Pregnant patients with SARS-CoV-2 infection early in pregnancy and with active infection exhibit an altered vaginal and oral microbiota that is passed on to infants

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Nov 7 2022

In a recent study posted to the medRxiv* preprint server, researchers investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during pregnancy (in the initial or late stages) or an active infection at delivery could alter the oral, intestinal, and vaginal microbiome and whether infantile microbiomes are correspondingly altered.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

About the study

In the present study, researchers assessed the oral, intestinal and vaginal microbiota alterations due to coronavirus disease 2019 (COVID-19) in pregnancy and whether the microbial changes vertically transferred to infants.

The study comprised 99 SARS-CoV-2-positive pregnant women (SP) and 38 healthy pregnant women (controls), respectively. SP microbial diversity was comparatively evaluated with that of controls, based on the pregnancy trimester during which COVID-19 was diagnosed, i.e., early (first and second trimesters), late (third trimester), and active (during delivery). Samples were obtained from expecting females during admissions for delivery.

The team performed RFC (random forest classification) analysis and assessments of Alpha diversity and Beta diversity inclusive of probable confounders such as antibiotic usage, race, mothers’ age, gestational diabetes, and pre-pregnancy body mass index (BMI). Stool samples were obtained from 46 and 23 SP and controls, respectively, one to two days post-partum, and RFC was applied for selecting COVID-19 estimation variables.

To assess the vaginal microbiome, 43 and 21 SP and controls, respectively, were sampled. The team also investigated whether the timing of COVID-19 during pregnancy influenced the vaginal microbiome composition. Infants were stratified based on delivery modes, and the anti-SARS-CoV-2 nucleocapsid (NP) protein immunoglobulin G (IgG) titers in cord blood were measured to determine maternal antibodies’ presence in infant blood. Further, fecal calprotectin (FCP) levels in infant stool samples were measured, and the association between FCP levels and taxa abundance was explored.

Results

The oral, intestinal, and vaginal SP microbial diversity was lowered, and women with early COVID-19 showed altered vaginal microbiomes and Streptococcus-dominated oral microbiomes compared to controls at delivery. COVID-19 during pregnancy was associated with lesser intestinal microbial richness, irrespective of the infection timing.

COVID-19 was estimated by a higher Dialister abundance and lower abundance of Phascolarctobacterium faecium, Anaerostipes, Prevotella buccalis, Porphyromonas uenonis, and Bacteroides. SPs showed lower vaginal microbial richness and higher inter-individual vaginal microbiome variability than controls, which was the least among those with early COVID-19.

The microbial composition among SPs differed from controls, and the compositional alterations were largely based on rare microbial taxa. Antibiotic use significantly impacted vaginal microbiome diversity among SPs. Among vaginal samples, COVID-19 was estimated by a greater Varibaculum abundance and lesser amounts of Anaerococcus sp., P. bennonis, P. buccalis, Peptoniphilus sp., D. invisus, B. longum, Arcanobacterium, P. acnes, S. agalactiae.

During the early gestation period, COVID-19 was estimated by a greater proportion of L. iners, Streptococcus and C. ureolyticus, and a lower proportion of P. Finegoldia, P. grossensis, P. bennonis, Dialister, P. timonensis and P. buccalis. Among SPs, active COVID-19 was estimated by a greater proportion of P. bivia, Varibaculum, and A.muciniphila, and a lesser proportion of P. grossensis, Finegoldia, P. bennonis and V. dispar.

The oral microbiome of SPs was estimated by a greater proportion of Prevotella species oral taxon 308 with a lower proportion of H. parainfluenzae, Campylobacter, F. nucleatum, and P. pleuritidis. Active COVID-19 was estimated by a greater proportion of H. parainfluenzae, P. melaninogenica, P. nanceiensis, and B. ovatus, and a lesser proportion of Veillonella parvula.

There were no significant associations between COVID-19 during gestation and Alpha or Beta diversity in the intestinal microbiomes of the infants overall. However,the intestinal microbiome of SP-borne infants was estimated by a higher and lower abundance of Enterococcus and Haemophilus parainfluenzae, respectively. Pre-pregnant BMI showed a negative association with the Alpha diversity proportion among the samples.

Infants born to SPs with active COVID-19 showed slightly higher FCP levels than the control-borne infants. Several taxa in active COVID-19 were associated positively with FCP, and SP-borne infants showed a significantly different bacterial composition than the control-borne ones. SP-borne infants were estimated by a greater proportion of Prevotella timonensis and a lesser proportion of Lactobacillus jensenii and Streptococcus. The team found significantly greater IgG titers in cord blood from expecting women with early and late COVID-19 compared to controls.

Conclusion

Overall, the study findings showed that COVID-19 during pregnancy, especially in the first and second pregnancy trimesters, was associated with long-term microbiome alterations among expecting women compromising the initial microbiome of their infants.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.