Higher hospitalization and mortality rates among SARS-CoV-2-infected persons in rural America

Abstract

Purpose: Rural communities are among the most underserved and resource-scarce populations in the United States. However, there are limited data on COVID-19 outcomes in rural America. This study aims to compare hospitalization rates and inpatient mortality among SARS-CoV-2-infected persons stratified by residential rurality.

Methods: This retrospective cohort study from the National COVID Cohort Collaborative (N3C) assesses 1,033,229 patients from 44 US hospital systems diagnosed with SARS-CoV-2 infection between January 2020 and June 2021. Primary outcomes were hospitalization and all-cause inpatient mortality. Secondary outcomes were utilization of supplemental oxygen, invasive mechanical ventilation, vasopressor support, extracorporeal membrane oxygenation, and incidence of major adverse cardiovascular events or hospital readmission. The analytic approach estimates 90-day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient adverse events while controlling for major risk factors using Kaplan-Meier survival estimates and mixed-effects logistic regression.

Findings: Of 1,033,229 diagnosed COVID-19 patients included, 186,882 required hospitalization. After adjusting for demographic differences and comorbidities, urban-adjacent and nonurban-adjacent rural dwellers with COVID-19 were more likely to be hospitalized (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI], 1.16-1.21 and aOR 1.29, CI 1.24-1.1.34) and to die or be transferred to hospice (aOR 1.36, CI 1.29-1.43 and 1.37, CI 1.26-1.50), respectively. All secondary outcomes were more likely among rural patients.

Conclusions: Hospitalization, inpatient mortality, and other adverse outcomes are higher among rural persons with COVID-19, even after adjusting for demographic differences and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.

Keywords: COVID-19; SARS-CoV-2; hospitalization; mortality; urban-rural health.

FIGURE 1

Data analysis plan. Figure 1 documents the data analysis plan, including steps for inclusion and exclusion of data partners based on the availability of 5‐digit ZIP Codes and robustness based on covariates of interest (measurement domain to calculate BMI and death domain for primary outcome). We also excluded patients with missing age or gender

FIGURE 2

N3C patient distribution. Figure 2 shows the geospatial distribution of the N3C COVID‐19‐positive population. N3C contains data from 65 data contributors from across the United States, 52 of whom include sufficient location information to spatially map by ZIP Code centroid. Of those sites, we selected 44 whose data met our minimum robustness qualifications for inclusion in our study. This bubble map is to scale with larger bubbles representing more patients. Numbers represent population distribution, in thousands

FIGURE 3

Forest plot showing the crude and adjusted odds ratios for adverse events by rural category in SARS‐CoV‐2‐infected persons in N3C, January 2020‐June 2021. Figure 3 shows the crude (A) and adjusted (B) odds ratios for being hospitalized, dying or being transferred to hospice after hospitalization, requiring any inpatient oxygen support, having a major adverse cardiovascular event, requiring invasive mechanical ventilation, requiring extracorporeal membrane oxygenation, or having a hospital readmission after initial hospitalization in the SARS‐CoV‐2‐infected population in N3C by rural category. Risk is similar between adjusted and unadjusted models, suggesting a real impact of rurality on adverse events. Adjusted models include adjustments for gender, race, ethnicity, BMI category, age, Charlson Comorbidity Index (CCI) composite score, rurality, quarter of diagnosis, and Census subregion. Data provider is included as a random effect in the adjusted models to account for differences across source data systems

FIGURE 4

Kaplan‐Meier survival curves in SARS‐CoV‐2‐infected patients over 90 days from hospital admission. Figure 4 shows Kaplan‐Meier survival estimates in hospitalized SARS‐CoV‐2 persons in N3C by rurality (A), Charlson Comorbidity Index category (B), body mass index category (C), and quarter of diagnosis (D). Events were censored at day 90 or if patients left the hospital prior to 90 days