We thank Dr. Niu and colleagues for their remark that prolonged glucocorticoid treatment increases the susceptibility to COVID-19 acquisition and decreases the response to vaccination (1). In relation to our study, the authors asked about the potential effects of concomitant glucocorticoid therapy on blunted vaccination responses in rituximab-treated patients with AID. It has been known since the 1970s that glucocorticoids reduce T cell (2, 3) and B cell (4, 5) activation and thereby inhibit mounting of adaptive immune responses against infections.

When interrogating whether background glucocorticoid treatment could have added to the reduced immune responses to vaccination or infection with SARS–CoV-2, we found no major exposure to glucocorticoid treatment in this cohort. Only 3 patients (1 vaccinated and 2 infected with SARS–CoV-2) were receiving glucocorticoids. Furthermore, doses of glucocorticoids were low (mean ± SD 4.6 ± 3.8 mg prednisolone/day). Hence, it is unlikely that the background glucocorticoids were responsible for the impaired immune response in the vaccinated patients or the patients with SARS–CoV-2 infection.

Another potential source of glucocorticoids in this context is their administration in combination with rituximab infusion, in which patients receive a single shot of 25 mg of prednisolone together with rituximab infusion. Previous data from patients with shock (6) and those experiencing asthma episodes (7, 8), in whom systemic bolus glucocorticoids are also frequently used for short-term treatment, have not shown that such treatment affected the responses to tetanus (6) or influenza vaccines (7, 8). Short-term glucocorticoid treatment also did not seem to affect the immune response to the SARS–CoV-2 vaccine (9). Therefore, we cannot assume that the single dose of glucocorticoids significantly contributed to the observed blunted humoral immune responses to SARS–CoV-2 in rituximab-treated patients.

The observation that T cell responses are maintained, while B cell responses are severely suppressed, in rituximab-treated patients with AIDs supports a specific effect of B cell–depleting agents rather than of glucocorticoids that would also impair T cell activation. These findings and the comments raised by Niu and colleagues, however, also suggest that continuous higher doses of glucocorticoids may be problematic in B cell–depleted patients, as immune responses to infection and vaccinations largely depend on intact T cell responses if B cells are absent.

我们感谢 Niu 博士及其同事的评论，即长期糖皮质激素治疗会增加对 COVID-19 感染的易感性并降低对疫苗接种的反应 ( 1 )。在我们的研究中，作者询问了联合糖皮质激素治疗对利妥昔单抗治疗的艾滋病患者疫苗接种反应减弱的潜在影响。自 20 世纪 70 年代以来，人们就知道糖皮质激素会减少 T 细胞 ( 2, 3 ) 和 B 细胞 ( 4, 5 ) 的激活，从而抑制针对感染的适应性免疫反应。

当询问背景糖皮质激素治疗是否会增加对疫苗接种或感染 SARS-CoV-2 的免疫反应减弱时，我们发现该队列中没有大量暴露于糖皮质激素治疗。只有 3 名患者（1 名接种疫苗，2 名感染 SARS-CoV-2）正在接受糖皮质激素治疗。此外，糖皮质激素的剂量较低（平均值±SD 4.6±3.8 mg泼尼松龙/天）。因此，背景糖皮质激素不太可能导致接种疫苗的患者或 SARS-CoV-2 感染患者的免疫反应受损。

在这种情况下，糖皮质激素的另一个潜在来源是与利妥昔单抗输注联合给药，其中患者接受单次注射 25 mg 泼尼松龙以及利妥昔单抗输注。先前来自休克患者 ( 6 ) 和哮喘发作患者 ( 7, 8 ) 的数据，这些患者也经常使用全身推注糖皮质激素进行短期治疗，但并未表明这种治疗会影响对破伤风 ( 6 ) 或流感疫苗 ( 7, 8 )。短期糖皮质激素治疗似乎也没有影响对 SARS-CoV-2 疫苗的免疫反应 ( 9 )。因此，我们不能假设单剂量糖皮质激素显着导致了在利妥昔单抗治疗的患者中观察到的针对 SARS-CoV-2 的体液免疫反应减弱。

在接受利妥昔单抗治疗的艾滋病患者中，T 细胞反应得到维持，而 B 细胞反应受到严重抑制，这一观察结果支持了 B 细胞耗竭剂的特定作用，而不是糖皮质激素也会损害 T 细胞活化。然而，这些发现以及 Niu 和同事提出的评论也表明，持续较高剂量的糖皮质激素对于 B 细胞耗尽的患者可能会出现问题，因为如果 B 细胞不存在，对感染和疫苗接种的免疫反应在很大程度上取决于完整的 T 细胞反应。