Progression to Critical Illness and Death in Patients With Breakthrough Hospitalizations

Abstract

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 < 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 < 0.001) and were less likely to progress to critical COVID-19 illness (33.3% vs 45.5%, P < 0.001); 28-day mortality was significantly lower in cases (11.0% vs 24.9%, P < 0.001). Symptom severity (OR 2.59, 95% CI 1.61–4.16, P < 0.001) and modified sequential organ failure assessment (mSOFA) score on presentation (OR 1.74, 95% CI 1.48–2.06, P < 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.

Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity

“…Moreover, patients with hybrid immunity were older and more likely to have underlying comorbidities than those with natural immunity. However, the median number of comorbidities was lower in patients with reinfection compared with breakthrough infections or hospitalization [35] , [36] . Immunocompromised patients who are at higher risk for breakthrough infections and reinfection represented almost a quarter of our cohort and had higher odds of disease progression, findings that were similar to previous reports [17] , [29] , [35] , [36] , [39] , [7] .…”

“…In contrast to breakthrough or postvaccine infections [24] , [25] , [35] , [38] , [39] , reinfections are more commonly reported in younger persons [13] , [18] , [24] , [25] , [3] , [31] , [4] . In the present study, the patient population was also younger, with a median age of 41 years.…”

“…Age and immunocompromised status, particularly among those with active malignancy, were risk factors for progression to critical illness. Older age, multiple comorbidities and immunocompromised state were risk factors for hospitalization and disease progression regardless of vaccination status [29] , [35] , [36] , [37] , [39] , [7] . Protection conferred by prior infection with or without vaccination, lower number of comorbidities and younger age may in part explain the similar hospitalization and low mortality rates.…”

Estimation of the effect of vaccination in critically ill COVID-19 patients, analysis using propensity score matching

“…Suleyman et al, showed vaccinated patients with breakthrough infection had reduced mortality (11%) as compared to unvaccinated patients (24.9%) ( p < 0.001), although the severity of illness was similar between study participants based on the modified SOFA score [ 21 ]. Lower mortality observed in the study could be due to inclusion of all the patients requiring hospitalisation.…”

The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic

“…While the above observations are extremely important for COVID-19-related healthcare planning and for briefing the general public on the benefits of vaccination, they are unable to answer a clinically relevant question whether patients hospitalised with COVID-19 have different mortality and other outcomes by vaccination status. Most studies investigating in-hospital mortality by vaccination status provide unadjusted estimates with varying results from beneficial [ 8 – 14 ], through neutral [ 15 – 18 ] to harmful [ 19 , 20 ] effects of vaccination. Given the fact that most countries prioritised high-risk patients (the elderly, those with comorbidities) for vaccination [ 21 ], these unadjusted estimates may reflect local factors and are less helpful for risk stratification of admitted patients.…”