Symptoms after first mRNA vaccine dose linked to previous SARS-CoV-2 infection

Previous SARS-CoV-2 exposure increased the odds of developing clinically significant symptoms following the first dose of a COVID-19 mRNA vaccine, researchers reported in JAMA Internal Medicine.

“These vaccines can elicit greater local and systemic reactions in persons with prior SARS-CoV-2 infection,” Amanda K. Debes, PhD, MS, an assistant scientist in the department of international health at the Johns Hopkins Bloomberg School of Public Health, and colleagues wrote. “Whether symptoms following vaccination are associated with effectiveness is unknown, and, therefore, anxiety can arise in persons who did not develop a reaction following vaccination.”

The researchers conducted a longitudinal study that analyzed S1 spike antibodies in serum samples and COVID-19 symptom questionnaires from 954 health workers within the Johns Hopkins Health System. The participants had their serum samples collected 14 or more days after receiving the second dose of either the Moderna or Pfizer mRNA vaccine. The researchers collected samples and questionnaires every 3 to 4 months.

Debes and colleagues reported that clinically significant symptoms were reported by 5% of the health workers after the first dose and 43% following the second dose. After adjusting for previous SARS-CoV-2 infection, age and sex, the odds for the workers experiencing clinically significant symptoms after receiving either dose were higher among health workers who were administered the Moderna vaccine compared with the Pfizer vaccine (first dose OR = 1.83; 95% CI, 0.96-3.5; second dose OR = 2.43; 95% CI, 1.73-3.4). After controlling for vaccine type, age and sex, previous exposure to SARS-CoV-2 was linked to increased odds of clinically significant symptoms following the first dose (OR = 4.38; 95% CI, 2.25-8.55) but not the second dose (OR = 0.6; 95% CI, 0.36-0.99).

In addition, regardless of symptoms, all but one of the 954 health workers developed spike IgG antibodies 14 or more days after receiving the second dose. The one health worker who did not was taking immunosuppressant medication, according to the researchers. They also found that reporting clinically significant symptoms, being aged younger than 60 years, being female, receiving the Moderna vaccine and having a previous SARS-CoV-2 exposure were independently associated with higher median IgG measurements after adjusting for time after the second dose.

“The role of higher antibody levels in preventing COVID-19 and providing lasting immunity remains unknown, however,” Debes and colleagues wrote. “Overall, the findings suggest that regardless of vaccine reactions or prior SARS-CoV-2 infection, either spike mRNA vaccine will provide a robust spike antibody response.”