Breakthrough SARS – CoV ‐2 Infections in Patients With Immune‐Mediated Disease Undergoing B Cell–Depleting Therapy: A Retrospective Cohort Analysis
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Abstract
Patients with immune‐mediated inflammatory diseases (IMIDs) receiving B cell–depleting therapy (BCDT) are among the most vulnerable to severe COVID‐19, as well as the most likely to suboptimally respond to SARS–CoV‐2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMID patients undergoing BCDT in order to identify breakthrough COVID‐19 infections and assess their outcomes.
Methods
In this retrospective cohort study, the pharmacy records and COVID‐19 registry at the Cleveland Clinic were searched using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes to identify IMIDs patients who 1) received treatment with BCDT, 2) were vaccinated against SARS–CoV‐2, and 3) experienced breakthrough infections. Each electronic medical record was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional odds regression models were used to examine the risk factors for severe outcomes.
Results
Of 1,696 IMID patients receiving BCDT, 74 developed breakthrough COVID‐19 prior to December 16, 2021. Outcomes were severe, with 29 patients hospitalized (39.2%), 11 patients requiring critical care (14.9%), and 6 deaths (8.1%). Outpatient anti–SARS–CoV‐2 monoclonal antibodies were used to treat 21 patients, with 1 hospitalization and no deaths. A comparator analysis examining 1,437 unvaccinated IMID patients receiving BCDT over the same time period identified 57 COVID‐19 cases (4.0%), with 28 requiring hospitalization (49.1%), including 7 deaths (12.3%).
Conclusion
IMID patients receiving BCDT regardless of vaccine status appear to be vulnerable to infection with SARS–CoV‐2, and use of BCDT is frequently associated with severe outcomes. Outpatient use of anti–SARS–CoV‐2 monoclonal antibody therapy appears to be associated with enhanced clinical outcomes.
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SciScore for 10.1101/2022.02.21.22271289: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The Cleveland Clinic Institutional Review Board approved this study. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Additional data on demographics (age, gender, race), comorbidities (BMI > 30, heart disease, pulmonary disease, chronic kidney disease, malignancy, smoking history), associated immunosuppressive medications, prednisone use and dosage, timing and duration of BCDT, vaccine type and number of doses, whether or not the patient received outpatient monoclonal antibody therapy for COVID-19, and clinical outcomes were extracted by individual chart review from patient … SciScore for 10.1101/2022.02.21.22271289: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The Cleveland Clinic Institutional Review Board approved this study. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Additional data on demographics (age, gender, race), comorbidities (BMI > 30, heart disease, pulmonary disease, chronic kidney disease, malignancy, smoking history), associated immunosuppressive medications, prednisone use and dosage, timing and duration of BCDT, vaccine type and number of doses, whether or not the patient received outpatient monoclonal antibody therapy for COVID-19, and clinical outcomes were extracted by individual chart review from patient electronic medical records. COVID-19suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, we have no direct comparator group of immunocompromised patients based on therapy, as it would be of interest to compare severity and outcomes to other patients on different immunosuppressive therapies. For now unfortunately large studies such as these have not been reported. Secondly, it is likely that unknown cases of mild or even asymptomatic infection may have been unreported or missed and certain data fields extracted from the chart review may have been missing especially from patients receiving their BCDT outside of our health care system. Thirdly, while we chose to examine patients given BCDTs in the year 2020, we did not account for ongoing BCDT through the end of the study which may have further contributed to immunosuppression. A recent study of rituximab in vasculitis patients demonstrated that antibody levels to S protein fell by greater than 50% within 4 weeks of drug administration 24. Finally, it would clearly be of interest to examine breakthrough infections in concert with assessing the status of patients’ integrated immune responses by assessing serologic responses, especially anti-Spike antibody titers, which have been associated with breakthrough infections in IMIDs patients 25, as well as B cell numbers and cell mediated immune responses. Unfortunately this was not possible in this retrospective study where such data were not gathered or were missing on the vast majority of patients. In terms of practical implicat...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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