Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study

Hansen, Christian Holm; Friis, Nikolaj Ulrik; Bager, Peter; Stegger, Marc; Fonager, Jannik; Fomsgaard, Anders; Gram, Mie Agermose; Christiansen, Lasse Engbo; Ethelberg, Steen; Legarth, Rebecca; Krause, Tyra Grove; Ullum, Henrik; Valentiner‐Branth, Palle

doi:10.2139/ssrn.4165630

Cited by 23 publications

(23 citation statements)

References 13 publications

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“…To our best knowledge, there still no robust evidence with real-word data regarding vaccine effectiveness against severe COVID-19 disease caused by BA.5. However, recent data from Denmark 8 (preprint) on severity of BA.5 among those vaccinated with booster suggested higher risk of hospitalization in BA.5 cases compared BA.2, that also corroborates our findings on less protection conferred by booster dose against hospitalization with BA.5 compared to BA.2.…”

Section: Discussionsupporting

confidence: 92%

“…Using case-case study design based on routinely collected data from electronic health records, this study showed no differences in odds of vaccination between BA.5 and BA.2 cases in Portuguese adult population, suggesting similar vaccine effectiveness against infection with BA.5 compared to BA.2. This result corroborates findings from the previous studies from the UK and Denmark which compared vaccine effectiveness against infection between BA.5 and BA.2 using similar methodological approach 8,11 . Our study showed that the SARS-CoV-2 Omicron BA.5 lineage was associated with higher odds of reinfection when compared to BA.2.…”

Section: Discussionsupporting

confidence: 91%

“…A severity assessment from South Africa (preprint) reported no differences in risk of severe hospitalization/death during BA.4/5 wave compared to BA.1 wave 12 . In contrast, recent study from Denmark reported higher odds of hospitalization among BA.5 cases compared to BA.2, even among those vaccinated with a booster dose 8 .…”

Section: Introductionmentioning

confidence: 61%

“…Early vaccine effectiveness and risk of reinfection assessment showed that BA.4/5 protection conferred by a previous infection was modest when the previous infection involved a pre-Omicron variant 10 . Recent studies from the UK 11 and Denmark (preprint) 8 reported no differences in odds of vaccination between BA.5 and BA.2 cases. A severity assessment from South Africa (preprint) reported no differences in risk of severe hospitalization/death during BA.4/5 wave compared to BA.1 wave 12 .…”

Section: Introductionmentioning

confidence: 94%

“…Additionally, there are some concerns that BA.5 could be more infectious and severe than other lineages of the Omicron 6–8 . Kimura and colleagues 6 found that, in cell cultures, BA.4/5 replicated more efficiently and were more fusogenic than BA.2.…”

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal

Kislaya

Casaca

Borges

et al. 2022

Preprint

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Background In a context of multiple Omicron lineages circulation, it is relevant to clarify the effect of vaccination and previous infections on the risk of infection and severe post-infection outcomes. Methods Using electronic health records and SARS-CoV-2 laboratory surveillance data, we conducted a case-case and a cohort study covering the period of Omicron BA.2/BA.5 lineage replacement in Portugal, to compare vaccine effectiveness of complete primary and booster dose against infection, COVID-19 hospitalization, and mortality. Variant classification was performed through whole-genome sequencing (WGS) or Spike Gene Target Failure (SGTF). Findings Between April 25 and June 10, 2022, within a total of 27702 collected samples, 55.5% were classified as BA.2 and the remaining as BA.5. We observed no evidence of reduced vaccine effectiveness for the primary complete vaccination (OR=1.07, CI95%:0.93-1.23) or booster dose vaccination (OR=0.96, CI95%:0.84-1.09) against BA.5 infection compared with BA.2. The protection against reinfection was inferior in BA.5 cases when compared with BA.2 (OR=1.44; CI95%:1.30-1.60). Among those infected with BA.5, booster vaccination was associated with 77% and 88% of reduction in risk of COVID-19 hospitalization and death, respectively, while higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively. Interpretation This study shows that the SARS-CoV-2 Omicron BA.5 lineage is associated with higher odds of reinfection compared with Omicron BA.2, regardless of the vaccination status. Although less effective compared with BA.2, COVID-19 booster vaccination still offers substantial protection against severe outcomes following BA.5 infection.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal

Kislaya

Casaca

Borges

et al. 2022

Preprint

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SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

et al. 2022

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Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

Hornsby,

Nicols,

Longet

et al. 2023

Nat Commun

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Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.

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Risk of Reinfection, Vaccine Protection, and Severity of Infection with the BA.5 Omicron Subvariant: A Danish Nation-Wide Population-Based Study

Cited by 23 publications

References 13 publications

SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal

SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal

SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

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