Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark

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:10.1016/s1473-3099(22)00595-3

Cited by 90 publications

(85 citation statements)

References 23 publications

(29 reference statements)

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“…We found higher risk of hospitalisation among confirmed cases during BA.5 than previously during BA.1 dominance. A similar increase in risk of hospitalisation was noted in a Danish study when contrasting BA.2 and BA.5 infections (4), but increasing selection in the confirmed cases during follow-up is an alternative explanation for these findings. It was not possible to assess changes vaccine protection against hospitalisation in our low-risk cohort.…”

Section: Discussionsupporting

confidence: 72%

“…The emergence of Omicron has markedly shortened the duration of the protection (5). Our study adds important new evidence in that respect by i) having a longer follow-up with Omicron dominance compared with previous studies (2-4) and ii) being able to stratify the protection further by Omicron subvariants. Although the protection against reinfection in the present study was mainly observed among persons previously infected with the BA.2 subvariant, differences in time since prior infection with BA.1 and BA.2 should be considered.…”

Section: Discussionsupporting

confidence: 50%

“…Similar protection from prior BA.1/BA.2 infection on BA.4/BA.5 infection, but with much wider confidence intervals, has also been observed in a study from Qatar (3). Protection exceeding 90% from BA.1/BA.2 has been reported in a Danish study, using test-negative controls (4), but their follow-up period with BA.5 dominance was relatively short, and waning immunity could not be assessed. Rapidly waning protection induced by prior BA.1/BA.2 infection has been reported from Portugal when contrasting reinfection risks three and five months later (5).…”

mentioning

confidence: 94%

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Protection against infection with the Omicron BA.5 subvariant among people with previous SARS-CoV-2 infection - surveillance results from southern Sweden, June to August 2022

Kahn

Bonander

Moghaddassi

et al. 2022

Preprint

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We evaluated the protection afforded by SARS-CoV-2 natural infection against reinfection among vaccinated during a calendar period from June to August 2022 when Omicron BA.5 was the dominating subvariant in Scania county, Sweden. We formed a study cohort (n = 71 592) mainly consisting of health care workers by restricting to people 18-64 years old who received their first vaccine dose relatively early (24 April 2021 or sooner). We used continuous density case-control 1:10 sampling matched for sex and age within the study cohort, and thereby obtained 1 114 cases during Omicron BA.5 dominance and 11 140 controls who were analysed with conditional logistic regression. Limited protection against reinfection was suggested from prior infection of virus variants before Omicron (11%, 95% confidence interval [CI] -10 to 28%]. By contrast, prior Omicron infection offered clear protection (65%, 95% CI 56-73%). For the Omicron BA.2 subvariant, stronger protection was suggested during early (85%, 95% CI 75-91%) than later BA.5 dominance (66%, 95% CI 48-78%). Lower protection was observed from the previous BA.1 subvariant (30%; 95% CI -4 to 53%). These findings suggest that natural infection from the Omicron subvariants contributes to short-term population protection against reinfection with the subvariant BA.5 among vaccinated, but wanes considerably 5-6 months after infection.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 50%

mentioning

confidence: 94%

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Protection against infection with the Omicron BA.5 subvariant among people with previous SARS-CoV-2 infection - surveillance results from southern Sweden, June to August 2022

Kahn

Bonander

Moghaddassi

et al. 2022

Preprint

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“…Reassuringly, however, our findings are consistent with previous evidence that vaccination remains protective against severe disease associated with the BA.4/BA.5 lineages, at levels comparable to those reported for the BA.2 lineage. 5,19–21 Within our large sample of 49,976 BA.2 cases and 59,556 BA.4/BA.5 cases, vaccination was not associated with statistically meaningful differences in estimates of protection against progression from an initial outpatient diagnosis to subsequent illness requiring ED presentation or either hospital or ICU admission. As our study is limited to infected cases who received clinical molecular testing, it is important to note our findings do not measure the effectiveness of prior infection or vaccination against infection with either lineage BA.4/BA.5 or BA.2 lineages.…”

Section: Discussionmentioning

confidence: 60%

“…9 Consistent with this finding, risk of hospital admission during the BA.4/BA.5 and BA.1 waves in South Africa did not differ within analyses of all diagnosed cases. 23 Whereas a population-based study in Denmark suggested moderately increased risk of hospital admission among BA.5 cases as compared to BA.2 cases, 21 this analysis did not include adjustment for potentially relevant confounders including individuals’ healthcare-seeking behavior and calendar time. Our analyses sought to adjust for these variables based on the observed association of prior vaccination or infection with heightened risk of BA.4/BA.5 breakthrough infection, and because patient and provider demand for clinical SARS-CoV-2 testing changed markedly over the course of the BA.2 and BA.4/BA.5 waves, as public health mitigation measures were relaxed and access to home antigen testing expanded.…”

Section: Discussionmentioning

confidence: 99%

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

Lewnard¹,

Hong²,

Tartof³

2022

Preprint

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Expansion of the SARS-CoV-2 BA.4/BA.5 Omicron lineages in populations with prevalent immunity from prior infection and vaccination has raised concerns about the association of these lineages with immune escape. Here we show that COVID-19 vaccination and documented prior infection are associated with reduced protection against infection with BA.4/BA.5. Compared to time-matched BA.2 cases, BA.4/BA.5 cases had 9% (95% confidence interval: 2-17%) and 27% (15-41%) higher adjusted odds of having received 3 and 4 COVID-19 vaccine doses, respectively, and 55% (39-71%) higher adjusted odds of documented infection ≥90 days previously. However, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held after correcting for potential exposure misclassification resulting from unascertained prior infections. Despite increased risk of BA.4/BA.5 breakthrough infection observed among previously vaccinated or infected individuals, the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages has persisted with BA.4/BA.5.

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Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine

McGrath,

Malhotra,

Miles

et al. 2023

JAMA Netw Open

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ImportanceNo data comparing the estimated effectiveness of coadministering COVID-19 vaccines with seasonal influenza vaccine (SIV) in the community setting exist.ObjectiveTo examine the comparative effectiveness associated with coadministering the BNT162b2 BA.4/5 bivalent mRNA COVID-19 vaccine (BNT162b2-biv [Pfizer BioNTech]) and SIV vs giving each vaccine alone.Design, Setting, and ParticipantsA retrospective comparative effectiveness study evaluated US adults aged 18 years or older enrolled in commercial health insurance or Medicare Advantage plans and vaccinated with BNT162b2-biv only, SIV only, or both on the same day between August 31, 2022, and January 30, 2023. Individuals with monovalent or another brand of mRNA bivalent COVID-19 vaccine were excluded.ExposureSame-day coadministration of BNT162b2-biv and SIV; receipt of BNT162b2-biv only (for COVID-19–related outcomes) or SIV only (for influenza-related outcomes) were the comparator groups. For adults aged 65 years or older, only enhanced SIVs were included.Main Outcomes and MeasuresCOVID-19–related and influenza-related hospitalization, emergency department (ED) or urgent care (UC) encounters, and outpatient visits.ResultsOverall, 3 442 996 individuals (57.0% female; mean [SD] age, 65 [16.7] years) were included. A total of 627 735 individuals had BNT162b2-biv and SIV vaccine coadministered, 369 423 had BNT162b2-biv alone, and 2 445 838 had SIV alone. Among those aged 65 years or older (n = 2 210 493; mean [SD] age, 75 [6.7] years; 57.9% female), the coadministration group had a similar incidence of COVID-19–related hospitalization (adjusted hazard ratio [AHR], 1.04; 95% CI, 0.87-1.24) and slightly higher incidence of emergency department or urgent care encounters (AHR, 1.12; 95% CI, 1.02-1.23) and outpatient visits (AHR, 1.06; 95% CI, 1.01-1.11) compared with the BNT162b2-biv–only group. Among individuals aged 18 to 64 years (n = 1 232 503; mean [SD] age, 47 [13.1] years; 55.4% female), the incidence of COVID-19–related outcomes was slightly higher among those who received both vaccines vs BNT162b2-biv alone (AHR point estimate range, 1.14-1.57); however, fewer events overall in this age group resulted in wider CIs. Overall, compared with those who received SIV alone, the coadministration group had a slightly lower incidence of most influenza-related end points (AHR point estimates 0.83-0.93 for those aged ≥65 years vs 0.76-1.08 for those aged 18-64 years). Negative control outcomes suggested residual bias and calibration of COVID-19–related and influenza-related outcomes with negative controls moved all estimates closer to the null, with most CIs crossing 1.00.Conclusions and RelevanceIn this study, coadministration of BNT162b2-biv and SIV was associated with generally similar effectiveness in the community setting against COVID-19–related and SIV-related outcomes compared with giving each vaccine alone and may help improve uptake of both vaccines.

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Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark

Cited by 90 publications

References 23 publications

Protection against infection with the Omicron BA.5 subvariant among people with previous SARS-CoV-2 infection - surveillance results from southern Sweden, June to August 2022

Protection against infection with the Omicron BA.5 subvariant among people with previous SARS-CoV-2 infection - surveillance results from southern Sweden, June to August 2022

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome

Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine

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