Predictors of COVID-19 Severity in Elderly Patients Infected by Omicron in China, 18 December 2022–5 February 2023

Figures & data

Table 1 Classification Criteria for Severity of COVID-19 Patients

Severity	Classification Criteria
Mild	Upper respiratory tract infection as the main manifestation, such as dry throat, sore throat, cough, fever, etc.
Moderate	Persistent high fever>3 days or/and cough, shortness of breath, etc, but respiratory rate (RR)<30 times/min, oxygen saturation >93% when breathing at rest. Imaging shows the characteristic manifestations of COVID-19 pneumonia.
Severe	In adults, any of the following criteria are met and cannot be explained by anything other than COVID-19 infection:1. Shortness of breath with RR>30 times/min; 2. At rest, oxygen saturation of finger is less than 93% when sucking air; 3. Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) <300mmHg.
Critical	Meet one of the following conditions: 1. Respiratory failure and the need for mechanical ventilation; 2. Shock; 3. With other organ failure and requiring ICU care.

Table 2 General Demographics and Clinical Symptoms of the 118 COVID-19 Patients

	All patients (n=118)	Non-severe (n=64)	Severe (n=38)	Death (n=16)	χ	P-value
General Information
Age (years)^b	79(68–84)	74.5(66–82)	80.50(73.75–83.25)	83.50(79.75–86.5)	12.07	0.002*
Male, n (%)^a	66(55.9)	36(56.3)	20(52.6)	10(62.5)	0.447	0.800
BMI (kg/m^2)^b	22.04(20.52–25.49)	23.59(21.51–25.75)	20.94(20.02–24.84)	21.76(20.70–24.66)	6.31	0.043*
Time to Admission (days)^b	10(7–12)	11(8–12)	8.5(7–12)	8.5(6–10)	4.96	0.084
Hospital Days (days)^b	12(9–14)	11(9–14)	14(12–16)	6(3.25–8.75)	39.57	<0.001*
Chronic underlying disease, n (%)^a	94(81.0)	52(81.3)	28(73.7)	14(87.5)	1.53	0.465
Hypertension, n (%)^a	64(54.2)	36(56.3)	18(47.4)	10(62.5)	1.256	0.534
Diabetes, n (%)^a	24(20.3)	10(15.6)	10(26.3)	4(25)	1.91	0.384
Malignant tumor, n (%)^a	8(6.8)	4(6.3)	4(10.5)	0(0)	2.01	0.364
Heart disease, n (%)^a	18(15.3)	10(15.6)	4(10.5)	4(25)	1.82	0.402
Other lung diseases, n (%) ^a	22(18.6)	12(18.8)	8(21.2)	2(12.5)	0.54	0.764
Respiratory failure, n (%) ^a	28(23.7)	6(9.4)	8(21.1)	14(87.5)	43.02	<0.001*
Electrolyte disorder, n (%)^a	28(23.7)	6(9.4)	6(15.8)	16(100)	59.53	<0.001*
Abnormal liver function, n (%)^a	24(20.3)	6(9.4)	12(31.6)	6(37.5)	10.53	0.005*
Clinical symptoms
Fever, n (%)^a	100(84.7)	56(87.5)	30(78.9)	14(87.5)	1.45	0.485
Chills, n (%)^a	38(32.2)	20(31.3)	10(6.3)	8(50.0)	2.93	0.232
Body aches, n (%)^a	32(27.1)	18(28.1)	8(21.1)	6(37.5)	1.60	0.450
Dyspnea, n (%)^a	74(62.7)	40(62.5)	20(52.6)	14(87.5)	5.81	0.055
Chest tightness, n (%)^a	32(27.1)	18(28.1)	8(21.1)	6(37.5)	1.60	0.450
Cough, n (%)^a	96(81.4)	58(90.6)	24(63.2)	14(87.5)	12.22	0.002*
Expectoration, (n, %)^a	94(79.7)	56(87.5)	24(63.2)	14(87.5)	9.34	0.009*
Fatigue, (n, %)^a	58(49.2)	32(50.0)	18(47.4)	8(50.9)	0.07	0.965
Poor appetite, n (%)^a	38(32.2)	16(25.0)	16(42.1)	6(37.5)	3.40	0.182
Headache, n (%)^a	22(18.6)	8(12.5)	10(26.3)	4(25.0)	3.46	0.177
Dizziness, n (%)^a	12(10.2)	4(6.3)	8(21.1)	0(0)	7.75	0.021*
Chest pain, n (%)^a	14(11.9)	4(6.3)	2(5.3)	8(50.0)	25.55	<0.001*
Sore throat, n (%)^a	18(15.3)	8(12.5)	6(15.8)	4(25.0)	1.55	0.462
Nausea, n (%)^a	12(10.2)	6(9.4)	2(5.3)	4(25.0)	4.86	0.088
Vomiting, n (%)^a	6(5.1)	4(6.3)	2(5.3)	0(0)	1.03	0.597

Notes: Numeric and categorical variables were reported as Med (iqr 25–75%) and frequency (%), respectively. All statistically significant values are reported in bold. ^aFrequency (%) and χ test between non-severe versus (severe diseases or death); ^bMed (iqr 25–75%) and Kruskal–Wallis One Way ANOVA test. *P<0.05.

Abbreviations: BMI, body mass index; Med, Median; iqr, Interquartile range.

Table 3 Laboratory Parameters in COVID-19 Patients Within 24 Hours After Admission

	Normal Range	All Patients (n=118)	Non-Severe (n=64)	Severe (n=38)	Death (n=16)	χ	P-value
Blood cell analysis
WBC (×109/L)^b	3.50–9.50	6.54(4.47–8.43)	6.51(4.83–7.60)	5.91(3.93–8.69)	8.5(7.15–11.04)	9.04	0.011*
Neutrophils (×109/L)^b	1.80–6.30	5.17(3.59–7.20)	4.96(3.76–6.47)	4.79(3.11–7.95)	7.52(5.73–10.48)	9.69	0.008*
Lymphocytes (×109/L)^b	1.10–3.20	0.67(0.46–1.16)	0.97(0.59–1.75)	0.58(0.40–0.71)	0.33(0.21–0.78)	28.07	<0.001*
Monocytes (×109/L)^b	0.10–0.60	0.37(0.21–0.54)	0.35(0.18–0.54)	0.31(0.21–0.52)	0.48(0.42–0.58)	5.33	0.07
Platelet (×109/L)^b	125.00–350.00	195.5(138.75–248.25)	205(172.75–277.00)	192.5(137.25–238.25)	130.50(95.00–202.75)	13.46	0.001*
Hemoglobin (g/L)^b	130.00–175.00	132(119–143.25)	137(119.25–147.00)	130.50(118.5–141.50)	129(113.00–136.25)	2.89	0.235
NLR (%)^b	-	6.81(3.99–10.63)	4.99(3.19–7.48)	7.89(5.60–14.02)	20.92(8.34–40.76)	35.73	<0.001*
MLR (%)^b	-	0.51(0.23–0.80)	0.30(0.15–0.64)	0.61(0.34–0.84)	1.17(0.57–2.43)	25.60	<0.001*
PLR (%)^b	-	264.94(168.07–378.33)	250.01(138.01–291.00)	307.28(224.24–513.85)	373.67(176.42–728.13)	12.65	0.002*
HALP (%)^b	-	17.26(10.70–33.36)	20.58(15.69–38.21)	12.82(9.19–24.30)	9.45(6.06–22.93)	16.48	<0.001*
Arterial blood gas analysis
PH^b	7.35–7.45	7.43(7.40–7.46)	7.43(7.41–7.46)	7.43(7.38–7.45)	7.40(7.19–7.48)	2.281	0.320
PCO2(mmHg)^b	35.00–45.00	36(32.20–40.30)	35.10(33.90–37.50)	37.30(33.10–41.90)	33.50(26.50–70.90)	6.40	0.041*
PO2(mmHg)^b	80.00–108.00	67.40(60.50–84.80)	84.2(63.25–93.40)	67(60.60–71.30)	46.40(30.43–63.83)	33.05	<0.001*
Oxygenation index^b	400–500	289(183–321)	295(264.50–322)	246(135–319)	141(132–228.75)	29.76	<0.001*
Liver function
ALT (U/L)^b	9.00–50.00	22.15(17.60–34.93)	20.15(15.73–24.20)	27(20.93–37.7)	40.05(19.53–50.88)	16.52	<0.001*
AST (U/L)^b	15.00–40.00	29.15(22.38–43.03)	26.40(18.35–35.03)	34.85(28.30–52.60)	43.15(30.50–110.85)	19.75	<0.001*
Total protein (g/L)^b	65.00–85.00	67.95(63.58–72.30)	69.55(65.78–74.25)	67.15(63.28–68.95)	61.45(59.73–67.60)	20.57	<0.001*
Albumin (g/L)^b	40.00–55.00	35.35(31.53–38.00)	36.30(33.88–38.10)	36(30.95–38.40)	31.60(30.13–34.00)	11.89	0.003*
Globulin (g/L)^b	20.00–40.00	32.90(29.78–35.48)	34.10(31.95–36.80)	30.95(28.55–33.23)	29.95(28.70–35.90)	14.40	0.001*
Fasting plasma glucose (mmol/L)^b	3.90–6.10	8.27(7.14–12.45)	7.21(6.21–9.26)	11.94(8.09–14.77)	10.10(8.15–13.28)	20.83	<0.001*
Triglycerides (mmol/L)^b	<1.70	0.90(0.71–1.27)	0.81(0.66–0.97)	1.17(0.77–2.24)	1.20(0.94–1.95)	21.91	<0.001*
Kidney function
BUN (mmol/L)^b	3.60–9.50	6.15(5.30–10.23)	5.85(5.13–6.95)	8.15(5.75–11.58)	11.85(7.48–28.08)	22.67	0.003*
Cr (μmol/L)^b	57.00–111.00	66(55.00–87.62)	63(54.25–72.00)	67.88(53.89–91.25)	89.50(69.61–105.50)	9.57	0.008*
PCT (ng/mL)^b	0.00–0.51	0.57(0.36–1.21)	0.41(0.30–1.50)	0.52(0.40–0.89)	1.12(0.67–4.23)	11.55	0.003*
CRP (mg/L)^b	<5	41.61(9.85–99.18)	12.05(3.30–72.48)	73.06(29.74–128.88)	86(70.30–105.14)	29.95	<0.001*
ESR (mm/H)^b	0.00–15.00	33(16.00–59.25)	32.5(16.00–55.75)	31(13.75–49.50)	48(32.25–76.50)	3.90	0.142
Urine sugar, n (%)^a	-	22(18.6)	6(9.4)	14(36.8)	2(12.5)	12.22	0.002*
Urinary protein, n (%)^a	-	12(10.2)	2(3.1)	6(15.8)	4(25.0)	8.57	0.014*
Myocardial enzyme profile
CK (U/L)^b	50.00–310.00	88(52.75–154.75)	73(46.71–101.00)	97.12(72.75–229.25)	150.50(113.75–194.50)	22.46	<0.001*
LDH (U/L)^b	120.00–250.00	270(221.00–362.73)	256(214.50–295.50)	299.75(231.50–369.70)	509.50(339.50–641.50)	22.50	<0.001*
HBDH (U/L)^b	72.00–182.00	178.2(152.55–233.40)	164(143.00–178.80)	202(177.93–231.00)	312.7(243.75–343.00)	34.09	<0.001*
CK-MB (U/L)^b	<19.00	9.31(6.65–12.10)	8.5(6.23–10.18)	10.80(7.53–13.79)	12.45(9.20–15.43)	11.87	0.003*
Hs-cTn (pg/mL)^b	0.00–19.80	8.11(5.03–13.19)	5.96(2.73–8.71)	11.15(7.63–19.23)	10.80(9.13–16.87)	23.56	<0.001*
Myoglobin (ng/mL)^b	17.40–105.70	50.05(34.78–82.00)	39(25.65–47.40)	77.50(56.45–89.83)	85.2(82.30–132.88)	46.85	<0.001*
Coagulation function
BNP (pg/mL)^b	0.00–100.00	67.20(38.58–121.40)	41.8(24.70–82.70)	90.45(60.35–180.05)	86.7(65.20–187.45)	24.66	<0.001*
D-dimer (ng/mL)^b	0.00–243.00	301(181.25–608.25)	262.5(161.75–420.00)	399.50(219.00–703.25)	456(285.50–2393.50)	12.29	0.002*
Fibrinogen (g/L)^b	2.38–4.98	3.94(2.97–4.67)	3.43(2.90–4.15)	4.14(3.74–4.67)	4.45(3.48–5.58)	8.39	0.015*
PT (S)^b	11.50–14.80	14.45(13.48–15.83)	14.35(13.23–15.48)	14.65(13.58–16.30)	14.60(13.23–17.18)	2.69	0.261
INR (%)^b	0.80–1.20	1.07(1.00–1.15)	1.05(1.00–1.13)	1.09(1.00–1.15)	1.09(0.97–1.37)	1.82	0.403
Immune cell subsets
T Lymphocytes (pcs/uL)^b	636.00–2040.00	395.74(219.36–516.23)	444.69(258.99–618.03)	344.90(218.73–451.73)	232.54(120.52–411.65)	17.99	<0.001*
B Lymphocytes (pcs/uL)^b	90.00–423.00	83(52.95–110.45)	103.78(60.12–132.29)	60.91(50.79–106.38)	56.89(37.35–67.05)	15.43	<0.001*
Th (pcs/uL)^b	378.00–1245.00	157(98.19–312.48)	211.65(110.50–330.89)	100.55(73.15–252.05)	95.95(48.42–160.15)	17.45	<0.001*
Ts (pcs/uL)^b	128.00–993.00	137.20(102.70–233.73)	212.49(101.13–325.55)	134.83(120.69–168.44)	103.68(72.86–123.68)	17.66	<0.001*
NK (pcs/uL)^b	93.00–580.00	144.86(105.15–248.30)	158.48(135.82–245.50)	104.95(76.09–235.97)	138.76(115.75–257.09)	9.60	0.008*
CD4+T cell subsets
Th1 (pcs/uL)^b	5.52–182.00	34.90(18.70–55.97)	50.01(22.63–79.21)	15.38(10.32–30.20)	38.85(29.66–47.41)	25.23	<0.001*
Th2 (pcs/uL)^b	4.04–21.00	2.52(2.15–4.62)	3.22(2.40–5.44)	2.33(1.15–4.36)	2.35(2.15–2.62)	9.68	0.008*
Th1/Th2 (%)^b	0.73–18.50	11.44(5.78–19.45)	12.40(6.53–22.71)	7.74(4.31–16.53)	15.22(6.68–21.42)	6.11	0.047*
Th17 (pcs/uL)^b	3.07–14.00	3.2(1.91–6.83)	5.45(2.64–8.15)	2.44(0.76–4.14)	2.53(1.61–6.55)	27.70	<0.001*
Treg (pcs/uL)^b	17.70–54.20	5.42(3.89–9.16)	7.44(4.41–13.26)	4.71(3.30–8.11)	3.80(2.59–5.08)	20.92	<0.001*
Th17/Treg (%)^b	0.09–4.47	0.54(0.32–0.88)	0.59(0.40–1.05)	0.38(0.24–0.56)	0.72(0.34–1.63)	16.74	<0.001*
Cytokines
IL-2 (pg/mL)^b	0.08–5.71	2.01(1.66–2.52)	2.07(1.59–2.73)	2.11(1.60–2.52)	1.94(1.81–2.07)	0.30	0.861
IL-4 (pg/mL)^b	0.10–2.80	1.73(0.97–3.34)	2.87(1.52–4.25)	1.35(0.95–2.32)	1.24(0.80–1.41)	17.72	<0.001*
IL-6 (pg/mL)^b	1.18–5.30	6.13(3.35–15.30)	6.83(2.74–19.23)	5.46(4.29–9.30)	9.08(5.23–15.01)	1.99	0.370
IL-10 (pg/mL)^b	0.91–4.91	3.80(3.43–4.97)	3.65(3.15–3.96)	4.76(3.51–6.25)	4.27(3.74–4.67)	12.60	0.002*
IL-17 (pg/mL)^b	<20.60	2.94(2.31–5.53)	4.12(2.45–5.47)	2.80(1.60–6.17)	2.93(1.75–5.48)	0.95	0.622
IFN-γ (pg/mL)^b	0.16–7.42	2.85(2.12–3.66)	3.12(2.31–4.04)	2.57(2.03–3.24)	2.43(1.95–3.02)	7.88	0.020*
TNF-α (pg/mL)^b	0.10–2.30	2.28(1.70–2.77)	2.42(1.73–2.89)	2.04(1.33–2.39)	2.33(1.90–2.55)	7.35	0.025*
Immunoglobulins
IgA (g/L)^b	0.70–4.00	2.24(1.42–3.05)	3.02(2.64–3.52)	1.44(0.93–1.82)	1.32(0.96–2.10)	59.25	<0.001*
IgG (g/L)^b	7.00–16.00	11.91(8.80–14.62)	14.47(13.21–15.23)	8.91(7.51–10.02)	8.94(8.05–10.53)	68.94	<0.001*
IgM (g/L)^b	0.40–2.30	0.73(0.58–1.11)	0.96(0.77–1.54)	0.58(0.51–0.69)	0.61(0.51–0.72)	48.96	<0.001*

Notes: Numeric variables were reported as Med (iqr 25–75%). All statistically significant values are reported in bold. ^aFrequency (%) and χ test between non-severe versus (severe diseases or death); ^bMed (iqr 25–75%) and Kruskal–Wallis One Way ANOVA test. *P<0.05.

Abbreviations: BMI, body mass index; Med, Median; iqr, Interquartile range; WBC, White blood cell; NLR, Neutrophil-to-lymphocyte ratio; MLR, Monocyte-to- lymphocyte ratio; PLR, Platelet-to-lymphocyte ratio; HALP, Hemoglobin, albumin, lymphocyte, and platelet score; ALT, Alanine transaminase; AST, Aspartate aminotransferase; BUN, Blood urea nitrogen; Cr, Creatinine; PCT, Procalcitonin; CRP, C-reactive protein; ESR, Erythrocyte sedimentation Rate; CK, Creatine kinase; LDH, lactic dehydrogenase; HBDH, α-hydroxybutyrate dehydrogenase; CK-MB, Creatine kinase-MB; Hs-cTn, High sensitivity troponin; BNP, B type natriuretic peptide; PT, Prothrombin time; INR, International Normalized Ratio; Th, Helper T cell; Ts, Suppressor T cell; NK, natural killer cell; IFN-γ, Interferon Gamma; TNF-α, Tumor necrosis factor-α.

Figure 1 ROC curve used to differentiate non-severe and severe COVID-19 patients. The area under the ROC curve (AUC) closer to 1 indicates the higher diagnostic accuracy. AUC data are presented as values (95% confidence intervals).

Abbreviations: ROC, receiver-operating curve; AUC, area under the curve.

Table 4 Multivariate Ordered Logistic Regression Analysis Used to Predict the Multivariate Predictors of Different Severity Levels

Indexes	Regression Coefficient	Standard Deviation	OR	95% CI	P-value
NLR	−0.046	0.027	0.955	0.906–1.007	0.090
MLR	−1.669	0.543	0.188	0.065–0.546	0.002
PLR	0.001	0.002	1.001	0.997–1.004	0.661
HALP	0.022	0.022	1.002	0.978–1.068	0.333

Notes: Statistically significant differences are emboldened. Odds ratios were given with 95% CI and p values.

Abbreviations: OR, odds ratio; CI, confidence intervals. NLR, Neutrophil-to-lymphocyte ratio; MLR, Monocyte-to- lymphocyte ratio; PLR, Platelet-to-lymphocyte ratio; HALP, Hemoglobin, albumin, lymphocyte, and platelet score.

Figure 2 (A–D) Probability of survival curve based on risk factors. (E) Multivariate Cox analyses. (A) Kaplan–Meier curves of NLR for COVID-19 patients; (B) Kaplan–Meier curves of MLR for COVID-19 patients; (C) Kaplan–Meier curves of PLR for COVID-19 patients; (D) Kaplan–Meier curves of HALP for COVID-19 patients; (E) Multivariate Cox analyses of NLR, MLR, PLR and HALP.

Abbreviations: WBC, white blood cell; NLR, Neutrophil-to-lymphocyte ratio; MLR, Monocyte-to- lymphocyte ratio; PLR, Platelet-to-lymphocyte ratio; HALP, Hemoglobin, albumin, lymphocyte, and platelet score; HR, Hazard ratio.