# Genital Dysbiosis and Different Systemic Immune Responses Based on the Trimester of Pregnancy in SARS-CoV-2 Infection

## TL;DR

Pregnant women infected with SARS-CoV-2 show immune and microbiome changes, with trimester-specific effects on newborns and immune responses.

## Contribution

This study reveals trimester-specific immune and microbiome responses in pregnant women with SARS-CoV-2 infection and their newborns.

## Key findings

- Infection in the first trimester is linked to better IgG transfer to newborns and lower inflammation.
- Later infections correlate with higher levels of pro-inflammatory cytokines like IL-8 and MCP-1.
- All infected women showed genital dysbiosis, but most newborns had reassuring outcomes.

## Abstract

Respiratory infections are common in pregnancy with conflicting evidence supporting their association with neonatal congenital anomalies, especially during the first trimester. We profiled cytokine and chemokine systemic responses in 242 pregnant women and their newborns after SARS-CoV-2 infection, acquired in different trimesters. Also, we tested transplacental IgG passage and maternal vaginal–rectal microbiomes. IgG transplacental passage was evident, especially with infection acquired in the first trimester. G-CSF concentration—involved in immune cell recruitment—decreased in infected women compared to uninfected ones: a beneficial event for the reduction of inflammation but detrimental to ability to fight infections at birth. The later the infection was acquired, the higher the systemic concentration of IL-8, IP-10, and MCP-1, associated with COVID-19 disease severity. All infected women showed dysbiosis of vaginal and rectal microbiomes, compared to uninfected ones. Two newborns tested positive for SARS-CoV-2 within the first 48 h of life. Notably, their mothers had acute infection at delivery. Although respiratory infections in pregnancy are reported to affect babies’ health, with SARS-CoV-2 acquired early during gestation this risk seems low because of the maternal immune response. The observed vaginal and rectal dysbiosis could be relevant for neonatal microbiome establishment, although in our series immediate neonatal outcomes were reassuring.