Introduction
Materials and methods
Study design and participants
Study variables
Sample size calculation
Specimen collection
Genotyping assay
DNA extraction
Genotyping of CXCL12 rs2839693
Statistical analyses
Results
Demographic and clinical characteristics of COVID-19 patients
No | (%) | |
---|---|---|
Age (years) | ||
≤ 65 | 144 | 48.0 |
> 65 | 156 | 52.0 |
Median (Range) | 66.00 (36–85) | |
Sex | ||
Male | 169 | 56.3 |
Female | 131 | 43.7 |
Smoking | ||
No | 182 | 60.7 |
Yes | 118 | 39.3 |
Vaccination(AstraZeneca or Pfizer) | ||
No | 92 | 30.7 |
Yes | 208 | 69.3 |
Co-morbid diseases | ||
None | 91 | 30.3 |
Hypertension | 107 | 35.7 |
Liver disease | 17 | 5.7 |
Renal disease | 39 | 13.0 |
DM | 78 | 26.0 |
Thyroid disease | 12 | 4.0 |
Heart disease | 13 | 4.3 |
Clinical course | ||
Mild or moderate illness | 156 | 52.0 |
Severe or critical illness | 144 | 48.0 |
Symptoms | ||
Fever | 73 | 24.3 |
Sore throat | 110 | 36.7 |
Dry cough | 161 | 53.7 |
Headache | 69 | 23.0 |
Dyspnea | 144 | 48.0 |
Diarrhea | 21 | 7.0 |
Myalgia | 123 | 41.0 |
Fatigue | 165 | 55.0 |
Nausea | 44 | 4.7 |
Vomiting | 15 | 5.0 |
Anosmia | 85 | 28.3 |
Gustatory dysfunction | 69 | 23.0 |
Dysarthria | 9 | 3.0 |
Physical examination, laboratory evaluation, and CT findings of COVID-19 patients
Physical examination findings on admission | No | (%) |
---|---|---|
Temperatures (°C) | ||
< 38.0 | 206 | 68.7 |
≥ 38.0 | 94 | 31.3 |
Median (Range) | 38.00 (36.2–40) | |
Laboratory investigation | ||
lymphocyte count (× 109/L) | ||
< 1.0 | 84 | 28.0 |
1.0–4.0 | 185 | 61.7 |
> 4.0 | 31 | 10.3 |
Median(Range) | 1.40 (0.4–5.8) | |
Leucocyte (× 109/L) | ||
< 4.0 | 61 | 20.3 |
4.0–10.0 | 142 | 47.3 |
> 10.0 | 97 | 32.4 |
Median(Range) | 7.70 (1.8–16.2) | |
Platelets × 103/mL | ||
≤ 100 | 44 | 14.7 |
> 100 | 256 | 85.3 |
Median(Range) | 244.00 (71–420) | |
CRP level (mg/L) | ||
≤ 5 | 50 | 16.7 |
> 5 | 250 | 83.3 |
Median(Range) | 48.00 (4–768) | |
Ferritin level (μg/L) | ||
≤ 300 | 100 | 33.3 |
> 300 | 200 | 66.7 |
Median(Range) | 404.50 (10–2500) | |
D-dimers level (μg/L) | ||
< 0.5 | 120 | 40.0 |
0.5–1.0 | 92 | 30.7 |
> 1.0 | 88 | 29.3 |
Median(Range) | 0.70 (0.1–3.3) | |
Imaging | ||
CT findings | ||
Normal | 27 | 9.0 |
Bilateral GGO | 205 | 68.3 |
Pneumonic consolidation | 107 | 35.7 |
Treatment and outcomes of COVID-19 patients
Treatment modalities | No | (%) |
---|---|---|
Antibiotic | 288 | 96.0 |
Antifungal | 18 | 6.0 |
Antiviral | 232 | 77.3 |
Glucocorticoids | 176 | 58.7 |
Clexane | 92 | 30.7 |
Oxygen therapy | ||
None | 73 | 24.3 |
Nasal cannula | 78 | 26.0 |
Mask oxygen | 150 | 50.0 |
Non-invasive mechanical ventilation | 64 | 21.3 |
Invasive mechanical ventilation | 18 | 6.0 |
Outcomes | ||
Home management | 78 | 26.0 |
Hospitalization without ICU | 78 | 26.0 |
ICU | 144 | 48.0 |
Death | 39 | 13.0 |
Duration of ICU stay (days) | ||
Median(Range) | 7.00 (1.0–13.0) | |
Duration of in-hospital stay (days) | ||
Median(Range) | 7.00 (1.0–15.0) | |
Duration of recovery (days) | ||
Median(Range) | 15.00 (2.0–48.0) |
Genetic findings of CXCL12 rs2839693 for COVID-19 patients
CXCL12 rs2839693 | Mild or moderate (n = 156) | Severe or critical (n = 144) | OR (95%CI) | P value* | ||
---|---|---|---|---|---|---|
No | % | No | % | |||
Genotypes | ||||||
CC | 126 | 80.8 | 83 | 57.6 | 0.32(0.19–0.54) | & < 0.001* |
CT | 30 | 19.2 | 54 | 37.5 | 2.52(1.50–4.25) | & < 0.001* |
TT | 0 | 0.0 | 7 | 4.9 | 0.47(0.41–0.53) | &0.005* |
CT + TT | 30 | 19.2 | 61 | 42.4 | 3.08(1.84–5.18) | & < 0.001* |
Alleles | ||||||
C | 282 | 90.4 | 220 | 76.4 | 2.91(1.83–4.62) | & < 0.001* |
T | 30 | 9.6 | 68 | 23.6 |
P value* | OR | 95% C.I | |||
---|---|---|---|---|---|
Lower | Upper | ||||
Severe or critical COVID19 | Genotyping of CXCL12 CC/CT + TT | < 0.001* | 3.034 | 1.805 | 5.098 |
Patient demographic data, comorbidity, and symptoms according to CXCL12 rs2839693 genotypes
CXCL12 rs2839693 | ||||||||
---|---|---|---|---|---|---|---|---|
CC (n = 209) | CT + TT (n = 91) | OR (95%CI) | P value* | CC (n = 209) | CT (n = 84) | TT (n = 7) | P value* | |
No. (%) | No. (%) | No. (%) | No. (%) | No. (%) | ||||
Age (years) | ||||||||
≤ 65 | 101(48.3) | 43(47.3) | 1.04 (0.64–1.71) | &0.900 | 101(48.3) | 42(50.0) | 1(14.3) | &0.189 |
> 65 | 108(51.7) | 48(52.7) | 108(51.7) | 42(50.0) | 6(85.7) | |||
Median (Range) | 66 (36–93) | 70 (47–82) | ------ | §0.221 | 66 (36–93) | 70 (47–82) | 62 (58–68) | §0.042* |
Sex | ||||||||
Male | 113(54.1) | 56(61.5) | 0.74 (0.45–1.22) | &0.256 | 113(54.1) | 52(61.9) | 4(57.1) | &0.473 |
Female | 96(45.9) | 35(38.5) | 96(45.9) | 32(38.1) | 3(42.9) | |||
Smoking | ||||||||
No | 131(62.7) | 51(56.0) | 1.32 (0.80–2.17) | &0.305 | 131(62.7) | 47(56.0) | 4 (57.1) | &0.556 |
Yes | 78(37.3) | 40(44.0) | 78(37.3) | 37(44.0) | 3(42.9) | |||
Vaccination(AstraZeneca or Pfizer) | ||||||||
No | 62(29.7) | 30(33.0) | 0.86 (0.51–1.46) | &0.588 | 62(29.7) | 27(32.1) | 3(2.9) | &0.714 |
Yes | 147(70.3) | 61(67.0) | 147(70.3) | 57 (67.9) | 4(57.1) | |||
Co-morbid diseases | ||||||||
None | 69(33.0) | 22(24.2) | 0.65 (0.37–1.13) | &0.135 | 69(33.0) | 22(26.2) | 0(0) | &0.109 |
Hypertension | 76(36.4) | 31(34.1) | 0.90 (0.54–1.52) | &0.793 | 76(36.4) | 29(34.5) | 2 (28.6) | &0.884 |
Liver disease | 10(4.8) | 7(7.7) | 1.66 (0.61–4.50) | &0.415 | 10(4.8) | 6(7.1) | 1(14.3) | &0.445 |
Renal disease | 23(11.0) | 16(17.6) | 1.73 (0.86–3.45) | &0.136 | 23(11.0) | 14(16.7) | 2(28.6) | &0.198 |
DM | 52(24.9) | 26(28.6) | 1.21 (0.70–2.10) | &0.567 | 52(24.9) | 23(27.4) | 3(42.9) | &0.534 |
Thyroid disease | 7(3.3) | 5(5.5) | 1.68 (0.52–5.43) | &0.522 | 7(3.3) | 5(6.0) | 0(0) | &0.508 |
Heart disease | 8(3.8) | 5(5.5) | 1.46 (0.47–4.59) | &0.543 | 8(3.8) | 5(6.0) | 0(0) | &0.514 |
Symptoms | ||||||||
Fever | 49(23.4) | 24(26.4) | 1.17 (0.66–2.06) | &0.661 | 49(23.4) | 20(23.8) | 4(57.1) | &0.123 |
Sore throat | 82(39.2) | 28(30.8) | 0.69 (0.41–1.16) | &0.193 | 82(39.2) | 26(31.0) | 2(28.6) | &0.373 |
Dry cough | 116(55.5) | 45(49.5) | 0.78 (0.48–1.28) | &0.378 | 116(55.5) | 42(50.0) | 3(42.9) | &0.587 |
Headache | 46(22.0) | 23(25.3) | 1.19 (0.67–2.13) | &0.553 | 46(22.0) | 21(25.0) | 2(28.6) | &0.807 |
Dyspnea | 83(39.7) | 61(67.0) | 3.09 (1.84–5.18) | & < 0.001* | 83(39.7) | 54(64.3) | 7(100) | & < 0.001* |
Diarrhea | 17(8.1) | 4(4.4) | 0.52 (0.17–1.59) | &0.327 | 17(8.1) | 3(3.6) | 1(14.3) | &0.286 |
Myalgia | 82(39.2) | 41(45.1) | 1.27 (0.77–2.09) | &0.373 | 82(39.2) | 39(46.4) | 2(28.6) | &0.419 |
Fatigue | 117(56.0) | 48(52.7) | 0.88 (0.54–1.44) | &0.616 | 117(56.0) | 45(53.6) | 3(42.9) | &0.753 |
Nausea | 31(14.8) | 13(14.3) | 0.96 (0.48–1.93) | &1.000 | 31(14.8) | 11(13.1) | 2(28.6) | &0.535 |
Vomiting | 9(4.3) | 6(6.6) | 1.57 (0.54–4.54) | &0.399 | 9(4.3) | 4(4.8) | 2(28.6) | &0.015* |
Anosmia | 63(30.1) | 22(24.2) | 0.74 (0.42–1.30) | &0.331 | 63(30.1) | 21(25.0) | 1(14.3) | &0.478 |
Gustatory dysfunction | 53(25.4) | 16(17.6) | 0.63 (0.34–1.17) | &0.179 | 53(25.4) | 15(17.9) | 1(14.3) | &0.331 |
Dysarthria | 4(1.9) | 5(5.5) | 2.98 (0.78–11.4) | &0.136 | 4(1.9) | 3(3.6) | 2(28.6) | & < 0.001* |
Clinical course | ||||||||
Mild or moderate illness | 126(60.3) | 30(33.0) | 3.09 (1.84–5.18) | & < 0.001* | 126(60.3) | 30(35.7) | 0(0) | & < 0.001* |
Severe or critical illness | 83(39.7) | 61(67.0) | 83(39.7) | 54(64.3) | 7(100) |
Laboratory evaluation and CT findings according to CXCL12 rs2839693 genotypes
CXCL12 rs2839693 | ||||||||
---|---|---|---|---|---|---|---|---|
CC (n = 209) | CT + TT (n = 91) | OR (95%CI) | P value* | CC (n = 209) | CT (n = 84) | TT (n = 7) | P value* | |
No. (%) | No. (%) | No.(%) | No. (%) | No. (%) | ||||
Laboratory investigation | ||||||||
lymphocyte count (× 109/L) | ||||||||
< 1.0 | 62(29.7) | 22(24.2) | ------ | #0.579 | 62(29.7) | 21(25.0) | 1(14.3) | #0.635 |
1.0–4.0 | 125(59.8) | 60(65.9) | 125(59.8) | 54(64.3) | 6(85.7) | |||
> 4.0 | 22(10.5) | 9(9.9) | 22(10.5) | 9(10.7) | 0(0) | |||
Median (Range) | 1.40 (0.4–5.4) | 1.40 (0.4–5.8) | ------ | §0.564 | 1.40 (0.4–5.4) | 1.40 (0.4–5.8) | 2.40 (0.6–3.1) | §0.603 |
Leucocyte (× 109/L) | ||||||||
< 4.0 | 44(21.1) | 17(18.7) | ------ | #0.614 | 44(21.1) | 16(19.0) | 1(14.3) | #0.894 |
4.0–10.0 | 95(45.5) | 47(51.6) | 95(45.5) | 43(51.2) | 4(57.1) | |||
> 10.0 | 70(33.5) | 27(29.7) | 70(33.5) | 25(29.8) | 2(28.6) | |||
Median (Range) | 7.7 (1.9–16.2) | 7.8 (1.8–15.2) | ------ | ^0.872 | 7.70 (1.9–16.2) | 7.75 (1.8–15.2) | 9.40 (2.8–12.2) | ^0.935 |
Platelets | ||||||||
≤ 100 | 28(13.4) | 16(17.6) | 0.73 (0.37–1.42) | &0.376 | 28(13.4) | 15(17.9) | 1(14.3) | &0.621 |
> 100 | 181(86.6) | 75(82.4) | 181(86.6) | 69(82.1) | 6(85.7) | |||
Median (Range) | 245.0 (71–420) | 241.0 (76–402) | ------ | §0.572 | 245.0 (71–420) | 240.0 (76–402) | 259.0 (86–320) | §0.724 |
CRP level (mg/L) | ||||||||
≤ 5 | 43(20.6) | 7(7.7) | 3.11 (1.34–7.21) | &0.006* | 43(20.6) | 7(8.3) | 0(0) | &0.019* |
> 5 | 166(79.4) | 84(92.3) | 166(79.4) | 77(91.7) | 7(100) | |||
Median (Range) | 48.0 (4–768) | 48.0 (4–768) | ------ | §0.823 | 48.0 (4–768) | 48.0 (4–768) | 48.0 (12–768) | §0.567 |
Ferritin level (μg/L) | ||||||||
≤ 300 | 77(36.8) | 23(25.3) | 1.73 (1.00–2.99) | &0.062 | 77(36.8) | 23(27.4) | 0(0) | &0.050* |
> 300 | 132(63.2) | 68(74.7) | 132(63.2) | 61(72.6) | 7(100) | |||
Median (Range) | 387.0 (12–2500) | 500.0 (10–2360) | ------ | §0.124 | 387.0 (12–2500) | 471.0 (10–2360) | 932.0 (369–1880) | §0.028* |
D-dimers level (μg/L) | ||||||||
< 0.5 | 90(43.1) | 30(33.0) | ------ | #0.104 | 90(43.1) | 29(34.5) | 1(14.3) | #0.009* |
0.5–1.0 | 65(31.1) | 27(29.7) | 65(31.1) | 27(32.1) | 0(0) | |||
> 1.0 | 54(25.8) | 34(37.4) | 54(25.8) | 28(33.3) | 6(85.7) | |||
Median (Range) | 0.60 (0.1–3.3) | 0.80 (0.1–3.1) | ------ | §0.017* | 0.60 (0.1–3.3) | 0.70 (0.1–3.1) | 2.0 (0.4–2.8) | §0.002* |
Imaging | ||||||||
CT findings | ||||||||
Normal | 23(11.0) | 4(4.4) | 0.37 (0.13–1.11) | &0.079 | 23(11.0) | 4(4.8) | 0(0) | &0.169 |
Bilateral GGO | 142(67.9) | 63(69.2) | 1.06 (0.62–1.81) | &0.893 | 142(67.9) | 58(69.0) | 5(71.4) | &0.968 |
Pneumonic consolidation | 69(33.0) | 38(41.8) | 1.46 (0.88–2.41) | &0.152 | 69(33.0) | 35(41.7) | 3(42.9) | &0.347 |
Treatment and outcomes according to CXCL12 rs2839693 genotypes
CXCL12 rs2839693 | ||||||||
---|---|---|---|---|---|---|---|---|
CC (n = 209) | CT + TT (n = 91) | OR (95%CI) | P value* | CC (n = 209) | CT (n = 84) | TT (n = 7) | P value* | |
No. (%) | No. (%) | No. (%) | No.(%) | No.(%) | ||||
Antibiotic | 203(97.1) | 85(93.4) | 0.42(0.13–1.34) | &0.196 | 203(97.1) | 78(92.9) | 7(100) | &0.207 |
Antifungal | 12(5.7) | 6(6.6) | 1.16(0.42–3.19) | &0.794 | 12(5.7) | 6(7.1) | 0(0) | &0.717 |
Antiviral | 155(74.2) | 77(84.6) | 1.92(1.00–3.66) | &0.052 | 155(74.2) | 71(84.5) | 6(85.7) | &0.138 |
Glucocorticoids | 116(55.5) | 60(65.9) | 1.55(0.93–2.59) | 0.099 | 116(55.5) | 55(65.5) | 5(71.4) | &0.230 |
Clexane | 57(27.3) | 35(38.5) | 1.67(0.99–2.81) | &0.058 | 57(27.3) | 30(35.7) | 5(71.4) | &0.022* |
Oxygen therapy | ||||||||
None | 64(30.6) | 9(9.9) | 0.25(0.12–0.53) | & < 0.001* | 64(30.6) | 9(10.7) | 0(0) | & < 0.001* |
Nasal cannula | 43(20.6) | 35(38.5) | 2.41(1.41–4.14) | &0.002* | 43(20.6) | 29(34.5) | 6(85.7) | & < 0.001* |
Mask oxygen | 96(45.9) | 54(59.3) | 1.72(1.04–2.83) | &0.044* | 96(45.9) | 50(59.5) | 4(57.1) | &0.102 |
Invasive mechanical ventilation | 8(3.8) | 10(11.0) | 3.10(1.18–8.14) | &0.031* | 8(3.8) | 10(11.9) | 0(0) | &0.025* |
Outcomes | ||||||||
Home management | 65(31.1) | 13(14.3) | 0.37(0.19–0.71) | &0.002* | 65(31.1) | 13(15.5) | 0(0) | &0.006* |
Hospitalization without ICU | 61(29.2) | 17(18.70 | 0.56(0.30–1.02) | &0.063 | 61(29.2) | 17(20.2) | 0(0) | &0.082 |
ICU | 83(39.7) | 61(67.0) | 3.09(1.84–5.18) | & < 0.001* | 83(39.7) | 54(64.3) | 7(100) | & < 0.001* |
Death | 21(10.0) | 18(19.8) | 2.21(1.11–4.38) | &0.026* | 21(10.0) | 13(15.5) | 5(71.4) | & < 0.001* |
Duration of ICU stay (days) | ||||||||
Median( Range) | 8.00(1–13) | 7.00(1–13) | ------ | §0.284 | 8.00(1–13) | 6.50(1–13) | 9.00(1–12) | §0.159 |
Duration of in-hospital stay (days) | ||||||||
Median(Range) | 7.50(1–15) | 7.00(1–15) | ------ | §0.856 | 7.50(1–15) | 7.00(1–15) | 12.00(6–15) | §0.035* |
Duration of recovery (days) | ||||||||
Median (Range) | 18.00(2–48) | 15.00(2–48) | ------ | §0.703 | 18.00(2–48) | 15.00(2–48) | 23.50(2–44) | §0.930 |