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Background Characterization of disease progression and outcomes after COVID-19-related hospitalization in vaccinated compared with unvaccinated individuals is limited. Methods Retrospective case-control study of symptomatic vaccinated (cases) and unvaccinated (controls) participants hospitalized for COVID-19 between December 30, 2020 and September 30, 2021 in Southeast Michigan. Hospitalized adult patients with lab-confirmed COVID-19 were identified through daily census report. Breakthrough infection was defined as detection of SARS-CoV-2 ≥ 14 days after completion of primary vaccination series. Association between prior vaccination and critical COVID-19 illness (composite of intensive care unit [ICU] admission, invasive mechanical ventilation (IMV), 28-day mortality) was determined. Results 210 (39%) fully vaccinated and 325 (61%) unvaccinated patients were evaluated. Compared with controls, cases were older, had more comorbidities (4 [3-7] vs 2 [1-4], p &amp;lt; 0.001), and were more likely to be immunocompromised. Cases had less severe symptoms compared to controls (2 [1-2] vs 2 [2-3], P &amp;lt; 0.001) and were less likely to progress to critical COVID-19 illness (33.3% vs 45.5%, P &amp;lt; 0.001); 28-day mortality was significantly lower in cases (11.0% vs 24.9%, P &amp;lt; 0.001). Symptom severity (OR 2.59, 95% CI 1.61–4.16, P &amp;lt; 0.001) and modified sequential organ failure assessment (mSOFA) score on presentation (OR 1.74, 95% CI 1.48–2.06, P &amp;lt; 0.001) were independently associated with development of critical COVID-19 illness. Prior vaccination (OR 0.528, 95% CI 0.307–0.910, P = 0.020) was protective. Conclusions COVID-19 vaccinated patients were less likely to develop critical COVID-19 illness and more likely to survive. Disease severity at presentation was predictor of adverse outcomes regardless of vaccination status.

Progression to Critical Illness and Death in Patients With Breakthrough Hospitalizations