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  ID Week
Oct 19, -23 2022
Washington DC

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Age, Immune Conditions, Comorbidities
Drive Severe COVID Risk After Vaccination

  IDWeek 2022, October 19-23, 2022, Washington, DC
Mark Mascolini
Older age, immunosuppressive drugs and immune-compromising conditions, and several common chronic conditions independently boosted odds of severe versus nonsevere COVID after vaccination in a nationwide retrospective analysis of more than 110,000 US veterans [1]. Getting a COVID vaccine booster halved odds of severe disease. This study is due to be published online around the time of IDWeek [2].
Breakthrough SARS-CoV-2 infection after receiving usually effective vaccines began to gain attention in mid-2021 and become more frequent after Omicron viral variants spread. US Veterans Administration (VA) researchers who conducted this study note that vaccination protects most people against development of severe COVID, but severe disease does develop in some vaccinated people. Getting a better understanding of which groups run a higher risk of severe COVID after vaccination could help promote booster vaccination and availability of antiviral drugs for early treatment.
To identify predictors of severe COVID after vaccination, the VA team tapped the nationwide database of veterans in care, most of them men. They focused on veterans who got a complete initial vaccination series (two doses of the Moderna or Pfizer vaccines or one dose of the Johnson & Johnson vaccine) before December 2021 and later had positive lab confirmation of COVID within the VA system. The study period ran from December 15, 2020 to February 28, 2022, a span in which the original SARS-CoV-2 strain, the Delta variant, and Omicron variants each took a turn as the predominant severe coronavirus in the US.
The main study outcome was severe breakthrough infection after vaccination, defined as death 2 to 28 days after a positive test or hospital admission within 14 days of a positive test plus a blood oxygen level below 94%, treatment with supplemental oxygen or dexamethasone, or mechanical ventilation. The VA researchers compared development of severe breakthrough COVID with development of a nonsevere breakthrough, defined as no hospital admission or hospital admission that did not meet the just-listed criteria for severe disease. They used multivariable logistic regression to identify independent predictors of severe breakthrough COVID versus nonsevere disease.
The research team could assess breakthrough COVID severity in 110,760 veterans averaging 60.8 years in age at vaccination, 88% of them men. The racial/ethnic makeup of the study group was 64.7% white, 24.3% black, and 10.2% Hispanic. While 48.9% got the Pfizer vaccine, 41.1% got the Moderna shot, and 10% got the Johnson & Johnson vaccine. Among the 110,760 breakthrough infections, the researchers counted 10,612 severe cases (9.6%) including 1555 deaths (1.4%).
Older age emerged as the strongest predictor of severe versus nonsevere breakthrough COVID. Compared with age 45-49, every additional 5 years of age further inflated odds of severe disease (see list below). But being younger than 40 (versus 45-59) trimmed odds of severe COVID more than 40%. Women had one third lower odds of severe COVID than men. The following list gives adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for these associations.
Female vs male: aOR 0.67, 95% CI 0.60 to 0.75
Age <40 years vs 45-49: aOR 0.57, 95% CI 0.44 to 0.75
Age 50-54 vs 45-49: aOR 1.60, 95% CI 1.27 to 2.01
Age 55-59 vs 45-49: aOR 2.24, 95% CI 1.80 to 2.78
Age 60-64 vs 45-49: aOR 3.24, 95% CI 2.64 to 3.99
Age 65-69 vs 45-49: aOR 4.82, 95% CI 3.93 to 5.92
Age 70-74 vs 45-49: aOR 6.63, 95% CI 5.42 to 8.11
Age 75-79 vs 45-49: aOR 8.72, 95% CI 7.10 to 10.7
Age 80 or older vs 45-49: aOR 16.6, 95% CI 13.5 to 20.4
Compared with the pre-Delta viral variant, regression analysis linked Omicron to half lower odds of severe COVID (aOR 0.49, 95% CI 0.42 to 0.56). Compared with the Pfizer vaccine, the Moderna vaccine was linked to 20% lower odds of severe COVID (aOR 0.79, 95% CI 0.75 to 0.83). Compared with the Pfizer shot, the J&J vaccine conferred 30% higher odds of severe COVID (aOR 1.30, 95% CI 1.20 to 1.41).
Getting a booster vaccine halved the odds of severe breakthrough COVID (aOR 0.50, 95% CI 0.44 to 0.57). Prior COVID infection lowered severe breakthrough odds about 30% (aOR 0.69, 95% CI 0.61 to 0.78). In the full cohort, longer time since vaccination or a booster were linked to "steady increases" in odds of severe COVID, findings "suggesting waning vaccine effectiveness." Getting any one of five immune-suppressive therapies after vaccination independently hoisted odds of severe COVID:
Chemotherapy: aOR 2.71, 95% CI 2.27 to 3.24
Cytokine-blocking therapy: aOR 1.66, 95% CI 1.32 to 2.09
Glucocorticoids: aOR 2.34, 95% CI 2.18 to 2.50
Leukocyte-inhibitory agents: aOR 2.80, 95% CI 2.39 to 3.28
Lymphocyte-depleting agents: aOR 2.07, 95% CI 1.57 to 2.72
And any of a dozen comorbidities independently raised odds of severe COVID versus nonsevere COVID:
Alzheimer's or dementia: aOR 2.01, 95% CI 1.83 to 2.20
Chronic kidney disease: aOR 1.59, 95% CI 1.49 to 1.69
Chronic obstructive pulmonary disease: aOR 1.65, 95% CI 1.54 to 1.76
Diabetes: aOR 1.25, 95% CI 1.19 to 1.32
Heart failure: aOR 1.74, 95% CI 1.61 to 1.88
HIV or AIDS: aOR 1.30, 95% CI 1.01 to 1.68
Leukemia or lymphoma: aOR 1.87, 95% CI 1.61 to 2.17
Lung cancer: aOR 1.61, 95% CI 1.36 to 1.92
Mobility impairments: aOR 1.92, 95% CI 1.63 to 2.26
Multiple sclerosis: aOR 2.86, 95% CI 2.17 to 3.78
Pressure ulcers: aOR 1.58, 95% CI 1.37 to 1.81
Schizophrenia: aOR 1.71, 95% CI 1.51 to 1.93
Severe breakthrough odds were higher in Native Americans than in whites, but the relatively small number of Native Americans in the analysis, 890, must be considered when trying to interpret this finding. Black or Hispanic race or ethnicity did not affect odds of severe COVID.
The VA team cautioned that their results can't be used to determine the best time for repeat boosting or whether everyone benefits from repeated boosting because they had only 5 months of data after boosters were recommended for people without immune-compromising conditions and even less follow-up for the general population.
1. Vo AD, Branch-Elliman W, La J, et al. Risk factors for severe COVID-19 breakthrough infections: a retrospective, nationwide cohort study. IDWeek 2022, October 19-23, 2022, Washington, DC. Abstract 788.
2. Vo AD, La J, Wu JTY, et al. Factors associated with severe COVID-19 among vaccinated adults treated in US Veterans Affairs Hospitals. JAMA Open Network. 2022.