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Authors: A.E. Budding, E. Sieswerda, B.B. Wintermans, M.P. Bos

Link to paper: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3582780

Journal/ Pre-Print: Lancet, pre-print

Tags: Bioinformatics, Microbiology, Clinical

Research Highlights

1. A pharyngeal microbiota cluster identified which correlated with a two-fold reduction in SARS-COV2 positivity in comparison to other observed clusters.

2. The pharyngeal microbiota clusters identified explain age-dependent susceptibility (strongly debatable).

3. A decrease in pharyngeal microbiota diversity was observed in samples of oldest patient group (age range: 80-90).

Summary 

The study claims to have identified a specific cluster of pharyngeal microbiota species associated with low SARS-COV2 positivity that is less common in aging individuals. They go on to hypothesize their observed inverse linear relationship between this “less positive” microbe cluster and patient age explains the enhanced susceptibility to SARS-COV2 in the elderly population. However, in our opinion these claims are not justified by the data and subsequent analysis provided (see main limitations for more detailed critique).

Impact for SARS-CoV2/COVID19 research efforts

This publication aimed to understand the role of the pharyngeal microbiota in SARS-CoV2/COVID19 disease and explore if differences of composition explain variability in disease course. However, this study fails to convincingly due so and rather merely provides food for thought if this is an area worth exploring in the future.

Study Type

· In silico study/bioinformatics study

· Patient Case study

Strengths and limitations of the paper

Novelty:

One of the first studies to date exploring the pharyngeal microbiota from elderly and young adults.

Standing in the field:

The study hints to a difference in pharyngeal microbiota between SARS-COV2 negative and positive patients and age, but due to a lack of healthy controls and comparable group sizes needs further verification. It does correlate however with other studies that find an age-related gut microbiome that correlates with SARS-COV2 infection.

Appropriate statistics:

No. There is no statistical support for the identification of two patient clusters from hierarchical clustering of pharyngeal microbiomes. It is also unclear what data has been treated as parametric, and what has been treated as non-parametric.

Translatability:

Larger and better controlled studies needed to ensure diagnostic or therapeutic strategies.

Main limitations:

· The microbiome IS-pro technique used to identify microbes was initially designed to detect gut microbiota with little to no information on how well this assay performs on pharyngeal samples, in particular concerning on claims of species level detection.

· The cluster apparently identified can be poorly visually distinguished from other clusters (possibly due to figure design) and as a reader it is not comprehensible why exactly this cluster was selected.

· It is also noted that this cluster was only seen when considering Firmicutes, Actinobacteria and Proteobacteria.

· It is not evident how they control for the gross differences in sample distribution within age groups when performing analysis.

· Overall sample size numbers are small which lead to the inability of sub clustering or detailed species analysis.

· There is no information on clinical data (in particular of antibiotic use, co-morbidities or detailed symptoms, outcomes), thus clustering observed could be due to many different unexplored factors.

· Even though investigating the differences within patients that all have SARS-COV2 symptoms but are only in part positive is interesting considering an inflammation driven microbiome, healthy age-matched controls are missing and vital in claiming an importance for the pharyngeal microbiota in disease.