SARS-CoV2 Infection During Pregnancy Causes Persistent Immune Abnormalities in Women Without Affecting the Newborns

Abstract

SARS-CoV2 infection in pregnancy and exposed newborns is poorly known. We performed a longitudinal analysis of immune system and determined soluble cytokine levels in pregnant women infected with SARS-CoV2 and in their newborns. Women with confirmed SARS-CoV2 infection and their exposed uninfected newborns were recruited from Hospital General Universitario Gregorio Marañón. Peripheral blood mononuclear cells (PBMCs), cord cells and plasma were collected at birth and 6 months later. Immunophenotyping of natural killer (NK), monocytes and CD4/CD8 T-cells were studied in cryopreserved PBMCs and cord cells by multiparametric flow cytometry. Up to 4 soluble pro/anti-inflammatory cytokines were assessed in plasma/cord plasma by ELISA assay. SARS-CoV2-infected mothers and their newborns were compared to matched healthy non-SARS-CoV2-infected mothers and their newborns. The TNFα and IL-10 levels of infected mothers were higher at baseline than those of healthy controls. Infected mothers showed increased NK cells activation and reduced expression of maturation markers that reverted after 6 months. They also had high levels of Central Memory and low Effector Memory CD4-T cell subsets. Additionally, the increased CD4- and CD8-T cell activation (CD154 and CD38) and exhaustion (TIM3/TIGIT) levels at baseline compared to controls remained elevated after 6 months. Regarding Treg cells, the levels were lower at infected mothers at baseline but reverted after 6 months. No newborn was infected at birth. The lower levels of monocytes, NK and CD4-T cells observed at SARS-CoV2-exposed newborns compared to unexposed controls significantly increased 6 months later. In conclusion, SARS-CoV2 infection during pregnancy shows differences in immunological components that could lead newborns to future clinical implications after birth. However, SARS-CoV2 exposed 6-months-old newborns showed no immune misbalance, whereas the infected mothers maintain increased activation and exhaustion levels in T-cells after 6 months.

IgG antispike persistence and immunophenotype in children infected by SARS‐CoV‐2

“…To obtain a complete view of the immune status after SARS‐CoV‐2 infection, we analysed the immunophenotype. Lymphocytopenia, which predominantly affects CD8 + cells, has been described following SARS‐CoV‐2 infection in children and adults 1,3,14,15 . This may be related to the higher risk of infection as a type of temporal immunodepression 16,17 .…”

“…Lymphocytopenia, which predominantly affects CD8 + cells, has been described following SARS-CoV-2 infection in children and adults. 1,3,14,15 This may be related to the higher risk of infection as a type of temporal immunodepression. 16,17 It has also been linked to the persistence of symptoms after a primary infection (long COVID syndrome).…”

COVID-19 in Pregnant Women, Maternal—Fetal Involvement, and Vertical Mother-to-Child Transmission: A Systematic Review

“…After delivery, the placenta was studied independently and interesting results were obtained, as there were findings of altered coagulation factors in the premature rupture of the placenta, a question related to the alteration in coagulation produced by COVID-19 [ 12 , 34 , 36 ].…”

“…Those problems that affect the respiratory system are viral pneumonia in the first place, requiring urgent admission to the intensive care unit, in addition to the fact that in pregnancy there is a 20% increase in the demand for oxygen and at the same time the residual capacity decreases [ 24 ]. This respiratory insufficiency can lead to an interruption of the placental flow and cause a miscarriage [ 34 , 36 ]. This problem not only affects the mother, but can also have an impact on the fetus, causing serious complications in its development and nervous system, as seems to be the pattern in adults [ 29 , 39 , 41 ].…”

Examination of cord blood at birth in women with SARS-CoV-2 exposure and/or vaccination during pregnancy and relationship to fetal complete blood count, cortisol, ferritin, vitamin D, and CRP

“…Current maternal-fetal research into SARS-CoV-2 (COVID-19) disease has centered upon the presence or absence of vertical disease transmission and passive transfer of maternal IgG in both naturally infected and vaccinated mothers ( 1 ). Vertical transmission of COVID-19 has been found to be rare ( 1 , 2 ). This is thought to be related to the significantly low number of ACE2 viral binding receptors in the placenta ( 1 , 3 ).…”