Review 2: "Comparison of adverse events between COVID-19 and Flu Vaccines"

RR:C19 Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: Pradhan et al. performed a descriptive analysis of COVID-19 and flu vaccine related adverse events using VAERS data. The research is timely and important. The authors note that there is similarity in the types of adverse events reported when the top 10 adverse events are looked at. The study findings may provide a basis for more focused studies in this area. Some of the issues of concern regarding this research which need to be considered are stated below:

1. Presence of duplicate reports in the VAERS database can affect the analysis outcome. Given the scientific community and public attention towards COVID vaccine safety, there is a higher chance of the same report being reported by different sources. If no deduplication measures have been used, this needs to be highlighted as a study limitation.

2. The AE term ‘central neuropathy’ includes events ranging from dizziness to hemiparesis/paralysis. Given that this was one of the common AE terms seen in this study, further data regarding the specific AE terms reported would have been useful. Also, there are several reports of GBS following influenza vaccination (although may not be causally related); the relatively smaller number of flu vaccine AE reports in the current study makes it difficult to comment on the possible differences in its occurrence with COVID or flu vaccine.

3. In Results, the authors use the phrase “more likely to experience” even when the RR and CI suggest a lesser risk. For example, “persons receiving first dose of Pfizer vaccine were 0.64 times more likely to experience pallor (95% CI: 0.44 to 0.95)”.

4. The Discussion is too brief and does not adequately describe the key differences or similarities in the AEs reported with the two vaccines. Since the authors intended the study findings to help address the issue of vaccine hesitancy, a clear articulation of the study findings is necessary. The statement “it appears that there were some common adverse events between Flu vaccines and COVID-19 vaccines” in Conclusion seems vague and may not be easily interpretable/actionable.

5. The authors state that rare AEs are difficult to detect. However, the current study was not designed to assess rare AEs since the analysis was confined to the top 10 AEs. One of the advantages of using VAERS data is to identify uncommon AEs and their potential relationship with use of a particular vaccine, although, as the authors rightly state, such studies need to be confirmed by further studies.

6. The authors mention regarding “lack of availability of time to each adverse event” in the study limitations. However, VAERS does contain ‘onset interval’ as a variable although the data may be missing in many reports.