ABSTRACT
BACKGROUND: Individuals who suffered a neurological adverse event after COVID-19 vaccine could hesitate and defer reimmunization. AIM: We examine the risk of recurrence following reimmunization among patients who developed a neurological event after first dose of COVID-19 mRNA vaccine. DESIGN: Observational study. METHODS: Individuals who developed an adjudicated neurological adverse event (based on Brighton Collaboration criteria) within 6 weeks of first dose of COVID-19 vaccine requiring hospitalization were enrolled into a multi-center national registry in Singapore. Neurological recurrence, defined by development of another neurological event within 6 weeks of second vaccine dose, was reviewed. Clinical characteristics were compared between patients who chose to proceed or withhold further vaccination, and between those who received timely (3-6 weeks) or delayed (>6 weeks) reimmunization. RESULTS: From 235 patients (median age, 67 years; 63% men) who developed an adjudicated neurological event after their first dose of mRNA vaccine between 30 December 2020 and 20 April 2021, 181 (77%) chose to undergo reimmunization. Those who decided against reimmunization were older (median age, 74 vs 66 years) and had greater physical disability following their primary neurological event (46% vs 20%, p < 0.001). Patients who suffered greater physical disability were 3 times more likely to delay their reimmunization (odds ratio 3.36, 95% CI: 1.76-6.40). Neurological recurrence was observed in only 4 individuals (3 with seizures and 1 with myasthenia gravis exacerbation). CONCLUSION: A prior neurological event should not necessarily preclude reimmunization and the decision to proceed with reimmunization should consider the overwhelming benefits conferred by vaccination towards ending this pandemic.
ABSTRACT
Importance: 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. Objective: 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. Exposures: SARS-CoV-2 infection or mRNA-based SARS-CoV-2 vaccines. Main Outcomes and Measures: 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. Results: Among 62â¯447 individuals diagnosed with SARS-CoV-2 infections included in this study, 58â¯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 3â¯006â¯662 individuals who received at least 1 dose of mRNA-based SARS-CoV-2 vaccine, 1â¯626â¯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 100â¯000 person-years (95% CI, 30.6-181.2 per 100â¯000 person-years) and 2.59 per 100â¯000 person-years (95% CI, 1.19-4.92 per 100â¯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). Conclusions and Relevance: 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.
Subject(s)
COVID-19 , Venous Thrombosis , Adolescent , Adult , Aged , Aged, 80 and over , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Intracranial Thrombosis/etiology , Male , Middle Aged , RNA, Messenger , SARS-CoV-2 , Singapore/epidemiology , Vaccination , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology , Young AdultABSTRACT
PURPOSE: To describe the spectrum of COVID-19 neurology in Singapore. METHOD: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions. RESULTS: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases. CONCLUSION: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.