tetano
Editor, Senior Moderator
Front Microbiol
. 2022 Jan 21;12:806902.
doi: 10.3389/fmicb.2021.806902. eCollection 2021.
Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice
Guohua Zhu[SUP] 1 [/SUP], Shujuan Du[SUP] 2 [/SUP], Yuyan Wang[SUP] 2 [/SUP], Xixi Huang[SUP] 1 3 [/SUP], Gaowei Hu[SUP] 2 [/SUP], Xin Lu[SUP] 1 [/SUP], Dajin Li[SUP] 1 3 [/SUP], Yizhun Zhu[SUP] 3 4 [/SUP], Di Qu[SUP] 2 [/SUP], Qiliang Cai[SUP] 2 [/SUP], Lu Liu[SUP] 1 3 [/SUP], Meirong Du[SUP] 1 3 5 [/SUP]
Affiliations
Abstract
Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females' fertility and causes different symptoms among pregnant and non-pregnant females remains unknown. Here, we examined the differences in viral loads, SARS-CoV-2-specific antibody titers, proinflammatory cytokines, and levels of T cell activation after SARS-CoV-2 sub-lethal infection between pregnant and non-pregnant human Angiotensin-Converting Enzyme II (ACE2) transgenic mouse models. Both mice showed elevated levels of viral loads in the lung at 4 days post-infection (dpi). However, viral loads in the pregnant group remained elevated at 7 dpi while decreased in the non-pregnant group. Consistent with viral loads, increased production of proinflammatory cytokines was detected from the pregnant group, and the IgM or SARS-CoV-2-specific IgG antibody in serum of pregnant mice featured delayed elevation compared with non-pregnant mice. Moreover, by accessing kinetics of activation marker expression of peripheral T cells after infection, a lower level of CD8[SUP]+[/SUP] T cell activation was observed in pregnant mice, further demonstrating the difference of immune-response between pregnant and non-pregnant mice. Although vertical transmission did not occur as SARS-CoV-2 RNA was absent in the uterus and fetus from the infected pregnant mice, a lower pregnancy rate was observed when the mice were infected before embryo implantation after mating, indicating that SARS-CoV-2 infection may interfere with mice's fertility at a specific time window. In summary, pregnant mice bear a weaker ability to eliminate the SARS-CoV-2 virus than non-pregnant mice, which was correlated with lower levels of antibody production and T cell activation.
Keywords: SARS-CoV-2; T cell activation; fertility; immune responses; pregnancy.
. 2022 Jan 21;12:806902.
doi: 10.3389/fmicb.2021.806902. eCollection 2021.
Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice
Guohua Zhu[SUP] 1 [/SUP], Shujuan Du[SUP] 2 [/SUP], Yuyan Wang[SUP] 2 [/SUP], Xixi Huang[SUP] 1 3 [/SUP], Gaowei Hu[SUP] 2 [/SUP], Xin Lu[SUP] 1 [/SUP], Dajin Li[SUP] 1 3 [/SUP], Yizhun Zhu[SUP] 3 4 [/SUP], Di Qu[SUP] 2 [/SUP], Qiliang Cai[SUP] 2 [/SUP], Lu Liu[SUP] 1 3 [/SUP], Meirong Du[SUP] 1 3 5 [/SUP]
Affiliations
- PMID: 35126335
- PMCID: PMC8814454
- DOI: 10.3389/fmicb.2021.806902
Abstract
Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females' fertility and causes different symptoms among pregnant and non-pregnant females remains unknown. Here, we examined the differences in viral loads, SARS-CoV-2-specific antibody titers, proinflammatory cytokines, and levels of T cell activation after SARS-CoV-2 sub-lethal infection between pregnant and non-pregnant human Angiotensin-Converting Enzyme II (ACE2) transgenic mouse models. Both mice showed elevated levels of viral loads in the lung at 4 days post-infection (dpi). However, viral loads in the pregnant group remained elevated at 7 dpi while decreased in the non-pregnant group. Consistent with viral loads, increased production of proinflammatory cytokines was detected from the pregnant group, and the IgM or SARS-CoV-2-specific IgG antibody in serum of pregnant mice featured delayed elevation compared with non-pregnant mice. Moreover, by accessing kinetics of activation marker expression of peripheral T cells after infection, a lower level of CD8[SUP]+[/SUP] T cell activation was observed in pregnant mice, further demonstrating the difference of immune-response between pregnant and non-pregnant mice. Although vertical transmission did not occur as SARS-CoV-2 RNA was absent in the uterus and fetus from the infected pregnant mice, a lower pregnancy rate was observed when the mice were infected before embryo implantation after mating, indicating that SARS-CoV-2 infection may interfere with mice's fertility at a specific time window. In summary, pregnant mice bear a weaker ability to eliminate the SARS-CoV-2 virus than non-pregnant mice, which was correlated with lower levels of antibody production and T cell activation.
Keywords: SARS-CoV-2; T cell activation; fertility; immune responses; pregnancy.