Inactivated SARS-CoV-2 vaccine does not influence the profile of prothrombotic antibody nor increase the risk of thrombosis in a prospective Chinese cohort  

新型冠状病毒灭活疫苗不影响免疫性血栓相关自身抗体水平,不增加血栓形成的风险:一项前瞻性中国人群队列研究

作　　者：Tingting Liu Jing Dai Zhitao Yang Xiaoqi Yu Yanping Xu Xinming Shi Dong Wei Zihan Tang Guanqun Xu Wenxin Xu Yu Liu Ce Shi Qi Ni Chengde Yang Xinxin Zhang Xuefeng Wang Erzhen Chen Jieming Qu 刘婷婷;戴菁;杨之涛;俞晓琦;徐燕萍;施新明;韦栋;唐子寒;许冠群;徐文心;刘禹;史册;倪琪;杨程德;张欣欣;王学锋;陈尔真;瞿介明(Department of Rheumatology and Immunology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Laboratory Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Emergency,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Infectious Diseases,Research Laboratory of Clinical Virology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Pulmonary and Critical Care Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Institute of Respiratory Diseases,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Shanghai Key Laboratory of Emergency Prevention,Diagnosis and Treatment of Respiratory Infectious Diseases,Shanghai 200025,China)

机构地区：[1]Department of Rheumatology and Immunology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [2]Department of Laboratory Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [3]Department of Emergency,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [4]Department of Infectious Diseases,Research Laboratory of Clinical Virology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [5]Department of Pulmonary and Critical Care Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [6]Institute of Respiratory Diseases,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [7]Shanghai Key Laboratory of Emergency Prevention,Diagnosis and Treatment of Respiratory Infectious Diseases,Shanghai 200025,China

出　　处：《Science Bulletin》2021年第22期2312-2319,M0004,共9页科学通报（英文版）

基　　金：supported by the Cultivation Project of Shanghai Major Infectious Disease Research Base(20dz2210500);the Shanghai Key Laboratory of Emergency Prevention,Diagnosis and Treatment of Respiratory Infectious Diseases(20dz2261100);the National Natural Science Foundation of China(81671589 and 81871272).

摘　　要：The presence of antiphospholipid antibodies was shown to be associated with thrombosis in coronavirus disease 2019(COVID-19)patients.Recently,according to reports from several studies,the vaccineinduced immune thrombotic thrombocytopenia is mediated by anti-platelet factor 4(PF4)-polyanion complex in adenovirus-vectored COVID-19 vaccine recipients.It is impendent to explore whether inactivated COVID-19 vaccine widely used in China influences prothrombotic autoantibody production and induces thrombosis.In this prospective study,we recruited 406 healthcare workers who received two doses,21 days apart,of inactivated severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine(BBIBP-CorV,Sinopharm).Paired blood samples taken before vaccination and four weeks after the second vaccination were used in detecting prothrombotic autoantibodies,including anticardiolipin(aCL),anti-b2 glycoprotein I(ab2GP1),anti-phosphatidylserine/prothrombin(aPS/PT),and anti-PF4-heparin.The seroconversion rate of SARS-CoV-2 specific antibodies was 95.81%(389/406)four weeks after vaccination.None of the subjects had spontaneous thrombosis or thrombocytopenia over a minimum follow-up period of eight weeks.There was no significant difference in the presence of all ten autoantibodies between samples collected before and after vaccination:for aCL,IgG(7 vs.8,P=0.76),IgM(41 vs.44,P=0.73),IgA(4 vs.4,P=1.00);anti-b2GP1,IgG(7 vs.6,P=0.78),IgM(6 vs.5,P=0.76),IgA(3 vs.5,P=0.72);aPS/PT IgG(0 vs.0,P=1.00),IgM(6 vs.5,P=0.76);aPF4-heparin(2 vs.7,P=0.18),and antinuclear antibody(ANA)(18 vs.21,P=0.62).Notably,seven cases presented with anti-PF4-heparin antibodies(range:1.18–1.79 U/mL)after vaccination,and none of them exhibited any sign of thrombotic disorder.In conclusion,inactivated SARS-CoV-2 vaccine does not influence the profile of antiphospholipid antibody and anti-PF4-heparin antibody nor increase the risk of thrombosis.新型冠状病毒感染的患者凝血功能异常与体内存在抗磷脂抗体相关并可导致血栓等不良预后事件.近期,有研究报道腺病毒载体新冠疫苗接种后,诱导产生的抗血小板因子4(PF4)抗体与接种者血栓事件及血小板减少相关.目前,新型冠状病毒灭活疫苗在中国广泛接种,其是否影响免疫性血栓相关自身抗体的产生和增加血栓事件已成为迫切需要探索的问题.本项前瞻性研究共招募了406名接种两剂新型冠状病毒灭活疫苗(BBIBP-Cor V,北京生物)的医务工作者,分别在接种前和接种第二剂后4周采集外周血样本,检测抗心磷脂(anti-cardiolipin antibody, aCL)抗体、抗β2糖蛋白I(anti-β2 glycoprotein I antibody, aβ2GP1)抗体、抗磷脂酰丝氨酸/凝血酶原(anti-phosphatidylserine/prothrombin antibody, aPS/PT)抗体和抗PF4-肝素复合物(anti-platelet factor 4-heparin antibody, aPF4-heparin)抗体.入组者接种第二剂疫苗4周后SARS-CoV-2抗体血清转化率为95.81%(389/406),自身抗体的阳性率及抗体水平在接种前后采集的样本中没有显著差异.在最少8周的随访期内,所有受试者均未出现血栓事件及血小板减少.综上所述,新型冠状病毒灭活疫苗不影响抗磷脂抗体和抗PF4-肝素抗体的水平,同时未增加血栓形成的风险.

关 键 词：Inactivated COVID-19 vaccine Antiphospholipid antibody Anti-PF4-heparin antibody THROMBOSIS THROMBOCYTOPENIA 

分 类 号：R392[医药卫生—免疫学]