The study compared the COVID-19 recovery, as measured by RT-PCR and blood biomarkers, between the intervention NOQ19 arm and placebo arm. Attrition rate in both the study groups was zero.
Table 1 demonstrates the demographic characteristics of the patients enrolled in the study. No significant differences in age or gender distribution were observed between the study groups. The two groups were also similar in height, weight, blood pressure and pulse rate at the time of enrollment. Vaccination status of the patients was also captured to analyse any change in response of the intervention between the partially and fully vaccinated groups. A significant difference was noted in the HR-CT score, SpO2 values, temperature and respiratory rate between the two groups at the time of enrollment..
According to Berkson’s bias, due to the increased rate of exposure during the study enrollment and likelihood of patients being admitted in the hospital, the intervention arm had more patients with severe or advanced symptoms than the placebo arm from the start of the study.32 This resulted in a higher number of patients being severe in the NOQ19 arm than in the placebo arm. Although patients were classified as severe, none of them were in ICU or on ventilation. At baseline, the NOQ19 arm had 41% moderate patients and 59% patients classified with severe disease, none of whom were on ventilation, while the placebo group consisted of 78% moderate and 22% patients classified with severe disease.
Table 1
Demographic characteristic of the patients in the study arms
Demography
|
|
NOQ19 (n=22)
|
Placebo (n=18)
|
p-value
|
Severity of disease n(%)
|
Mild
|
0
|
0
|
|
Moderate
|
9 (41%)
|
14 (78%)
|
|
Severe
|
13 (60%)
|
4 (22%)
|
|
Age
|
Mean (SD)
|
53.64 (16.23)
|
44.44 (16.13)
|
0.08*
|
Median
|
55.5
|
42
|
Range
|
22 – 78 (56)
|
21 – 75 (54)
|
Gender n(%)
|
Male
|
9 (59%)
|
9 (50%)
|
0.57
|
Female
|
13 (41%)
|
9 (50%)
|
Height Mean (SD)
|
|
167.2(6.8)
|
166.9 (7.3)
|
0.92
|
Weight Mean (SD)
|
|
70.2 (14.2)
|
73.6 (9.8)
|
0.39
|
Pulse Rate (per min.)
Mean (SD)
|
|
99 (14.1)
|
91 (13.8)
|
0.10
|
Respiratory Rate
(per min.) Mean (SD)
|
|
26 (4.5)
|
24 (3.9)
|
0.14
|
Temperature Mean (SD)
|
|
99.6 (1.3)
|
98.5 (0.9)
|
0.003*
|
SpO2
Mean (SD)
|
|
90.09 (4.71)
|
93.89 (4.1)
|
0.02*
|
Blood Pressure Mean (SD)
|
Systolic
|
134 (16.1)
|
128 (20.2)
|
0.29
|
Diastolic
|
80 (10.8)
|
77 (10.7)
|
0.39
|
CT- Score n(%)
|
Moderate
|
9 (41%)
|
14 (78%)
|
0.03*
|
Severe
|
13 (60%)
|
4 (22%)
|
Vaccination (n)
|
Full Vaccination
|
2
|
3
|
<0.001**
|
Non- Vaccination
|
14
|
13
|
Partial Vaccination
|
6
|
2
|
Smoker (n)
|
|
5
|
4
|
0.969
|
Alcohol (n)
|
|
4
|
3
|
0.9
|
* p value <0.05 - Significant
** p value <0.001 - highly significant
Table 2 demonstrates the inter and intra group analysis of COVID-19 recovery and viral load reduction as measured by RT-PCR negativity rate at different time points. Among the NOQ19 arm, 23% (n=5) of the patients were negative on Day 7 while only 11% (n=2) patients were negative in the placebo group. However on Day 10, the number of patients who were negative in the intervention arm was 37% (n=8), and 50% (n=9) in the placebo arm. At both the time points the difference was not statistically significant between the groups. However, when the patients were grouped by severity of disease (moderate and severe), and analysed thereafter, a significant increase in the number of patients turning RT-PCR negative on day 7 was observed among both moderate and severe patients in the NOQ19 arm. Among the severe patients, the NOQ19 arm demonstrated an early recovery.
Table 2
Percentage Population with RT-PCR Negative test at Day7 and Day 10
RT-PCR Negative Test
|
NOQ19 (n= 22 )
n (%)
|
Placebo Arm (n=18)
n (%)
|
Intergroup p value
|
Total Population
|
Day 0
|
0(0%)
|
0(0%)
|
|
Day 7
|
5 (23%)
|
2(11%)
|
0.423
|
p value (Day 0 vs. 7)
|
0.048*
|
0.48
|
|
Day 10
|
9(41%)
|
9(50%)
|
0.523
|
p value (Day 0 vs.10)
|
0.004*
|
0.0001**
|
|
RT-PCR Negative Test
|
NOQ19 (n= 6)
n (%)
|
Placebo Arm (n=14)
n (%)
|
|
Moderate Population
|
Day 0
|
0(0%)
|
0(0%)
|
|
Day 7
|
2(22%)
|
2(14%)
|
0.6588
|
p value (Day 0 vs. 7)
|
0.1690
|
0.1648
|
|
Day 10
|
6 (67%)
|
9(64%)
|
0.9124
|
p value (Day 0 vs.10)
|
0.0039*
|
0.0003**
|
|
RT-PCR Negative Test
|
NOQ19 (n= 13)
n (%)
|
Placebo Arm (n=4)
n (%)
|
|
Severe Population
|
Day 0
|
0(0%)
|
0(0%)
|
|
Day 7
|
3(23%)
|
0(0%)
|
0.287
|
p value (Day 0 vs. 7)
|
0.0821
|
Not applicable
|
|
Day 10
|
3(23%)
|
0(0%)
|
0.374
|
p value (Day 0 vs.10)
|
0.0821
|
Not applicable
|
|
* p value <0.05 - Significant
** p value <0.001 - highly significant
Table 3 depicts the blood biomarker progression in both the study arms. Significant differences in temperature, immune markers and blood parameters were noted between the two groups on the day of admission. The values for IL-6, a cytokine marker, were significantly higher in the NOQ19 group as compared to placebo group at baseline (p=0.02). IL-6 showed a significant reduction from day 0 to day 10 in both the arms (intra group p<0.001). However, the mean reduction was greater in the NOQ19 arm (2.2 units) as compared to placebo (1 unit). Similar trends were observed for S. Ferritin, CRP and D-Dimer. The baseline values for all the markers were much higher in the NOQ19 arm than the placebo arm. The intragroup p values were significant for all markers in both arms, except D-Dimer, signifying that both the arms showed an improvement. However for all clinical markers, NOQ19 showed a greater improvement as seen by the mean difference.
Due to the differences in severity of disease between the two arms, the data was further divided into moderate and severe groups. It was analysed individually for both the arms because the sample size in each sub-group varied between the arms. Table 4 demonstrates the difference in blood parameters in severe patients among the NOQ19 and placebo arm. Except D-dimer, all the blood markers significantly improved by Day 10 in the NOQ19 arm. However, a significant improvement was not noted in the placebo arm, probably because of small sample size. Therefore, the data was not presented.
Table 3
Blood Parameter Inter and Intra group Analysis at Day 0, Day7 and Day 10
Parameters
|
|
NOQ19 (n=22)
|
Placebo Arm (n=18)
|
Intergroup p- value
|
IL-6
|
Day 0 Mean (SD)
|
10.3 (6.7)
|
6.4 (3.0)
|
0.02*
|
DAY10
Mean (SD)
|
8.1 (5.5)
|
5.4 (2.8)
|
0.005*
|
IntraGroup p value
|
<0.001**
|
<0.001**
|
|
Mean Difference
|
2.2
|
1
|
|
S. Ferritin
|
Day 0 Mean (SD)
|
892.9 ( 471.6)
|
649.1 (386.5)
|
0.08
|
DAY10
Mean (SD)
|
752.5 (347.2)
|
563.1 (297.5)
|
0.071
|
IntraGroup p value
|
0.014*
|
0.001**
|
|
Mean Difference
|
140.4
|
86
|
|
D-dimer
|
Day 0 Mean (SD)
|
748.1 (394.6)
|
497.3 (261.9)
|
0.021*
|
DAY10
Mean (SD)
|
641.1 (283.3)
|
445.8 (225.3)
|
0.02*
|
IntraGroup p value
|
0.113
|
0.045*
|
|
Mean Difference
|
107
|
51.5
|
|
CRP
|
Day 0 Mean (SD)
|
6.7 (3.7)
|
4.8 (2.8)
|
0.073
|
DAY10
Mean (SD)
|
5.0 (3.0)
|
3.4 (1.6)
|
0.04*
|
IntraGroup p value
|
0.001**
|
0.015*
|
|
Mean Difference
|
1.7
|
1.4
|
|
* p value <0.05 - Significant
** p value <0.001 - Highly Significant
TABLE 4: Analysis of Blood parameters among Severe patients in both the arms n=16
|
Day 0 Mean (SD)
|
Day 10 Mean (SD)
|
p value (intragroup)
|
D-Dimer
|
956.16 (358.42)
|
777.07 (249.54)
|
0.116
|
CRP
|
8.45 (3.5)
|
5.80 (3.0)
|
0.001**
|
IL-6
|
12.86 (7.3)
|
9.54 (6.3)
|
0.0003**
|
Ferritin
|
1118.15 (446.99)
|
897.23 (314.22)
|
0.0016*
|
* p value <0.05 - Significant
** p value <0.001 - Highly Significant
The intervention group reported no adverse events or side effects upon taking NOQ19 daily.