Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Blood Sampling
2.2. Flow Cytometry for Main Peripheral Blood Lymphocytes
2.3. Flow Cytometry for B and T Cell Subsets and Monocyte Subpopulations
2.4. TLR Protein Expression in PBMCs
2.5. SARS-Cov2 T-Specific Response Assessment by Flow Cytometry
2.6. Determination of Circulating IL-6
2.7. Statistical Analysis
3. Results
3.1. Patient Demographics and Baseline Characteristics at COVID-19 Onset
3.2. Innate-Immune Compartment Assessment at Admission
3.3. Adaptive Immune Compartment Assessment at Admission
3.4. SARS-CoV-2 Specific T Cells Response in Active COVID-19 Disease
3.5. Assessment of the Immune Parameters as a Prognosis Factor
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mild (n = 73) | Moderate–Severe (n = 82) | p-Value | Reference Values | |
---|---|---|---|---|
Demographic | ||||
Age (years) | 59 (47–77) | 72 (63–79) | <0.001 | NA |
Gender (% female) | 43 (58.90%) | 26 (31.71%) | 0.001 | NA |
Comorbidities | ||||
Hypertension | 30 (41.10%) | 43 (52.44%) | NS (0.158) | NA |
Type II diabetes | 11 (15.07%) | 17 (20.73%) | NS (0.360) | NA |
Heart disease | 12 (16.44) | 20 (24.39%) | NS (0.222) | NA |
Respiratory disease | 6 (8.22%) | 8 (9.76%) | NS (0.739) | NA |
Obesity | 12 (16.44) | 11 (13.41%) | NS (0.597) | NA |
Biochemical parameters | ||||
C-reactive protein (mg/dL) | 2.9 (0.9–6.6) | 6.5 (3.0–10.7) | 0.001 | 0.1–0.5 |
Ferritin (ng/mL) | 203.5 (105.5–603) | 535 (224–1135) | <0.001 | 10–291 |
D-dimer (ng/mL) | 540 (313–992) | 702 (389–1309) | NS (0.199) | 0–500 |
Troponin (ng/mL) | 5 (3–14) | 11 (6–21) | 0.006 | 0–40 |
LDH (IU/L) | 227 (173–277) | 274 (223–362) | <0.001 | 120–246 |
O2 saturation at admission (%) | 97 (96–98) | 95 (93–97) | <0.001 | NA |
Complete blood count | ||||
Lymphocytes (%) | 23.40 (16.00–32.75) | 16.65 (10.80–24.90) | 0.001 | 20.0–50.0 |
Neutrophils (%) | 64.85 (54.35–74.40) | 74.00 (65.30–81.40) | <0.001 | 42.0–75.0 |
Monocytes (%) | 8.70 (6.85–11.85) | 7.05 (4.70–10.00) | 0.003 | 2.0–13.0 |
Lymphocytes count (×103) | 1.20 (0.80–1.80) | 0.90 (0.70–1.20) | 0.001 | 1.2–5.0 |
Neutrophils (×103) | 3.45 (2.30–4.90) | 4.15 (2.70–5.90) | NS (0.077) | 1.4–7.5 |
Monocytes (×103) | 0.53 ± 0.27 | 0.45 ± 0.26 | 0.051 | 0.2–1.0 |
Serum immune factors | ||||
IgG (mg/dL) | 1094.91 ± 351.20 | 1096.39 ± 344.30 | NS (0.979) | 734–1486 |
IgM (mg/dL) | 98.18 (73.85–134.31) | 82.68 (51.42–133.88) | NS (0.078) | 41–201 |
IgA (mg/dL) | 262.36 ± 155.21 | 279.47 ± 135.86 | NS (0.454) | 49–401 |
C3 (mg/dL) | 131.50 ± 33.02 | 133.32 ± 30.60 | NS (0.724) | 77–203 |
C4 (mg/dL) | 31.04 (25.26–37.02) | 35.44 (27.86–40.22) | 0.019 | 7.7–50.5 |
IL-6 (ng/dL) | 26.68 (8.12–54.20) | 33.88 (7.46–125.0) | 0.048 | 0–30 |
Mild (n = 73) | Moderate–Severe (n = 82) | p-Value | |
---|---|---|---|
Monocytes | |||
Classic (%CD14+CD16−) | 70.34 (55.9–79.6) | 71.1 (49.5–82.2) | NS (0.896) |
Intermediate (%CD14+CD16+) | 27.9 (17.4–39.9) | 27.0 (15.2–42.9) | NS (0.677) |
Non-classic (%CD14−CD16+) | 3.4 (1.2–6.6) | 1.5 (0.6–3.5) | 0.010 |
TLR expression | |||
TLR3 | 1.1 (0.8–1.7) | 1.1 (0.9–1.6) | NS (0.956) |
TLR4 | 2.1 (1.0–3.1) | 1.7 (1.1–2.6) | NS (0.593) |
TLR7 | 1.4 (1.0–2.3) | 1.3 (1.0–2.1) | NS (0.631) |
NK cells | |||
%CD16/56 | 13.77 (10.71–23.1) | 17.25 (11.7–25.9) | NS (0.097) |
%NKT | 5.05 (3.205–10.945) | 4.52 (3.76–9.25) | NS (0.746) |
# CD16/56 | 169 (114–277) | 159 (98–230) | NS (0.205) |
# NKT | 59 (32.5–130) | 44 (30–71) | 0.019 |
CD56+CD16− | 4.2 (2.5–9.7) | 3.2 (1.6–5.1) | 0.014 |
CD56+CD16+ | 95.8 (90.3–97.5) | 96.8 (94.8–98.3) | 0.014 |
ILCs | |||
ILC1 (Lin−CD127+CD117−CD294−) | 2.33 (1.33–4.64) | 1.66 (0.94–3.88) | NS (0.198) |
ILC2 (Lin−CD127+CD117+CD294+) | 0.32 (0.13–0.73) | 0.25 (0.11–0.44) | NS (0.497) |
ILC3 (Lin−CD127+CD117+CD294−) | 0.28 (0.14-0.60) | 0.11 (0.06-0.21) | 0.00028 |
Mild (n = 73) | Moderate–Severe (n = 82) | p-Value | |
---|---|---|---|
T helper subsets (CD4+) | |||
CD4+CD27+CD28+ | 86.7 (73.9–93.9) | 87.1 (75.2–93.6) | NS (0.782) |
CD4+CD27−CD28+ | 4.8 (3.1–8.1) | 4.3 (2.5–7.2) | NS (0.695) |
CD4+CD27+CD28− | 0.6 (0.3–1.0) | 0.8 (0.3–1.2) | NS (0.724) |
CD4+CD27−CD28− | 6.5 (1.0–16.8) | 6.7 (2.0–13.6) | NS (0.927) |
CD4+CXCR3+CCR6− (Th1) | 23.9 (18.3–34.8) | 20.1 (15.3–30.0) | 0.057 |
CD4+CXCR3+ (Th1/Th17) | 12.6 (8.7–16.0) | 9.6 (7.1–14.0) | 0.039 |
CD4+CXCR3−CCR6+ (Th17) | 12.3 ± 5.0 | 12.4 ± 5.2 | NS (0.907) |
CD4+CD45RO+ (Memory Th) | 62.8 (50.4–71.9) | 58.1 (40.2–72.0) | NS (0.064) |
CD4+CD45RO−CD62L+ (Naïve) | 19.7 (12.7–29.3) | 18.5 (9.9–31.3) | NS (0.290) |
CD4+CD45RO+CD62L+ (TCM) | 46.4 ± 13.9 | 48.3 ± 15.8 | NS (0.234) |
CD4+CD45RO+CD62L− (TEM) | 24.5 (17.8–38.5) | 21.3(11.5–42.8) | NS (0.252) |
CD4+CD45RO−CD62L− (TEMRA) | 1.4 (0.5–3.8) | 1.3 (0.6–3.9) | NS (0.957) |
CD4+CD45RO+CXCR3+CCR6−(Memory Th1) | 32.2 (26.9–44.4) | 28.7 (24.0–38.0) | NS (0.030) |
CD4+CD45RO+CXCR3+ (Memory Th1/Th17) | 19.4 (16.1–25.2) | 23.2 (17.5–26.0) | NS (0.137) |
CD4+CD45RO+CXCR3−CCR6+ (Memory Th17) | 21.1 ± 8.7 | 18.5 ± 7.9 | NS (0.098) |
CD4+CXCR3−CCR6−CD294+ (Th2) | 1.0 (0.7–1.7) | 0.8 (0.4–1.3) | NS (0.830) |
CD4+CD45RO+CXCR5+PD1+ (Tfh) | 0.2 (0.1–0.4) | 0.3 (0.1–0.5) | NS (0.153) |
CD4+CD127−CD25+ (Tregs) | 6.4 (5.5–7.5) | 5.7 (4.3–7.2) | NS (0.063) |
T cytotoxic subsets (CD8+) | |||
CD8+CD27+CD28+ | 57.1 (31.4–71.1) | 37.6 (21.5–53.2) | 0.004 |
CD8+CD27−CD28+ | 2.1 (1.2–3.7) | 2.2 (1.1–3.7) | NS (0.580) |
CD8+CD27+CD28− | 10.2 (7.4–16.2) | 12.0 (6.5–19.0) | NS (0.219) |
CD8+CD27−CD28− | 27.7 (15.8–53.1) | 44.5 (24.4–63.2) | 0.019 |
CD8+CXCR3+ (Tc1/Tc17) | 4.9 (3.2–9.5) | 3.0 (1.8–4.6) | 0.0003 |
CD8+CD45RO+ (Memory Tc) | 42.9 (34.9–57.7) | 42.2 (35.2–57.6) | NS (0.749) |
CD8+CD45RO−CD62L+ (Naïve) | 25.9 (14.8–40.8) | 19.2 (10.3–28.8) | 0.026 |
CD8+CD45RO+CD62L+ (TCM) | 15.0 (10.0–19.2) | 14.1 (8.8–21.7) | NS (0.942) |
CD8+CD45RO+CD62L− (TEM) | 30.9 (23.9–38.7) | 31.6 (22.6–44.6) | NS (0.780) |
CD8+CD45RO−CD62L− (TEMRA) | 21.0 (11.8–34.4) | 26.1 (14.3–38.1) | NS (0.125) |
CD8+CD45RO+CXCR3+ (Memory Tc1/Tc17) | 2.5 (1.4–6.6) | 2.8 (1.2–5.1) | 0.0002 |
CD8+DR+CD38+ | 11.2 (5.3–20.5) | 13.8 (8.8–25.6) | 0.028 |
B lymphocytes | |||
B naïve (CD27−IgD+) | 65.3 (47.8–75.5) | 63.8 (48.3–75.0) | NS (0.656) |
B unswitched (CD27+IgD+) | 15.4 (9.0–23.4) | 11.5 (8.3–21.5) | NS (0.196) |
B switched (CD27+IgD−) | 15.9 (8.5–24.1) | 17.0 (9.8–25.5) | NS (0.478) |
Plasmablasts (CD19+ CD20lowCD27hi CD38hi) | 1.9 (0.8–5.8) | 5.3 (1.6–9.7) | 0.002 |
Parameter | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
p | Odds | CI | p | Odds | CI | |
Age | <0.001 | 1.033 | 1.013–1.053 | 0.015 | 1.038 | 1.007–1.069 |
Ferritin | <0.001 | 1.001 | 1.001–1.002 | 0.021 | 1.001 | 1.001–1.002 |
D-dimer | 0.226 | 1.000 | 1.000–1.000 | 0.01 | 1.000 | 1.000–1.001 |
Absolute lymphocyte count | 0.002 | 0.999 | 0.999–1.000 | 0.023 | 0.999 | 0.998–1.000 |
C4 | 0.016 | 1.041 | 1.007–1.075 | 0.110 | 1.036 | 0.992–1.082 |
% of CD8+CD27−CD28− | 0.023 | 1.017 | 1.002–1.031 | 0.701 | 1.004 | 0.985–1.023 |
% of non-classical monocytes | 0.288 | 0.18 | 0.000–29.826 | 0.908 | 1.712 | 0.000–0.000149 |
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San Segundo, D.; Arnáiz de las Revillas, F.; Lamadrid-Perojo, P.; Comins-Boo, A.; González-Rico, C.; Alonso-Peña, M.; Irure-Ventura, J.; Olmos, J.M.; Fariñas, M.C.; López-Hoyos, M. Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients. Biomedicines 2021, 9, 917. https://doi.org/10.3390/biomedicines9080917
San Segundo D, Arnáiz de las Revillas F, Lamadrid-Perojo P, Comins-Boo A, González-Rico C, Alonso-Peña M, Irure-Ventura J, Olmos JM, Fariñas MC, López-Hoyos M. Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients. Biomedicines. 2021; 9(8):917. https://doi.org/10.3390/biomedicines9080917
Chicago/Turabian StyleSan Segundo, David, Francisco Arnáiz de las Revillas, Patricia Lamadrid-Perojo, Alejandra Comins-Boo, Claudia González-Rico, Marta Alonso-Peña, Juan Irure-Ventura, José Manuel Olmos, María Carmen Fariñas, and Marcos López-Hoyos. 2021. "Innate and Adaptive Immune Assessment at Admission to Predict Clinical Outcome in COVID-19 Patients" Biomedicines 9, no. 8: 917. https://doi.org/10.3390/biomedicines9080917