An Immunological Perspective: What Happened to Pregnant Women After Recovering From COVID-19?

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has been raging around the world since January 2020. Pregnancy places the women in a unique immune scenario which may allow severe COVID‐19 disease. In this regard, the potential unknown effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mothers and fetuses have attracted considerable attention. There is no clear consistent evidence of the changes in the immune status of pregnant women after recovery from COVID-19. In this study, we use multiparameter flow cytometry and Luminex assay to determine the immune cell subsets and cytokines, respectively, in the peripheral blood and umbilical cord blood from pregnant women recovering from COVID-19 about 3 months (n=5). Our results showed decreased percentages of Tc2, Tfh17, memory B cells, virus-specific NK cells, and increased percentages of naive B cells in the peripheral blood. Serum levels of IL-1ra and MCP-1 showed a decreased tendency in late recovery stage (LRS) patients. Meanwhile, there was no significant difference in immune cell subsets in the umbilical cord blood. The placentas from LRS patients showed increased CD68+ macrophages infiltration and mild hypoxic features. The inflammatory damage of the placenta may be related to the antiviral response. Since the receptors, ACE2 and TMPRSS2, utilized by SARS-CoV-2 are not co-expressed in the placenta, so it is extremely rare for SARS-CoV-2 to cause infection through this route and the impact on the fetus is negligible.

Integrated immune networks in SARS-CoV-2 infected pregnant women reveal differential NK cell and unconventional T cell activation

“…Furthermore, in a comparison of cytokine levels during pregnancy and at one-year post-partum, Graham et al (2017) found that pro-inflammatory IL-18, TNFα and MCP-1 were reduced during pregnancy while IL-10 remained unchanged. Pregnant women with COVID-19 shared similar cytokine and chemokine profiles as non-pregnant women, with the exception of eotaxin and GRO-a, while key differences between COVID-19 and healthy pregnant women have been observed in IL-12p70, MIP-1β, RANTES (Chen et al, 2021;Zhao et al, 2021). Our analysis showed that IL-18 was elevated during pregnancy regardless of disease state, which has been shown to cause TCR-independent activation of MAIT cells (Loh et al, 2016).…”

“…A systematic review of clinical laboratory findings determined that a low white blood cell count was the only significant difference between the pregnant and nonpregnant COVID-19 immune responses (Areia and Mota-Pinto, 2020). However, pregnant or post-partum women who had recovered from COVID-19 had lower T follicular helper type 17 cells (T FH 17), memory B cells, total and 'virus'-specific (CD56 + NKP46 + ) NK cells compared to healthy pregnant women (Zhao et al, 2021). Cytokine profiles differed between healthy pregnant women and those with COVID-19 (Chen et al, 2021;Zhao et al, 2021).…”

“…However, pregnant or post-partum women who had recovered from COVID-19 had lower T follicular helper type 17 cells (T FH 17), memory B cells, total and 'virus'-specific (CD56 + NKP46 + ) NK cells compared to healthy pregnant women (Zhao et al, 2021). Cytokine profiles differed between healthy pregnant women and those with COVID-19 (Chen et al, 2021;Zhao et al, 2021). Despite reports to date on specific immune parameters, a comprehensive analysis of immune perturbations in early and late stages of COVID-19 during pregnancy is lacking.…”

Molecular evidence suggesting the persistence of residual SARS‐CoV‐2 and immune responses in the placentas of pregnant patients recovered from COVID‐19

“… 21 , 23 Maternal inflammatory responses at the maternal–foetal interface, mediated through macrophages and T cells, are induced after SARS‐CoV‐2 infection, and these responses could persist for as long as 3 months after COVID‐19 recovery. 4 , 24 , 25 , 26 …”

“…Pregnant women are a high‐risk population for severe COVID‐19 and exhibit high mortality owing to their unique immune status 21,23 . Maternal inflammatory responses at the maternal–foetal interface, mediated through macrophages and T cells, are induced after SARS‐CoV‐2 infection, and these responses could persist for as long as 3 months after COVID‐19 recovery 4,24‐26 …”