A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19

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Figure 1.
CONSORT flow diagram for supplements for COVID-19 study.
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Figure 4.
Supplements for COVID-19 symptom score regression analysis.
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Figure 5.
Supplements for COVID-19 quality of life regression analysis.
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Figure 2.
Initial survey was filled out electronically by participant after establishing REDCap interface and completed with the research coordinator's telephone-based assistance to clarify any concerns.
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Figure 3.
Daily survey (2 Pages) was sent electronically by REDCap to participant daily from day 2 until day 14 and once again on day 30.

Table 1.

Baseline Demographic Characteristics by Group of All Study Participants

	Placebo (n = 34)	Vitamin C (n = 32)	Melatonin (n = 32)	P-Value
Age, median (IQR), years	54 (11)	50 (9)	52 (14)	0.30
Body mass index (BMI), median (IQR)	33 (12)	32 (7)	31 (9)	0.57
Female sex, n (%)	24 (71%)	19 (59%)	21 (66%)	0.63
Diabetes, n (%)	6 (18%)	5 (16%)	5 (16%)	0.97
Asthma or chronic obstructive pulmonary disease, n (%)	8 (24%)	7 (22%)	4 (13%)	0.48
High blood pressure, n (%)	11 (32%)	7 (22%)	7 (22%)	0.53
Smoking, n (%)	4 (12%)	1 (3%)	2 (6%)	0.38
Completed COVID immunization before completing study, n (%)	0 (0%)	1 (3%)	1 (3%)	0.58
Received monoclonal antibody therapy (Bamlanivimab), before completing study, n (%)	3 (9%)	0 (0%)	3 (9%)	0.21
Enrolled in cancer registry at time of study, n (%)	3 (9%)	2 (6%)	4 (13%)	0.69
Days from symptom onset to consent, median (IQR)	4 (2)	4 (2)	4 (1)	0.11
Days from consent to taking supplements, median (IQR)	2 (0)	2 (2)	2 (2)	0.92
Median baseline total symptom score (IQR)	18 (18)	24 (17.5)	27 (22)	0.37
Median baseline total activity score (IQR)	13.5 (25)	19.5 (23.5)	27 (19)	0.35

Demographic variables by group. P-values calculated by Kruskal-Wallis for: age, BMI, day ranges, and baseline scores; χ² for: sex, diabetes, asthma/COPD, high blood pressure, smoking, completed COVID-19 immunization before enrollment, Bamlanivimab, and cancer registry status.
Abbreviations: IQR, interquartile range.

Table 2.

Average Symptom Score for Participants per Group on Representative Days

	Baseline	Day 3	Day 9	Day 14	Day 30
Placebo (SD)	22.24 (14.21)	13.70 (9.16)	5.42 (6.69)	3.38 (4.09)	2.21 (3.57)
Vitamin C (SD)	24.59 (11.81)	12.86 (8.67)	7.00 (5.71)	4.42 (4.48)	3.87 (9.72)
Melatonin (SD)	26.38 (14.97)	18.40 (13.52)	6.05 (6.76)	4.59 (8.40)	4.09 (6.07)

Table 3.

Average Quality-of-Life Score for Participants per Group on Representative Days

	Baseline	Day 3	Day 9	Day 14	Day 30
Placebo (SD)	18.62 (16.11)	12.07 (12.59)	5.35 (9.67)	4.00 (8.57)	3.79 (8.23)
Vitamin C (SD)	21.41 (14.52)	13.83 (12.22)	6.84 (8.09)	6.04 (8.11)	6.40 (14.39)
Melatonin (SD)	23.53 (14.92)	20.96 (16.14)	8.05 (12.61)	5.00 (11.48)	2.55 (4.20)

Table 4.

Symptom Score Spline Regression Analysis Slope Coefficients

	Coefficient	Std. Err.	P-Value	95% Interval
First segment slope spline (days 1 to 3)
Referent Group (Placebo)	−2.86	0.55	<0.001	(−3.93, −1.79)
Vitamin C	1.11	0.76	0.14	(−0.37, 2.6)
Melatonin	1.23	0.77	0.11	(−0.29, 2.74)
Second segment slope spline (days 3 to 9)
Referent Group (Placebo)	−1.09	0.15	<0.001	(−1.39, −0.8)
Vitamin C	0.22	0.21	0.31	(−0.2, 0.63)
Melatonin	−0.63	0.22	0.003	(−1.06, −0.21)
Third segment slope spline (days 9 to 14)
Referent Group (Placebo)	−0.08	0.19	0.69	(−0.46, 0.3)
Vitamin C	−0.48	0.27	0.08	(−1.01, 0.05)
Melatonin	−0.04	0.28	0.88	(−0.6, 0.51)

Note: these slope coefficients represent change over a very short period of time, ie 3-4 days.
Correlates with Figure 2.

Table 5.

Quality-of-Life Score Spline Regression Analysis Slope Coefficients

	Coefficient	Std. Err.	P-Value	95% Interval
First segment slope spline (days 1 to 3)
Referent Group (Placebo)	−3.31	0.76	<0.001	(−4.79, −1.82)
Vitamin C	1.28	1.05	0.22	(−0.78, 3.33)
Melatonin	2.23	1.07	0.04	(0.13, 4.34)
Second segment slope spline (days 3 to 9)
Referent Group (Placebo)	−0.71	0.21	0.001	(−1.11, −0.3)
Vitamin C	−0.45	0.29	0.12	(−1.03, 0.12)
Melatonin	−1.16	0.30	<0.001	(−1.75, −0.57)
Third segment slope spline (days 9 to 13)
Referent Group (Placebo)	−0.23	0.27	0.39	(−0.76, 0.3)
Vitamin C	−0.02	0.38	0.96	(−0.76, 0.72)
Melatonin	−0.23	0.39	0.56	(−1, 0.54)

Note: these slope coefficients represent change over a very short period of time, ie 3-4 days.
Correlates with Figure 3.