Backgrounds:

Immunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability and efficacy.

Methods

To investigate the safety and the immunogenicity profiles of BNT162b2 mRNA COVID-19 vaccine among people living with HIV, we enrolled 28 HIV-infected patients under ART and 65 healthy controls (HCs) with no previous history of COVID-19. Immunogenicity was evaluated by measuring anti-RBD and anti-trimeric Abs, along with the frequency of SARS-CoV-2 specific CD4+CD40L+T cells. Samples were collected before vaccination (baseline, D0), at the second dose (D21), at 4 weeks (D28) and 6 months (D180) after the first dose. T and B cell phenotypes were investigated. Proteomic profiles at D0 and D28 were assessed with a Proximity Extension Assay (Olink) on plasma samples.

Results:

All vaccinated HIV-infected patients mounted anti-SARS-CoV-2 humoral responses between D21 and D28 similarly to HCs, albeit lower titers of anti-trimeric S Abs were detected at D28 compared to HC (p=0.0098). Only PBMCs of HIV+ demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T populations. At 6 months, follow-up HIV+ showed similar maintenance of anti-SARS-CoV-2 Abs to HC. To explore whether these immunogenicity results could be linked to a particular proteomic outline, we correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the two study groups.

Conclusions/Learning Points:

Responses of ART-treated HIV+ compared to HC, characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose scheduled at 6 months, similarly to HC.

Backgrounds:

The effect of SARS-CoV-2 on altering the gut microbiome have been investigated since the beginning of the pandemic. To our knowledge, this is the first observational cohort study on the correlations between gut microbiota (GM) and COVID-19 infection in children.

Methods

The GM profile was investigated by 16S rRNA targeted-metagenomics to analyze ecology and inferred functions of COVID-19 patients compared to healthy subjects (CTRLs). Multiple machine learning (ML) models were exploited. Correlation between ASVs abundances and inflammatory protein levels was investigated using R software.

Results:

The GM in COVID-19 patients (N=67) was characterized by reduction of alfa-diversity compared to CTRLs (p <0.05). In the GM of COVID-19 children an increase of Faecalibacterium, Fusobacterium, Neisseria and decrease of Bifidobacterium, Blautia, Ruminococcus, Collinsella, Coprococcus, Eggerthella, Akkermansia were reported, compared to CTRLs (FDR<0.05). ML models for GM biomarker prediction in COVID-19 patients, compared to CTRLs, identified: Actinomyces, Alistipes, Faecalibacterium, Anaerostipes, Phascolarctobacterium, Dorea, Clostridium, Prevotella, Oscillospira, Staphylococcus, Rominococcus.

The KO-based prediction of GM functional profile of COVID-19, compared to CTRLs, highlighted lipopolysaccharide and peptidoglycan biosynthesis, amino acids biosynthesis, alanine, aspartate and glutamate metabolism specifically associated to COVID-19 patients; while PPAR signaling pathway; ether lipid metabolism; fatty acid degradation; valine, leucine and isoleucine degradation to CTRLs subjects.

A statistically significant positive correlation between Bacteroidetes and pro-inflammatory cytokines (e.g., ITGA11, CLECA4 and DNER) was observed.

Conclusions/Learning Points:

Our study provides a specific characterization of the GM of pediatric COVID-19. Unlike adult, high levels of Faecalibacterium were reported as a specific treat of the COVID-19 in children. GM profile and intrinsic GM anti-inflammatory and fermentative properties may play a central role in the low severity of COVID-19 in children.