ABSTRACT
Objective: To describe the spectrum of acute neurological disorders among hospitalized patients who recently received COVID-19 mRNA vaccination. Background: The unprecedented pace of COVID-19 vaccine development, use of novel mRNA technology and large-scale vaccination programs have engendered concerns of adverse events following immunization. Design/Methods: We performed a multi-centre prospective observational study in 7 public acute hospitals. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system(CNS) syndromes, cerebrovascular disorders, peripheral nervous system(PNS) disorders, autonomic nervous system(ANS) disorders and immunization stressrelated responses(ISRR). To contextualize our findings, data from National Immunization Registry was probed for the total number and demographic of individuals vaccinated in the corresponding period. Results: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273);915,344 (65.5%) completed 2 doses. Four hundred and fifty-seven (0.03%) patients were referred for neurological complaints [median age 67 years, 61.5% males;95.8% received BNT162b2 and 4.2% mRNA-1273];classified into 73 (16.0%) CNS syndromes, 286 (62.6%) cerebrovascular disorders, 59 (12.9%) PNS disorders, 0 ANS disorders and 39 (8.5%) ISRRs. Twenty-seven had cranial mononeuropathy, 11 of whom had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis;none associated with thrombocytopenia. Five had mild flares of immune-mediated diseases. Conclusions: Our observational study does not establish causality of the described disorders to vaccines and is limited by lack of baseline incidence data of several conditions. Nevertheless, we did not observe any obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.
ABSTRACT
Objective: To describe the neurological disorders associated with COVID-19 in Singapore. Background: Various neurological disorders have been reported in COVID-19 patients. Postulated mechanisms include hypercoagulopathy, dysimmunity, inflammation and direct viral invasion. The incidence and relationship to SARS-CoV-2, considering the confounding effect of a surge in COVID-19 cases on healthcare systems, are unclear. Design/Methods: This was a prospective, nation-wide, multi-centre, cohort study of patients with microbiologically-confirmed COVID-19 referred for any neurological complaints With in 3 months of infection. Neurological diagnoses and relationship to COVID-19 were made by consensus guided by contemporaneous published case definitions. Results: Between March-July 2020, 47,572 patients [median age 34 (1-102) years, 98% males] were diagnosed with COVID-19 in Singapore. Of 90 patients referred for neurological disorders, 39 [median age 41 (27-73) years, 97% males] were deemed related to COVID-19 and categorised as: i) Central nervous system syndromes - 3 encephalitis, 1 acute disseminated encephalomyelitis;ii) Cerebrovascular disorders - 19 acute ischemic stroke/transient ischemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT) and 2 intracerebral haemorrhage;iii) Peripheral nervous system - 7 mono/polyneuropathy;iv) Autonomic nervous system - 4 limited dysautonomia. Fifty-one other patients had pre/co-existent neurological conditions (headache, seizure, mononeuropathies and functional neurological disorders) unrelated to COVID-19. Encephalitis 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;remarkably 63.2% had asymptomatic COVID-19. CVT was more frequent than expected and occurred in patients with mild/asymptomatic COVID-19. The pathophysiology of COVID-19 neurology appeared to be dysimmunity and/or prothrombotic tendency. There were no neurological complications in all 81 paediatric COVID-19 cases. Conclusions: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. The relatively few cases recorded was probably because our outbreak affected mainly healthy young men with mild/asymptomatic COVID-19 and the pandemic did not unduly affect the Singapore healthcare system.
ABSTRACT
Background: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection. Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain. Objectives: We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients. Methods: A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020. All studies reporting AIS occurrence in COVID-19 patients were included. Results: A total of 39 studies comprising 135 patients were studied. The pooled incidence of AIS in COVID-19 patients from observational studies was 1.2% (54/4466) with a mean age of 63.4 ± 13.1 years. The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8. Laboratory investigations revealed an elevated mean D-dimer (9.2 ± 14.8 mg/L) and fibrinogen (5.8 ± 2.0 g/L). Antiphospholipid antibodies were detected in a significant number of cases. The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62.1%, 64/103), followed by multiple vascular territory (26.2%, 27/103). A high mortality rate was reported (38.0%, 49/129). Conclusion: We report the pooled incidence of AIS in COVID-19 patients to be 1.2%, with a high mortality rate. Elevated D-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis.