Inflammation parameters predict fatal outcome in male COVID-19 patients in a low case-fatality area – a population-based registry study

Figures & data

Table 1. Multivariable analysis for parameters of 90-d case-fatality in patients with laboratory-confirmed COVID-19 treated in specialized healthcare hospitals and stratified by sex.

a
Male patients N = 316	Univariate analysis				Multivariable analysis
	Died	Survived
	N = 47 (15)	N = 269 (85)	OR (95% CI)	p Value	OR (95% CI)	p Value
Age >65 years	36 (77)	76 (28)	8.31 (4.02 − 17.2)	.000	12.1 (1.54 − 95.9)	.018
Hypertension	23 (49)	94 (35)	1.78 (0.96 − 3.33)	.067	–	–
Diabetes mellitus	20 (43)	57 (21)	2.76 (1.44 − 5.27)	.002	–	–
Coronary artery disease	10 (21)	17 (6)	4.01 (1.71 − 9.41)	.001	–	–
Dementia diagnosis	7 (15)	9 (3)	5.06 (1.78 − 14.3)	.001	–	–
Malignancy	15 (32)	14 (5)	8.54 (3.78 − 19.3)	.000	–	–
ICU treatment	19 (40)	65 (24)	2.09 (1.10 − 3.98)	.023	–	–
Lymphocytes >0.85 E9/l^a	11 (23)	180 (67)	0.16 (0.07 − 0.35)	.000	0.02 (0.002 − 0.26)	.002
D-dimer >1.15 mg/l^a	16 (34)	63 (23)	3.39 (1.38 − 8.39)	.006	7.29 (1.01 − 52.6)	.049
C-reactive protein >110 mg/l^a	33 (70)	50 (19)	11.4 (5.52 − 23.7)	.000	15.4 (1.87 − 127)	.011
b
Female patients N = 269	Univariate analysis				Multivariable analysis
	Died	Survived
	N = 21 (8)	N = 248 (92)	OR (95% CI)	p Value	OR (95% CI)	p Value
Age >65 years	19 (90)	66 (27)	26.1 (5.94 − 116)	.000	10.6 (2.05 − 54.5)	.005
Hypertension	14 (67)	92 (37)	3.39 (1.32 − 8,71)	.008	−	−
Diabetes mellitus	3 (14)	48 (19)	0.69 (0.20 − 2.45)	.569	−	−
Coronary artery disease	3 (14)	7 (3)	5.74 (1.37 − 24.1)	.008	−	−
Dementia diagnosis	10 (48)	5 (2)	44.1 (12.9 − 151)	.000	25.5 (2.95 − 221)	.003
Malignancy	2 (10)	17 (7)	1.43 (0.31 − 6.65)	.647	−	−
ICU treatment	4 (19)	43 (17)	1.12 (0.36 − 3.50)	.843	−	−
C-reactive protein >81 mg/l^a	13 (62)	68 (27)	4.15 (1.59 − 10.9)	.002	7.32 (1.44 − 37.2)	.016

^a Median cut-off values from statistically significant ROC analyses according to Youden index (Figures 4 and 5).

Data are patients (%) and odds ratios (OR) (95% confidence intervals).

Figure 2. (A–C) Peak and median creatinine and alanine aminotransferase (N = 562) and thromboplastin time (N = 341) for laboratory-confirmed COVID-19 patients in specialized healthcare hospitals stratified by mortality and intensive care unit (ICU) and sub-grouped by sex. ICU patients (N = 132) and deceased patients (N = 68). Data are median (quartiles). ***p Value < .001, **p Value < .01 and *p Value < .05.

Figure 3. (A–C) Peak and median ferritin (N = 338), d-dimer (N = 356) and C-reactive protein (N = 562) in patients with laboratory-confirmed COVID-19 and treated in specialized healthcare hospitals stratified by mortality and intensive care unit (ICU) and sub-grouped by sex. ICU patients (N = 132) and deceased patients (N = 68). Data are median (quartiles). ***p Value < .001, **p Value < .01 and *p Value < .05.

Figure 4. (A,B) Receiver operating characteristic (ROC) curves for associating inflammatory parameters to case-fatality during 90 d follow-up in patients with laboratory-confirmed COVID-19 infection treated in specialized healthcare hospital. Among male (A) COVID-19 patients the ROC analysis was statistically significant for peak and median leucocyte, neutrophil, monocyte, lymphocyte and thrombocyte values: Sensitivity for peak and median values, respectively: leucocytes 62 and 71%, neutrophils 76 and 76%, monocytes 62 and 76%, lymphocytes 81 and 71% and thrombocytes 62 and 62%. Specificity for peak and median values, respectively: leucocytes 59 and 62%, neutrophils 72 and 73%, monocytes 66 and 73%, lymphocytes 70 and 77% and thrombocytes 60 and 63%. Cut-off values for peak and median: leucocytes 7.95 E9/l and 6.65 E9/l, neutrophils 7.05 E9/l and 4.95 E9/l, monocytes 0.55 E9/l and 0.35 E9/l, lymphocytes 1.15 E9/l and 0.85 E9/l and thrombocytes 360 E9/l and 230 E9/l. Among female (B) COVID-19 patients the ROC analysis was statistically significant for peak and median lymphocyte and thrombocyte values: Sensitivity for peak and median, respectively: lymphocytes 77 and 62% and thrombocytes 77 and 69%. Specificity for peak and median, respectively: lymphocyte 69 and 72% and thrombocytes 76 and 68%. Cut-off values for peak and median, respectively: lymphocytes 1.25 E9/l and 0.95 E9/l and thrombocytes 243 E9/l and 215 E9/l.

Figure 5. (A,B) Receiver operating characteristic (ROC) curves for associating inflammatory parameters to case-fatality during 90 d follow-up in patients with laboratory-confirmed COVID-19 infection treated in specialized healthcare hospital. Among male (A) COVID-19 patients the ROC analysis was statistically significant for peak and median C-reactive protein, ferritin and d-dimer values and peak creatinine value. Sensitivity, peak and median: C-reactive protein 75 and 88%, ferritin 69 and 69%, d-dimer 88 and 75% and peak creatinine 69%. Specificity, peak and median: C-reactive protein 62 and 76%, ferritin 75 and 72%, d-dimer 83 and 72% and peak creatinine 67%. Cut-off values, peak and median: C-reactive protein 89 and 110 mg/l, ferritin 1347 and 1310 ug/l, d-dimer 2.15 mg/l and 1.15 ug/l and peak creatinine 81 umol/l. Among female (B) COVID-19 patients the ROC analysis was statistically significant for peak and median C-reactive protein and peak creatinine value. Sensitivity, peak and median: C-reactive protein 73 and 82%. Specificity, peak and median: C-reactive protein 70 and 64%. Cut-off values, peak and median: C-reactive protein 87 and 81 mg/l.