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.
The authors of this manuscript find that several systemic symptoms (chills, headache, feeling unwell and tiredness) and two biometric measures (change in max skin temp and min heart rate) following the 2nd COVID-19 dose correlate with neutralizing antibodies (nAB) measured 6 months following vaccination. The majority of the aforementioned variables also correlated with higher nAB measured 1 month following vaccination. The authors suggest that public health messaging reframing systemic side effects as beneficial could improve vaccine uptake.
The authors have conducted a thoughtful and thorough analysis of their study data. I suggest including more detail on the Type II F-tests conducted in the methods section; currently the methods indicate 4 hypothesis tests conducted on each exposure (systemic side effect and biometric measure) but does not explicitly define these tests. In my experience, unless a reader is very familiar with Type II F-tests, typically requiring extensive statistical training, most readers will not understand what hypothesis tests / models are being compared. The authors use the word "predict" instead of "associated with" in many places in the paper; the analysis conducted is one to determine association not to evaluate the quality of systemic side effect and biometric measures as predictors for nAB at 1- and 6-months following vaccination. Aside from mislabeling association as prediction, the results are interpreted accurately. However, I challenge the author's conclusion that their study's findings support reframing systemic side effects as beneficial (to increase vaccine uptake). Although the authors found statistically significant differences in nAB when comparing presence or absence of systemic side effects, they need to subsequently argue that the size of the differences observed would translate to better protection by the vaccine. The nAB levels are all very high and I don’t believe there are studies to support a threshold for nAB to designate protection vs. not (or even to define what constitutes protection). In addition, the authors should acknowledge the potential downside to the suggested messaging, e.g. persons who don't experience side effects after initial vaccination may NOT seek boosters since they may assume no systemic side effects indicate poor vaccine response (which is certainly NOT supported by any studies) so no reason to continue to get boosters if they aren’t offering protection.