Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

Huang et al.

https://www.medrxiv.org/content/10.1101/2020.03.15.20033472v1 (posted on 17/3/2020)

SUMMARY

Using single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with ongoing or recovered COVID-19 infection, and healthy controls, this study found that genes involved in the type I interferon response and MAPK signalling are upregulated during an ongoing infection. Interestingly, COVID-19-recovered patients had significantly decreased MAPK-pathway gene expression compared to healthy controls which might reflect disease-specific health effects of COVID-19. The TCR and BCR repertoire was also sequenced at a single cell level. They found 2 highly expressed BCRs from 2 patients and 4 patients with closely related TCRs, suggesting COVID-19 specificity. Further work is needed to validate their specificity.

RESEARCH HIGHLIGHTS

1. PBMCs from COVID-19-infected patients upregulate the type I interferon response
2. COVID-19-recovered patients have significantly decreased MAPK-pathway gene expression compared to healthy controls
3. Closely related TCR clones were found in 4 patients, indicating these possibly recognize SARS-CoV-2.
4. High frequency BCR clones were found in 2 patients, indicating these possibly recognize SARS-CoV-2.

RESEARCH IMPACT

No immediate impact for the clinic. They may have found SARS-CoV-2-reactive antibody clones but this has to be confirmed in functional experiments.

METHODOLOGY

Single cell mRNA sequencing

Single cell TCR & BCR V(D)J sequencing

RT-PCR of mixed PBMC

STRENGTHS AND WEAKNESSES OF THE PAPER

Strengths:

• Single cell RNAseq as well as single cell TCR & BCR profiling of 10 Covid-19 patients was performed, which could be useful for further analysis once data is available
• Potentially interesting effect of MAPK downregulation in patients recovered from COVID-19, needs further investigation

Weaknesses:

• Data is not (yet) analysed nor interpreted to its full potential. The data is not yet publicly available.
• Important QC parameters for the scRNAseq are not reported and figures are hardly readable, making it difficult to judge the rigour of data acquisition and analysis.
• Statistical analysis was only used to compare patients vs. controls, not to compare e.g. severe to moderate patients.
• The seq results were not appropriately confirmed by other methods, making it very difficult to translate findings to the clinic.
• Some samples are skipped without obvious explanation (e.g. Fig.2E Compares pathways enriched in moderate patients (3-6) to healthy controls, but this excludes moderate patients 7,8,9, and there is no patient no.6 according to TS1)
• 1 influenza A patient is not enough to conclude that there is meaningful difference between the response to COVID-19 and Influenza A.