Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In a prospective cohort study of individuals vaccinated against SARS-CoV-2, symptomatic patients had higher levels of neutralizing antibodies (nAB) compared to those who did not report any symptoms.

2. For every 1°C increase in skin temperature, there was an increase in nAB value one month later and a greater increase in nAB six months later.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

The benefits of the COVID-19 vaccines, including reduced severity, are shown to degrade over time, necessitating booster doses. Despite plentiful supply, at the time of the study, only 17% of participating adults had received a booster, citing concern about side effects as a major worry. This study hoped to reframe the illness felt post booster shot vaccination as signs of a healthy immune response through measurements of long-term nAB. Some of the biometric measurements included skin temperature (ST), respiratory rate (RR), and heart rate (HR). Self-reported daily symptoms and biometric data were collected at six months to predict nAB concentrations. For the samples, serum from patients was mixed with a pseudovirus, which allowed the expression of luciferase in susceptible cells. Approximately three days later, luciferase substrate was added, and the corresponding luminescence was used to compare levels of nAB across various sample categories. Mixed analysis models in R were used to evaluate across many groupings previously deemed significant in COVID analysis. Some limitations include rapidly changing strains of COVID-19 as well as the vaccine and applicability to people who had previously been infected with COVID-19. Overall, participants experiencing symptoms after the SARS-Cov-2 vaccination had higher levels of nAB compared to individuals who did not experience any symptoms.

In-Depth [prospective cohort]:

To learn if short-term side effects of the SARS-CoV-2 vaccine are associated with a nAB response, a prospective cohort study was conducted. It included 363 participants in the symptom data collection and 147 in the biometric-related data analysis. These participants met the eligibility criteria of being 18 years or older, had no immune-related diseases (such as autoimmune conditions), nor active cancer and were not taking medications known to affect the immune system (such as steroids). If participants had a positive test result on the anti-spike IgG antibody test or the anti-nucleocapsid IgG antibody test, they were excluded from the study as this meant they had previously been infected by SARS-CoV-2. Other reasons for exclusion included previous vaccination with the Ad26.COV2.S, or incomplete or missing data. A total of 91.5% of participants who reported having experienced at least one symptom after the first dose also reported having at least one symptom after the second dose. Similarly, 74.1% of participants who experienced no symptoms after the first dose, reported at least one symptom after the second. There was a significant interaction between outcome time points and vaccination-induced change in nightly 99th-percentile ST at the second dose but not at the first. Each 1°C increase in skin temperature was associated with a 1.8-fold increase in nAB after 1 month and a 3.1-fold increase in nAB after 6 months. By combining self-reported symptoms and biometric data to predictive nAB models, this study showed that after a second dose of vaccine, symptoms had a 1.4-1.6 factor increase in nAB levels. The nAB level was approximately double on average in participants reporting seven symptoms compared to zero symptoms. In summary, SARS-Cov-2 vaccination side effects were associated with elevated nAB levels.

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