Arturo Gómez López de Las Huertas

Background/Objectives: Post-market surveillance of COVID-19 vaccines is vital. This study analyzed EudraVigilance data (Jan 2021–Dec 2023) to detect potential safety signals linking COVID-19 vaccines and specific neurological adverse events (aseptic meningitis, Guillain–Barré syndrome, polyradiculoneuropathies, multiple sclerosis, transverse myelitis, neuromyelitis optica). It also explored the impact of non-healthcare professional reports on disproportionality analysis. Methods: EudraVigilance reports were analyzed to quantify neurological events for 5 COVID-19 vaccines and 47 comparators. Disproportionality was assessed using the Proportional Reporting Ratio (PRR). Spearman’s correlation (SCC) was used to examine the impact of non-healthcare professional reports on PRR. Results: An analysis of 4,159,820 COVID-19 vaccine and 114,025 comparator reports showed a reporting decline over time. A higher proportion of adverse drug event reports were submitted by non-healthcare professionals for COVID-19 vaccines compared to control vaccines, a trend observed consistently across 2021 (57.3% vs. 33%, p < 0.001), 2022 (59.4% vs. 36.5%, p = 0.001), and 2023 (42% vs. 24.36%, p = 0.006). In 2023, significant signals (PRR ≥ 2) were found between Jcovden© and polyradiculoneuropathy (PRR 5.4, IC 95% 3.98–7.32), multiple sclerosis (PRR 2.72, IC 95% (1.08–6.87), transverse myelitis (PRR 4.68, IC 95% 1.02–21.35) and neuromyelitis optica (PRR 7.79, IC 95% 3.5–17.37). In addition, both Spikevax© and Comirnaty© showed significant signals with multiple sclerosis (PRR 2.50, IC 95% 1.70–3.68, and PRR 2.33, IC 95% 1.68–3.24) and transverse myelitis (PRR 3.50, IC 95% 1.66–7.50 and PRR 3.58, IC 95% 1.85–6.93). A significant negative correlation between the proportion of reports from non-healthcare professionals and the case/no-case ratio was found (SCC = −0.4683, p = 0.009). Conclusions: While some significant signals emerged in 2023, the combined three-year data showed no vaccine exceeding the PRR threshold of 2. High-quality data and bias mitigation strategies are crucial for accurate PRR estimation in pharmacovigilance and public health.

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case–control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome.

Severe acute respiratory syndrome coronavirus 2 caused the global COVID-19 pandemic and public health crisis, and it led to the rapid development of COVID-19 vaccines, which can cause rare and typically mild hypersensitivity reactions (HRs). Delayed HRs to COVID-19 vaccines have been reported, and the excipients polyethylene glycol (PEG)2000 and polysorbate 80 (P80) are the suspected culprits. Skin patch tests do not help in diagnosing delayed reactions. We aimed to perform lymphocyte transformation tests (LTT) with PEG2000 and P80 in 23 patients with suspected delayed HRs. Neurological reactions (n = 10) and myopericarditis reactions (n = 6) were the most frequent complications. Seventy-eight percent (18/23) of the study patients were admitted to a hospital ward, and the median time to discharge was 5.5 (IQR, 3–8) days. Some 73.9% of the patients returned to baseline condition after 25 (IQR, 3–80) days. LTT was positive in 8/23 patients (5/10 neurological reactions, 2/4 hepatitis reactions and 1/2 rheumatologic reactions). All myopericarditis cases had a negative LTT. These preliminary results indicate that LTT with PEGs and polysorbates is a useful tool for identifying excipients as causal agents in HRs to COVID-19 vaccines and can play an important role in risk stratification in patients with HRs.