Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Standard of Care Blood Analyses
2.3. Fingerprinting the Circulating Proteome
2.4. Statistics
3. Results
3.1. Patient Stratification, Clinical and Standard of Care Laboratory Assessment
3.2. Plasma Proteins Associated to COVID-19 Status
3.3. Comparison of Hospitalized and Non-Hospitalized COVID-19 Patients
3.4. Proteome Analyses in Hospitalized COVID-19 Patients with Regard to Clinical Outcome
3.5. A Proteomic Fingerprint Predicts Outcome
4. Discussion
4.1. How Can Proteomic Fingerprinting Help Clinicians Better Understand COVID-19?
4.2. What Are the Advantages of Our Analysis Design?
4.3. What Distinguishes Patients with SARS-CoV-2 Infection from Patients with Similar Symptoms but Negative PCR Results?
4.4. Which Plasma Proteins Indicate a Severe Outcome in COVID-19 Patients?
4.5. What Are Clinical Implications and Do Possible Therapeutic Targets Exist?
4.6. Can the Multiplexed Proteomics Technique Be Implemented in Clinical Routine as a Diagnostic Method?
4.7. Concluding Remarks
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Non-COVID-19 Group | COVID-19 Group | ||||||
---|---|---|---|---|---|---|---|
(N = 44) | (N = 97) | ||||||
Parameter | Valid Values | Median Value | Interquartile Ranges | Valid Values | Median Value | Interquartile Ranges | p-Value |
ADM | 44 | 8.05 | 6.96, 8.74 | 95 | 7.64 | 7.21, 8.54 | 0.5725400 |
CCL23 | 41 | 10.43 | 9.99, 11.58 | 96 | 10.41 | 9.65, 10.99 | 0.0787430 |
CTSL1 | 44 | 8.73 | 8.52, 8.99 | 95 | 8.62 | 8.43, 8.91 | 0.6467800 |
CXCL10 | 41 | 9.88 | 8.96, 11.07 | 96 | 12.69 | 11.90, 13.34 | 0.0000004 |
CXCL11 | 41 | 10.30 | 9.90, 11.15 | 96 | 12.05 | 10.75, 12.53 | 0.0000039 |
CXCL5 | 41 | 12.18 | 11.29, 12.50 | 96 | 11.52 | 10.83, 12.04 | 0.0006775 |
DCN | 44 | 3.99 | 3.70, 4.39 | 95 | 4.12 | 3.70, 4.57 | 0.4066400 |
Gal9 | 44 | 4.76 | 4.13, 5.11 | 95 | 5.70 | 5.10, 6.58 | 0.0000001 |
HGF | 41 | 7.72 | 7.16, 8.19 | 96 | 7.45 | 6.76, 8.15 | 0.4525200 |
IFNgamma | 41 | 2.33 | 2.33, 3.01 | 96 | 4.67 | 2.96, 6.01 | 0.0000160 |
IL18 | 44 | 7.64 | 7.22, 8.07 | 95 | 8.33 | 7.80, 8.75 | 0.0007774 |
IL18R1 | 41 | 7.35 | 7.08, 7.56 | 96 | 7.92 | 7.53, 8.45 | 0.0000445 |
IL27 | 44 | 3.20 | 2.87, 3.69 | 95 | 3.36 | 3.01, 3.90 | 0.5745600 |
IL6 | 44 | 4.18 | 2.42, 6.56 | 95 | 4.72 | 3.50, 5.84 | 0.0639610 |
KIM1 | 44 | 8.21 | 7.47, 8.81 | 95 | 7.86 | 7.08, 8.79 | 0.7888000 |
LIFR | 41 | 4.33 | 4.04, 4.54 | 96 | 4.63 | 4.35, 4.90 | 0.0005687 |
LPL | 44 | 7.49 | 6.99, 8.16 | 95 | 7.52 | 6.94, 8.03 | 0.8819400 |
MCP1 | 41 | 11.72 | 11.33, 12.14 | 96 | 12.33 | 11.65, 12.82 | 0.0240940 |
MCP2 | 41 | 8.81 | 8.37, 9.16 | 96 | 10.69 | 9.81, 11.58 | 0.00000001 |
MCP3 | 41 | 3.98 | 3.43, 4.95 | 96 | 5.43 | 4.55, 6.77 | 0.0003295 |
MERTK | 44 | 6.55 | 6.23, 6.83 | 95 | 6.96 | 6.56, 7.26 | 0.0007555 |
MMP1 | 41 | 13.25 | 12.28, 14.66 | 96 | 13.00 | 11.86, 13.89 | 0.0007128 |
MMP12 | 44 | 6.41 | 5.64, 7.37 | 95 | 5.80 | 4.97, 6.93 | 0.1359200 |
OPG | 41 | 9.35 | 8.83, 9.99 | 96 | 9.11 | 8.65, 9.78 | 0.1229900 |
PDL1 | 41 | 4.39 | 4.06, 4.64 | 96 | 5.14 | 4.74, 5.61 | 0.0000002 |
TNF | 41 | 1.59 | 1.21, 2.03 | 96 | 2.15 | 1.80, 2.63 | 0.0002014 |
TNFRSF10A | 44 | 2.52 | 1.97, 2.96 | 95 | 2.49 | 2.09, 3.23 | 0.8851000 |
TRAIL-R2 | 44 | 6.33 | 5.76, 7.17 | 95 | 6.05 | 5.48, 7.01 | 0.2625300 |
Median and Interquartile Ranges for Non-Outcomes | Median and Interquartile Ranges for Outcomes | p-Values Non-Outcome vs. Outcome | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ICU | MV | TE | Death | ICU | MV | TE | Death | ICU | MV | TE | Death | |
29 (54.72%) | 37 (69.81%) | 47 (88.68%) | 46 (86.79%) | 24 (45.28%) | 16 (30.19%) | 6 (11.32%) | 7 (13.21%) | |||||
SoC analytes | ||||||||||||
CRP | 36.5 (14.6–62.6) | 35.3 (15.8–66.1) | 44.4 (16.5–89.7) | 45.3 (16.4–106) | 110 (25.8–155) | 140 (59.8–216) | 187 (39.4–265) | 53.7 (22.8–129) | 0.020 | 0.011 | 0.175 | 0.637 |
PCT | 0.10 (0.08–0.24) | 0.10 (0.08–0.24) | 0.10 (0.08–0.25) | 0.11 (0.08–0.26) | 0.17 (0.10–0.30) | 0.20 (0.10–0.62) | 0.47 (0.20–0.78) | 0.11 (0.10–0.25) | 0.241 | 0.160 | 0.082 | 0.897 |
WBC | 6.35 (5.33–8.51) | 6.62 (5.27–8.63) | 6.35 (5.26–8.62) | 7.12 (5.29–10.3) | 7.49 (5.13–10.9) | 7.64 (5.33–12.0) | 9.35 (9.12–10.5) | 5.65 (5.05–7.35) | 0.372 | 0.416 | 0.106 | 0.325 |
LDH | 300 (266–399) | 295 (263–438) | 322 (271–504) | 340 (269–563) | 509 (439–684) | 509 (453–718) | 461 (447–589) | 432 (300–460) | 0.014 | 0.006 | 0.196 | 0.978 |
PEA analytes | ||||||||||||
ADM | 8.37 (7.40–8.78) | 8.30 (7.38–8.66) | 8.37 (7.49–8.80) | 8.28 (7.44–8.65) | 8.41 (7.54–8.82) | 8.64 (8.16–8.90) | 8.50 (7.77–8.75) | 8.98 (8.76–9.12) | 0.1207000 | 0.0472670 | 0.5869700 | 0.0000932 |
CCL23 | 10.5 (9.92–10.9) | 10.5 (9.92–11.1) | 10.8 (10.2–11.2) | 10.6 (10.1–11.1) | 11.1 (10.6–11.6) | 11.2 (10.7–11.6) | 10.7 (9.81–11.1) | 11.3 (10.8–11.6) | 0.0006146 | 0.0018489 | 0.8367700 | 0.0551560 |
CTSL1 | 8.72 (8.52–9.03) | 8.75 (8.52–9.03) | 8.75 (8.53–9.04) | 8.80 (8.52–9.10) | 8.86 (8.68–9.18) | 8.86 (8.70–9.26) | 9.17 (8.88–9.18) | 8.78 (8.67–8.99) | 0.0085455 | 0.0472670 | 0.0173740 | 0.3078300 |
CXCL10 | 12.6 (12.0–13.3) | 12.7 (12.0–13.3) | 12.9 (12.0–13.3) | 12.7 (11.2–13.3) | 13.1 (11.9–13.5) | 13.1 (12.4–13.6) | 13.6 (10.7–13.8) | 13.7 (13.2–13.8) | 0.0669700 | 0.1257600 | 0.0160730 | 0.0024786 |
CXCL11 | 11.8 (10.9–12.4) | 11.9 (10.8–12.5) | 12.2 (10.9–12.5) | 12.0 (10.7–12.5) | 12.5 (11.3–12.7) | 12.4 (12.1–12.6) | 12.6 (11.2–12.6) | 12.6 (12.6–12.6) | 0.1027300 | 0.1931000 | 0.3580900 | 0.0109360 |
CXCL5 | 11.6 (11.2–12.2) | 11.5 (11.1–12.0) | 11.5 (11.1–12.0) | 11.4 (11.1–12.0) | 11.3 (10.8–12.0) | 11.3 (11.1–12.2) | 11.2 (11.1–12.0) | 11.7 (10.6–12.3) | 0.6541900 | 0.2407300 | 0.1392900 | 0.0403690 |
DCN | 4.35 (3.84–4.77) | 4.22 (3.83–4.71) | 4.35 (3.84–4.82) | 4.30 (3.84–4.70) | 4.41 (4.01–4.75) | 4.64 (4.37–5.10) | 4.60 (4.42–4.72) | 5.31 (4.56–5.62) | 0.0475360 | 0.0009899 | 0.0154320 | 0.0074615 |
Gal9 | 5.90 (5.10–6.77) | 5.90 (5.08–6.77) | 5.93 (5.14–6.72) | 5.78 (5.08–6.72) | 5.99 (5.21–6.82) | 6.05 (5.59–6.82) | 6.27 (4.59–7.00) | 6.60 (6.05–6.86) | 0.7322500 | 0.5908400 | 0.1927500 | 0.0442300 |
HGF | 7.54 (7.25–8.20) | 7.54 (7.31–8.20) | 7.64 (7.32–8.23) | 7.56 (7.32–8.36) | 8.00 (7.44–8.59) | 8.16 (7.59–8.59) | 8.25 (7.71–8.41) | 8.16 (7.83–8.27) | 0.0354240 | 0.0452030 | 0.3725600 | 0.1236400 |
IFNgamma | 4.59 (2.60–6.00) | 4.63 (2.79–6.04) | 4.80 (3.19–6.03) | 4.67 (3.15–6.03) | 4.95 (3.64–5.63) | 4.89 (3.20–5.21) | 3.50 (2.40–4.86) | 4.53 (3.09–5.31) | 0.1746500 | 0.6409200 | 0.8324600 | 0.8324600 |
IL18 | 8.42 (8.09–8.71) | 8.36 (8.05–8.67) | 8.44 (8.14–8.86) | 8.43 (8.09–8.90) | 8.51 (8.16–9.41) | 8.64 (8.27–9.56) | 8.42 (7.60–9.17) | 8.66 (8.26–9.03) | 0.3469200 | 0.0557820 | 0.3616600 | 0.3725600 |
IL18R1 | 8.05 (7.60–8.42) | 8.05 (7.59–8.53) | 8.09 (7.61–8.49) | 7.98 (7.61–8.47) | 8.35 (7.70–8.62) | 8.23 (7.84–8.55) | 8.12 (7.65–8.59) | 8.55 (8.30–8.64) | 0.4282800 | 0.2964400 | 0.8367700 | 0.1236400 |
IL27 | 3.70 (3.27–4.15) | 3.62 (3.07–3.98) | 3.68 (3.09–4.11) | 3.62 (3.04–3.96) | 3.67 (3.06–4.04) | 3.90 (3.45–4.35) | 3.68 (3.43–4.13) | 4.42 (4.05–4.49) | 0.3287600 | 0.0472670 | 0.4544500 | 0.0074615 |
IL6 | 4.84 (4.33–5.55) | 4.86 (4.33–6.01) | 5.27 (4.66–6.61) | 5.05 (4.40–6.26) | 6.43 (5.37–6.96) | 6.74 (5.60–7.31) | 5.84 (4.36–6.54) | 6.62 (5.55–6.80) | 0.0000044 | 0.0000002 | 0.3580900 | 0.0319650 |
KIM1 | 8.51 (8.13–9.53) | 8.38 (7.75–9.07) | 8.41 (7.71–9.08) | 8.37 (7.69–9.09) | 8.06 (7.62–8.85) | 8.68 (7.78–9.32) | 8.72 (7.96–9.39) | 9.01 (8.68–9.35) | 0.1353200 | 0.1374300 | 0.8455500 | 0.0442300 |
LIFR | 4.66 (4.42–4.94) | 4.73 (4.49–4.92) | 4.80 (4.50–4.93) | 4.76 (4.50–4.92) | 4.84 (4.66–4.93) | 4.84 (4.67–5.10) | 4.93 (4.66–4.99) | 5.07 (4.86–5.38) | 0.0197430 | 0.0853480 | 0.3725600 | 0.0551560 |
LPL | 7.72 (6.81–8.44) | 7.72 (7.06–8.29) | 7.66 (7.09–8.35) | 7.62 (7.07–8.10) | 7.65 (7.41–8.14) | 7.65 (7.51–8.67) | 7.78 (7.54–8.37) | 8.73 (8.10–9.06) | 0.4779700 | 0.1412000 | 0.5225300 | 0.0001652 |
MCP1 | 12.4 (11.8–12.8) | 12.3 (11.8–12.8) | 12.5 (11.8–13.0) | 12.5 (11.7–13.0) | 13.0 (12.1–13.5) | 13.3 (12.6–13.7) | 13.4 (12.0–13.8) | 13.5 (13.0–13.7) | 0.0000581 | 0.0000419 | 0.0545020 | 0.0024786 |
MCP2 | 10.5 (9.34–11.2) | 10.8 (9.24–11.7) | 10.8 (9.48–11.5) | 10.8 (9.26–11.5) | 11.1 (9.60–12.0) | 11.0 (9.95–12.0) | 12.0 (9.91–12.0) | 12.2 (11.3–12.4) | 0.0934230 | 0.4824300 | 0.0545020 | 0.0024786 |
MCP3 | 5.42 (4.70–6.70) | 5.59 (4.72–6.74) | 6.11 (4.76–7.09) | 6.11 (4.76–7.16) | 6.93 (5.98–7.87) | 7.43 (6.39–8.22) | 7.66 (5.99–8.11) | 7.29 (5.63–8.11) | 0.0001310 | 0.0000231 | 0.0024786 | 0.0571620 |
MERTK | 6.96 (6.79–7.39) | 6.96 (6.79–7.40) | 7.02 (6.82–7.37) | 6.97 (6.80–7.37) | 7.10 (6.89–7.43) | 7.16 (6.95–7.43) | 7.32 (6.72–7.79) | 7.25 (7.04–7.52) | 0.1706600 | 0.1503800 | 0.0580550 | 0.2731700 |
MMP1 | 13.6 (12.8–14.1) | 13.5 (12.5–14.0) | 13.5 (12.6–14.2) | 13.4 (12.5–14.0) | 13.5 (12.5–14.3) | 14.1 (12.6–14.5) | 14.0 (12.9–14.3) | 14.3 (14.1–14.5) | 0.1102800 | 0.0158300 | 0.5116700 | 0.0551560 |
MMP12 | 6.34 (5.38–7.30) | 5.98 (5.27–7.14) | 6.10 (5.28–7.30) | 5.84 (5.23–6.98) | 5.87 (5.22–7.21) | 6.36 (5.24–7.54) | 5.75 (5.34–6.70) | 7.32 (6.92–7.99) | 0.2720700 | 0.2977100 | 0.8455500 | 0.1061200 |
OPG | 9.54 (8.97–10.1) | 9.50 (8.97–9.92) | 9.52 (8.97–10.1) | 9.55 (8.97–9.93) | 9.59 (9.02–10.1) | 9.82 (9.40–10.2) | 9.72 (9.59–10.0) | 10.1 (9.69–10.2) | 0.0499440 | 0.0242520 | 0.0109360 | 0.0551560 |
PDL1 | 5.04 (4.81–5.46) | 5.19 (4.81–5.61) | 5.34 (4.90–5.73) | 5.29 (4.82–5.72) | 5.49 (5.17–5.82) | 5.49 (5.29–5.80) | 5.25 (4.59–5.68) | 5.49 (5.33–5.77) | 0.0006113 | 0.0528220 | 0.8324600 | 0.1714200 |
TNF | 2.49 (2.02–2.87) | 2.33 (1.89–2.79) | 2.32 (1.92–2.77) | 2.18 (1.83–2.65) | 2.05 (1.85–2.41) | 2.23 (1.92–2.63) | 2.31 (1.76–2.46) | 2.72 (2.63–3.10) | 0.0669310 | 0.4650900 | 0.9491500 | 0.1859300 |
TNFRSF10A | 2.74 (2.40–3.25) | 2.65 (2.40–3.27) | 2.87 (2.44–3.43) | 2.73 (2.41–3.41) | 3.16 (2.50–3.61) | 3.30 (2.68–3.72) | 3.02 (2.46–3.53) | 3.25 (2.91–3.68) | 0.0168280 | 0.0074506 | 0.5225300 | 0.1002400 |
TRAILR2 | 6.40 (5.83–7.09) | 6.40 (5.77–7.08) | 6.75 (5.91–7.22) | 6.52 (5.85–7.09) | 7.01 (6.46–7.35) | 7.16 (6.71–7.63) | 7.06 (6.41–7.16) | 7.18 (7.07–7.85) | 0.0004393 | 0.0000823 | 0.5869700 | 0.0125550 |
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Bauer, W.; Weber, M.; Diehl-Wiesenecker, E.; Galtung, N.; Prpic, M.; Somasundaram, R.; Tauber, R.; Schwenk, J.M.; Micke, P.; Kappert, K. Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection. Viruses 2021, 13, 2456. https://doi.org/10.3390/v13122456
Bauer W, Weber M, Diehl-Wiesenecker E, Galtung N, Prpic M, Somasundaram R, Tauber R, Schwenk JM, Micke P, Kappert K. Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection. Viruses. 2021; 13(12):2456. https://doi.org/10.3390/v13122456
Chicago/Turabian StyleBauer, Wolfgang, Marcus Weber, Eva Diehl-Wiesenecker, Noa Galtung, Monika Prpic, Rajan Somasundaram, Rudolf Tauber, Jochen M. Schwenk, Patrick Micke, and Kai Kappert. 2021. "Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection" Viruses 13, no. 12: 2456. https://doi.org/10.3390/v13122456
APA StyleBauer, W., Weber, M., Diehl-Wiesenecker, E., Galtung, N., Prpic, M., Somasundaram, R., Tauber, R., Schwenk, J. M., Micke, P., & Kappert, K. (2021). Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection. Viruses, 13(12), 2456. https://doi.org/10.3390/v13122456