Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Patients’ Characteristics
2.3. In-Hospital Treatment
2.4. Pidotimod and Historical Control Group
2.5. PBMC Isolation and Stimulation
2.6. Multiplex Cytokine Analyses
2.7. Quantigene Plex Gene Expression Assay
2.8. Neutrophil to Lymphocyte Ratio
2.9. Study Outcomes
2.10. Statistical Analysis
3. Results
3.1. Patients’ Clinical Characteristics
3.2. Clinical Outcomes
3.3. Neutrophil to Lymphocyte Ratio
3.4. Cytokine and Chemokine Plasma Levels
3.5. SARS-CoV-2 Specific Immune Profile
4. Discussion
Study Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pidotimod (N = 16) | Controls (N = 16) | p-Value | |
---|---|---|---|
Males, n (%) | 8 (50) | 8 (50) | 1.000 |
Age, years | 60 (55–71) | 61 (54–69) | 0.867 |
Arterial hypertension, n (%) | 9 (56) | 8 (50) | 0.719 |
Diabetes mellitus, n (%) | 4 (25) | 4 (25) | 1.000 |
Ischaemic heart disease, n (%) | 3 (19) | 3 (19) | 1.000 |
COPD, n (%) | 2 (13) | 1 (6) | 0.310 |
From symptoms onset to admission, days | 6 (4–10) | 8 (5–11) | 0.323 |
Variables at admission | |||
PaO2, mmHg | 73 (66–90) | 90 (83–140) | 0.005 |
PaO2/FiO2, mmHg | 218 (165–289) | 244 (168–294) | 0.669 |
PaO2/FiO2 200–300 mmHg, n (%) | 7 (44) | 6 (37) | 0.719 |
PaO2/FiO2 100–200 mmHg, n (%) | 9 (56) | 10 (63) | 0.719 |
CPAP, n (%) | 4 (40) | 6 (37) | 0.446 |
Glasgow coma scale, score | 15 (15–15) | 15 (15–15) | 0.780 |
C reactive protein, mg/L | 50 (24–138) | 69 (41–148) | 0.381 |
D-dimer, mg/L FEU | 558 (421–811) | 787 (574–1362) | 0.070 |
From admission to PDT start, days | 1 (1–1.5) | -- | -- |
From symptoms to PDT start, days | 7 (5–11.5) | -- | -- |
Variables 7 days post admission | |||
PaO2, mmHg | 74 (66–87) | 72 (67–83) | 0.953 |
PaO2/FiO2, mmHg | 342 (288–380) | 273 (196–338) | 0.033 |
PaO2/FiO2 200–300 mmHg, n (%) | 0 | 4 (25) | 0.033 |
PaO2/FiO2 <200 mmHg, n (%) | 5 (31) | 6 (37) | 0.710 |
C reactive protein, mg/L | 50 (24–138) | 69 (41–148) | 0.381 |
D-dimer, mg/L FEU | 661 (409–951) | 764 (585–1183) | 0.196 |
In-hospital treatments | |||
Systemic corticosteroids | 15 (94) | 12 (75) | 0.144 |
Antibiotics, n (%) | 3 (19) | 8 (50) | 0.063 |
LMWH, n (%) | 16 (100) | 16 (100) | 0.310 |
Prophylactic dose, n (%) | 11 (69) * | 14 (87) * | 0.200 |
Therapeutic dose, n (%) | 6 (37) | 4 (25) | 0.446 |
Clinical outcomes | |||
CPAP at 7 days, n (%) | 1 (6) | 4 (25) | 0.144 |
Invasive mechanical ventilation, n (%) | 0 | 1 (6) | 0.310 |
Tranferred to ICU, n (%) | 0 | 1 (6) | 0.310 |
Lenght of stay, days | 10 (8–14) | 11 (8–21) | 0.770 |
From symptoms to discharge, days | 17 (13–23) | 18 (16–31) | 0.358 |
Death HDRU, n (%) | 0 | 0 | -- |
Death ICU, n (%) | 0 | 1 (6) | 0.310 |
Discharged to low intensity, n (%) | 1 (12) | 7 (44) | 0.014 |
Pidotimod (N = 16) | Controls (N = 16) | p-Value | |
---|---|---|---|
At admission | |||
WBC count at admission, ×106/µL | 7450 (5990–10,840) | 6010 (5380–11,740) | 0.520 |
Neutrophil count, ×106/µL | 8580 (5150–11,010) | 8740 (4800–11,890) | 0.670 |
Lymphocyte count, ×106/µL | 750 (590–1350) | 820 (610–1610) | 0.520 |
NLR | 7.45 (2.7–12.9) | 6.85 (4.1–10.3) | 0.809 |
NLR ≥ 6.5 | 10 (62) | 8 (50) | 0.476 |
Pidotimod start | |||
WBC count at admission, ×106/µL | 6820 (5950–9890) | 6420 (5360–10,900) | 0.773 |
Neutrophil count, ×106/µL | 5480 (4030–8740) | 5310 (4220–9010) | 0.865 |
Lymphocyte count, ×106/µL | 1100 (590–1370) | 990 (730–1540) | 0.538 |
NLR | 6.35 (2.3–9.3) | 5.4 (4.8–7.1) | 0.081 |
NLR ≥ 6.5 | 8 (50) | 8 (50) | 1.000 |
7 days post Pidotimod start | |||
WBC count at admission, ×106/µL | 9090 (8000–10,982) | 7330 (5420–12,032) | 1.000 |
Neutrophil count, ×106/µL | 6920 (5280–7480) | 6180 (4020–11,810) | 0.076 |
Lymphocyte count, ×106/µL | 2055 (1360–3255) | 1000 (750–1510) | 0.003 |
NLR | 2.9 (1.7–4.6) | 5.5 (3.4–7.1) | 0.037 |
NLR ≥ 6.5 | 1 (6) | 6 (37.5) | 0.033 |
A | Unstimulated | SARS-CoV-2 | FLU | ||||||
T0 vs. T1 | T0 vs. T2 | T1 vs. T2 | T0 vs. T1 | T0 vs. T2 | T1 vs. T2 | T0 vs. T1 | T0 vs. T2 | T1 vs. T2 | |
IL-1RA | ns | ns | ns | ns | ns | ns | 0.0026671 | 0.050791 | ns |
IL-4 | ns | ns | ns | ns | ns | ns | ns | ns | ns |
IL-5 | ns | ns | ns | 0.0107572 | ns | ns | ns | ns | ns |
IL-6 | ns | ns | ns | ns | ns | ns | 0.0520084 | ns | ns |
IL-8 | ns | ns | ns | ns | ns | ns | 0.0304641 | 0.0212915 | ns |
IL-9 | 0.0468253 | ns | ns | ns | ns | ns | ns | ns | ns |
FGF-basic | ns | ns | ns | ns | ns | ns | 0.0410918 | ns | ns |
G-CSF | ns | ns | 0.025881 | 0.0533785 | ns | ns | ns | ns | ns |
GM-CSF | ns | ns | ns | ns | ns | ns | 0.0520894 | ns | ns |
IFN-γ | ns | ns | ns | ns | ns | ns | 0.0057612 | 0.0265163 | ns |
MCP-1 | ns | ns | ns | ns | ns | ns | 0.0025601 | 0.0519345 | ns |
MIP-1α | ns | ns | 0.0419556 | 0.0369439 | ns | ns | ns | ns | ns |
MIP-1β | ns | ns | ns | ns | 0.0474791 | ns | ns | ns | ns |
TNF-α | ns | ns | ns | 0.0110859 | ns | ns | ns | ns | ns |
VEGF | ns | ns | ns | ns | ns | 0.0524005 | ns | ns | ns |
B | Unstimulated | SARS-CoV-2 | FLU | ||||||
T0 vs. T1 | T0 vs. T2 | T1 vs. T2 | T0 vs. T1 | T0 vs. T2 | T1 vs. T2 | T0 vs. T1 | T0 vs. T2 | T1 vs. T2 | |
TLR1 | ns | ns | ns | ns | ns | ns | ns | 0.0181312 | 0.0520254 |
TLR8 | ns | ns | ns | ns | ns | ns | ns | 0.0373754 | 0.0170549 |
HLAA | ns | ns | ns | 0.0366873 | ns | ns | ns | ns | ns |
CCL3 | ns | 0.0446018 | ns | 0.0513275 | 0.0417868 | ns | ns | ns | ns |
CXCL10 | ns | ns | ns | ns | ns | ns | 0.0127521 | ns | ns |
IL10 | ns | ns | ns | ns | 0.0276853 | 0.0035351 | ns | ns | ns |
CD14 | ns | 0.0089948 | 0.0274998 | ns | 0.0039326 | 0.0350016 | 0.0290724 | 0.0017886 | 0.0113182 |
SLPI | ns | 0.0492902 | ns | ns | ns | ns | ns | 0.0433022 | ns |
CAMP | ns | ns | ns | ns | ns | ns | ns | ns | 0.0535916 |
BPI | ns | ns | 0.0540071 | ns | ns | ns | ns | ns | ns |
IFITM1 | ns | ns | ns | ns | ns | 0.0407747 | ns | ns | ns |
HAVCR2 | ns | ns | ns | ns | ns | 0.0474798 | ns | ns | ns |
BIRK3 | ns | ns | ns | ns | ns | 0.0266934 | ns | ns | ns |
NFKB1 | ns | 0.0248691 | ns | ns | ns | ns | ns | 0.0058548 | 0.0509105 |
SIGLEC1 | ns | ns | ns | ns | ns | ns | 0.013669 | ns | 0.0138821 |
MPO | ns | ns | ns | ns | ns | 0.0253309 | ns | ns | ns |
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Santus, P.; Radovanovic, D.; Garziano, M.; Pini, S.; Croce, G.; Fuccia, G.; Spitaleri, D.; Biasin, M.; Clerici, M.; Trabattoni, D. Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia. J. Clin. Med. 2021, 10, 5765. https://doi.org/10.3390/jcm10245765
Santus P, Radovanovic D, Garziano M, Pini S, Croce G, Fuccia G, Spitaleri D, Biasin M, Clerici M, Trabattoni D. Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia. Journal of Clinical Medicine. 2021; 10(24):5765. https://doi.org/10.3390/jcm10245765
Chicago/Turabian StyleSantus, Pierachille, Dejan Radovanovic, Micaela Garziano, Stefano Pini, Giuseppe Croce, Giuseppe Fuccia, Debora Spitaleri, Mara Biasin, Mario Clerici, and Daria Trabattoni. 2021. "Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia" Journal of Clinical Medicine 10, no. 24: 5765. https://doi.org/10.3390/jcm10245765