Relationship between Humoral Response in COVID-19 and Seasonal Influenza Vaccination

Abstract

There is evidence that vaccination against seasonal influenza can improve innate immune responses to COVID-19 and decrease disease severity. However, less is known about whether it could also impact the humoral immunity in SARS-CoV-2 infected patients. The present study aimed to compare the SARS-CoV-2 specific humoral responses (IgG antibodies against nucleocapsid; anti-N, receptor binding domain; anti-RBD, subunit S2; anti-S2, and envelope protein; anti-E) between non-hospitalized, COVID-19 unvaccinated, and mild COVID-19 convalescent patients who were and were not vaccinated against influenza during the 2019/2020 epidemic season (n = 489 and n = 292, respectively). The influenza-vaccinated group had significantly higher frequency and titers of anti-N antibodies (75 vs. 66%; mean 559 vs. 520 U/mL) and anti-RBD antibodies (85 vs. 76%; mean 580 vs. 540 U/mL). The prevalence and concentrations of anti-S2 and anti-E antibodies did not differ between groups (40-43%; mean 370-375 U/mL and 1.4-1.7%; mean 261-294 U/mL) and were significantly lower compared to those of anti-RBD and anti-N. In both groups, age, comorbidities, and gender did not affect the prevalence and concentrations of studied antibodies. The results indicate that influenza vaccination can improve serum antibody levels produced in response to SARS-CoV-2 infection.

Keywords: SARS-CoV-2; adaptive immunity; heterologous protection; immunology; pandemic; trained immunity.

Figure 1

Serum titers (median and interquartile range) of IgG antibodies against SARS-CoV-2 nucleocapsid protein (anti-N), receptor binding domain of spike protein (anti-RBD), subunit S2 of spike protein (anti-S2), and envelope protein (anti-E) in mild COVID-19 convalescent individuals not vaccinated (I-VAX-) and vaccinated (I-VAX+) against seasonal influenza. The p-value refers to the difference between these groups examined with the Mann–Whitney U test. Different small letters (a, b) above bars indicate a significant difference between antibody concentrations within the I-VAX- group, while different capital letters (A, B) indicate it within the I-VAX+ group (Kruskal–Wallis ANOVA with Dunn’s post hoc test).