Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis

Figures & data

Table 1 Baseline Clinical Characteristics of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020

	All		ICU Transfer		Deaths
	n	%	n	%	n	%
n	2111		271		239
Sex - men	1154	54.7	200	73.8	148	61.9
Age – mean (std) Q1-median-Q3	65.8 (17.2) 55-67-79		63.2 (11.0) 56-64-72		81.2 (9.9) 75-83-89
Age 18–29	67	3.2	1	0.4	0	0
Age 30–39	118	5.6	6	2.2	0	0
Age 40–49	168	8	27	10	2	0.8
Age 50–59	380	18	60	22.1	7	2.9
Age 60–69	451	21.4	91	33.6	22	9.2
Age 70–79	401	19	73	26.9	56	23.4
Age 80–89	380	18	13	4.8	105	43.9
Age >89	146	6.9	0	0	47	19.7
Charlson index V1^a- mean (std) Q1-median-Q3	4.5 (2.7) 2-4-6		4.0 (2.1) 2-4-5		6.9 (2.2) 5-7-8
Charlson index V2^b- mean (std) Q1-median-Q3	1.4 (1.7) 0-1-2		1.3 (1.5) 0-1-2		2.4 (2.0) 1-2-3
Chronic condition(s)
Hypertension	956	45.3	129	47.6	150	62.8
Diabetes mellitus	571	27	90	33.2	81	33.9
Cancer disease	246	11.7	32	11.8	42	17.6
Chronic respiratory diseases	393	18.6	47	17.3	62	25.9
Chronic heart diseases	520	24.6	59	21.8	116	48.5
Obesity	495	23.4	103	38	39	16.3
Hypothyroidism	210	9.9	22	8.1	31	13
Asthma	159	7.5	19	7	16	6.7
Obstructive sleep apnoea	112	5.3	21	7.7	15	6.3
Other inflammatory disease	97	4.6	12	4.4	16	6.7
Medications
Metformin	336	15.9	50	18.5	34	14.2
Beta blocking agents	404	19.1	55	20.3	74	31.0
Verapamil	28	1.3	3	1.1	4	1.7
HMG CoA reductase inhibitors	418	19.8	57	21.0	64	26.8
Fibrates	26	1.2	3	1.1	6	2.5
Dihydropyridine derivatives	557	26.4	89	32.8	96	40.2
Angiotensin II receptor blockers	357	16.9	54	19.9	44	18.4
ACE inhibitors	251	11.9	34	12.5	30	12.6
Tobacco consumption	210	9.9	34	12.5	24	10.0
Pulmonary CT-scanner
Missing	208	9.9	16	5.9	33	13.8
Normal	229	10.8	10	3.7	13	5.4
Minimal	496	23.5	22	8.1	31	13
Intermediate	717	34	90	33.2	69	28.9
Severe	461	21.8	133	49.1	93	38.9
Clinical symptoms
Fever	601	28.5	112	41.3	67	28
Cough	1023	48.5	146	53.9	79	33.1
Rhinitis	127	6	8	3	3	1.3
Anosmia	258	12.2	39	14.4	9	3.8
Ageusia	255	12.1	42	15.5	10	4.2
Dyspnoea	942	44.6	171	63.1	134	56.1
Thoracic pain	172	8.1	13	4.8	5	2.1
NEWS score – mean (std) Q1-median-Q3	5.7 (2.8) 4-6-8		7.0 (2.5) 5-7-9		8.3 (2.4) 7-8-10
NEWS 0–4	735	34.8	41	15.1	11	4.6
NEWS 5–6	580	27.5	75	27.7	48	20.1
NEWS ≥7	796	37.7	155	57.2	180	75.3
Mode of hospitalisation
Other wards	193	9.1	8	3	20	8.4
Firstly outpatient then hospitalisation	270	12.8	20	7.4	6	2.5
Directly from day clinic	496	23.5	58	21.4	23	9.6
From ICU	38	1.8	38	14	0	0
From emergency department	1114	52.8	147	54.2	190	79.5
Treatments
HCQ-AZ	1270	60.2	158	58.3	93	38.9
Zinc	1302	61.7	170	62.7	161	67.4
Dexamethasone	530	25.1	169	62.4	121	50.6

Notes: ^aCharlson index with age. ^bCharlson index without age.

Table 2 COVID-19 Hospitalized Patients Not Prescribed with Hydroxychloroquine and Azithromycin Combination (n = 841), Marseille, France, 2020

	n	%
Not proposed by the physician	251	29.9
Refused the combined treatment	33	3.9
Contraindication	529	62.9
Prolonged QTc	90	10.7
Other cardiac disorder	126	15.0
Risk of drug interactions	201	23.9
Ophthalmologic	5	0.6
Other contraindication	107	12.7
Other	28	3.3
Total	841	100.0

Table 3 List of Adverse Events (n = 224) Among 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020

	n	%
At least one adverse event	224	10.6
Diarrhoea	74	3.51
Prolonged QTc	38	1.8
-QT > 500 ms	11	0.52
-Expansion > 60 ms and QT < 500 ms	13	0.62
-Expansion < 60 ms and QT < 500 ms	14	0.66
Nausea/vomiting	35	1.66
Abdominal pain/other digestive troubles	29	1.37
Acute renal failure	21	0.99
Cytolysis/cholestasis	20	0.95
Neuropsychiatric signs (mood disorder, insomnia, nervousness)	17	0.81
Skin disorders	16	0.76
Oral candidiasis	14	0.66
Headache	13	0.62
Anorexia	12	0.57
Fainting	9	0.43
Blurred vision and other visual disturbance	5	0.24
Dizziness	4	0.19
Palpitations/tachycardia	4	0.19
Paraesthesia	2	0.09
Trembling	1	0.05

Figure 1 Baseline clinical and biological characteristics of 2111 COVID-19 hospitalized patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France, 2020 - multiple correspondence analysis. For the multiple correspondence analysis, all variables were active except for clinical outcome (death status) and treatment groups (HCQ-AZ/No HCQ-AZ). The red dots represents patients who died and green dots patients who did not die. Blue squares represent the treatment groups variable. Ellipses: 90% confidence ellipses around clinical outcome categories (death/no death).

Table 4 Comparison of Treatment Groups (HCQ-AZ vs No HCQ-AZ, n = 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020)

	Unweighted Sample			Propensity Weighted Sample
	HCQ-AZ	No HCQ-AZ	P*	HCQ-AZ	No HCQ-AZ	P*
	N = 1270	N = 841		N = 1270	N = 841
Age mean (std)	63.0 (16.7)	70.0 (17.2)	<0.001	65.6 (15.0)	65.1 (21.4)	0.558
Men (%)	54.8%	54.5%	0.876	55.0%	55.6%	0.778
NEWS score
0–4	38.3%	29.5%	<0.001	35.0%	35.5%	0.963
5–6	27.8%	27.0%		27.3%	26.8%
>6	33.9%	43.5%		37.7%	37.7%
Comorbidities
Hypertension	40.3%	52.8%	<0.001	45.0%	44.8%	0.912
Diabetes mellitus	26.0%	28.7%	0.176	26.9%	26.5%	0.861
Cancer disease	11.3%	12.2%	0.489	12.0%	12.2%	0.853
Chronic respiratory diseases	16.2%	22.2%	0.001	18.6%	19.0%	0.820
Chronic heart diseases	17.4%	35.6%	<0.001	24.4%	24.5%	0.980
Obesity	22.9%	24.3%	0.476	23.2%	23.3%	0.969
Hypothyroidism	8.4%	12.2%	0.004	9.7%	9.6%	0.912
Asthma	7.3%	7.8%	0.655	7.6%	7.8%	0.875
Other inflammatory disease	3.9%	5.7%	0.047	4.6%	4.6%	0.977
Treatments (other than HCQ-AZ)
Zinc	57.2%	68.5%	<0.001	61.9%	61.6%	0.888
Corticosteroids	19.8%	33.1%	<0.001	25.5%	25.6%	0.970

Note: *Chi-square/Fisher’s exact or Student’s t-test where appropriate.

Table 5 Association Between Treatment Groups (HCQ-AZ vs No HCQ-AZ) and Death – Multivariable Cox Proportional-Hazards Model (n = 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020)

	HR 95% CI^a	p
Treatment group (ref. No HCQ-AZ)	0.68 0.52–0.88	0.0037
Age (ref 18–54)
55–64	2.59 0.83–8.09	0.1023
65–74	4.71 1.62–13.68	0.0044
>74	12.70 4.49–35.96	<0.0001
Sex men (ref. women)	1.31 0.99–1.74	0.0566
NEWS score (ref. 0–4)
5–6	3.28 1.65–6.55	0.0007
>6	6.13 3.15–11.95	<0.0001
Number of comorbidities
Hypertension	1.11 0.84–1.47	0.4697
Diabetes mellitus	1.01 0.76–1.35	0.9374
Cancer disease	1.10 0.78–1.55	0.5923
Chronic respiratory diseases	1.33 0.95–1.85	0.0925
Chronic heart diseases	1.56 1.19–2.04	0.0012
Obesity	0.66 0.45–0.95	0.0260
Hypothyroidism	1.15 0.77–1.71	0.4971
Asthma	1.14 0.64–2.03	0.6668
Other inflammatory disease	2.01 1.21 −3.35	0.0071
Treatments (other than HCQ-AZ)
Zinc	0.63 0.47–0.84	0.002
Corticosteroids	2.56 1.92–3.40	<0.0001

Note: ^aHazard ratio 95% CI.

Figure 2 Association between treatment group (HCQ-AZ vs No HCQ-AZ) and death according to age, sex, comorbidities, severity and co-medications - stratified multivariable Cox proportional-hazards models (n=2111 COVID-19 hospitalized patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France, 2020).

Figure 3 Kaplan–Meier curve of survival according to treatment groups (propensity weighted sample, n = 2111 COVID-19 hospitalized patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France, 2020). Log rank test: p = 0.0135.

Figure 4 Kaplan–Meier curve of survival according to treatment groups (propensity weighted sample, n = 1018 COVID-19 patients treated with HCQ-AZ ± zinc (no corticosteroid) in Marseille, France 2020). Log rank test: p=0.0011. Adjusted hazard ratio: 0.39 0.23–0.67 (p<0.001).