Table 1 Baseline Characteristics of All Patients
Variable |
All Patients(n=54) |
Vitamin C(n=26) |
Placebo(n=28) |
P Value |
Demographics |
|
Age, years |
67.4±12.4 |
67.1±10.6 |
67.7±14.0 |
0.86 |
|
Gender, male, n, % |
36(66.7) |
14(53.8) |
22(78.6) |
0.08 |
|
Height, cm |
168.8±6.6 |
167.0±6.9 |
170.8±5.8 |
0.08 |
|
Weight, kg |
62.0±10.5 |
59.7±11.2 |
64.4±9.4 |
0.16 |
Centres |
|
Zhongnan Hospital of Wuhan University, n, % |
10(18.5) |
5(19.2) |
5(17.9) |
- |
|
Leishenshan (Thunder God Mountain) Hospital, n, % |
38(70.4) |
18(69.2) |
20(71.4) |
- |
|
Taihe Hospital, n, % |
6(11.1) |
3(11.5) |
3(10.7) |
- |
General condition on randomization day |
|
Highest temperature, ℃ |
37±1.0 |
37.3±0.8 |
37.4±1.1 |
0.65 |
|
Highest Heart rate, times/min |
93.2±18.4 |
96.6±18.6 |
90.2±18.1 |
0.21 |
|
Lowest MAP, mmHg |
91.0(17.9) |
88.4(16.6) |
93.4(18.9) |
0.31 |
|
Highest RR, times/min |
25[20-36] |
25[21-31] |
24[20-30] |
0.19 |
|
Lowest SPO2, % |
93[88-98] |
93[81-98] |
93[90-97] |
0.93 |
|
APACHE II score |
13.5[10.3-15.8] |
14.0[11.0-16.0] |
13.0[9.5-15.0] |
0.24 |
|
GCS score |
15.0[14.5-15.0] |
15.0[13.0-15.0] |
15.0[15.0-15.0] |
0.75 |
Comorbidities, n, % |
|
Diabetes |
16(29.6) |
7(26.9) |
9(32.1) |
0.77 |
|
Hypertension |
24(44.4) |
10(38.5) |
14(50.0) |
0.42 |
|
Coronary heart disease |
12(22.2) |
4(15.40 ) |
8(28.6) |
0.33 |
|
Chronic lung disease |
3(5.6) |
1(3.8) |
2(7.1) |
1.00 |
|
Chronic renal failure |
1(1.85) |
1(3.8) |
0(0.0) |
0.48 |
|
Malignant tumor |
3(5.6) |
3(11.5) |
0(0.0) |
0.11 |
|
Nervous system diseases |
11(20.4) |
7(26.9) |
4(14.3) |
0.32 |
Median duration of symptoms before HDIVC therapy, days |
17.0[11.0-25.0] |
22.0[11.0-33.0] |
15.0[11.0-22.0] |
0.18 |
Other treatments during 7-days HDIVC therapy |
Corticosteroid use, n, % |
18(33.3) |
8(36.4) |
109(38.5) |
1.00 |
Antibiotic, n, % |
51(94.4) |
24(92.3) |
27 (96.4) |
1.00 |
Net fluid balance, mL/kg/24 h |
|
Day 1 |
190[-1487-662] |
252[-252-810] |
155[-520-499] |
0.39 |
|
Day 2 |
156[-349 -653] |
192[-508-883] |
121[-90 -577] |
0.94 |
|
Day 3 |
62[-703-768] |
-240[-1004 -233] |
463[5-1351] |
0.02 |
|
|
|
|
|
|
|
|
Data were expressed as mean ± standard deviation, as median [interquartile range], or as numbers (percentage). Comparisons were performed using Student’s t test, Wilcoxon–Man–Whitney, Chi square, or Fischer’s exact.
Abbreviations: SD, standard deviation; IQR, interquartile range; APACHE, Acute Physiology and Chronic Health Evaluation; GCS, Glasgow coma scale; HDIVC: high dose intravenous vitamin C.
Table 2 Outcomes in a Trial of HDIVC in patients with Covid-19.
Variable |
Day |
Vitamin C(n=26) |
Placebo(n=28) |
Difference, Coefficient (95% CI) |
P Value |
SOFA scores |
1 |
3.5[3-6.8] |
2.0[3.0-5.0] |
0.7(-0.9 to 2.3) |
0.37 |
3 |
4.0[2.0-8.0] |
4.0[3.0-7.0] |
-0.3(-2.6 to 1.9) |
0.50 |
7 |
3.0[2.0-5.8] |
6.0[2.50-8.0] |
-1.14(-3.1 to 0.8) |
0.24 |
Lowest P/F |
1 |
188.7±95.4 |
210.6±128.5 |
34.6(-91.9 to 48.0) |
0.53 |
3 |
217.3±96.5 |
189.5±101.9 |
30.7(-34.3 to 89.9) |
0.37 |
7 |
228.5±72.6 |
150.7±75.3 |
22.1(33.2 to 122.5) |
0.01 |
Advanced life support, n, % |
|
CRRT |
1 |
1(3.8) |
3(10.7) |
OR0.3(0.0 to 3.5) |
0.61 |
|
7 |
3(12.5) |
1(3.8) |
OR3.57(0.4 to 36.9) |
0.34 |
|
ECMO |
1 |
1(3.8) |
2(7.1) |
OR0.5(0.0 to 6.0) |
1.00 |
|
7 |
0(0.0) |
2(9.1) |
OR0.5(0.4 to 0.7) |
0.50 |
|
Vasopressor use |
1 |
9(36.0) |
6(21.4) |
OR2.1(0.6 to 6.9) |
0.36 |
|
7 |
4(16.7) |
4(17.4) |
OR1.2(0.4 to 3.8) |
1.00 |
|
Oxygen-support category |
|
HFNC |
1 |
7(26.9) |
11(39.3) |
OR0.6(0.2 to 1.8) |
0.40 |
|
7 |
11(47.8) |
9(39.1) |
OR14.3(0.4 to 4.6) |
0.77 |
|
NIV |
1 |
7(26.9) |
7(25.0) |
OR1.1(0.3 to 3.7) |
1.00 |
|
7 |
7(30.4) |
2(8.7) |
OR4.6(0.8 to 25.2) |
0.14 |
|
IMV |
1 |
10(38.5) |
11(39.3) |
OR1.0(0.3 to 2.9) |
1.00 |
|
7 |
10(43.5) |
11(47.8) |
OR0.8(0.3 to 2.7) |
1.00 |
Complications, n, % |
|
Septic shock |
9(34.6) |
8(28.6) |
OR1.3(0.4 to 2.4) |
0.77 |
|
Acute cardiac injury |
7(26.9) |
13(48.1) |
OR0.4(0.1 to 1.3) |
0.16 |
|
Acute liver injury |
12(48.0) |
13(48.1) |
OR1.0(0.3 to 3.0) |
1.00 |
|
Acute kidney injury |
3(12.0) |
6(22.2) |
OR0.5(0.1 to 2.2) |
0.50 |
|
Coagulation disorders |
9(34.6) |
7(25.9) |
OR1.5(0.5 to 5.0) |
0.56 |
Outcomes |
|
HFNC days to day 28, days |
0.5[0.0 -8.3] |
2.0[0.0 -7.0] |
0.2(-2.9 to 3.3) |
0.85 |
|
NIV days to day 28, days |
0.0[0.0 -3.3] |
0.0[0.0 -1.8] |
1.2(-1.2 to 3.7) |
0.68 |
|
IMV days to day 28, days |
1.5[0.0 -19.0] |
6.0[0.0-16.0] |
-0.8(-6.4 to 4.9) |
0.60 |
|
IMV- free days to day 28, days c |
26.5[1.5-28.0] |
10.5[0.0 -28.0] |
4.8(-2.3 to 11.9) |
0.56 |
|
Patients’ condition deterioration, n, % d |
3(11.5) |
6(24.0) |
0.4(0.1 to 1.7) |
0.19 |
|
Patients’ condition improvement, n, % e |
5(19.2) |
6(21.4) |
0.9(0.2 to 3.3) |
0.84 |
|
ICU mortality, n, % |
5(19.2) |
10(35.7) |
HR0.6(0.7 to 1.6) |
0.23 |
|
ICU mortality of patients with SOFA ≥3, n, % |
4(18.2) |
10(50.0) |
HR0.2(0.1 to 0.9) |
0.03 |
|
ICU stay, days |
23.6±14.6 |
18.4±13.2 |
5.2(-2.4 to 12.8) |
0.17 |
|
Hospital mortality, n, % |
5(19.2) |
10(35.7) |
HR0.6(0.7 to 1.6) |
0.23 |
|
Hospital mortality of patients with SOFA ≥3, n, % |
4(18.2) |
10(50.0) |
HR0.2(0.1 to 0.9) |
0.03 |
|
Hospital stay, days |
36.3±16.2 |
33.8±16.4 |
2.4(-7.1 to 11.9) |
0.61 |
|
28-day mortality, n, % |
5(19.2) |
9(32.1) |
HR0.5(0.1 to 1.8) |
0.36 |
|
28-days mortality of patients with SOFA ≥3, n, % |
4(18.2) |
9(45.0) |
HR0.3(0.1 to 1.1) |
0.06 |
Data were expressed as mean ± standard deviation, as median [interquartile range], or as numbers (percentage). Hazard ratio and 95% CI were estimated by Cox proportional risk model. Odd ratio with 95% CI were calculated by binary logistic regression for the rest. Absolute diference was expressed as a percentage with the 95% CI range. P values were calculated by logistic regression.
a Acute cardiac injury was defined as the serum levels of troponin I were above the 99th percentile upper reference limit or new abnormalities were shown in electrocardiography and echocardiography.
b Acute kidney injury was identified according to the Kidney Disease: Improving Global Outcomes definition.
c IMV-free days were defined as the number of days a patient was extubated from mechanical ventilation, after ICU admission to day 28. Days requiring reintubation were subtracted. If the patient died in the hospital post extubation, a value of zero was assigned.
d Patients’ condition deterioration was defined that the patient required HFNC or NIV on day 1, and transferred to ECMO, or IMV, or dead on day 7.
e Patients’ condition improvement was defined that the patient required ECMO or IMV on day 1 and transferred to HFNC, or NIV, or discharged from ICU on day 7.
Abbreviations: HDIVC: high dose intravenous vitamin C; COVID-19, coronavirus disease 2019; SD, standard deviation; IQR, interquartile range; HR, hazard ratio; OR, odd ratio; CI, confidence interval; SOFA: sequential organ failure assessment; P/F, PaO2/FiO2; CRRT, continuous renal replacement therapy; ECMO, extracorporeal membrane oxygenation; HFNC, high flow nasal cannula; IV, invasive ventilation; IMV, invasive mechanical ventilation; NIV, noninvasive mechanical ventilation; ICU, intensive care unit.
Table 3 Laboratory findings in a Trial of HDIVC in patients with Covid-19.
Variable |
Day |
Vitamin C(n=26) |
Placebo(n=28) |
Difference, Coefficient (95% CI) |
P Value |
Leukocyte count, 10^9 |
1 |
9.50±5.04 |
11.45±7.22 |
-1.95(-5.38 to -1.47) |
0.26 |
3 |
8.59[5.74-11.48] |
8.44[7.09-12.23] |
-0.40(-3.50 to 2.70) |
0.67 |
7 |
10.23±6.73 |
9.64±5.41 |
0.59(-2.96 to 4.14) |
0.74 |
Neutrophil count, 10^9 |
1 |
8.21±4.81 |
10.19±7.08 |
-1.98(-5.31 to 1.35) |
0.24 |
3 |
6.19[4.52-10.45] |
7.07[5.68-9.94] |
-0.51(-3.48 to 2.47) |
0.50 |
7 |
8.05±6.47 |
8.15±5.45 |
-0.11(-3.58 to 3.37) |
0.95 |
Neutrophil ratio, % |
1 |
83.50±9.63 |
85.83±9.92 |
-2.33(-7.74 to -3.07) |
0.39 |
3 |
85.65[77.05-91.42] |
83.30[75.53-91.78] |
4.03(-6.32 to 14.38) |
0.70 |
7 |
78.45±15.76 |
81.66±11.45 |
-3.21(-11.22 to 4.79) |
0.42 |
IL-6 |
1 |
22.56[8.87-85.54] |
54.73[12.34-145.47] |
-6.21(-129.71 to 117.29) |
0.61 |
3 |
113.10[21.80-288.73] |
37.24[5.59-85.28] |
92.44(-25.13 to 210.01) |
0.07 |
7 |
19.42[10.59-29.16] |
158.00[15.29-259.60] |
-165.76(-301.72 to -29.79) |
0.04 |
Lymphocyte count, 10^9 |
1 |
0.55[0.36-0.99] |
0.53[0.37-0.95] |
0.09(-0.17 to 0.36) |
0.49 |
3 |
0.56[0.33-0.95] |
0.71[0.47-1.05] |
-2.61(-8.59 to 3.37) |
0.50 |
7 |
0.81[0.43-1.05] |
0.65[0.42-0.97] |
1.11(-0.76 to 2.98) |
0.25 |
Lymphocyte ratio, % |
1 |
9.68±6.97 |
8.12±7.33 |
1.62(-2.32 to 5.57) |
0.41 |
3 |
10.08±9.22 |
8.71±4.90 |
1.37(-2.67 to 5.40) |
0.88 |
7 |
13.14±11.31 |
6.83[5.05 -13.42] |
3.34(-2.13 to 8.81) |
0.23 |
PCT, ng/mL |
1 |
0.16[0.08-0.6] |
0.19[0.05-0.53] |
-9.94(-29.28 to 9.41) |
0.80 |
3 |
0.35[0.09-3.22] |
0.31[0.08-1.11] |
-6.59(-20.46 to 7.28) |
0.84 |
7 |
0.26[0.13-14.79] |
0.20[0.07-0.74] |
13.28(-17.91 to 44.48) |
0.18 |
CRP, mg/L |
1 |
39.86[3.91-86.85] |
56.84[40.19-100.20] |
-23.16(-69.46 to 23.14) |
0.19 |
3 |
43.52[3.41- 65.72] |
66.34[29.76-107.39] |
-4.78(-68.08 to 58.53) |
0.28 |
7 |
29.47[10.95-110.93] |
30.20[2.3-131.70] |
-12.60(-75.34, 50.14) |
0.68 |
Total bilirubin, umol/L |
1 |
8.55[6.78- 15.60] |
10.80[7.40-18.30] |
-1.45(-7.30 to 4.41) |
0.28 |
3 |
8.40[6.70-16.10] |
14.85[9.85-25.48] |
-9.46(-18.33 to -0.59) |
0.03 |
7 |
8.30[6.53-16.15] |
15.30[9.03-27.68] |
-4.19(-15.88 to 7.50) |
0.11 |
, umol/L |
1 |
64.20[46.58-85.45] |
64.20[52.00 -81.70] |
26.35(-50.86 to 103.56) |
0.57 |
3 |
60.30[37.65-80.38] |
70.35[49.80-100.88] |
2.52(-39.89 to -44.93) |
0.15 |
7 |
57.50[39.95-71 ] |
63.50[51.70-104.50] |
-12.43(-45.59 to 20.73) |
0.13 |
BUN, mmol/L |
1 |
7.11[4.48-11.10] |
6.50[4.90-9.94] |
9.34(-8.75 to 27.44) |
0.84 |
3 |
7.58±5.01 |
8.56[5.13-11.39] |
-2.10(-5.22 to -1.02) |
0.11 |
7 |
8.48±5.69 |
7.80[5.10-10.50] |
-0.73(-4.12 to 2.66) |
0.48 |
PT, s |
1 |
13.25[12.35-14.63] |
12.90[12.50-13.80] |
-0.58(-2.35 to 1.19) |
0.97 |
3 |
13.90±3.24 |
13.25[12.70-15.05] |
-0.29(-1.97 to 1.39) |
0.33 |
7 |
12.99±2.55 |
13.05[12.35-14.60] |
-0.27(-1.67 to 1.14) |
0.08 |
Data were expressed as mean ± standard deviation, as median [interquartile range]. Odd ratio with 95% CI were calculated by binary logistic regression for the rest. P values were calculated by logistic regression.
Abbreviations: SD, standard deviation; IQR, interquartile range; HR, hazard ratio; OR, odd ratio; CI, confidence interval; HDIVC: high dose intravenous vitamin C; COVID-19, coronavirus disease 2019; SD, standard deviation; IQR, interquartile range; PCT, procalcitonin; CRP, C-reactive protein; BUN, blood urea nitrogen; PT, prothrombin time,IL-6, interleukin-6.