Monoclonal Antibody Treatment of Breakthrough COVID-19 in Fully Vaccinated Individuals with High-Risk Comorbidities
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Updated: Oct 13, 2025

Dynamic Monitoring of Seroconversion using a Multianalyte Immunobead Assay for Covid-19
Published on: February 16, 2022
Dennis M Bierle1, Ravindra Ganesh1, Sidna Tulledge-Scheitel1
1Mayo Clinic, Rochester, Minnesota, USA.
Insights
Fully vaccinated individuals can experience breakthrough COVID-19. Monoclonal antibody treatment significantly reduced hospitalization risk in high-risk vaccinated patients with mild to moderate COVID-19.
Area of Science:
- Infectious Diseases
- Vaccinology
- Immunology
Background:
- Breakthrough coronavirus disease 2019 (COVID-19) is possible in fully vaccinated individuals.
- Understanding clinical outcomes in this population is crucial for public health management.
Purpose of the Study:
- To assess the clinical outcomes of breakthrough COVID-19 in fully vaccinated individuals.
- To identify factors associated with hospitalization and the effectiveness of treatments.
Main Methods:
- A cohort study of 1395 fully vaccinated individuals who developed COVID-19.
- Analysis of hospitalization rates by day 28.
- Evaluation of the association between medical comorbidities and hospitalization.
- Assessment of antispike monoclonal antibody treatment efficacy.
Main Results:
- 7.7% of vaccinated individuals required hospitalization by day 28.
- Hospitalization risk was significantly associated with the number of medical comorbidities.
- Antispike monoclonal antibody treatment was linked to a substantially lower risk of hospitalization (OR, 0.227; P < .001).
- The number needed to treat (NNT) to prevent one hospitalization varied significantly by comorbidity status.
Conclusions:
- Monoclonal antibody treatment demonstrates significant benefit in reducing hospitalization among vaccinated high-risk individuals with mild to moderate COVID-19.
- Comorbidity status is a key determinant of hospitalization risk in vaccinated breakthrough cases.
Background:
Breakthrough coronavirus disease 2019 (COVID-19) may occur in fully vaccinated persons.
Methods:
We assessed the clinical outcomes of breakthrough COVID-19 in fully vaccinated individuals.
Results:
In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID- 19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Antispike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (odds ratio, 0.227; 95% confidence interval, 0.128-0.403; P < .001). The number needed to treat (NNT) to prevent 1 hospitalization was 225 among the lowest risk patient group compared with NNT of 4 among those with highest numbers of medical comorbidity.
Conclusions:
Monoclonal antibody treatment is associated with reduced hospitalization in vaccinated high-risk persons with mild to moderate COVID-19.
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