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pmid:33693030

Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection.

Elettra Barberis · Virginia V Vanella · Marco Falasca · Valeria Caneapero · Giuseppe Cappellano · Davide Raineri · Marco Ghirimoldi · Veronica De Giorgis · Chiara Puricelli · Rosanna Vaschetto · Pier Paolo Sainaghi · Stefania Bruno · Antonio Sica · Umberto Dianzani · Roberta Rolla · Annalisa Chiocchetti · Vincenzo Cantaluppi · Gianluca Baldanzi · Emilio Marengo · Marcello Manfredi

Frontiers in molecular biosciences · 2021 doi:10.3389/fmolb.2021.632290

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complete

Experiment

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Data

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Analysis

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pmid:33693030
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2026-11-01T15:41:28Z
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2026-11-01T21:24:51Z
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paper object · 10 fields
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title
Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection.
doi
10.3389/fmolb.2021.632290
pmid
33693030
authors array · 20 items
[0]
Elettra Barberis
[1]
Virginia V Vanella
[2]
Marco Falasca
[3]
Valeria Caneapero
[4]
Giuseppe Cappellano
[5]
Davide Raineri
[6]
Marco Ghirimoldi
[7]
Veronica De Giorgis
[8]
Chiara Puricelli
[9]
Rosanna Vaschetto
[10]
Pier Paolo Sainaghi
[11]
Stefania Bruno
[12]
Antonio Sica
[13]
Umberto Dianzani
[14]
Roberta Rolla
[15]
Annalisa Chiocchetti
[16]
Vincenzo Cantaluppi
[17]
Gianluca Baldanzi
[18]
Emilio Marengo
[19]
Marcello Manfredi
journal
Frontiers in molecular biosciences
year
2021
abstract
Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes' response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes' involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19-associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers-such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component-were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes' significant contribution to several processes-such as inflammation, coagulation, and immunomodulation-during SARS-CoV-2 infection. The study's data are available via ProteomeXchange with the identifier PXD021144.
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Spearman correlations were performed, and only correlations with p < 0.05 were considered and shown in Supplementary Table S5–S9.
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sections[9] "2.7 Association of Exosome Cargo with Pathologically Relevant Clinical Indices" paragraph 2
quote
Spearman correlations were performed, and only correlations with p < 0.05 were considered and shown in Supplementary Table S5–S9.
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The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.
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sections[21] "Data Availability Statement" paragraph 2
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The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.
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The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.
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Mapping the Host Circulating Exosome Response to SARS-CoV-2
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Comparison of modulated exosomal proteins with regulated serum proteins in COVID-19 patients reported in literature. Protein modulation (Up or Down) is indicated.
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2.8 Circulating Exosomes are Potential Biomarkers of COVID-19
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TABLE 1
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Comparison of modulated exosomal proteins with regulated serum proteins in COVID-19 patients reported in literature. Protein modulation (Up or Down) is indicated.
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[1]
Plasma-exosome
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[2]
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−
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APOH
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[2]
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[3]
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[4]
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[5]
−
[10] array · 6 items
[0]
C1R
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[2]
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[3]
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[4]
−
[5]
Up
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C1S
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−
[2]
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[3]
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[4]
−
[5]
Up
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C4BPA
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[4]
Up
[5]
−
[13] array · 6 items
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C9
[1]
Up
[2]
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[3]
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[4]
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[5]
−
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CLEC3B
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−
[2]
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−
[5]
−
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Up
[2]
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[3]
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[4]
−
[5]
Up
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CST3
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−
[2]
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−
[5]
−
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[2]
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[3]
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[4]
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[5]
−
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[1]
Up
[2]
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[3]
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[4]
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[1]
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[4]
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[2]
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[4]
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Down
[2]
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[3]
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[4]
−
[5]
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FN1
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[2]
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[3]
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[4]
−
[5]
−
[23] array · 6 items
[0]
GSN
[1]
Down
[2]
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[3]
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[4]
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[5]
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HP
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Up
[2]
−
[3]
−
[4]
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[5]
Up
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IGHV1-2
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Down
[2]
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[3]
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[4]
−
[5]
−
[26] array · 6 items
[0]
IGHV3-15
[1]
−
[2]
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[3]
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[4]
−
[5]
−
[27] array · 6 items
[0]
IGHV3–23
[1]
Down
[2]
Down
[3]
Up
[4]
−
[5]
−
[28] array · 6 items
[0]
IGHV3–9
[1]
Down
[2]
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[3]
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[4]
−
[5]
−
[29] array · 6 items
[0]
IGHV4–28
[1]
−
[2]
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[3]
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[4]
−
[5]
−
[30] array · 6 items
[0]
IGHV4–38–2
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[2]
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[3]
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[4]
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[5]
−
[31] array · 6 items
[0]
IGKV1–5
[1]
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[2]
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[3]
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[4]
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[5]
−
[32] array · 6 items
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IGKV4–1
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[3]
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[5]
−
[33] array · 6 items
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ITIH1
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−
[2]
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[3]
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−
[5]
−
[34] array · 6 items
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ITIH2
[1]
−
[2]
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[3]
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[5]
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ITIH3
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[3]
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Up
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ITIH4
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[3]
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LYZ
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Up
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[5]
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section[10]/table-wrap[1]#T1
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Characteristics of the patients included in the discovery phase study.
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4.1 Patients
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TABLE 2
caption
Characteristics of the patients included in the discovery phase study.
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[0] array · 3 items
[0]
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[1]
Non-COVID-19 patients
[2]
COVID-19 patients
[1] array · 4 items
[0]
Healthy Control (N=7)
[1]
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[2]
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[0]
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[0]
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[3]
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9
[3]
5
[4]
4
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[0]
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[1]
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[2]
64.3 ± 16.5
[3]
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[4]
58.7 ± 8.8
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[0]
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[2]
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[3]
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[4]
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[0]
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[1]
[2]
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[3]
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[4]
3.6 ± 3.5
[10] array · 5 items
[0]
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[1]
[2]
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[3]
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[4]
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[0]
Time from admission to severe (days)
[12] array · 5 items
[0]
Mean ± SD
[1]
[2]
[3]
[4]
3.8 ± 2.9
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[0]
Range
[1]
[2]
[3]
[4]
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[0]
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[0]
Fever
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[2]
8
[3]
4
[4]
4
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[2]
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[3]
5
[4]
2
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[2]
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[3]
0
[4]
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[0]
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[2]
1
[3]
1
[4]
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[19] array · 5 items
[0]
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3
[3]
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[4]
1
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2
[3]
1
[4]
1
[21] array · 5 items
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1
[4]
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1
[3]
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[4]
1
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[2]
1
[3]
1
[4]
0
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[0]
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[0]
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[2]
4
[3]
1
[4]
3
[26] array · 5 items
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Diabetes
[1]
[2]
6
[3]
2
[4]
4
[27] array · 5 items
[0]
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[2]
9
[3]
6
[4]
3
[28] array · 5 items
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Cardiovascular system
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[2]
6
[3]
3
[4]
3
[29] array · 5 items
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Other endocrine system
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[2]
2
[3]
0
[4]
2
[30] array · 5 items
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Chronic kidney
[1]
[2]
3
[3]
0
[4]
3
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[2]
4
[3]
1
[4]
3
[32] array · 1 item
[0]
Oxygen saturation index (%)
[33] array · 5 items
[0]
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[1]
[2]
93.4 ± 7.1
[3]
94.3 ± 4.4
[4]
92.1 ± 10.5
[34] array · 5 items
[0]
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[1]
[2]
71.0 − 99.0
[3]
86.0 − 99.0
[4]
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note
Characteristics of the patients included in the validation phase study.
structure object · 5 fields
pmcid
PMC7937875
section_index
13
section_title
4.1 Patients
row_count
33
column_count
9
table object · 8 fields
label
TABLE 3
caption
Characteristics of the patients included in the validation phase study.
rows array · 33 items
[0] array · 3 items
[0]
Variables
[1]
COVID-19
[2]
Non-COVID-19
[1] array · 9 items
[0]
Sex–no.
[1]
Total (N=36)
[2]
Non-Critical (N=23)
[3]
Critical (N=13)
[4]
Total (N=29)
[5]
Non-Critical (N=8)
[6]
Critical (N=6)
[7]
Healthy Control (N=8)
[8]
Healed (N=7)
[2] array · 9 items
[0]
Male
[1]
21
[2]
13
[3]
8
[4]
12
[5]
5
[6]
3
[7]
2
[8]
2
[3] array · 9 items
[0]
Female
[1]
15
[2]
10
[3]
5
[4]
17
[5]
3
[6]
3
[7]
6
[8]
5
[4] array · 1 item
[0]
Age-year
[5] array · 9 items
[0]
Mean ± SD
[1]
65.6 ±17.6
[2]
66.5 ± 20.6
[3]
53.8 ± 10.7
[4]
60.4 ± 17.0
[5]
76 ± 12.9
[6]
68.6 ± 8.9
[7]
50.4 ± 5.4
[8]
46.8 ± 17.6
[6] array · 9 items
[0]
Range
[1]
35.0 − 101.0
[2]
35.0 − 101.0
[3]
49.0 − 84.0
[4]
30.0 − 96.0
[5]
59.0 − 96.0
[6]
56.0 − 82.0
[7]
43.0 − 56.0
[8]
30.0 − 72.0
[7] array · 1 item
[0]
Time from Onset to Admission, Days
[8] array · 9 items
[0]
Mean ± SD
[1]
4.3 ± 4.5
[2]
4.5 ± 5.0
[3]
4 ± 3.6
[4]
4.8 ± 6.1
[5]
5.7 ± 7.0
[6]
1.0 ± 0.0
[7]
[8]
[9] array · 9 items
[0]
Range
[1]
1.0 − 19.0
[2]
1.0 − 19.0
[3]
1.0 − 10.0
[4]
1.0 − 21.0
[5]
1.0 − 21.0
[6]
1.0 − 1.0
[7]
[8]
[10] array · 1 item
[0]
Time from Admission to Severe, Days
[11] array · 9 items
[0]
Mean ± SD
[1]
[2]
[3]
3.1 ± 2.8
[4]
[5]
[6]
3.0 ± 4.9
[7]
[8]
[12] array · 9 items
[0]
Range
[1]
[2]
[3]
1.0 − 8.0
[4]
[5]
[6]
1.0 − 13.0
[7]
[8]
[13] array · 1 item
[0]
Symptoms–no.
[14] array · 9 items
[0]
Fever
[1]
18
[2]
11
[3]
7
[4]
3
[5]
1
[6]
2
[7]
[8]
[15] array · 9 items
[0]
Cough
[1]
16
[2]
11
[3]
5
[4]
3
[5]
0
[6]
3
[7]
[8]
[16] array · 9 items
[0]
Headache
[1]
0
[2]
0
[3]
0
[4]
2
[5]
0
[6]
2
[7]
[8]
[17] array · 9 items
[0]
fatigue
[1]
3
[2]
2
[3]
1
[4]
3
[5]
0
[6]
3
[7]
[8]
[18] array · 9 items
[0]
Dyspnea
[1]
8
[2]
6
[3]
2
[4]
5
[5]
1
[6]
4
[7]
[8]
[19] array · 9 items
[0]
Diarrhea
[1]
4
[2]
2
[3]
2
[4]
0
[5]
0
[6]
0
[7]
[8]
[20] array · 9 items
[0]
Chest pain
[1]
1
[2]
1
[3]
0
[4]
2
[5]
0
[6]
2
[7]
[8]
[21] array · 9 items
[0]
Abdomial Pain
[1]
2
[2]
1
[3]
1
[4]
0
[5]
0
[6]
0
[7]
[8]
[22] array · 9 items
[0]
vomit
[1]
1
[2]
1
[3]
0
[4]
1
[5]
1
[6]
0
[7]
[8]
[23] array · 1 item
[0]
Comorbility–no.
[24] array · 9 items
[0]
Hypertension
[1]
10
[2]
5
[3]
5
[4]
6
[5]
4
[6]
2
[7]
[8]
[25] array · 9 items
[0]
Diabetes
[1]
8
[2]
4
[3]
4
[4]
1
[5]
0
[6]
1
[7]
[8]
[26] array · 9 items
[0]
Respiratory system
[1]
4
[2]
2
[3]
2
[4]
1
[5]
1
[6]
0
[7]
[8]
[27] array · 9 items
[0]
Cardiovascolar system
[1]
16
[2]
8
[3]
8
[4]
1
[5]
0
[6]
1
[7]
[8]
[28] array · 9 items
[0]
Other Endocrine system
[1]
1
[2]
0
[3]
1
[4]
8
[5]
8
[6]
0
[7]
[8]
[29] array · 9 items
[0]
Chronic Kidney
[1]
3
[2]
1
[3]
2
[4]
1
[5]
1
[6]
0
[7]
[8]
[30] array · 1 item
[0]
Oxygen saturation index–%
[31] array · 9 items
[0]
Mean ± SD
[1]
91.3 ± 7.4
[2]
93.3 ± 5.2
[3]
97.4 ± 9.6
[4]
92.1 ± 5.6
[5]
94.0 ± 4.1
[6]
85.5 ± 6.4
[7]
[8]
[32] array · 9 items
[0]
Range
[1]
71.0 − 99.0
[2]
81.0 − 99.0
[3]
71.0 − 98.0
[4]
81.0 − 99.0
[5]
87.0 − 99.0
[6]
81.0 − 90.0
[7]
[8]
locator
section[13]/table-wrap[2]#T3
gaps array · 2 items
[0]
asset:data:geo:PXD021144 not downloaded
[1]
asset:data:geo:PXD021144 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
family
principal_component_analysis
specific
pca
label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
Principal component analysis
[1] object · 10 fields
id
method-2
family
clustering
specific
hierarchical
label
Clustering
dsl_operations array · 1 item
[0]
hierarchical_cluster
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
feature_matrix
evidence object · 3 fields
score
0.8
band
high
quote
dendrogram
[2] object · 10 fields
id
method-3
family
null
specific
null
label
Spearman correlations
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
Spearman correlations were performed, and only correlations with p < 0.05 were considered and shown in Supplementary Table S5–S9.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
PXD021144
resolved_accessions array · 1 item
[0]
PXD021144
statements array · 1 item
[0]
The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.
basis
The paper names PXD021144 in ProteomeXchange and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
pca_fit
assets array · 5 items
[0]
source:pmid:33693030
[1]
data:geo:PXD021144
[2]
asset:table:pmid:33693030:1
[3]
asset:table:pmid:33693030:2
[4]
asset:table:pmid:33693030:3
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:PXD021144
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:27:47Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
40884
completion_tokens
963
cached_tokens
520
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:33693030
type
paper
label
pmid:33693030
[1] object · 3 fields
id
source:pmid:33693030
type
manuscript
label
PMID 33693030 full text
[2] object · 3 fields
id
data:geo:PXD021144
type
dataset
label
GEO PXD021144
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:33693030
type
paper
label
pmid:33693030
[1] object · 3 fields
id
source:pmid:33693030
type
manuscript
label
PMID 33693030 full text
[2] object · 3 fields
id
data:geo:PXD021144
type
dataset
label
GEO PXD021144
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-33693030
type
extraction
used array · 1 item
[0]
source:pmid:33693030
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-PXD021144
type
accession_resolution
used array · 1 item
[0]
data:geo:PXD021144
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:33693030
parent_hash
sha256:2d44f4f62605c81240c4bc08ed4c887f7c50b64a3a075b0a27aa5d709bd4e6f8
fork_of
null
gaps array · 7 items
[0]
asset:data:geo:PXD021144 licence not read
[1]
asset:data:geo:PXD021144 not downloaded
[2]
execution.not_run
[3]
method.reader_named_unmapped
[4]
review.human_critique
[5]
review.independent_reader
[6]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
western_blot
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
d to several control analyses. Nanosight and Western blotting were employed to characterize the quality of
order_basis
paper_text_order:2989
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
principal_component_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
pca_fit
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Principal component analysis
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33693030", "kind": "science-record", "revision": 6, "content_hash": "sha256:d848b62f07f42de779d04245641c467013a5f993deda3d66f7ac289f81d3c9c5", "created_at": "2026-11-01T15:41:28Z", "updated_at": "2026-11-01T21:24:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Circulating Exosomes Are Strongly Involved in SARS-CoV-2 Infection.", "doi": "10.3389/fmolb.2021.632290", "pmid": "33693030", "authors": ["Elettra Barberis", "Virginia V Vanella", "Marco Falasca", "Valeria Caneapero", "Giuseppe Cappellano", "Davide Raineri", "Marco Ghirimoldi", "Veronica De Giorgis", "Chiara Puricelli", "Rosanna Vaschetto", "Pier Paolo Sainaghi", "Stefania Bruno", "Antonio Sica", "Umberto Dianzani", "Roberta Rolla", "Annalisa Chiocchetti", "Vincenzo Cantaluppi", "Gianluca Baldanzi", "Emilio Marengo", "Marcello Manfredi"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Knowledge of the host response to the novel coronavirus SARS-CoV-2 remains limited, hindering the understanding of COVID-19 pathogenesis and the development of therapeutic strategies. During the course of a viral infection, host cells release exosomes and other extracellular vesicles carrying viral and host components that can modulate the immune response. The present study used a shotgun proteomic approach to map the host circulating exosomes' response to SARS-CoV-2 infection. We investigated how SARS-CoV-2 infection modulates exosome content, exosomes' involvement in disease progression, and the potential use of plasma exosomes as biomarkers of disease severity. A proteomic analysis of patient-derived exosomes identified several molecules involved in the immune response, inflammation, and activation of the coagulation and complement pathways, which are the main mechanisms of COVID-19-associated tissue damage and multiple organ dysfunctions. In addition, several potential biomarkers-such as fibrinogen, fibronectin, complement C1r subcomponent and serum amyloid P-component-were shown to have a diagnostic feature presenting an area under the curve (AUC) of almost 1. Proteins correlating with disease severity were also detected. Moreover, for the first time, we identified the presence of SARS-CoV-2 RNA in the exosomal cargo, which suggests that the virus might use the endocytosis route to spread infection. Our findings indicate circulating exosomes' significant contribution to several processes-such as inflammation, coagulation, and immunomodulation-during SARS-CoV-2 infection. The study's data are available via ProteomeXchange with the identifier PXD021144.", "claims": [{"id": "claim-method", "statement": "Spearman correlations were performed, and only correlations with p < 0.05 were considered and shown in Supplementary Table S5–S9.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33693030", "locator": "sections[9] \"2.7 Association of Exosome Cargo with Pathologically Relevant Clinical Indices\" paragraph 2", "quote": "Spearman correlations were performed, and only correlations with p < 0.05 were considered and shown in Supplementary Table S5–S9."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33693030", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33693030"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD021144"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD021144"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33693030", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2021.632290", "sha256": "sha256:722e3c3c67f7bca619504c2840c3b1ec2bcc6d2da5f5be9fef27772a74e90c9e", "bytes": 56890, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2021.632290", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7937875", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD021144", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD021144", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD021144", "version": null, "note": "The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets G for this study can be found in the proteomexchange database Project accession: PXD021144.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Mapping the Host Circulating Exosome Response to SARS-CoV-2", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33693030:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:59adb571368a56784e9a19b708cd6b4a323d8ffd65c3108f8c9cd9a45648ef40", "bytes": 2379, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#T1", "version": null, "note": "Comparison of modulated exosomal proteins with regulated serum proteins in COVID-19 patients reported in literature. Protein modulation (Up or Down) is indicated.", "structure": {"pmcid": "PMC7937875", "section_index": 10, "section_title": "2.8 Circulating Exosomes are Potential Biomarkers of COVID-19", "row_count": 52, "column_count": 6}, "table": {"label": "TABLE 1", "caption": "Comparison of modulated exosomal proteins with regulated serum proteins in COVID-19 patients reported in literature. Protein modulation (Up or Down) is indicated.", "rows": [["", "Plasma-exosome", "Serum (22)", "Serum (23)", "Serum (24)"], ["Gene", "Non-critical", "Critical"], ["A1BG", "Up", "Up", "−", "−", "Up"], ["ACTB", "−", "Up", "−", "−", "Up"], ["AHSG", "−", "Up", "Down", "−", "−"], ["ALB", "Up", "−", "Down", "−", "−"], ["APO2", "Up", "−", "−", "Down", "−"], ["APOD", "Up", "−", "−", "Up", "−"], ["APOF", "−", "Up", "Up", "−", "−"], ["APOH", "Down", "Up", "−", "Down", "−"], ["C1R", "Down", "Down", "−", "−", "Up"], ["C1S", "−", "Down", "−", "−", "Up"], ["C4BPA", "Down", "Down", "−", "Up", "−"], ["C9", "Up", "−", "Up", "−", "−"], ["CLEC3B", "−", "Down", "Down", "−", "−"], ["CRP", "Up", "Up", "Up", "−", "Up"], ["CST3", "−", "Up", "Up", "−", "−"], ["F13B", "Down", "Down", "Down", "−", "−"], ["FCN2", "Up", "−", "Down", "Down", "−"], ["FGA", "Down", "Down", "-", "−", "Up"], ["FGB", "Down", "Down", "-", "−", "Up"], ["FGG", "Down", "Down", "-", "−", "Up"], ["FN1", "Down", "Down", "-", "−", "−"], ["GSN", "Down", "Down", "Down", "−", "Down"], ["HP", "Up", "−", "−", "−", "Up"], ["IGHV1-2", "Down", "−", "Up", "−", "−"], ["IGHV3-15", "−", "Down", "Up", "−", "−"], ["IGHV3–23", "Down", "Down", "Up", "−", "−"], ["IGHV3–9", "Down", "Down", "Up", "−", "−"], ["IGHV4–28", "−", "Down", "Up", "−", "−"], ["IGHV4–38–2", "Down", "−", "Up", "−", "−"], ["IGKV1–5", "Down", "−", "Up", "−", "−"], ["IGKV4–1", "Down", "−", "Up", "−", "−"], ["ITIH1", "−", "Down", "Down", "−", "−"], ["ITIH2", "−", "Down", "Down", "−", "−"], ["ITIH3", "Up", "−", "Down", "Up", "Up"], ["ITIH4", "Up", "−", "Down", "Up", "Up"], ["LRG1", "Up", "Up", "Up", "−", "−"], ["LYZ", "−", "Up", "Up", "−", "−"], ["ORM1", "Up", "Up", "Up", "Up", "−"], ["PGLYRP2", "Down", "−", "Down", "−", "−"], ["PON1", "Up", "−", "Down", "−", "−"], ["PPBP", "Up", "Up", "Down", "−", "−"], ["S100A8", "−", "Up", "Up", "−", "−"], ["S100A9", "−", "Up", "Up", "−", "−"], ["SAA4", "Up", "Up", "−", "Up", "−"], ["SERPINA3", "Up", "Up", "Up", "Up", "−"], ["SERPINA6", "−", "Up", "Down", "−", "−"], ["SERPING1", "Up", "Up", "Up", "−", "−"], ["TIMP1", "Up", "Up", "Up", "−", "−"], ["VCAM1", "Up", "Up", "−", "Up", "−"], ["VWF", "−", "Down", "Up", "−", "−"]], "row_count": 52, "column_count": 6, "numeric_cells": 14, "header_rows": 2, "locator": "section[10]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33693030:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e9fb5d9ce45b7b2b8fa7bcfb6d3540e5158df896dd19c2db86bbb3d6fd93f262", "bytes": 1545, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T2", "version": null, "note": "Characteristics of the patients included in the discovery phase study.", "structure": {"pmcid": "PMC7937875", "section_index": 13, "section_title": "4.1 Patients", "row_count": 35, "column_count": 5}, "table": {"label": "TABLE 2", "caption": "Characteristics of the patients included in the discovery phase study.", "rows": [["Variable", "Non-COVID-19 patients", "COVID-19 patients"], ["Healthy Control (N=7)", "Total (N=17)", "Non-critical (N=10)", "Critical (N=7)"], ["Sex (no.)"], ["Male", "2", "8", "5", "3"], ["Female", "5", "9", "5", "4"], ["Age (year)"], ["Mean ± SD", "51.4 ± 4.8", "64.3 ± 16.5", "68.3 ± 19.7", "58.7 ± 8.8"], ["Range", "43.0 − 56.0", "37.0 − 97.0", "37.0 − 97.0", "47.0 − 70.0"], ["Time from onset to admission (days)"], ["Mean ± SD", "", "5.2 ± 5.0", "6.2 ± 5.8", "3.6 ± 3.5"], ["Range", "", "1.0 − 18", "1.0 − 18.0", "1.0 − 9.0"], ["Time from admission to severe (days)"], ["Mean ± SD", "", "", "", "3.8 ± 2.9"], ["Range", "", "", "", "1.0 − 8.0"], ["Symptoms (n°)"], ["Fever", "", "8", "4", "4"], ["Cough", "", "6", "5", "2"], ["Headache", "", "0", "0", "0"], ["Fatigue", "", "1", "1", "0"], ["Dyspnea", "", "3", "2", "1"], ["Diarrhea", "", "2", "1", "1"], ["Chest pain", "", "1", "1", "0"], ["Abdominal pain", "", "1", "0", "1"], ["Vomiting", "", "1", "1", "0"], ["Comorbidity (n°)"], ["Hypertension", "", "4", "1", "3"], ["Diabetes", "", "6", "2", "4"], ["Respiratory system", "", "9", "6", "3"], ["Cardiovascular system", "", "6", "3", "3"], ["Other endocrine system", "", "2", "0", "2"], ["Chronic kidney", "", "3", "0", "3"], ["Digestive system", "", "4", "1", "3"], ["Oxygen saturation index (%)"], ["Mean ± SD", "", "93.4 ± 7.1", "94.3 ± 4.4", "92.1 ± 10.5"], ["Range", "", "71.0 − 99.0", "86.0 − 99.0", "71.0 − 98.0"]], "row_count": 35, "column_count": 5, "numeric_cells": 84, "header_rows": 2, "locator": "section[13]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33693030:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:88eaa552d05a6a71254dfe9f02d26c95f773cdb9797c92a821bf0c847531691d", "bytes": 2176, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[2]#T3", "version": null, "note": "Characteristics of the patients included in the validation phase study.", "structure": {"pmcid": "PMC7937875", "section_index": 13, "section_title": "4.1 Patients", "row_count": 33, "column_count": 9}, "table": {"label": "TABLE 3", "caption": "Characteristics of the patients included in the validation phase study.", "rows": [["Variables", "COVID-19", "Non-COVID-19"], ["Sex–no.", "Total (N=36)", "Non-Critical (N=23)", "Critical (N=13)", "Total (N=29)", "Non-Critical (N=8)", "Critical (N=6)", "Healthy Control (N=8)", "Healed (N=7)"], ["Male", "21", "13", "8", "12", "5", "3", "2", "2"], ["Female", "15", "10", "5", "17", "3", "3", "6", "5"], ["Age-year"], ["Mean ± SD", "65.6 ±17.6", "66.5 ± 20.6", "53.8 ± 10.7", "60.4 ± 17.0", "76 ± 12.9", "68.6 ± 8.9", "50.4 ± 5.4", "46.8 ± 17.6"], ["Range", "35.0 − 101.0", "35.0 − 101.0", "49.0 − 84.0", "30.0 − 96.0", "59.0 − 96.0", "56.0 − 82.0", "43.0 − 56.0", "30.0 − 72.0"], ["Time from Onset to Admission, Days"], ["Mean ± SD", "4.3 ± 4.5", "4.5 ± 5.0", "4 ± 3.6", "4.8 ± 6.1", "5.7 ± 7.0", "1.0 ± 0.0", "", ""], ["Range", "1.0 − 19.0", "1.0 − 19.0", "1.0 − 10.0", "1.0 − 21.0", "1.0 − 21.0", "1.0 − 1.0", "", ""], ["Time from Admission to Severe, Days"], ["Mean ± SD", "", "", "3.1 ± 2.8", "", "", "3.0 ± 4.9", "", ""], ["Range", "", "", "1.0 − 8.0", "", "", "1.0 − 13.0", "", ""], ["Symptoms–no."], ["Fever", "18", "11", "7", "3", "1", "2", "", ""], ["Cough", "16", "11", "5", "3", "0", "3", "", ""], ["Headache", "0", "0", "0", "2", "0", "2", "", ""], ["fatigue", "3", "2", "1", "3", "0", "3", "", ""], ["Dyspnea", "8", "6", "2", "5", "1", "4", "", ""], ["Diarrhea", "4", "2", "2", "0", "0", "0", "", ""], ["Chest pain", "1", "1", "0", "2", "0", "2", "", ""], ["Abdomial Pain", "2", "1", "1", "0", "0", "0", "", ""], ["vomit", "1", "1", "0", "1", "1", "0", "", ""], ["Comorbility–no."], ["Hypertension", "10", "5", "5", "6", "4", "2", "", ""], ["Diabetes", "8", "4", "4", "1", "0", "1", "", ""], ["Respiratory system", "4", "2", "2", "1", "1", 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