Department of Neurology, National Neuroscience Institute, Singapore.
Centre of Quantitative Medicine, Duke-NUS Medical School, Singapore.
JAMA Netw Open. 2022 Mar 1;5(3):e222940. doi: 10.1001/jamanetworkopen.2022.2940.
Reports of cerebral venous thrombosis (CVT) after messenger RNA (mRNA)-based SARS-CoV-2 vaccination has caused safety concerns, but CVT is also known to occur after SARS-CoV-2 infection. Comparing the relative incidence of CVT after infection vs vaccination may provide a better perspective of this complication.
To compare the incidence rates and clinical characteristics of CVT following either SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines.
DESIGN, SETTING, AND PARTICIPANTS: Between January 23, 2020, and August 3, 2021, this observational cohort study was conducted at all public acute hospitals in Singapore, where patients hospitalized with CVT within 6 weeks of SARS-CoV-2 infection or after mRNA-based SARS-CoV-2 vaccination (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) were identified. Diagnosis of SARS-CoV-2 infection was based on quantitative reverse transcription-polymerase chain reaction or positive serology. National SARS-CoV-2 infection data were obtained from the National Centre for Infectious Disease, Singapore, and vaccination data were obtained from the National Immunisation Registry, Singapore.
SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines.
Clinical characteristics, crude incidence rate (IR), and incidence rate ratio (IRR) of CVT after SARS-CoV-2 infection and after mRNA SARS-CoV-2 vaccination.
Among 62 447 individuals diagnosed with SARS-CoV-2 infections included in this study, 58 989 (94.5%) were male; the median (range) age was 34 (0-102) years; 6 CVT cases were identified (all were male; median [range] age was 33.5 [27-40] years). Among 3 006 662 individuals who received at least 1 dose of mRNA-based SARS-CoV-2 vaccine, 1 626 623 (54.1%) were male; the median (range) age was 50 (12-121) years; 9 CVT cases were identified (7 male individuals [77.8%]; median [range] age: 60 [46-76] years). The crude IR of CVT after SARS-CoV-2 infections was 83.3 per 100 000 person-years (95% CI, 30.6-181.2 per 100 000 person-years) and 2.59 per 100 000 person-years (95% CI, 1.19-4.92 per 100 000 person-years) after mRNA-based SARS-CoV-2 vaccination. Six (66.7%) received BNT162b2 (Pfizer-BioNTech) vaccine and 3 (33.3%) received mRNA-1273 (Moderna) vaccine. The crude IRR of CVT hospitalizations with SARS-CoV-2 infection compared with those who received mRNA SARS-CoV-2 vaccination was 32.1 (95% CI, 9.40-101; P < .001).
The incidence rate of CVT after SARS-CoV-2 infection was significantly higher compared with after mRNA-based SARS-CoV-2 vaccination. CVT remained rare after mRNA-based SARS-CoV-2 vaccines, reinforcing its safety.
重要性：信使 RNA（mRNA）- 基于 SARS-CoV-2 疫苗接种后发生的脑静脉血栓形成（CVT）的报告引起了安全性担忧，但已知 CVT 也会在 SARS-CoV-2 感染后发生。比较感染与疫苗接种后 CVT 的相对发病率可能会更好地了解这种并发症。
目的：比较 SARS-CoV-2 感染或基于 mRNA 的 SARS-CoV-2 疫苗接种后 CVT 的发生率和临床特征。
设计、设置和参与者：这项观察性队列研究于 2020 年 1 月 23 日至 2021 年 8 月 3 日在新加坡所有公立急性医院进行，在此期间，在 SARS-CoV-2 感染后 6 周内或在接受基于 mRNA 的 SARS-CoV-2 疫苗（BNT162b2 [辉瑞-生物技术]或 mRNA-1273 [莫德纳]）接种后住院的患者中诊断为 CVT。SARS-CoV-2 感染的诊断基于定量逆转录聚合酶链反应或阳性血清学。国家 SARS-CoV-2 感染数据来自新加坡国家传染病中心，疫苗接种数据来自新加坡国家免疫登记处。
暴露：SARS-CoV-2 感染或基于 mRNA 的 SARS-CoV-2 疫苗。
主要结果和措施：CVT 在 SARS-CoV-2 感染后的临床特征、发生率（IR）和发病率比值比（IRR）以及基于 mRNA 的 SARS-CoV-2 疫苗接种后的发生率。
结果：在这项研究中纳入的 62447 名诊断为 SARS-CoV-2 感染的患者中，58989 名（94.5%）为男性；中位数（范围）年龄为 34（0-102）岁；发现 6 例 CVT 病例（均为男性；中位数 [范围]年龄为 33.5 [27-40] 岁）。在接受至少 1 剂基于 mRNA 的 SARS-CoV-2 疫苗的 3006662 名患者中，1626623 名（54.1%）为男性；中位数（范围）年龄为 50（12-121）岁；发现 9 例 CVT 病例（7 名男性患者[77.8%]；中位数 [范围]年龄：60 [46-76] 岁）。SARS-CoV-2 感染后 CVT 的发生率为 83.3/100000 人年（95%CI，30.6-181.2/100000 人年），mRNA 基于 SARS-CoV-2 疫苗接种后为 2.59/100000 人年（95%CI，1.19-4.92/100000 人年）。其中 6 例（66.7%）接种了 BNT162b2（辉瑞-生物技术）疫苗，3 例（33.3%）接种了 mRNA-1273（莫德纳）疫苗。与接种 mRNA SARS-CoV-2 疫苗相比，SARS-CoV-2 感染后 CVT 住院的发生率为 32.1（95%CI，9.40-101；P<0.001）。
结论和相关性：SARS-CoV-2 感染后 CVT 的发病率明显高于基于 mRNA 的 SARS-CoV-2 疫苗接种后。基于 mRNA 的 SARS-CoV-2 疫苗接种后 CVT 仍然很少见，这进一步证明了其安全性。
