Virus World

One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as “long COVID”) which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC–MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay.

The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.

Published in Scientific Reports (August 1, 2023):

https://doi.org/10.1038/s41598-023-39049-x 

A recent publication by a Stanford scientist, Bali Pukendran, reviews how the microbiome may play a key role in vaccines efficacy.

Multiples examples have highlighted the role of the microbiota. Earlier studies have evaluated the role of the microbiota small animal models in which  depletion of their microbiota by antibiotics or the testing with germ-free animals resulted in reduced vaccine efficacies. Other studies in human have helped understand how the microbiome influences vaccine's responses by monitoring the vaccine's  signature. The use of  artificial intelligence has been used to predict immune responses.

Immunization with influenza vaccines led to the discovery of potential  links with the microbiota.  The inactivated influenza vaccine induces expression of Toll-like-receptor 5 (TLR5), a key protein recognizing  bacterial components and triggering an innate immune response. Mice deficient in tlr5 induce poor anti-influenza antibody  responses upon vaccination. Similar results have been observed with an adjuvant-free polio vaccine, but not with vaccines containing adjuvants, suggesting that the microbiota may act as an endogenous adjuvant, and may play an even more important role when the individuals have no pre-existing immunity against the pathogen the are immunized against.

Several studies have revealed that in addition to specific gene signatures, antibiotics also lead to significant changes in the blood metabolome, including changes in bile acids that have been shown to modulate inflammatory responses in humans. Furthermore, age may increase gut permeability, exacerbating the effects of the bacterial metabolome and perhaps playing a role in the limited  vaccine efficacy observed in elderly patients.

These findings highlights the importance of avoiding antibiotic use during vaccination, especially in children, where pre-existing responses may be limited. They also highlight the importance to stratify patients in vaccine trials by their microbiomes and bacterial metabolomes, to better elucidate which patients better response to future experimental vaccines.

Published in Science (29 November , 2019):

https://doi.org/10.1126/science.aau6975