Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants

Abstract

Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). Gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.

Keywords: HIV; SARS-CoV-2; bacterial microbiome; gut; longitudinal; mothers and infants; virome.

Figure 1.

Kenyan women living with HIV (WLHIV), hiv-negative women, and infants.

Figure 2.

Mother–infant beta diversity over time.

Figure 3.

Stool samples community states, relative abundance, and differential analysis of bacterial microbiome and virome. (a) Relative abundance of bacteria at species level, clustered using k-means on weighted Bray–Curtis distances. Plot labeled with community state groups. Statistical significance assessed by multinominal logit models and p-value adjusted for multiple comparison. Significant comparisons represented by color. Multinomial analyses determined if specific bacterial community states were associated with maternal HIV status, mothers versus infants, SARS-CoV-2 status, antibiotic use, postpartum time, or time since weaning. (b) Relative abundance of viruses at family level. Plots are separated by infant or maternal samples and ordered by increasing month of life or post-partum time. (c) MaAslin2Aslin2 assigned differential bacteria for mother and infant samples. (d) MaAslin2Aslin2 assigned differential viral contigs by month of life for infants.

Figure 4.

Trajectory change in microbiome and virome after SARS-CoV-2 infection in women and infants. (a) Linear regression plot of maternal bacterial alpha diversities against post-partum time. Colors represent infection status at time of sample collection. Statistical significance of interaction between post-partum time and SARS-CoV-2 assessed by linear mixed effect model. (b) Linear regression plot of SARS-CoV-2 seropositive (same for below) women’s bacterial alpha diversity by time since SARS-CoV-2. Colors represent seropositivity (same for below) status at sample collection. Statistical significance assessed by linear mixed effect model. Statistical significance of interaction between time since SARS-CoV-2 and SARS-CoV-2 positivity assessed by linear mixed effect model. (c) Bacterial weighted Bray-Curtis PCoA of women by SARS-CoV-2 infection status. Colors represent infection status at time of sample collection. Statistical significance assessed by PERMANOVA. (d) Linear regression plot of infant bacterial alpha diversities against month of life. Colors represent infection status at time of sample collection. Statistical significance of interaction between month of life and SARS-CoV-2 assessed by linear mixed effect model. (e) Bacterial weighted Bray-Curtis PCoA of infants by SARS-CoV-2 infection status. Colors represent infection status at time of sample collection. Statistical significance assessed by PERMANOVA. (f) Linear regression plot of maternal viral alpha diversities against post-partum time. Colors represent infection status at time of sample collection. Statistical significance of interaction between post-partum time and SARS-CoV-2 assessed by linear mixed effect model. (g) Viral weighted Bray–Curtis PCoA of women by SARS-CoV-2 infection status. Colors represent infection status at time of sample collection. Statistical significance assessed by PERMANOVA. (h) Linear regression plot of SARS-CoV-2 infected women viral alpha diversity by time since SARS-CoV-2. Colors represent infection status at sample collection. Statistical significance assessed by linear mixed effect model. Statistical significance of interaction between time since SARS-CoV-2 and SARS-CoV-2 positivity assessed by linear mixed effect model. (i) Linear regression plot of infant viral alpha diversities against month of life. Colors represent infection status at time of sample collection. Statistical significance assessed by linear mixed effect model. Statistical significance of interaction between month of life and SARS-CoV-2 assessed by linear mixed effect model. (j) Viral weighted Bray–Curtis PCoA of infants by SARS-CoV-2 infection status. Colors represent infection status at time of sample collection. Statistical significance assessed by PERMANOVA.

Figure 5.

Change in microbiome and virome at first SARS-CoV-2 positive infection visit sample in women and infants against all SARS-CoV-2 negative visit samples.