Dataset Information

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

ABSTRACT: The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remain unclear. Here, we combine a multiomics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Oliver Popp

LAB HEAD: Philipp Mertins

PROVIDER: PXD030785 | Pride | 2022-01-17

REPOSITORIES: Pride

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			Action	DRS
	Gonzo_20200901_OP_HS_CoV_PlasmaPoolFrac_DDA_fr_01.raw	Raw
	Gonzo_20200901_OP_HS_CoV_PlasmaPoolFrac_DDA_fr_02.raw	Raw
	Gonzo_20200901_OP_HS_CoV_PlasmaPoolFrac_DDA_fr_03.raw	Raw
	Gonzo_20200901_OP_HS_CoV_PlasmaPoolFrac_DDA_fr_04.raw	Raw
	Gonzo_20200901_OP_HS_CoV_PlasmaPoolFrac_DDA_fr_05.raw	Raw

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Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection.

Pekayvaz Kami K Leunig Alexander A Kaiser Rainer R Joppich Markus M Brambs Sophia S Janjic Aleksandar A Popp Oliver O Nixdorf Daniel D Fumagalli Valeria V Schmidt Nora N Polewka Vivien V Anjum Afra A Knottenberg Viktoria V Eivers Luke L Wange Lucas E LE Gold Christoph C Kirchner Marieluise M Muenchhoff Maximilian M Hellmuth Johannes C JC Scherer Clemens C Rubio-Acero Raquel R Eser Tabea T Deák Flora F Puchinger Kerstin K Kuhl Niklas N Linder Andreas A Saar Kathrin K Tomas Lukas L Schulz Christian C Wieser Andreas A Enard Wolfgang W Kroidl Inge I Geldmacher Christof C von Bergwelt-Baildon Michael M Keppler Oliver T OT Munschauer Mathias M Iannacone Matteo M Zimmer Ralf R Mertins Philipp P Hubner Norbert N Hoelscher Michael M Massberg Steffen S Stark Konstantin K Nicolai Leo L

Nature communications 20220223 1

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airwa ...[more]

PMID: 35197461

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Project description:Pathogenic mechanisms underlying severe SARS-CoV2 infection remain largely unelucidated. High-throughput sequencing technologies that capture genome and transcriptome information are key approaches to gain detailed mechanistic insights from infected cells. These techniques readily detect both pathogen and host-derived sequences, providing a means of studying host-pathogen interactions. Recent studies have reported the presence of host-virus chimeric (HVC) RNA in RNA-seq data from SARS-CoV2 infected cells and interpreted these findings as evidence of viral integration in the human genome as a pathogenic mechanism. Since SARS-CoV2 is a positive sense RNA virus that replicates in the cytoplasm it does not have a nuclear phase in its life cycle, so it is biologically unlikely to be in a location where splicing events could result in genome integration. Here, we investigated the biological authenticity of HVC events. In contrast to true biological events, e.g. mRNA splicing and genome rearrangement events, which generate reproducible chimeric sequencing fragments across different biological isolates, we found that HVC events across >100 RNA-seq libraries from patients with COVID-19 and SARS-CoV2 infected cell lines, were highly irreproducible. RNA-seq library preparation is inherently error-prone due to random template switching during reverse transcription of RNA to cDNA. By counting chimeric events observed when constructing an RNA-seq library from human RNA and spike-in RNA from an unrelated species, such as fruit-fly, we estimated that ~1% of RNA-seq reads are artifactually chimeric. In SARS-CoV2 RNA-seq we found that the frequency of HVC events were, in fact, no more frequent than this background “noise”. Finally, we developed a novel experimental approach to enrich SARS-CoV2 sequences from bulk RNA of infected cells. This method enriched viral sequences but did not enrich for HVC events, suggesting that the majority of HVC events are, in all likelihood, artifacts of library construction. In conclusion, our findings indicate that HVC events observed in RNA-sequencing libraries from SARS-CoV2 infected cells are extremely rare and are likely artifacts arising from either random template switching of reverse-transcriptase and/or sequence alignment errors. Therefore, the observed HVC events do not support SARS-CoV2 fusion to cellular genes and/or integration into human genomes.