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Clinical Outcomes of Patients Previously Treated with B-Cell Depletion Therapy Hospitalized with COVID-19: Results from the Johns Hopkins Crown Registry

20 Pages Posted: 11 Mar 2022

See all articles by William Mayer Garneau

William Mayer Garneau

Johns Hopkins University - Division of Hospital Medicine

Tao Liang

Johns Hopkins University

Kunbo Wang

Johns Hopkins University

Yanxun Xu

Johns Hopkins University

Douglas E. Gladstone

Johns Hopkins University

Robin K. Avery

Johns Hopkins University

Franco R. D’Alessio

Johns Hopkins University

Matthew Louis Robinson

Johns Hopkins University - School of Medicine

Sarina K. Sahetya

Johns Hopkins University

Brian T. Garibaldi

Johns Hopkins University

Maria Veronica Dioverti-Prono

Johns Hopkins University

More...

Abstract

Background:  Biologic therapies that target B-cell function are effective for a range of medical conditions.  Patients treated with such therapies do not reliably generate robust humoral responses which may increase their risk for severe viral infections, including SARS-CoV2.This study sought to characterize outcomes for patients previously treated with B-cell depleting drugs who were hospitalized with COVID-19 compared to similar patients by demographic background, comorbidities, clinical status and COVID19-specific treatment received. 

Methods:  Registry data was reviewed to identify patients treated with B-cell depletion therapy who were hospitalized with COVID-19 from March 1, 2020 to November 30, 2021. 30-day mortality was the primary outcome, secondary outcomes included time to severe illness or death and time to clinical improvement. Overlap weighting method was applied to adjust for treatment bias, and Cox proportional-hazards models were used to analyze outcomes of interest. Age, BMI and COVID-19 specific medications were included in regression models as covariates.  A prespecified subgroup analysis was conducted to examine effects in patients with B-cell treatment ≤ 90 days prior to COVID-19 hospitalization.   

Results  9,233 patients were admitted to the Johns Hopkins Medicine health system between March 1, 2020 and November 2021. 50 patients were identified that had been treated with B-cell depletion therapy who were hospitalized with COVID-19.  212 were selected as the control group via matching across selected variables.  B-cell treated patients experienced a 30-day mortality of 6.0% compared to 4.2% in controls which was not statistically significant in overlap weight adjusted regression analysis, adjusted hazard ratio 1.13 (95%CI 0.23 to 5.48). The time to severe illness or death was 2.4 days (IQR 0.5 to 4.0 days) in the B-cell treated patients and 2.1 days (IQR 0.9 to 4.3 days) among controls, adjusted hazard ratio 1.01 (95% CI 0.47 to 2.18).  Patients treated with B-cell depletion experienced a statistically significant longer time to clinical improvement, adjusted HR 0.66 (95% CI 0.47-0.94).  The median time to improve or discharge was 6.3 days in B-cell depleted group (IQR 3.3 to 11.2 days) and 4.1 days in the matched control (IQR 2.1 to 7.7 days).  These results were similar in subgroup analysis for patients who received B-cell depletion in the 90 days prior to hospitalization. 

Interpretation  Patients treated with B-cell depletion were found to have more prolonged hospital courses however they did not experience higher mortality or a time to severe illness compared to controls.  With appropriate close follow-up and clinical care, individuals can still receive life-saving B-cell depleting therapies in the middle of a pandemic.  Further work should be devoted to characterizing the course of these patients considering new therapies and variants.

Funding Information: KW and YX report funding from Johns Hopkins inHealth, BG reports funding from the JHU COVID-19 Research Response Program, SKS reports funding from the NIH-NHLBI K23HL155507 and the Parker B. Francis Foundation. RA reports study/grant support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, Regeneron, and Takeda/Shire. DG reports no funding sources. MR reports funding from the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases. FD reports funding from NIH-NHLBI (R01 HL131812).

Declaration of Interests: None to declare.

Ethics Approval Statement: The registry is administered by the Core for Clinical Research Data Acquisition and this research was approved by their data management team as well as the Johns Hopkins Institutional Review Board.

Keywords: Lymphocyte Depletion, B-Lymphocytes, B-cell, SARS-CoV-2, COVID-19, Rituximab, immunocompromised

Suggested Citation

Garneau, William Mayer and Liang, Tao and Wang, Kunbo and Xu, Yanxun and Gladstone, Douglas E. and Avery, Robin K. and D’Alessio, Franco R. and Robinson, Matthew Louis and Sahetya, Sarina K. and Garibaldi, Brian T. and Dioverti-Prono, Maria Veronica, Clinical Outcomes of Patients Previously Treated with B-Cell Depletion Therapy Hospitalized with COVID-19: Results from the Johns Hopkins Crown Registry. Available at SSRN: https://ssrn.com/abstract=4030554 or http://dx.doi.org/10.2139/ssrn.4030554

William Mayer Garneau (Contact Author)

Johns Hopkins University - Division of Hospital Medicine ( email )

Baltimore, MD
United States

Tao Liang

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Kunbo Wang

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Yanxun Xu

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Douglas E. Gladstone

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Robin K. Avery

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Franco R. D’Alessio

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Matthew Louis Robinson

Johns Hopkins University - School of Medicine

MD

Sarina K. Sahetya

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Brian T. Garibaldi

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

Maria Veronica Dioverti-Prono

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States