Main Findings
The findings of our study indicated that the composition of vaginal
microbiota was unfavorably affected by COVID-19 disease and there was a
prominent dysbiosis during active COVID-19 infection. Intrauterine
infection is a well-established reason for preterm birth. The most
common and genuine pathway is that microorganisms can access the
amniotic cavity by ascending from the vagina and cervix, resulting in
the development of intrauterine infection and subsequent inflammatory
response in fetoplacental tissues that eventuates preterm birth16,17. Since evidence on the relation of dysbiosis in
vaginal microbiota and preterm birth is accumulating, we can speculate
that one of the mechanisms for the explanation of increased rate of
COVID-19-associated PTB may be vaginal dysbiosis5,18,19.
Vaginal dysbiosis is defined as an increase of alpha diversity in
vaginal microbiome communities 20. The study found
that the Shannon index was remarkably high (1.16) in the COVID-19 group
compared to the healthy controls (0.75). Recent studies have revealed
that vaginal dysbiosis has a negative impact on vaginal protective
mechanisms via increasing local pro-inflammatory effectors21,22.
We identified diminished Lactobacillus communities in women with
COVID-19 disease, particularly more profound in those with moderate or
severe disease (77%) when compared to the healthy controls (93%;
P=0.04). Lactobacillus delbrueckii (P=0.046) significantly
decreased among women with COVID-19. Within-subgroup analysis,Lactobacillus gasseri (L. gasseri) disappeared in patients with
moderate or severe disease. It is well-established that pregnant women
with low amounts of L. crispatus, L. gasseri, or L. jensenii in
their vaginal microbiota are more likely to deliver before term9,23. In a case-control study, the abundance ofL. gasseri was found to be associated with decreased risk of
early spontaneous preterm birth 24.
In the longitudinal study with three patients, we didn’t perform
analysis at the species level because of the small sample size. There
was approximately a 40% decline in the relative abundance of Firmicutes
and Bacteroides during the active COVID-19 period, which was sustained
after recovery. In addition, the abundance of Actinobacteria was the
highest in the active disease stage compared to the pre and post
COVID-19 periods. Ceccarani et al. revealed that the vaginal flora of
healthy women was constituted of mainly Firmicutes and Bacteroidetes,
albeit with a low abundance of Actinobacteria 25. In
view of our findings, it would be considered that SARS-CoV-2 infection
negatively affects the vaginal compositions of pregnant women.