Review 1:  No Evidence that Analgesic Use After COVID-19 Vaccination Negatively Impacts Antibody Responses

Justin Reese

doi:doi:10.1162/2e3983f5.6c9028b5

No evidence that analgesic use after COVID-19 vaccination negatively impacts antibody responses

by Bonnie J. Lafleur, Lisa White, Michael D. Dake, Janko Nikolich-Zugich, Ryan Sprissler, and Deepta Bhattacharya

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dx.doi.org

Description

AbstractVaccines against SARS-CoV-2, the virus that causes COVID-19, showed high efficacy against symptomatic illness caused by the ancestral strain. Yet recent variants such as Omicron and its sublineages substantially escape vaccine-induced neutralizing antibodies. In response, bivalent mRNA booster vaccines updated to better match the BA.4-5 lineages have been made available. Yet the reactogenicity of these vaccines might negatively impact willingness to receive the booster immunization. While serious side effects following vaccination are rare, mRNA vaccines frequently lead to mild adverse events such as injection site pain, lymphadenopathy, myalgia, and fever. Over-the-counter analgesics might mitigate some of these mild adverse events, but animal models of SARS-CoV-2 infection have shown that non-steroidal anti-inflammatory drugs (NSAIDs) substantially reduce antiviral antibody responses, which are the best correlates of protection against COVID-19. It remains unknown whether these same inhibitory effects are seen in humans after mRNA vaccination. We surveyed 6,010 individuals who received COVID-19 vaccines regarding analgesic use and correlated these results with Spike-specific antibody levels. We found no negative impact of analgesic use on antibody levels, and in fact observed slightly elevated concentrations of anti-Spike antibodies in individuals who used painkillers. Logistic regression analyses demonstrated a higher proportion of those experiencing fatigue and muscle aches between NSAID users and those not taking pain medication, suggesting that the elevated antibody levels were likely associated with inflammation and mild adverse events rather than analgesic use per se. Together, our results suggest no detriment to painkiller use to alleviate symptoms after vaccination against COVID-19.

RR:C19 Evidence Scale rating by reviewer:

Not informative. The flaws in the data and methods in this study are sufficiently serious that they do not substantially justify the claims made. It is not possible to say whether the results and conclusions would match that of the hypothetical ideal study. The study should not be considered as evidence by decision-makers.

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Review:
The authors describe a study which analyzes the effect of NSAIDs on the antibody response to COVID-19 vaccination. This is important since NSAID use to ameliorate the unpleasant effects of COVID-19 vaccination is likely common, and therefore knowledge about NSAID effects on antbody response is very useful.

One possible problem with the study design is that it relies on self-reporting of NSAID use. Actual use of NSAID is likely higher, so the authors should make an effort to determine how accurate the captured NSAID use is. Does the measured rate of NSAID use comport with the use reported previously in literature? (The study also relies on self-reporting of vaccination, but it seems likely that this self-reporting is more accurate.)

Another issue is confounding by indication. Those who opt to use NSAIDs are likely disproportionately those with a greater immune response and therefore likely have a stronger antibody response.

Finally, the authors should show a Table 1 figure to describe the demographics of the treated and untreated groups in order to assess how these two groups differ, and assess other possible sources of confounding. The author might also consider propensity matching in order to better align the treated and untreated groups.