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.