Pulmonary Division, Rabin Medical Center, Beilinson Campus, 49100, Petach Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Respir Res. 2022 Sep 1;23(1):226. doi: 10.1186/s12931-022-02155-x.
Patients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy.
We conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4-6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021.
All patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207-811] AU/ml vs. 820.75 [IQR, 459-1313] AU/ml; P < 0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P < 0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [IQR, 4.25-165] AU/ml vs. 970.1 [IQR, 505-1926] AU/ml; P < 0.001).
IPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4-6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4-6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.
患有间质性肺病 (ILD) 的患者患严重 COVID-19 感染的风险很高。此外，他们的抗炎和抗纤维化治疗可能会导致免疫抑制。然而，尚未评估他们对信使 RNA SARS-CoV-2 疫苗产生足够免疫反应的能力。因此，我们旨在评估接受抗纤维化治疗的特发性肺纤维化 (IPF) 患者和接受抗炎治疗的非特发性间质性肺病 (ILD) 患者接受 BNT162b2 疫苗后的体液反应。
我们进行了一项观察性前瞻性队列研究，以评估ILD 患者接受两剂 BNT162b2 疫苗后的抗刺突 (S-IgG) 抗体水平。该队列包括 40 名接受抗纤维化治疗的特发性肺纤维化 (IPF) 患者和 29 名接受抗炎治疗的非特发性间质性肺病 (ILD) 患者。为了测量 S-IgG 滴度，所有患者在第二次疫苗接种后 4-6 个月抽取一次血清学检测。此外，还从 107 名健康对照患者的健康对照组中创建了一个年龄和性别匹配的对照组。该研究在 2021 年 6 月至 8 月期间在拉宾医学中心（以色列）进行。
抗纤维化组的所有患者均呈血清阳性（40/40），与匹配的对照组（P=1.0）一致。与匹配的对照组相比，抗纤维化组的抗体滴度中位数明显较低（361.10 [IQR，207-811] AU/ml 与 820.75 [IQR，459-1313] AU/ml；P<0.001）。与健康对照组的 100%（29/29）相比，抗炎组中仅有 48.3%（14/29）的患者呈血清阳性（P<0.001）。与健康对照组相比，抗炎组的抗体滴度中位数明显较低（39.6 [IQR，4.25-165] AU/ml 与 970.1 [IQR，505-1926] AU/ml；P<0.001）。
接受抗纤维化治疗的 IPF 患者在接受两剂 BNT162b2 疫苗后会产生足够的免疫反应，并且在接种疫苗后 4-6 个月保持 100%的血清阳性率。然而，与健康对照组相比，他们的抗体滴度有所降低。接受抗炎治疗的非特发性间质性肺病患者中，有 48%的患者在第二次疫苗接种后 4-6 个月呈血清阴性。此外，利妥昔单抗治疗甚至与其他抗炎治疗相比，会导致显著的免疫抑制。
