Is there a diurnal variation of COVID-19 patients warranting presentation to the health centre? A chronobiological observational cross-sectional study

Figures & data

Figure 1. Number of participants, and missing data for each parameter. N: number of valid files; M: males; and F: females.

Figure 2. Patients’ distribution frequency per TOD (n = 1094). Data was processed using a One-way ANOVA with *** Means a significant difference compared to 00-04 h for male, female and overall. ^### Means a significant difference compared to 04-08 h for male, female and overall.

Table 1. Clinical, haematological and biochemical data at different TOD (in hours) in COVID-19 patients (n = 1094).

	Data (unit)	N°	00–04	04–08	08–12	12–16	16–20	20–00	p Value
Clinical data	Cycle-threshold (au)	1094	23.1 (6.1)	21.5 (6.3)	23.4 (5.8)	23.1 (5.8)	23.6 (6.2)	23.4 (5.7)	NS
	Temperature (°C)	763	36.9 (0.7)	37.2 (0.7)	37.2 (0.6)	37.3 (0.7)	37.3 (0.7)	37.2 (0.6)	NS
	Resting heart rate (bpm)	838	83.2 (13.4)*^abcde	91.4 (16.9)	92.3 (15.4)	92.3 (15.1)	91.8 (14.5)	97.6 (18.7)*^eiklm	<0.001
	SpO2 (%)	892	97.4 (1.6)*^abcde	97.5 (1.8)	97.8 (1.5)	98.1 (1.3)	98.3 (1.4)	98.2 (1.3)	<0.001
Haematological data	Leukocytes (10^3/μl)	663	5.6 (2.6)	5.9 (2.4)	6.1 (1.9)	5.9 (2.6)	5.8 (1.6)	6.1 (2.2)	NS
	Neutrophils (10^3/μl)	663	3.3 (2.4)	3.6 (2.9)	3.3 (1.5)	3.9 (2.7)	3.1 (1.4)	3.2 (1.8)	NS
	Erythrocytes (10^6/μl)	663	4.9 (0.7)	5.9 (2.5)*^afghi	5.1 (0.6)	5.2 (0.6)	4.9 (0.7)	4.9 (0.7)	<0.001
	Thrombocytes (10^3/μl)	663	203 (83)	210 (82)	260 (89)*^afj	228 (72)	234 (64)	255 (66)	<0.001
Biochemical data	Urea (mmol/l)	663	6.3 (2.6)*^abcde	4.7 (1.7)	4.3 (1.9)	3.8 (1.3)	3.2 (1.1)	4.2 (1.4)	<0.001
	Albumin (g/l)	663	40.9 (7.2)	41.3 (3.1)	41.4 (6.3)	42.1 (6.5)	43.1 (6.8)	52.1 (25.9)^*eiklm	<0.001
	Glucose (mmol/l)	663	8.5 (4.4)*^abcde	7.7 (3.1)*^ghi	7.7 (3.9)	6.7 (2.9)	5.9 (3.1)	5 (0.7)	<0.001

Data were expressed as mean (SD).

n: total number of patients; N: number of patient with valid files (i.e. after excluding files with missing data); NS: not significant; SpO₂: oxy-haemoglobin saturation.

*ANOVA^: significantly different from other TOD at p < 0.05.

• • 00–04 vs. ^a04–08 or ^b08–12 or ^c12–16 or ^d16–20 or ^e20–00.

• • 04–08 vs. ^f08–12 or ^g12–16 or ^h16–20 or ⁱ20–00.

• • 08–12 vs. ^j12–16 or ^k20–00.

• • 12–16 vs. ^l20–00.

• • 16–20 vs. ^m20–00.

Figure 3. Male-Female comparison of different clinical, haematological and biochemical data at different TOD. Data was assessed using a two-way ANOVA followed by Bonferroni post-hoc test. *, ** and *** Significant sex-based difference at p < 0.05, p < 0.01 and p < 0.001. ^•, ^•• and ^••• Means significant TOD difference in females at p < 0.05, p < 0.01 and p < 0.001. ^#, ^## and ^### means significant TOD difference in males at p < 0.05, p < 0.01 and p < 0.001.

Table 2 Correlation-coefficient (r) between different clinical, haematological and biochemical data (n = 274).

		Clinical data					Haematological data				Biochemical data
		Age	CT	TEM	HR	SpO2	LEU	NEU	ERY	PLT	URE	ALB	GLC
Data	TOD	–0.97*^a	0.04	0.07	0.16*^c	0.14*^c	0.01	–0.16	–0.06	0.06	–0.36*^b	0.23*^c	–0.27*^c
Clinical data	Age		–0.03	–0.06	–0.19*^c	–0.14*^c	–0.02	0.11	0.06	–0.06	0.34*^b	–0.27*^c	0.26*^c
	CT			–0.14*^c	–0.16*^c	0.02	0.22*^c	0.21	0.01	0.25*^c	–0.07	–0.05	–0.06
	TEM				0.31*^b	–0.09*^c	0.08	0.17	–0.02	–0.11	–0.04	0.07	0.06
	HR					–0.11*^c	0.08	0.08	0.00	0.02	–0.14*^c	–0.02	0.10
	SpO2						–0.14*^c	–0.29*^c	–0.14*^c	0.07	–0.03	0.04	–0.13*^c
Haematological data	LEU								0.01	0.39*^b	–0.07	0.04	–0.02
	NEU									0.38*^b	–0.02	–0.14	0.11
	ERY									–0.17*^c	0.05	–0.03	0.10
	PLT										–0.14*^c	–0.03	–0.05
Biochemical data	URE											–0.02	0.11
	ALB												–0.12

ALB: albumin; CT: cycle threshold; ERY: erythrocytes; HR: resting heart rate; LEU: leukocytes; NEU: neutrophils; PLT: platelets; SpO₂: oxy-haemoglobin saturation; TEM: temperature; TOD: time of day; URE: urea.

*p < 0.05.

‘r’ was considered.

^aHigh when it was > 0.70.

^bFair if it was between 0.30 and 0.50.

^cWeak or having no association if it was <0.30.

Data availability statement

All data analysed and reported in this study are available from the first author on reasonable request.