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. 2024 Mar 5:15:1350288.
doi: 10.3389/fimmu.2024.1350288. eCollection 2024.

The effect of SARS-CoV-2 infection and vaccination on Th17 and regulatory T cells in a pregnancy cohort in NYC

Frederieke A J Gigase  1   2 , Mara Graziani  1   3 , Juliana Castro  1 , Corina Lesseur  4 , Anna-Sophie Rommel  1 , Tammy Flores  1 , M Mercedes Perez-Rodriguez  1 , Siobhan Dolan  5 , Joanne Stone  6 , Teresa Janevic  6   7 , Whitney Lieb  6   8 , Veerle Bergink  1   6   8   9 , Lot D de Witte  1   3   10
Affiliations

The effect of SARS-CoV-2 infection and vaccination on Th17 and regulatory T cells in a pregnancy cohort in NYC

Frederieke A J Gigase et al. Front Immunol. .

Abstract

Disturbances in T-cells, specifically the Th17/Treg balance, have been implicated in adverse pregnancy outcomes. We investigated these two T-cell populations following pre-pregnancy and pregnancy SARS-CoV-2 infection and COVID-19 vaccination in 351 participants from a pregnancy cohort in New York City (Generation C; 2020-2022). SARS-CoV-2 infection status was determined via laboratory or medical diagnosis and COVID-19 vaccination status via survey and electronic medical records data. Peripheral blood mononuclear cells (PBMCs) were collected at routine prenatal visits throughout gestation (median 108 days; IQR 67-191 days) with repeated measures for 104 participants (29.6%). T-cell populations CD4+/CD3+, Th17/CD4+, Treg/CD4+ and the Th17/Treg ratio were quantified using flow cytometry. Results showed that inter-individual differences are a main influencing factor in Th17 and Treg variance, however total variance explained remained small (R2 = 15-39%). Overall, Th17 and Treg populations were not significantly affected by SARS-CoV-2 infection during pregnancy in adjusted linear mixed models (p>0.05), however comparison of repeated measures among SARS-CoV-2 infected participants and non-infected controls suggests a relative increase of the Th17/Treg ratio following infection. In addition, the Th17/Treg ratio was significantly higher after SARS-CoV-2 infection prior to pregnancy (10-138 weeks) compared to controls (β=0.48, p=0.003). COVID-19 vaccination was not associated with Th17 and Treg cells. Our findings suggest an impact of SARS-CoV-2 infection on the Th17/Treg ratio, likely depending on severity of infection, yet the observed trends and their potential consequences for pregnancy outcomes require further investigation. Our study contributes to growing evidence that COVID-19 vaccination during pregnancy does not lead to an exacerbated immune response.

Keywords: COVID-19 pandemic; COVID-19 vaccination; SARS-CoV-2 infection; Th17; Treg; ratio.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Characterizing T-cell populations in a large pregnancy cohort in NYC (n=351). (A) SARS-CoV-2 infection status and COVID-19 vaccination status was determined for all participants. (B) Gestational age at sampling: samples were collected throughout gestation at a median of 108 days (IQR 67-191 days). (C) Variance partition analysis of the variance in T cell populations explained by various maternal, technical, and COVID-19 pandemic-related factors. (D) Variance partition results showing the variance explained by various maternal, technical, and COVID-19 pandemic-related factors in each T-cell population. (E) Principal component analysis showing the distribution of SARS-CoV-2 infection status and COVID-19 vaccination status across T-cell populations.
Figure 2
Figure 2
T-cell populations and IL-17A following SARS-CoV-2 infection and COVID-19 vaccination. (A) Distribution of the percentage of CD4+, Th17, Treg cells and the Th17/Treg ratio throughout gestation across SARS-CoV-2 infection status. (B) Violin plots of the distribution of the percentage of CD4+, Th17, Treg cells and the Th17/Treg ratio across SARS-CoV-2 infection status. (C) Distribution of the percentage of CD4+, Th17, Treg cells and the Th17/Treg ratio throughout gestation across COVID-19 vaccination status. (D) Violin plots of the distribution of the percentage of CD4+, Th17, Treg cells and the Th17/Treg ratio across COVID-19 vaccination status. (E) Violin plots of the distribution of IL-17A levels (pg/ml) per SARS-CoV-2 infection status and COVID-19 vaccination status.
Figure 3
Figure 3
Sensitivity analysis of participants with a repeated measure prior to and after SARS-CoV-2 infection (n=22) (left panels) and a gestational age matched control group of non-infected participants (n=88) (right panels). Percentages of CD4+ (A), Th17 (B), Treg (C) and the Th17/Treg ratio (D) were not significantly different following SARS-CoV-2 infection. In the gestational age matched control group of non-infected participants (n=88), the Th17/Treg ratio was significantly lower in the second sample compared to the first measurement. Corrected p-values are shown (Benjamini Hochberg).
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