated naturally recovered COVID-19 patients. As the protective immunity following the infection wanes within few months, studies of re-infection after prolonged duration is needed. Hence we assessed the potential of re-infection by Delta, Delta AY.1 and B.1 in COVID-19 recovered hamsters after 3 months of infection. Re-infection with Delta and B.1 variants in hamsters showed reduced viral shedding, lung pathology and lung viral load, whereas the upper respiratory tract viral load remained similar to that of first infection. The reduction in viral load and lung pathology after re-infection with Delta AY.1 variant was not marked. Further we assessed the disease characteristics of Delta AY.1 to understand whether it has any replication advantage over Delta variant and B.1 variant, an early isolate in Syrian hamsters. Body weight changes, viral load in respiratory organs, lung pathology, cytokine response and neutralizing antibody response were assessed. Delta AY.1 variant produced milder disease in comparison to Delta variant and the neutralizing response was similar against Delta, B.1 and B.1.351 variant in contrast to Delta or B.1 infected hamsters which showed a significant reduction in neutralization titres against B.1.351. Elevation of IL-6 levels was observed post infection in hamsters after primary infection. The prior infection could not produce sterilizing immunity but the protective effect was evident following reinfection. This indicates the importance of the transmission prevention efforts even after achieving herd immunity.
Research in context
Evidence before this study
Secondary infections with Delta variant are being widely reported and there are reports of increased disease severity. Delta sub lineages with K417N substitution has caused concern worldwide due to the presence of the same substitution in Beta variant, a Variant of Concern known for its immune evasion. The information on the biological characteristics of this sub lineage is also scanty.
Added value of this study
The present study showed that the secondary infection with Delta variant does not show any evidence of increased disease severity in hamster model. Delta AY. 1 variant produces mild disease in Syrian hamsters in contrast to severe disease caused by Delta variant. Delta, B.1 and AY.1 variant infected hamster sera showed comparable cross neutralizing response against each other. In contrast to the lower neutralizing response shown by B.1 and Delta variant infected animals against B.1.351 variant, Delta AY.1 showed comparable response as that with other variants.
Implications of the available evidence
SARS-CoV-2 infections do not produce sterilizing immunity but protect from developing severe disease in case of Delta variant re-infection indicating the importance of the transmission prevention efforts even after achieving herd immunity. Delta AY. 1 infection in hamsters did not show any evidence of speculated immune evasion.
Article activity feed
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SciScore for 10.1101/2021.11.28.470293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Ethics statement: The ethical approval for the study was received from Institutional Animal Ethics Committee (Approval no: NIV/IAEC/2021/ MCL/01), ICMR-National Institute of Virology, Pune and all the animal experiments were performed in adherence with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals, Government of India. Sex as a biological variable For the re-infection study, 12 female hamsters, 16-18 weeks old which were previously infected with B.1 variant of SARS-CoV-2 (with an infectious dose of 104,5 TCID50) after 3 months of initial infection were used (Figure 1a). Randomization IgG response and neutralizing antibody levels were … SciScore for 10.1101/2021.11.28.470293: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Ethics statement: The ethical approval for the study was received from Institutional Animal Ethics Committee (Approval no: NIV/IAEC/2021/ MCL/01), ICMR-National Institute of Virology, Pune and all the animal experiments were performed in adherence with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals, Government of India. Sex as a biological variable For the re-infection study, 12 female hamsters, 16-18 weeks old which were previously infected with B.1 variant of SARS-CoV-2 (with an infectious dose of 104,5 TCID50) after 3 months of initial infection were used (Figure 1a). Randomization IgG response and neutralizing antibody levels were checked and animals were divided into 3 groups randomly. Blinding The samples were coded and were blindly scored. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 1 Anti-SARS-CoV-2 IgG detection: The serum samples were tested for IgG antibodies by an in-house developed ELISA22. Anti-SARS-CoV-2 IgGsuggested: NoneIgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Briefly, inactivated SARS-CoV-2 antigen/ Vero CCL81 cell lysate coated microtiter plates were blocked with liquid plate sealer. Vero CCL81suggested: NoneSoftware and Algorithms Sentences Resources Data analysis: Graph pad Prism version 9.2.0 software was used for the descriptive statistics and statistical analysis. Graph pad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study had limitation of small sample size too. In conclusion, the present study shows re-infection with Delta variants or B. 1 variant post 3 months of prior B.1 variant infection could reduce the SARS-CoV-2 virus shedding and reduce disease severity. Delta AY.1 variant produced mild disease and generated cross neutralising antibodies against B.1, Delta and Beta variants. The findings indicate that primary infection can produce protective immunity against a further infection for at least 3 months and can reduce severity of infection in hamsters.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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