CASE PRESENTATION: We report the first case of Longitudinal Extensive Transverse Myelitis (LETM) in Malaysia following administration of the chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine. A 25-year-old female presented with bilateral lower limb weakness and inability to walk with a sensory level up to T8 with absent visual symptoms. Urgent gadolinium-enhanced magnetic resonance imaging (MRI) of the spine showed long segment TM over the thoracic region. Cerebrospinal fluid autoantibodies for anti-aquaporin-4 and anti-myelin-oligodendrocyte were negative. A diagnosis of LETM following vaccination was made, and the patient was started on a high dose of intravenous methylprednisolone. The patient eventually made a recovery following treatment.
CONCLUSION: LETM is a rare but serious adverse reaction following vaccination. Previously reported cases showed an onset of symptoms between 10 to 14 days post-vaccination, suggesting a delayed immunogenic reaction. However, the incidence of myelitis in COVID-19 is much more common, far greater than the risk associated with vaccination.
METHODS: A randomised controlled experiment was conducted from 29 April to 7 June 2021, which coincided with the early phases of the national vaccination programme when vaccine uptake data were largely unavailable. 5784 Malaysians were randomly allocated into 14 experimental arms and exposed to one or two messages that promoted COVID-19 vaccination. Interventional messages were applied alone or in combination and compared against a control message. Outcome measures were assessed as intent to both take the vaccine and recommend it to healthy adults, the elderly, and people with pre-existing health conditions, before and after message exposure. Changes in intent were modelled and we estimated the average marginal effects based on changes in the predicted probability of responding with a positive intent for each of the four outcomes.
RESULTS: We found that persuasive communication via several of the experimented messages improved recommendation intentions to people with pre-existing health conditions, with improvements ranging from 4 to 8 percentage points. In contrast, none of the messages neither significantly improved vaccination intentions, nor recommendations to healthy adults and the elderly. Instead, we found evidence suggestive of backfiring among certain outcomes with messages using negative attribute frames, risky choice frames, and priming descriptive norms.
CONCLUSION: Message frames that briefly communicate verbatim facts and stimulate rational thinking regarding vaccine safety may be ineffective at positively influencing vaccine-hesitant individuals. Messages intended to promote recommendations of novel health interventions to people with pre-existing health conditions should incorporate safety dimensions.
TRIAL REGISTRATION NUMBER: NCT05244356.
RESULTS: This work describes a computational methodology to achieve this analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A viruses as examples. Our methodology has been implemented as an analytical pipeline that brings significant advancement to the field of reverse vaccinology, enabling systematic screening of known sequence data in nature for identification of vaccine targets. This includes key steps (i) comprehensive and extensive collection of sequence data of viral proteomes (the virome), (ii) data cleaning, (iii) large-scale sequence alignments, (iv) peptide entropy analysis, (v) intra- and inter-species variation analysis of conserved sequences, including human homology analysis, and (vi) functional and immunological relevance analysis.
CONCLUSION: These steps are combined into the pipeline ensuring that a more refined process, as compared to a simple evolutionary conservation analysis, will facilitate a better selection of vaccine targets and their prioritization for subsequent experimental validation.