Dataset Information

Identification of serum prognostic biomarkers of severe COVID-19 using a quantitative proteomic approach

ABSTRACT: The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yayoi Kimura

PROVIDER: PXD021702 | JPOST Repository | Tue Nov 02 00:00:00 GMT 2021

REPOSITORIES: jPOST

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Dataset's files

Source:

			Action	DRS
	20200612QE_COVID_11_S_s_1.raw	Raw
	20200612QE_COVID_1_S_s_1.raw	Raw
	20200612QE_COVID_21_S_s_1.raw	Raw
	20200612QE_COVID_25_S_s_1.raw	Raw
	20200612QE_COVID_2_S_s_1.raw	Raw

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Publications

Identification of serum prognostic biomarkers of severe COVID-19 using a quantitative proteomic approach.

Kimura Yayoi Y Nakai Yusuke Y Shin Jihye J Hara Miyui M Takeda Yuriko Y Kubo Sousuke S Jeremiah Sundararaj Stanleyraj SS Ino Yoko Y Akiyama Tomoko T Moriyama Kayano K Sakai Kazuya K Saji Ryo R Nishii Mototsugu M Kitamura Hideya H Murohashi Kota K Yamamoto Kouji K Kaneko Takeshi T Takeuchi Ichiro I Hagiwara Eri E Ogura Takashi T Hasegawa Hideki H Tamura Tomohiko T Yamanaka Takeharu T Ryo Akihide A

Scientific reports 20211019 1

The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass s ...[more]

PMID: 34667241

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Project description:SARS-CoV-2 primarily affects the respiratory system but extra-pulmonary manifestations in individuals with COVID-19 are commonly seen. All major organ systems have been reported to be affected by SARS-CoV-2 and complications arising from ensuing organ dysfunction significantly increase the mortality rate of COVID-19. Yet, despite the clinical importance of systemic involvement of SARS-CoV-2, little is known about the pathogenesis of extra-pulmonary complications of COVID-19. Here, we create a murine model of SARS-CoV-2 induced severe systemic toxicity and multi- organ involvement by expressing the human ACE2 transgene in multiple tissues using an adeno associated virus (serotype 9) followed by administration of the SARS-CoV-2 virus intra-peritoneally. The animals develop a profound phenotype within 7 days of SARS-CoV-2 infection with severe weight loss, morbidity and failure to thrive, that necessitated euthanasia. We demonstrate that following a robust anti-viral immune response, there is metabolic suppression of oxidative phosphorylation and the tri- carboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia and splenic atrophy mirroring human COVID-19 phenotypes with adverse prognosis. Animals had a significantly lower heart rate and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. An organ wide metabolic reprogramming consistent with depression of oxidative phosphorylation led to utilization of peripheral fat stores and gross accumulation of fat in the heart and other vital organs. We perform metabolomic profiling of peripheral blood and identify a panel of TCA cycle metabolites that serve as biomarkers of depressed oxidative phosphorylation, several of these markers been noted in human clinical studies to be associated with adverse prognosis. Finally, we observed that SARS-CoV-2 induces epigenetic changes with a significant number of differentially methylated sites in vital organs, across the whole host cell genome, that affects expression of immune response genes and could in part contribute to dysregulated gene expression in affected tissues. Our model suggests that SARS-CoV- 2 induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.