Ohki Yutaro, Kawabe Mayuko, Yamamoto Izumi, Katsumata Haruki, Nakada Yasuyuki, Kobayashi Akimitsu, Urabe Fumihiko, Miki Jun, Yamada Hiroki, Kimura Takahiro, Matsuo Nanae, Tanno Yudo, Horino Tetsuya, Ohkido Ichiro, Yamamoto Hiroyasu, Yokoo Takashi
Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Front Microbiol. 2022 Jun 9;13:922042. doi: 10.3389/fmicb.2022.922042. eCollection 2022.
The mortality rate due to COVID-19 in kidney transplant recipients (KTRs) is 16.8 to 32%. Vaccination against COVID-19 is expected to contribute to the prevention of infection, severe disease, and mortality; however, it has been reported that the humoral response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in KTRs is poor. Vaccination strategies against COVID-19 vary from country to country, and in Japan, the third dose is given 6 months after the second dose. Few studies have evaluated long-term humoral responses after the second dose of SARS-CoV-2 mRNA vaccine. In addition, the superiority of BNT162b2 vaccine and mRNA-1,273 vaccine in KTRs regarding humoral response is controversial.
Ninety-four KTRs were administered a second dose of the BNT162b2 or mRNA-1,273 vaccines, and anti-spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 antibody levels were measured 5 months (149.2 ± 45.5 days) later. The cutoff value of anti-S antibodies was defined ≥50 AU/ml and 1.4 Index for anti-N antibodies. The primary outcome was the rate of seropositivity, and factors associated with an appropriate humoral response were assessed by univariate and multivariate analysis.
Of 94 KTRs, only 45 (47.9%) patients were positive for anti-S antibodies. The median anti-S SARS-CoV-2 IgG antibody titers was 35.3 (Interquartile range 3.8 to 159.7). Anti-N SARS-CoV-2 IgG antibodies in all patients were < 1.4 Index. Response to SARS-CoV-2 mRNA vaccines were 43.2 and 65% for BNT162b2 and mRNA-1,273, respectively ( = 0.152). In comparison with high-dose, low-dose of mycophenolic acid was a robust factor associated with an adequate humoral response.
The long-term humoral response after a second dose of SARS-CoV-2 mRNA vaccine in Japanese KTRs was poor. In comparison with high-dose, low-dose mycophenolic acid was related to an appropriate humoral response. Five months is too long to wait for a 3rd dose after 2nd dose of SARS-CoV-2 vaccine in KTRs. In this cohort, there was no statistical difference in humoral response to the BNT162b2 and mRNA-1,273 vaccines. Additional large observational studies and meta-analyses are needed to clarify the factors related to an appropriate humoral immune response to COVID-19 vaccination.
肾移植受者（KTRs）中因新冠病毒病（COVID-19）导致的死亡率为16.8%至32%。接种COVID-19疫苗有望有助于预防感染、重症疾病和死亡；然而，据报道，KTRs对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）信使核糖核酸（mRNA）疫苗的体液免疫反应较差。各国针对COVID-19的疫苗接种策略各不相同，在日本，第三剂疫苗在第二剂接种6个月后接种。很少有研究评估第二剂SARS-CoV-2 mRNA疫苗后的长期体液免疫反应。此外，BNT162b2疫苗和mRNA-1273疫苗在KTRs体液免疫反应方面的优越性存在争议。
94名KTRs接种了第二剂BNT162b2或mRNA-1273疫苗，并在5个月（149.2±45.5天）后测量了抗刺突（抗S）和抗核衣壳（抗N）SARS-CoV-2抗体水平。抗S抗体的临界值定义为≥50 AU/ml，抗N抗体的临界值为1.4指数。主要结局是血清学阳性率，并通过单因素和多因素分析评估与适当体液免疫反应相关的因素。
在94名KTRs中，只有45名（47.9%）患者抗S抗体呈阳性。抗S SARS-CoV-2 IgG抗体滴度中位数为35.3（四分位间距3.8至159.7）。所有患者的抗N SARS-CoV-2 IgG抗体均<1.4指数。BNT162b2和mRNA-1273对SARS-CoV-2 mRNA疫苗的反应分别为43.2%和65%（P=0.152）。与高剂量相比，低剂量霉酚酸是与充分体液免疫反应相关的一个有力因素。
日本KTRs接种第二剂SARS-CoV-2 mRNA疫苗后的长期体液免疫反应较差。与高剂量相比，低剂量霉酚酸与适当的体液免疫反应有关。在KTRs中，接种第二剂SARS-CoV-2疫苗后等待第三剂的时间长达5个月太久了。在该队列中，BNT162b2疫苗和mRNA-1273疫苗的体液免疫反应无统计学差异。需要更多大型观察性研究和荟萃分析来阐明与COVID-19疫苗接种适当体液免疫反应相关的因素。
