Predictors of Breakthrough SARS-CoV-2 Infection after Vaccination

Walmsley, Sharon; Nabipoor, Majid; Lovblom, Leif Erik; Ravindran, Rizani; Colwill, Karen; McGeer, Alison; Dayam, Roya Monica; Manase, Dorin; Gingras, Anne-Claude; ,

doi:10.3390/vaccines12010036

Cited by 3 publications

(5 citation statements)

References 71 publications

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“…Our findings align with those of Smits et al [24], who examined four specific comorbidities and observed that patients with two or more of these conditions also faced a greater risk than would be expected based on the individual effects of each comorbidity. This contrasts with the findings of Walmsley et al [25], who did not identify significant variations in the rate of breakthrough infections among individuals with underlying comorbidities. Theses investigators acknowledged that this discrepancy may be due to the low number of participants with comorbid diseases in their study, which could have hindered the identification of a clear association.…”

Section: Discussioncontrasting

confidence: 99%

“…In contrast to our findings regarding older individuals, multiple studies have identified younger age as a risk factor for COVID-19 breakthrough infection[14, 25, 34] . It’s important to note that these studies varied in design, cohort size, and follow-up duration, which may have influenced their ability to capture current evolving trends.…”

Section: Discussioncontrasting

confidence: 99%

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Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals

Moreno-Echevarria,

Caputo,

Camp

et al. 2024

Preprint

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Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals

Moreno-Echevarria,

Caputo,

Camp

et al. 2024

Preprint

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“…Given the poor outcomes of older adults to COVID-19 infection [ 47 , 48 ], concern had been raised as to the lower overall antibody responses and waning immunity in older vaccinees [ 49 , 50 , 51 ]. In the main STOPCoV study, we found that binding antibody responses were not different in our two age groups (>70 years and 30–50 years) [ 19 , 36 ]. In this sub-study, age group was not an independent predictor for lower neutralizing antibody responses to Wuhan or the variants after controlling for the number of vaccine doses.…”

Section: Discussionmentioning

confidence: 83%

“…Similarly, Alonso et al [ 20 ], in a study of healthy vaccinated healthcare workers, concluded that neither neutralizing antibody levels nor binding antibody levels measured at 30 days post-vaccination can be used as predictors of breakthrough infection. In the main STOPCoV study, no binding antibody levels for protection were identified [ 19 ]. Our study receipt of the Original/Omicron BA.4/5 vaccine showed the strongest association with protection from a breakthrough infection.…”

Section: Discussionmentioning

confidence: 99%

“…With vaccine fatigue and declining population vaccine uptake, correlates of protection from infection continue to be explored. We, among others, have shown that binding antibody levels cannot define protection or guide the frequency of vaccine boosters [ 16 , 17 , 18 , 19 ]. Although studies have suggested that neutralizing antibodies are more predictive, no threshold values have been established, and cross protection against variant strains has had limited study [ 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Declining Levels of Neutralizing Antibodies to SARS-CoV-2 Omicron Variants Are Enhanced by Hybrid Immunity and Original/Omicron Bivalent Vaccination

Walmsley,

Nabipoor,

et al. 2024

Vaccines

Self Cite

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We determined neutralizing antibody levels to the ancestral Wuhan SARS-CoV-2 strain and three Omicron variants, namely BA.5, XBB.1.5, and EG.5, in a heavily vaccinated cohort of 178 adults 15–19 months after the initial vaccine series and prospectively after 4 months. Although all participants had detectable neutralizing antibodies to Wuhan, the proportion with detectable neutralizing antibodies to the Omicron variants was decreased, and the levels were lower. Individuals with hybrid immunity at the baseline visit and those receiving the Original/Omicron bivalent vaccine between the two sampling times demonstrated increased neutralizing antibodies to all strains. Both a higher baseline neutralizing antibody titer to Omicron BA.5 and hybrid immunity were associated with protection against a breakthrough SARS-CoV-2 infection during a 4-month period of follow up during the Omicron BA.5 wave. Neither were associated with protection from a breakthrough infection at 10 months follow up. Receipt of an Original/Omicron BA.4/5 vaccine was associated with protection from a breakthrough infection at both 4 and 10 months follow up. This work demonstrates neutralizing antibody escape with the emerging Omicron variants and supports the use of additional vaccine doses with components that match circulating SARS-CoV-2 variants. A threshold value for neutralizing antibodies for protection against reinfection cannot be determined.

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Anti‐Spike IgG antibodies as correlates of protection against SARS‐CoV‐2 infection in the pre‐Omicron and Omicron era

Seekircher,

Astl,

Tschiderer

et al. 2024

Journal of Medical Virology

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Anti‐Spike IgG antibodies against SARS‐CoV‐2, which are elicited by vaccination and infection, are correlates of protection against infection with pre‐Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti‐Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS‐CoV‐2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS‐CoV‐2 infection ascertained by self‐report or seroconversion of anti‐Nucleocapsid antibodies. At the time of their earliest available anti‐Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8–55.2), with 45.3% being female, 41.3% having a prior SARS‐CoV‐2 infection, and 75.5% having received at least one dose of a COVID‐19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS‐CoV‐2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7–12.4). The age‐ and sex‐adjusted hazard ratio for SARS‐CoV‐2 associated with having twice the anti‐Spike IgG antibody titer was 0.875 (95% credible interval 0.868–0.881) overall, 0.842 (0.827–0.856) during 2021, and 0.884 (0.877–0.891) during 2022 (all p < 0.001). The associations were similar in females and males (Pinteraction = 0.673) and across age (Pinteraction = 0.590). Higher anti‐Spike IgG antibody titers were associated with reduced risk of incident SARS‐CoV‐2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti‐Spike IgG antibody continues to be a suitable correlate of protection against newer SARS‐CoV‐2 variants.

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Predictors of Breakthrough SARS-CoV-2 Infection after Vaccination

Cited by 3 publications

References 71 publications

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals

Declining Levels of Neutralizing Antibodies to SARS-CoV-2 Omicron Variants Are Enhanced by Hybrid Immunity and Original/Omicron Bivalent Vaccination

Anti‐Spike IgG antibodies as correlates of protection against SARS‐CoV‐2 infection in the pre‐Omicron and Omicron era

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