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.
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.