Dysregulated Inflammatory Cytokine Levels May Be Useful Markers in a Better Up-Dated Management of COVID-19
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study and Population Design
2.2. Multiplex Cytokine Assay
2.3. Human Cytokines Sandwich ELISA Array
2.4. Principal Component Analysis (PCA)
2.5. Statistical Analysis
2.6. Ethics
3. Result
3.1. Concentrations of IL-10, IP-10, TNF-α, IL-1β, IL-27, and IL-8 Are Deregulated in Serum from Patients with COVID-19
3.2. IL-1β, IL-10, IL-27, IP-10, and TNF-α Dysregulations Are Confirmed by ELISA Assay in an Extended Cohort
3.3. IP-10 and TNF-α Dysregulations Are Associated with COVID Severity
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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2 doses of BNT162b2 vaccinated healthy donors (HDs) (number) | 10 |
Male (%) | 10 |
Female (%) | 90 |
Average age ± SD | 41.6 ± 12.06 |
Not vaccinated patients (PZ) (number) | 29 |
Male (%) | 65.51 |
Female (%) | 62.07 |
Average age ± SD (years) | 60.31 ± 15.89 |
Time elapsed since end of infection (days) ± SD | 71.86 ± 29.94 |
Mild (number) | 15 |
Mild (%) | 51.7 |
Severe (number) | 14 |
Severe (%) | 48.2 |
Healthy donors (HD) (number) | 25 |
Not vaccinated | 6 |
3 doses of BNT162b2 vaccinated | 19 |
Male (%) | 28 |
Female (%) | 72 |
Average age ± SD | 47.27 ± 16.18 |
Patients (PZ) (number) | 33 |
Not vaccinated | 24 |
3 doses of BNT162b2 vaccinated | 9 |
Male (%) | 66.7 |
Female (%) | 33.3 |
Average age ± SD (years) | 47.48 ± 16.29 |
Time elapsed since end of infection (days) ± SD | 63 ± 71.53 |
(1° group) 2–30 days (number) | 14 |
Average time elapsed since end of infection (days) | 15 ± 9.20 |
(2° group) 31–60 days (number) | 12 |
Average time elapsed since end of infection (days) | 39 ± 6.68 |
(3° group) 70–207 days (number) | 7 |
Average time elapsed since end of infection (days) | 161 ± 94.98 |
Mild (number) | 7 |
Mild (%) | 21.21 |
Severe (number) | 3 |
Severe (%) | 9.09 |
Pauci-symptomatic (number) | 8 |
Pauci-symptomatic (%) | 24.24 |
Pneumonia (number) | 15 |
Pneumonia (%) | 45.45 |
(a) | ||||
Odds Ratio of Event = Severe COVID-19 | ||||
Variable | Estimate | 95% CL | p-Value | |
IP10_T0 high vs. low * | 2.62 | 0.53 | 13.10 | 0.240 |
* high: ≥the top quintile vs. low: <the top quintile (i.e., ≥873 vs. <873). | ||||
(b) | ||||
Odds Ratio of Event = Severe COVID-19 | ||||
Variable | Estimate | 95% CL | p-Value | |
TNF-α_T0 high vs. low * | 2.58 | 0.54 | 13.15 | 0.239 |
* high: ≥the top quintile vs. low: <the top quintile (i.e., ≥153 vs. <153). | ||||
(c) | ||||
Odds Ratio of High IP-10 Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 11.33 | 1.05 | 122.55 | 0.046 |
* high: ≥the top quintile vs. low: <the top quintile (i.e., ≥363 vs. <363). | ||||
(d) | ||||
Odds Ratio of High TNF-α Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
TNF-α high vs. low * | 18.00 | 1.69 | 191.52 | 0.017 |
* high: ≥the top quintile vs. low: <the top quintile (i.e., ≥212 vs. <212). | ||||
(e) | ||||
Adjusted Odds Ratio of High IP-10 Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 13.51 | 1.08 | 191.80 | 0.050 |
IP-10 at T0 ** | 2.62 | 0.77 | 8.84 | 0.120 |
* high: ≥top quintile vs. low: <top quintile (i.e., ≥363 vs. <363) | ||||
** for one natural log increment | ||||
(f) | ||||
Adjusted Odds Ratio of High TNF-α Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 16.52 | 0.83 | 328.37 | 0.066 |
TNF-α at T0 ** | 35.70 | 1.41 | 906.61 | 0.030 |
* high: ≥80th percentile vs. low: <80th perc. (i.e., ≥212 vs. <212) | ||||
** for one natural log increment | ||||
(g) | ||||
Adjusted Odds Ratio of High IP-10 Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVOD-19 vs. non-severe | 11.78 | 1.15 | 120.28 | 0.037 |
months from negative test ** | 1.25 | 0.47 | 3.34 | 0.656 |
* high: ≥top quintile vs. low: <top quintile (i.e., ≥363 vs. <363) | ||||
** for 3 months increments | ||||
(h) | ||||
Adjusted Odds Ratio of High TNF-α Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 4.62 | 0.24 | 90.05 | 0.312 |
months from negative test ** | 10.90 | 0.50 | 253.71 | 0.128 |
* high: ≥80th percentile vs. low: <80th perc. (i.e., ≥212 vs. <212) | ||||
** for 3 months increment | ||||
(i) | ||||
Odds Ratio of Event = Severe COVID-19 | ||||
Variable | Estimate | 95% CL | p-Value | |
IL-10 low vs. high * | 1.47 | 0.21 | 10.20 | 0.699 |
* low: ≤second quintile vs. high: >second quintile (i.e., ≤1.3 vs. >1.3) | ||||
(j) | ||||
Odds Ratio of Low IL-10 Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 8.17 | 1.42 | 47.02 | 0.019 |
* low: ≤second quintile vs. high: >second quintile (i.e., ≤1.3 vs. >1.3) | ||||
(k) | ||||
Odds Ratio of Low IL-10 Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 6.43 | 1.05 | 39.40 | 0.032 |
Il-10 at T0 ** | 2.86 | 0.47 | 17.54 | 0.256 |
* low: ≤second quintile vs. high: >second quintile (i.e., ≤3.9 vs. >3.9) ** for one natural log increment | ||||
(l) | ||||
Odds Ratio of Low IL-10 Concentration at T1 * | ||||
Variable | Estimate | 95% CL | p-Value | |
severe COVID-19 vs. non-severe | 4.47 | 0.51 | 39.52 | 0.178 |
months from negative test ** | 2.27 | 0.18 | 29.05 | 0.528 |
* low: ≤second quintile vs. high: >second quintile (i.e., ≤3.9 vs. >3.9) ** for 3 months increment |
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Iuliano, M.; Mongiovì, R.M.; Parente, A.; Kertusha, B.; Carraro, A.; Marocco, R.; Mancarella, G.; Del Borgo, C.; Fondaco, L.; Grimaldi, L.; et al. Dysregulated Inflammatory Cytokine Levels May Be Useful Markers in a Better Up-Dated Management of COVID-19. Curr. Issues Mol. Biol. 2024, 46, 8890-8902. https://doi.org/10.3390/cimb46080525
Iuliano M, Mongiovì RM, Parente A, Kertusha B, Carraro A, Marocco R, Mancarella G, Del Borgo C, Fondaco L, Grimaldi L, et al. Dysregulated Inflammatory Cytokine Levels May Be Useful Markers in a Better Up-Dated Management of COVID-19. Current Issues in Molecular Biology. 2024; 46(8):8890-8902. https://doi.org/10.3390/cimb46080525
Chicago/Turabian StyleIuliano, Marco, Roberta Maria Mongiovì, Alberico Parente, Blerta Kertusha, Anna Carraro, Raffaella Marocco, Giulia Mancarella, Cosmo Del Borgo, Laura Fondaco, Lorenzo Grimaldi, and et al. 2024. "Dysregulated Inflammatory Cytokine Levels May Be Useful Markers in a Better Up-Dated Management of COVID-19" Current Issues in Molecular Biology 46, no. 8: 8890-8902. https://doi.org/10.3390/cimb46080525