Imaging and Clinical Features of COVID-19 Breakthrough Infections: A Multicenter Study

Abstract

Background Since vaccines against COVID-19 became available, rare breakthrough infections have been reported despite their high efficacies. Purpose To evaluate the clinical and imaging characteristics of patients with COVID-19 breakthrough infections and compare them with those of unvaccinated patients with COVID-19. Materials and Methods In this retrospective multicenter cohort study, the authors analyzed patient (aged ≥18 years) data from three centers that were registered in an open data repository for COVID-19 between June and August 2021. Hospitalized patients with baseline chest radiographs were divided into three groups according to their vaccination status. Differences between clinical and imaging features were analyzed using the Pearson χ² test, Fisher exact test, and analysis of variance. Univariable and multivariable logistic regression analyses were used to evaluate associations between clinical factors, including vaccination status and clinical outcomes. Results Of the 761 hospitalized patients with COVID-19, the mean age was 47 years and 385 (51%) were women; 47 patients (6%) were fully vaccinated (breakthrough infection), 127 (17%) were partially vaccinated, and 587 (77%) were unvaccinated. Of the 761 patients, 412 (54%) underwent chest CT during hospitalization. Among the patients who underwent CT, the proportions without pneumonia were 22% of unvaccinated patients (71 of 326), 30% of partially vaccinated patients (19 of 64), and 59% of fully vaccinated patients (13 of 22) (P < .001). Fully vaccinated status was associated with a lower risk of requiring supplemental oxygen (odds ratio [OR], 0.24 [95% CI: 0.09, 0.64; P = .005]) and lower risk of intensive care unit admission (OR, 0.08 [95% CI: 0.09, 0.78; P = .02]) compared with unvaccinated status. Conclusion Patients with COVID-19 breakthrough infections had a significantly higher proportion of CT scans without pneumonia compared with unvaccinated patients. Vaccinated patients with breakthrough infections had a lower likelihood of requiring supplemental oxygen and intensive care unit admission. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Schiebler and Bluemke in this issue.

Graphical abstract

Figure 1:

Study flow diagram. KICC-19 = Korean Imaging Cohort for COVID-19, RT-PCR = reverse transcriptase polymerase chain reaction.

Figure 2:

Representative cases showing pneumonia extents and patterns on chest radiographs and CT images. (A, B) Images in a 65-year-old woman with a breakthrough infection 2 months after a second dose of the BNT162b2 vaccine (fully vaccinated). The patient had a history of hypertension. (A) Chest radiograph obtained at admission shows no abnormal opacification in either lung. The chest radiograph extent of pneumonia was scored as 0 (no evidence of pneumonia). (B) Axial chest CT image at the lower lobe level (obtained on the same day) is negative for pneumonia; the extent of pneumonia at CT was scored as 0 (no evidence of pneumonia). (C, D) Images in a 48-year-old man 1 month after a first dose of the ChAdOx1 nCoV-19 vaccine (partially vaccinated). The patient had no history of comorbidity. (C) Chest radiograph obtained at admission shows no abnormal opacification in either lung. The chest radiograph extent of pneumonia was scored as 0 (no evidence of pneumonia). (D) Axial chest CT image obtained on the same day shows unilateral ground-glass opacity with a nonrounded morphologic feature in the left lower lobe (arrows). The extent of pneumonia at CT was scored as 1 (1%–25% involvement) and this case was classified as an indeterminate appearance of COVID-19 according to the RSNA chest CT classification system. (E, F) Images in a 36-year-old man with no history of vaccination for COVID-19 and no history of comorbidity. (E) Chest radiograph obtained at admission shows no abnormal opacification in either lung. The chest radiograph extent of pneumonia was scored as 0 (no evidence of pneumonia). (F) Axial chest CT image obtained on the same day shows unilateral ground-glass opacity with a nonrounded morphologic feature and nonperipheral distribution in the left upper lobe (arrows). The extent of pneumonia at CT was scored as 1 (1%–25% involvement), and this case was classified as an indeterminate appearance of COVID-19 according to the RSNA chest CT classification system. (G, H) Images in a 58-year-old man with no history of COVID-19 vaccination and a history of hypertension and diabetes. He required supplemental oxygen on admission and was admitted to the intensive care unit 1 day later. (G) Chest radiograph at admission shows patchy ground-glass opacities in the middle to lower zones of both lungs. The chest radiograph extent of pneumonia was scored as 2 (>25% involvement). (H) Axial chest CT image obtained on the same day shows multifocal ground-glass opacities with a crazy-paving appearance in bilateral lungs. The extent of pneumonia at CT was scored as 2 (>25% involvement) and was classified as a typical appearance of COVID-19 according to the RSNA chest CT classification system.

Figure 3:

Bar graphs show (A) initial and (B) follow-up chest radiograph scores in the 761 patients according to vaccination status. (A) The proportion of patients with an initial chest radiograph score of 0 was greater in the fully vaccinated group than in the partially vaccinated or unvaccinated groups, but not significantly so (P = .37). (B) The proportion of patients with a chest radiograph score of 0 during follow-up was also greatest in the fully vaccinated group, but not significantly so (P = .78). CXR = chest radiograph.

Figure 4:

Bar graphs show (A) CT scores and (B) patterns for the 412 patients who underwent chest CT during hospitalization according to vaccination status. (A) The proportion of patients with a CT score of 0 was significantly greater in the fully vaccinated group than in the unvaccinated group (P < .001). * = Bonferroni-adjusted P value, which was determined by multiplying the raw P value by 3. (B) Among patients with pneumonia, CT patterns were not significantly different between the groups (P = .22).

Figure 5:

Bar graphs show CT scores and patterns of the 308 patients at center 1 according to vaccination status. At center 1, patients with asymptomatic or mild symptoms were hospitalized and initial chest CT scans were obtained in all patients. (A) The proportion of patients with a CT score of 0 was significantly greater in the fully vaccinated group than in the partially or unvaccinated groups (P = .04 and .01, respectively). * = Bonferroni-adjusted P value, which was determined by multiplying the raw P value by 3. (B) Among patients with pneumonia, CT patterns were not significantly different between the groups (P = .46).