Clinical outcomes and immunological features of COVID-19 patients receiving B-cell depletion therapy during the Omicron era

Abstract

Background: The clinical outcomes and immunological features of coronavirus disease 2019 (COVID-19) patients receiving B-cell depletion therapy (BCDT), especially in Omicron variant era, have not been fully elucidated. We aimed to investigate the outcomes and immune responses of COVID-19 patients receiving BCDT during the Omicron period.

Methods: We retrospectively compared clinical outcomes between COVID-19 patients treated with BCDT (the BCDT group) and those with the same underlying diseases not treated with BCDT (the non-BCDT group). For immunological analyses, we prospectively enrolled COVID-19 patients receiving BCDT and immunocompetent COVID-19 patients as controls. We measured humoral and cellular immune responses using the enzyme-linked immunosorbent assay and flow cytometry.

Results: Severe to critical COVID-19 was more frequent in the BCDT group than in the non-BCDT group (41.9% vs. 28.3%, p = .030). BCDT was an independent risk factor for severe to critical COVID-19 (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.21–4.04, p = .010) as well as for COVID-19-related mortality (aOR 4.03, 95% CI 1.17–13.86, p = .027). Immunological analyses revealed that patients receiving BCDT had lower anti-S1 IgG titres and a tendency to higher proportions of activated CD4⁺ T-cells than the controls.

Conclusions: BCDT was associated with worse COVID-19 outcomes in the Omicron period. Humoral immune response impairment and T-cell hyperactivation were the main immunological features of COVID-19 patients treated with BCDT, which may have contributed to the worse outcomes of COVID-19 in this population.

Keywords:

• B-cell depletion therapy
• covid-19
• mortality
• immune response
• antibody

Authors contributions

CML, MK, S-wP, CKK, C-HL, H-RK, and WBP conceived and designed the project. CML, MK, S-wP, CKK, C-HL, H-RK, WBP, and M-dO analysed the data. CML, CKK, PGC, NJK, HJJ, M-dO, and WBP collected the samples. CML, S-wP, CKK, HMS, C-HL, and WBP performed the serologic analysis. MK and H-RK performed the flow cytometric analysis. CML, MK, S-wP, CKK, C-HL, HMS, H-RK, and WBP wrote the manuscript with the help of all authors. C-HL, H-RK, and WBP had full access to all data in the study and took responsibility for the integrity of the data and the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The original data generated during this study are presented in the article and/or Supplementary Material. Further inquiries can be directed to the corresponding authors.

Additional information

Funding

This work was supported in part by grant no 03-2022-0130 from the SNUH Research Fund and by the Bio and Medical Technology Development Program of the National Research Foundation (NRF), the Korean government (MSIT) (grant number 2021M3A9I2080496 to H-RK and WBP; grant number 2018M3A9H4055197 to H-RK), the Creative-Pioneering Researchers Program through Seoul National University (to WBP, C-HL and H-RK), the Ministry of Trade, Industry and Energy (MOTIE), and the Korea Institute for Advancement of Technology (KIAT) (Neutralizing Antibody Development Support Centre, grant number P0017147 to C-HL).