To the editor:
We thoroughly examined the article titled “Exaggerated immune response to fungal keratitis post-COVID-19 vaccination” by Nakajima I et al. where the authors postulate that the exacerbation of Fusarium keratitis in this case may be secondary to the Pfizer-BioNTech COVID-19 vaccination. Yet, we would like to address several concerns regarding this hypothesis.
Keratitis due to Fusarium spp is challenging due to its high risk of recurrence and torpid evolution. Close monitoring and long-term treatment are highly recommended to avoid premature recurrences. Even with the appropriate antifungal therapy as in this case, the therapeutic response in fungal keratitis can be unpredictable and variable, leading to potential clinical worsening. Hence, the recurrence observed in this case may be due to a setback in the clinical evolution rather than secondary to the vaccination. The pharmacokinetics of topical drugs are highly variable, depending on multiple factors, such as antifungal resistance or suboptimal drug penetration, leading to fluctuations in disease severity. In this case, the clinical worsening could be, in fact, due to a suboptimal therapeutic response. Thus, reassessment of the topical regimen, initiation of systemic antifungals or even consideration of therapeutic keratoplasty may be contemplated.
The temporal association between two events does not necessarily imply causation. Likewise, most of the post-vaccine reactions are coincidental rather than causative. They typically manifest with mild-to-moderate systemic effects rather than exacerbations of localized infections. Moreover, most ocular side effects linked to the Pfizer-BioNTech COVID-19 vaccine have been associated with vascular or autoimmune mechanisms.
As pointed out by the authors, IL-17 plays an important role in fungal infections, promoting neutrophil recruitment. Moreover, COVID-19 infection and vaccination may induce a transient increase in IL-17 levels. However, the inflammatory response to filamentous fungi such as Fusarium or Aspergillus is complex and highly regulated, involving multiple receptors, cytokines, cells and organelles. For this reason, an increase in IL-17 does not necessarily correlate with a local inflammatory reaction worsening.
Applying the Bradford Hill criteria for causality, the evidence supporting a causal link between the COVID-19 vaccination and the recurrence of fungal keratitis appears weak. The lack of consistency, specificity, solid biological plausibility and absence of a clear dose-response relationship suggests that the keratitis recurrence is more likely a part of the natural disease course rather than a direct effect of vaccination. Thus, we recommend further studies involving larger populations and a thorough analysis of post-vaccination cases in similar clinical scenarios to better establish any potential association between COVID-19 vaccines and the exacerbation of fungal keratitis or other localized infections.
Declaration of Generative AI and AI-assisted technologies in the writing process
During the preparation of this work the authors used ChatGPT-4 to check grammar and spelling. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
Declaration of Competing Interest
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgment
None.
References
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