Transverse Myelitis Following SARS‐CoV‐2 Vaccination: A Pharmacoepidemiological Study in the World Health Organization's Database

Abstract

Background Transverse myelitis (TM) has recently been associated by health authorities with Ad26.COV2.S (Janssen/Johnson & Johnson), one of the 5 US Food and Drug Administration (FDA) or European Medicines Agency (EMA) labeled severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines. It is unknown whether a similar association exists for the other FDA or EMA labeled SARS‐CoV‐2 vaccines (BNT162b2 [Pfizer/BioNTech], mRNA‐1273 [Moderna], ChAdOx1nCov‐19 [Oxford–AstraZeneca], and NVX‐CoV2373 [Novavax]). This study aimed to evaluate the association between SARS‐CoV‐2 vaccine class and TM. Methods This observational, cross‐sectional, pharmacovigilance cohort study examined individual case safety reports from VigiBase, the World Health Organization's pharmacovigilance database. We first conducted a disproportionality analysis with the information component (IC) using the reports of TM that occurred within 28 days following exposure to the FDA or EMA labeled SARS‐CoV‐2 vaccines, from December 1, 2020 (first adverse event related to a SARS‐CoV‐2 vaccine) to March 27, 2022. Second, we analyzed the clinical features of SARS‐CoV‐2 vaccine‐associated TM cases reported in VigiBase. Results TM was significantly associated both with the messenger ribonucleic acid (mRNA)‐based (n = 364; IC 025 = 0.62) and vector‐based (n = 136; IC 025 = 0.52) SARS‐CoV‐2 vaccines that are authorized by the FDA or the EMA. Conclusions Findings from this observational, cross‐sectional pharmacovigilance study showed that mRNA‐based and vector‐based FDA/EMA labeled SARS‐CoV‐2 vaccines can be associated with TM. However, because TM remains a rare event, with a previously reported rate of 0.28 cases per 1 million vaccine doses, the risk–benefit ratio in favor of vaccination against SARS‐CoV‐2 virus remains unchallenged. Rather, this study suggests that clinicians should consider the diagnosis of TM in patients presenting with early signs of spinal cord dysfunction after SARS‐CoV‐2 vaccination. ANN NEUROL 2022

Seasonal Variation in Neurologic Hospitalizations in the United States

“…23 However, transverse myelitis had a later peak (late fall/winter) than other neuroinflammatory disorders, which may be due to cases of transverse myelitis associated with viral infections or vaccinations. 24,25 Despite a large and growing body of literature on seasonality in neurologic disease, direct comparisons between existing studies are challenging as they are conducted in different geographic areas using variable data sources and case ascertainment methods. By using a large, nationally representative database of inpatient hospitalizations in the United States, we are able to not only validate previous findings at a national level but also compare the relative magnitude of seasonal variation across different diseases.…”

“…Influenza vaccination has been associated with a transiently lower risk of multiple sclerosis exacerbation, so it is possible that this is true of other demyelinating diseases such as optic neuritis and neuromyelitis optica 23 . However, transverse myelitis had a later peak (late fall/winter) than other neuroinflammatory disorders, which may be due to cases of transverse myelitis associated with viral infections or vaccinations 24, 25 …”

Neurologic Complications of COVID-19

“…Other inflammatory CNS conditions including autoimmune encephalitis have also been reported in temporal association with COVID-19 vaccines. Causality is uncertain, and the degree of risk beyond the background rate has been difficult to ascertain 88,94,95 …”

“…Causality is uncertain, and the degree of risk beyond the background rate has been difficult to ascertain. 88,94,95 Guillain-Barré syndrome is often associated with preceding infections or vaccinations. Onset is typically within 6 weeks of vaccine exposure.…”

Sensitivity and specificity in signal detection with the reporting odds ratio and the information component

“…In a selection of studies on worsening of myasthenia in antibiotics, 10 antidepressants and neuroleptics, 17 QT prolongation in neuroleptics, 22 transverse myelitis after COVID-19 vaccination, 23 the 30 most frequent ADRs in edoxaban 24 and induction of PML by immunosuppressant drugs 9 there is a large range of expected ADR frequency. The error rates of the drugs in these studies as obtained from simulations with the respective values for P0 and N are shown in Figure 7 together with a simulation for the full range of ADR frequencies with P0 = 0.01 and N = 1 000 000 for expected case numbers below the position of peak n. Figure 3 shows that for n = 3 false positive rates of 0.05 are possible when in fact 0.025 was intended.…”