Indicators of stress hematopoiesis in the blood predict COVID-19 progression in patients over 65 years old

Figures & data

Table 1. Differences between baseline characteristics in all patients according to COVID-19 progression (One-way ANOVA).

Parameter (mean ± SD)	COVID-19 progression		p value
	Yes	No
Age (years)	70.95 ± 13.29	65.78 ± 13.56	0.000
SaO2 (mmHg)	84.83 ± 12.23	92.99 ± 5.14	0.000
CRP (mg/L)	120.17 ± 80.72	104.21 ± 98.41	0.028
LDH (mg/L)	1026.62 ± 792.63	749.13 ± 305.52	0.000
IL-6 (pg/ml)	146.69 ± 331.98	65.42 ± 116.88	0.041
The CBC parameters
LIC (x10^9/L)	0.240 ± 142	0.188 ± 91	0.000
RDW (%)	12.03 ± 0.97	11.66 ± 0.74	0.000
PDW (%)	17.58 ± 3.13	16.72 ± 2.72	0.000
RBC (x10^12/L)	4.442 ± 0.746	4.532 ± 0.767	0.111
HGB (g/L)	133.83 ± 23.17	135.48 ± 19.06	0.289
HCT (%)	40.5 ± 6.65	40.8 ± 5.35	0.538
MCV (fL)	91.40 ± 6.09	90.81 ± 5.99	0.192
WBC (x10^9/L)	10.868 ± 6.854	9.137 ± 11.883	0.025
NEU (x10^9/L)	8.812 ± 5.733	6.712 ± 3.406	0.000
LY (x10^9/L)	1.347 ± 2.336	1.221 ± 736	0.280
MO (x10^9/L)	0.544 ± 474	0.493 ± 318	0.076
EO (x10^9/L)	0.100 ± 85	0.081 ± 59	0.000
BA (x10^9/L)	0.094 ± 160	0.076 ± 302	0.320
PLT (x10^9/L)	220.23 ± 109.15	240.91 ± 114.29	0.014
PCT (%)	0.203 ± 0.09	0.217 ± 0.09	0.047
MPV (fL)	9.39 ± 1.23	9.17 ± 0.99	0.010
P/LIC (x10^9/L)	1.271,7 ± 1.483,9	1.549,8 ± 1.174,6	0.012

CBC – complete blood counts, SaO2 – Hemoglobin saturation with O2, CRP – C reactive protein, LDH – lactate dehydrogenase, IL-6 – interleukin 6. LIC - large immature cells, RDW - red blood cell distribution width, PDW - platelets distribution width, RBC – erythrocytes, HGB – hemoglobin, HCT – hematocrit, MCV – mean cell volume, WBC – leukocytes, NEU - neutrophils, LY - lymphocytes, MO - monocytes, EO - eosinophils, BA - basophils, PLT – platelets, PCT – plateletcrit, MPV – mean platelet volume.

Table 2. Differences between baseline parameters according to the patients’ age.

	Age ≥ 65 year	Age < 65 year	p value
COVID-19 progression	43.9%	27.1%	0.000
Males, n (%)	51.5%	62.4%	0.005
Comorbidity (%)Hypertension T2DM	84.8% 66.5% 23.0%	65.0% 49.2% 16.2%	0.000 0.000 0.030
SaO2 < 90%	41.5%	27.9%	0.000
CRP (mg/L)	110.74 ± 73.02	108.94 ± 119.97	0.779
LDH (mg/L)	850.54 ± 642.87	859.23 ± 353.76	0.805
IL-6 (pg/ml)	139.66 ± 339.01	77.05 ± 130.49	0.116

SaO2 – Hemoglobin saturation with O2, T2DM – type 2 diabetes mellitus. CRP – C reactive protein, LDH – lactate dehydrogenase, IL-6 – interleukin 6.

Table 3. Differences between baseline characteristics according to the COVID-19 progression (One-way ANOVA).

	Age ≥ 65 year		p value	Age < 65 year		p value
Progression	Yes	No		Yes	No
SatO2 (mmHg)	84.34 ± 12.37	92.33 ± 5.67	0.000	86.07 ± 11.86	93.91 ± 4.13	0.000
CRP (mg/L)	119.98 ± 80.56	103.98 ± 66.32	0.022	121.54 ± 82.05	104.37 ± 130.92	0.316
LDH (mg/L)	1016.78 ± 911.56	725.17 ± 295.08	0.000	1054.28 ± 372.56	784.15 ± 316.81	0.000
IL-6 (pg/ml)	189.66 ± 409.72	44.04 ± 44.53	0.052	77.79 ± 111.50	76.46 ± 145.18	0.963
CBC parameters
LIC (x10^9/L)	241.47 ± 143.73	187.25 ± 92.26	0.000	236.72 ± 138.66	190.71 ± 91.98	0.003
RDW (%)	12.17 ± 0.98	11.78 ± 0.75	0.000	11.65 ± 0.84	11.49 ± 0.71	0.139
PDW (%)	17.88 ± 3.14	16.99 ± 2.71	0.001	16.68 ± 2.98	16.34 ± 2.70	0.379
RBC	4.388 ± 0.746	4.427 ± 0.866	0.596	4.567 ± 0.686	4.681 ± 0.537	0.259
HGB	132.42 ± 24.28	132.76 ± 19.98	0.862	137.57 ± 18.92	139.34 ± 17.06	0.467
HCT	40.14 ± 6.98	40.06 ± 5.69	0.891	41.48 ± 5.43	41.82 ± 5.67	0.619
MCV	91.64 ± 6.62	91.71 ± 6.40	0.906	90.67 ± 4.21	89.53 ± 5.13	0.092
WBC	10.904 ± 7.113	9.565 ± 15.240	0.236	10.587 ± 5.933	8.552 ± 3.694	0.001
NEU	8.796 ± 5.771	6.662 ± 3.469	0.000	8.727 ± 5.587	6.794 ± 3.329	0.001
LY	1.400 ± 2.619	1.262 ± 852	0.417	1.156 ± 1.131	1.164 ± 530	0.936
MO	550 ± 512	517 ± 353	0.404	520 ± 341	458 ± 257	0.116
EO	98.9 ± 73.3	85.2 ± 63.7	0.030	103 ± 113	76.5 ± 51.1	0.011
BA	99.4 ± 17.9	88.2 ± 39.3	0.699	77.6 ± 70.7	57.9 ± 36.7	0.003
PLT	211.691 ± 105.607	239.809 ± 117.779	0.007	243.639 ± 116.083	243.113 ± 109.401	0.973
PCT	19.74 ± 8.86	21.73 ± 9.52	0.019	21.76 ± 9.61	21.63 ± 8.48	0.912
MPV	9.46 ± 1.26	9.22 ± 1.07	0.027	9.15 ± 1.11	9.10 ± 0.89	0.704
P/LIC	1259.16 ± 1642.86	1576.92 ± 1348.57	0.028	1307.97 ± 889.97	1517.07 ± 894.63	0.108

SatO2 – Hemoglobin saturation with O2, CRP – C reactive protein, LDH – lactate dehydrogenase, IL-6 – interleukin 6. CBC – complete blood counts, LIC - large immature cells, RDW - red blood cell distribution width, PDW - platelet distribution width, RBC – erythrocytes, HGB – hemoglobin, HCT – hematocrit, MCV – mean cell volume, WBC – leukocytes, NEU - neutrophils, LY - lymphocytes, MO - monocytes, EO - eosinophils, BA - basophils, PLT – platelets, PCT – plateletcrit, MPV – mean platelet volume.

Figure 1. The ROC curve analyses presenting the complete blood counts parameters significantly associated with COVID-19 progression in all patients. Figure 1. Legend: ROC - receiver operating characteristic, AUC – area under the curve, LIC - large immature cells, RDW - red blood cell distribution width, PDW - platelets distribution width, WBC – leukocytes, NEU - neutrophils, PLT – platelets, PCT – plateletcrit, P/LIC – ratio of platelets and LIC.

Table 4. Cut-off points from ROC curve analysis and results of the binomial logistic regressions to COVID-19 progression.

	Cut-offs, Youden’s index	Sen / Spec. (%)	Wald	Odds	95%CI		p value
					Lower	Upper
LIC x10^9/L	0.305	30.8 / 89.0	8.458	2.511	1.551	4.066	0.000
RDW (%)	11.55	68.7 / 48.7	13.174	2.110	1.410	3.159	0.000
NEU x10^9/L	7.665,0	47.7 / 71.6	6.942	1.650	1.137	2.395	0.008
PLT x10^9/L	184.500	44.3 / 64.9	10.071	0.556	0.387	0.799	0.002
Aged ≥ 65
LIC x10^9/L	0.305	30.4 / 89.1	14.442	3.166	1.747	5.736	0.000
RDW (%)	12.15	40.8 / 74.3	8.314	2.081	1.265	3.425	0.004
NEU x10^9/L	9.495,0	35.5 / 83.9	8.317	2.137	1.275	3.581	0.004
PLT x10^9/L	178.500	46.3 / 67.3	9.799	0.494	0.317	0.768	0.002

Sen/Spec. – sensitivity / specificity, CI – confidence interval, LIC - large immature cells, RDW - red blood cell distribution width, NEU - neutrophils, PLT – platelets.

Data availability statement

The data that support the findings of this study are available on reasonable request from the corresponding author, J. M.