Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may reduce the transmission of and achieve population immunity against the COVID-19 pandemic, which accounted for more than 3.75million deaths worldwide. With World Health Organization's (WHO) effort on ensuring equitable access to COVID-19 vaccines, vaccination rate may increase in the near future.

On the other hand, vaccination hesitancy has emerged as a major hindrance on the global vaccination campaigns in certain areas due to safety concerns, social factors, and public health policies. For instance, a recent survey conducted in Hong Kong showed a low vaccine acceptance rate of 37%. Long-term safety concerns and post-vaccination events relayed by the social media maybe reasons for vaccination hesitancy. Among which, cerebrovascular accidents (CVA) after vaccination were one of the most frequently reported post-vaccination events. These reports ranged from ischemic strokes in elderly patients with multiple cardiovascular co-morbidities, to hemorrhage strokes in otherwise "young-and-fit" adults. While many of these events were investigated by the COVID-19 immunization expert committee, an important premise to address the apprehension of CVA after vaccination is the provision of evidence-based information of the impact of COVID-19 vaccines on brain health.

In this prospective, longitudinal, observational study, we aim to elucidate the relationship between COVID-19 vaccines and cerebrovascular health in healthy citizens in a population-based cohort.

We shall recruit all consecutive citizens from a prospective, population-based cohort from the CUHK Brain Health Longitudinal Study free of clinically evident neurological diseases. The CUHK Brain Health Longitudinal Study cohort comprises of an epidemiologically representative sample from all socio-economic classes in the 18 districts of Hong Kong with reference to government census data. All citizens received baseline cognitive assessment and evaluation of metabolic risk factors. Baseline micro- and macro-cerebrovascular abnormalities were evaluated by MRI brain on recruitment.

We shall phone contact the citizens who met the inclusion criteria to enquire their vaccination plan. Citizens who received COVID-19 vaccination (SinoVac or BioNTech) and willing to join the study, our services coordinator, co-investigator or principal investigator will interview and explain the study in details and obtain the participant's consent. After signing the consent, the participant shall undergo a 2nd MRI brain 16 weeks (+/-4 weeks) after the 2nd dose of vaccination. The control group is defined as citizens who have not received any COVID-19 vaccines nor clinically/serologically evident SARS-CoV-2 infection.

We shall collect the following information for the vaccination group:

Demographic data ; Medical co-morbidities ; Laboratory tests at baseline and 16 weeks (+/-4 weeks) after 2nd dose of vaccine and serological testing for IgG antibody. We shall conduct a face-to-face assessment 16 weeks (+/-4 weeks) after the 2nd dose of COVID-vaccine for evaluation of any clinical events, followed by a phone visit every 6 months. Cognitive assessment by MoCA will be performed at baseline, 16 weeks (+/-4 weeks) then every 12 months after the 2nd dose of COVID-19 vaccine.

On the other hand, we shall collect the following information for the control group:

Demographic data ; Medical co-morbidities ; Laboratory tests at baseline and serological testing for Immunoglobulin G (IgG) antibody to exclude past COVID-19 infection prior to the second MRI brain.The timing of the second MRI brain, laboratory tests, clinical and cognitive assessment in the control group will be matched with the timing in the vaccination group are available.

The proposed study does not involve formulating new diagnoses or directly offering treatment for neurological and/or psychiatric conditions. All patients admitted to PWH or other medical institutes will be treated according to the standard care at the corresponding institution, regardless of their decision to participate in this repository. Should results from this study lead to discovery of one or more factors associated with development of brain disease, the principal investigators, co-investigators, or study coordinator will inform, counsel and offer diagnostic and/or therapeutic recommendations to participants accordingly. The participants may be referred to relevant departments for follow-up clinical visits.

Safe and effective SARS-CoV-2 vaccines may reduce the transmission of and achieve population immunity against the COVID-19 pandemic, which accounted for more than 3.75million deaths worldwide. However, vaccination hesitancy has emerged as a major hindrance on the global vaccination campaigns in certain areas due to safety concerns, social factors, and public health policies. The proposed study will allow us to address the apprehension of cerebrovascular accidents after vaccination is the provision of evidence-based information of the impact of COVID-19 vaccines on brain health.

Inclusion Criteria:

All consecutive citizens in the CUHK Brain Health Longitudinal Study cohort who received baseline MRI brain.

Exclusion Criteria:

1. Citizens with clinically evident stroke or dementia prior to recruitment; or
2. Citizens who are unable to provide an informed consent; or
3. Citizen with contraindications to MRI brain, e.g., non-MRI compatible implants, claustrophobia, etc; or
4. Citizens who had no baseline MRI brain assessment.

1. Chinese ONLY 2. Hong Kong Resident