Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients
Abstract
:1. Introduction
2. Results
2.1. Demographic Data
2.2. Increased NET Products in Plasma of COVID-19 Patients
2.3. Plasma of COVID-19 Patients Induced NETs
2.4. Reduction in NET and mRNA Expression by Enoxaparin Pretreatment In Vitro
2.5. Effects of Enoxaparin Prophylaxis in COVID-19 Patients
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Human Neutrophil Isolation
4.3. Detection of NETs
4.4. Quantification of NETs
4.5. Quantification of Cytokines and NET Products
4.6. Measurement of mRNA Expression
4.7. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Mild (n = 10) | Moderate (n = 10) | Severe (n = 10) | p-Value |
---|---|---|---|---|
Gender (Female) | 42.6% | 33.3% | 16.7% | NA |
(NA) | (NA) | (NA) | ||
Mean Age (yr) | 32.71 | 50.00 | 48.67 | 0.29 |
(16–49) | (34–71) | (18–84) | ||
Mean Weight (kg) | 62.08 | 69.00 | 68.70 | 0.74 |
(49–72) | (60–80) | (85–56) | ||
Mean BMI (kg/m2) | 22.39 | 25.72 | 26.76 | 0.34 |
(17.78–24.34) | (24.03–27.36) | (23.31–31.22) | ||
Underlying diseases | ||||
Diabetes | 0 | 2 | 1 | 0.263 |
Hypertension | 0 | 1 | 1 | 0.521 |
Dyslipidemia | 0 | 0 | 1 | 0.319 |
Chronic kidney disease | 0 | 0 | 2 | 0.089 |
Others (e.g., allergy) | 0 | 0 | 0 | 0.298 |
Parameter | Mild (n = 10) | Moderate (n = 10) | Severe (n = 10) | p-Value |
---|---|---|---|---|
Red cell count | 5.08 | 4.82 | 5.05 | 0.26 |
(4.59–5.81) | (4.08–5.35) | (4.11–6.55) | ||
Hemoglobin | 13.41 | 13.58 | 13.33 | 0.78 |
(10.2–15.2) | (10.3–15.2) | (12.2–15.5) | ||
Hematocrit | 40.80 | 40.45 | 39.48 | 0.84 |
(38.6–45.9) | (32.4–46.9) | (33.6–45.8) | ||
MCV | 80.34 | 83.97 | 78.95 | 0.33 |
(66.7–90.8) | (78.2–88.7) | (69.9–84.6) | ||
MCH | 26.41 | 28.17 | 26.75 | 0.88 |
(22.2–29.3) | (25.2–31.8) | (23.4–29.7) | ||
MCHC | 32.87 | 33.60 | 33.85 | 0.01 |
(32.3–33.3) | (31.8–36.3) | (31.0–36.3) | ||
RDW | 12.94 | 12.62 | 12.87 | 0.96 |
(11.6–14.4) | (11.0–14.0) | (12.1–15.2) | ||
White cell count | 4428.57 | 4795.00 | 5628.33 | 0.15 |
(2490–7550) | (3410–7650) | (3460–8220) | ||
Neutrophil% | 46.34 | 60.63 | 64.48 | 0.30 |
(34.8–58.8) | (45.3–82.1) | (37.8–77.7) | ||
Neutrophil # | 2070.00 | 2913.33 | 3786.67 | 0.26 |
(1230–3720) | (1960–5200) | (1310–6390) | ||
Lymphocyte% | 44.14 | 30.82 | 26.42 | 0.17 |
(31.8–52.0) | (10.6–44.6) | (9.6–53.2) | ||
Lymphocyte # | 1918.57 | 1448.33 | 1353.33 | 0.82 |
(1050–3260) | (360–2110) | (450–1840) | ||
NLR | 1.12 | 2.86 | 3.58 | 0.07 |
(0.67–1.85) | (1.02–7.78) | (0.71–8.09) | ||
Monocyte % | 7.67 | 7.75 | 8.53 | 0.40 |
(5.4–9.9) | (4.7–10.3) | (5.4–9.4) | ||
Monocyte # | 331.43 | 385.00 | 465.00 | 0.14 |
(170–410) | (220–790) | (290–730) | ||
Eosinophils % | 1.46 | 0.53 | 0.23 | 0.10 |
(0–2.8) | (0–1.7) | (0–0.8) | ||
Eosinophils # | 65.71 | 33.33 | 11.67 | 0.05 |
(0–130) | (0–130) | (0–40) | ||
Basophils % | 0.39 | 0.27 | 0.18 | 0.50 |
(0–0.7) | (0–0.7) | (0–0.4) | ||
Basophils # | 14.29 | 15.00 | 10.00 | 0.47 |
(0–30) | (0–50) | (0–30) | ||
Platelet count | 205,857.14 | 207,500.00 | 199,666.67 | 0.30 |
(34,000–327,000) | (138,000–298,000) | (144,000–282,000) | ||
MPV | 10.68 | 10.70 | 11.32 | 0.52 |
(10.3–12.1) | (9.3–11.8) | (10.1–13.3) |
Parameter | Mild (n = 10) | Moderate (n = 10) | Severe (n = 10) | p-Value |
---|---|---|---|---|
AST | 18.00 | 31.83 | 62.00 | 0.004 |
(12–25) | (18–68) | (26–182) | ||
ALT | 15.86 | 39.83 | 45.00 | 0.04 |
(6–38) | (19–81) | (13–109) | ||
ALP | 57.71 | 66.50 | 73.33 | 0.22 |
(45–97) | (89–43) | (37–137) | ||
Total billirubin | 0.52 | 0.57 | 0.75 | 1.00 |
(0.29–1.05) | (0.28–0.91) | (0.53–1.06) | ||
Direct billirubin | 0.20 | 0.23 | 0.36 | 0.24 |
(0.11–0.37) | (0.11–0.39) | (0.18–0.67) | ||
Serum total protein | 8.15 | 7.80 | 8.00 | 0.98 |
(7.9–8.4) | (7.6–8.0) | (7.8–8.4) | ||
Serum albumin | 4.30 | 3.98 | 3.77 | 0.40 |
(4.1–4.7) | (3.6–4.3) | (3.1–4.4) | ||
Serum creatinine | 0.89 | 0.78 | 1.34 | 0.04 |
(0.61–1.39) | (0.50–0.96) | (0.81–2.20) | ||
Blood urea nitrogen | 12.57 | 10.50 | 14.33 | 0.62 |
(7–20) | (7–14) | (10–22) | ||
serum IL-6 | NA | NA | 1680 | NA |
(NA) | (NA) | 1680 | ||
serum hs-CRP | NA | 43.61 | 102.85 | 0.14 |
(NA) | (16.95–110.32) | (21.38–230.37) | ||
serum procalcitonin | NA | 0.05 | 0.28 | 0.08 |
(NA) | (0.02–0.12) | (0.05–1.01) | ||
serum ferritin | NA | 687.65 | 1464.24 | 1.00 |
(NA) | (346.5–884.1) | (620–4609) | ||
serum LDH | NA | 242.33 | 375.33 | 0.23 |
(NA) | (200–299) | (198–556) | ||
d Na | 139.33 | 137.67 | 136.83 | 0.38 |
(136–142) | (133–142) | (129–141) | ||
d K | 3.55 | 3.43 | 3.42 | 0.88 |
(3.2–3.9) | (3.0–3.8) | (2.7–3.8) | ||
d Cl | 106.33 | 102.50 | 90.17 | 0.07 |
(104–109) | (99–107) | (21–106) | ||
d HCO3 | 25.17 | 25.33 | 21.67 | 0.03 |
(23–28) | (23–27) | (12–26) |
Parameter | Mild (n = 10) | Moderate (n = 10) | Severe (n = 10) | p-Value |
---|---|---|---|---|
D-Dimer | NA | 364.36 | 1290.29 | 0.02 |
(NA) | (308.95–411.6) | (794.55–1884.02) | ||
PT | NA | 12.83 | 13.20 | 0.01 |
(NA) | (11.9–14.3) | (12.8–13.5) | ||
INR | NA | 1.12 | 1.15 | 0.01 |
(NA) | (1.04–1.25) | (1.12–1.18) | ||
APTT | NA | 25.30 | 31.40 | 0.30 |
(NA) | (23.0–27.3) | (23.4–56.3) | ||
Fibrinogen | NA | 5.22 | 4.66 | 0.41 |
(NA) | (4.86–5.91) | (4.02–5.91) |
Target Genes | Forward Primers | Reverse Primers |
---|---|---|
PAD4 | 5′-CGAAGACCCCCAAGGACT-3′ | 5′-AGGACAGTTTGCCCCGTG-3′ |
NFKB | 5′-GCAGCACTACTTCTTGACCACC-3′ | 5′-TCTGCTCCTGAGCATTGACGTC-3′ |
SYK | 5′-CGTATGAGCCAGAACTTGCACC-3′ | 5′-CTTTCGGTCCAGGTAAACCTCC-3′ |
PKC | 5′-GAGGGACACATCAAGATTGCCG-3′ | 5′-CACCAATCCACGGACTTCCCAT-3′ |
ERK | 5′-TGGCAAGCACTACCTGGATCAG-3′ | 5′-GCAGAGACTGTAGGTAGTTTCGG-3′ |
ACTB | 5′-CACCATTGGCAATGAGCGGTTC-3′ | 5′-AGGTCTTTGCGGATGTCCACGT-3′ |
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Saithong, S.; Saisorn, W.; Tovichayathamrong, P.; Filbertine, G.; Torvorapanit, P.; Wright, H.L.; Edwards, S.W.; Leelahavanichkul, A.; Hirankarn, N.; Chiewchengchol, D. Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients. Int. J. Mol. Sci. 2022, 23, 4805. https://doi.org/10.3390/ijms23094805
Saithong S, Saisorn W, Tovichayathamrong P, Filbertine G, Torvorapanit P, Wright HL, Edwards SW, Leelahavanichkul A, Hirankarn N, Chiewchengchol D. Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients. International Journal of Molecular Sciences. 2022; 23(9):4805. https://doi.org/10.3390/ijms23094805
Chicago/Turabian StyleSaithong, Supichcha, Wilasinee Saisorn, Punyot Tovichayathamrong, Grace Filbertine, Pattama Torvorapanit, Helen L. Wright, Steven W. Edwards, Asada Leelahavanichkul, Nattiya Hirankarn, and Direkrit Chiewchengchol. 2022. "Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients" International Journal of Molecular Sciences 23, no. 9: 4805. https://doi.org/10.3390/ijms23094805