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. 2023 Jan 5;18(1):e0279968.
doi: 10.1371/journal.pone.0279968. eCollection 2023.

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative

Affiliations

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative

Alfred Jerrod Anzalone et al. PLoS One. .

Abstract

Background: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality.

Methods: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period.

Results: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures.

Conclusions: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Number vaccination and breakthrough infection density by week by rurality, January 1, 2021—December 20, 2021.
aBars represent number vaccinated and lines represent breakthrough infection rates.
Fig 2
Fig 2. Kaplan Meier cumulative incidence curves for SARS-CoV-2 breakthrough infection following two mRNA vaccinations in adults, January 1, 2021 –December 20, 2021.
Fig 3
Fig 3. Univariable and multivariable Cox-proportional hazard ratios for SARS-CoV-2 breakthrough infection following two mRNA vaccinations by community factors, January 1, 2021 –December 20, 2021.
A. Univariable Hazard Ratios for Key Factors Evaluated Independently. B. Multivariable* Hazard Ratios for Key Factors Evaluated Independently. *Models adjusted for age, gender, race/ethnicity, comorbid conditions, prior SARS-CoV-2 infection, vaccine manufacturer, period of vaccination (relative to Delta dominance), and US Census region. Full model specifications available in S2 and S3 Tables in S1 File.
Fig 4
Fig 4. Multivariable Cox-proportional hazard ratios for SARS-CoV-2 breakthrough infection following two mRNA vaccinations in adults by combined key factors, January 1, 2021 –December 20, 2021.
Fig 5
Fig 5. Differences in 30-day severity* based on vaccination status in persons infected with SARS-CoV-2, January 1, 2021 –December 20, 2021.
*Severity categories following SARS-CoV-2 infection classified as outpatient-only visit (no hospitalization within 30 days of diagnosis), COVID-associated hospitalization (within 30 days of diagnosis), COVID-19-associated adverse event (mechanical ventilation, ECMO, or death or transfer to hospice within 30 days of diagnosis).

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