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San Francisco – The occurrence of systemic side effects after vaccination against COVID-19 with mRNA vaccine is associated with a stronger formation of SARS-CoV-2 neutralizing antibodies (nAB) in the follow-up. Therefore, short-term side effects could probably be seen as a positive sign of better long-term protection against new infections (Annals of Internal Medicine2024; DOI: 10.7326/M23-2956).

Previously, other studies have described that the occurrence of side effects to a COVID-19 vaccination was associated with a higher formation of anti-SARS-CoV-2 immunoglobulins. However, in most antibody measurements, the properties of the antibodies were not considered in a differentiated manner. Special analyses of the nABs have rarely been taken into account so far, and when they have been, the results have sometimes been contradictory.

To gain a better understanding of the formation of nABs when short-term side effects previously occurred after the 2nd vaccination dose with mRNA vaccine, American scientists have set up a prospective cohort study. In this study, 363 adults (65.6% female, average age: 52.4 years) from the San Francisco region who had not yet been vaccinated against SARS-CoV-2 or had been exposed to SARS-CoV-2 infection were vaccinated in 2021 with 2 doses of either BNT162b2 or mRNA-1273.

Serum nAB titers were analyzed after one and 6 months after the second vaccination dose. In addition, the presence or absence of 13 potential side effects was asked on 6 consecutive days after each dose. A portion of the vaccination cohort (n=147, 66.0% female, mean age: 58.8 years) also underwent biometric measurements. These included changes in skin temperature, heart rate, heart rate variability and respiratory rate as a result of COVID-19 vaccination.

Of the 13 side effects surveyed, 4 were statistically significant predictors of the formation of nABs, the study authors report. When short-term side effects such as chills, fatigue, malaise and headache occurred after the 2nd dose, these people developed 1.4 to 1.6 times higher nAB titers after one and 6 months after vaccination than those without these 4. On average, respondents who reported a total of 7 symptoms had about twice as high nAB titers as participants without symptoms.

The number of symptoms and aspects of the biometric measurements (especially vaccine-related changes in skin temperature and heart rate) were positively associated with the formation of nAB over both follow-up time points. For example, a 1 °C increase in skin temperature after the 2nd dose was associated with a 1.8-fold higher nAB titer one month later and with a 3.1-fold higher nAB titer 6 months later.

This work provides additional evidence that greater long-term protection can be built up when COVID-19 vaccination causes short-term side effects. The authors conclude that their results could be relevant, for example, for counseling patients who are predominant in concerns about vaccine side effects.

If they represent a relevant barrier to getting vaccinated at all or taking the second dose of vaccine, the current findings could be encouraging. However, their results cannot be generalized to people with previous SARS-CoV-2 vaccination or infection, the study authors point out. © cw/aerzteblatt.de