Distinct Immunological Profiles Help in the Maintenance of Salivary Secretory IgA Production in Mild Symptoms COVID-19 Patients

Abstract

Background: Relevant aspects regarding the SARS-CoV-2 pathogenesis and the systemic immune response to this infection have been reported. However, the mucosal immune response of the upper airways two months after SARS-CoV-2 infection in patients with mild/moderate symptoms is still not completely described. Therefore, we investigated the immune/inflammatory responses of the mucosa of the upper airways of mild/moderate symptom COVID-19 patients two months after the SARS-CoV-2 infection in comparison to a control group composed of non-COVID-19 healthy individuals.

Methods: A cohort of 80 volunteers (age 37.2 ± 8.2), including non-COVID-19 healthy individuals (n=24) and COVID-19 patients (n=56) who presented mild/moderate symptoms during a COVID-19 outbreak in Brazil in November and December of 2020. Saliva samples were obtained two months after the COVID-19 diagnosis to assess the levels of SIgA by ELISA and the cytokines by multiplex analysis.

Results: Salivary levels of SIgA were detected in 39 volunteers into the COVID-19 group and, unexpectedly, in 14 volunteers in the control group. Based on this observation, we distributed the volunteers of the control group into without SIgA or with SIgA sub-groups, and COVID-19 group into without SIgA or with SIgA sub-groups. Individuals with SIgA showed higher levels of IL-10, IL-17A, IFN-γ, IL-12p70, IL-13, and IFN-α than those without SIgA. In intergroup analysis, the COVID-19 groups showed higher salivary levels of IL-10, IL-13, IL-17A, and IFN-α than the control group. No statistical differences were verified in the salivary levels of IL-6 and IFN-β. Lower IL-12p70/IL-10 and IFN-γ/IL-10 ratios were found in the control group without SIgA than the control group with SIgA and the COVID-19 group with SIgA.

Conclusion: We were able to present, for the first time, that associations between distinct immunological profiles can help the mucosal immunity to maintain the salivary levels of SIgA in COVID-19 patients two months after the SARS-CoV-2 infection.

Keywords: SARS-CoV-2; cytokines; interferon; interleukin; mucosal immunity; saliva.

Figure 1

Comparison of the levels of salivary specific-SIgA for SARS-CoV-2 between control and COVID-19 groups with or without the presence of SIgA. The level of significance was established at 5% (*p < 0.05; **p < 0.05; ****p < 0.0001).

Figure 2

Comparison of the salivary cytokines levels of IL-6 (A), IL-10 (B), IL-12p70 (C), IL-13 (D), IL-17 (E), IFN-α (F), IFN-β (G), and IFN-γ (H) between control without or with SIgA and COVID-19 without or with SIgA group. Values are presented in the median and interquartile range. Statistical analysis: Mann-Whitney test. The level of significance was established at 5% (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001).

Figure 3

Comparison of the salivary cytokines ratios of IL-6/IL-10 (A), IL-12p70/IL-10 (B), IL-13/IL-10 (C), IL-17/IL-10 (D), IFN-α/IL-10 (E), IFN-β/IL-10 (F), and IFN-γ/IL-10 (G) between control without or with SIgA and COVID-19 without or with SIgA group. Values are presented in the median and interquartile range. Statistical analysis: Kruskal Wallis test. The level of significance was established at 5% (*p < 0.05; **p < 0.01).

Figure 4

Summarized representation of the main results found in the study. The boxes representing the cytokines are colored in black color indicating an increase in their concentration when compared to the other groups. The arrows represent the correlations found in the study, in which positive correlations appear in gray and negative in orange.