Comparative analysis of COVID-19 critically ill patients across four pandemic waves in Greece

Kokkoris, Stelios; Goufa, Aikaterini; Tsilivarakis, Dimitrios; Kavallieratos, Fotios; Minatsi, Georgia; Papadaki, Despoina; Pranti, Aikaterini; Zakynthinos, Spyros; Kotanidou, Anastasia; Routsi, Christina

Comparative analysis of COVID-19 critically ill patients across four pandemic waves in Greece

Volume 11 (2025): Issue 4 (October 2025)

By: Stelios Kokkoris, Aikaterini Goufa, Dimitrios Tsilivarakis, Fotios Kavallieratos, Georgia Minatsi, Despoina Papadaki, Aikaterini Pranti, Spyros Zakynthinos, Anastasia Kotanidou and Christina Routsi

Open Access

|Oct 2025

Figures & Tables

Distribution of ICU admissions, corresponding variant predominance across different waves, and mortality throughout the pandemic. Abbreviations: ICU, intensive care unit.

Kaplan-Meier survival curves among the four waves. Abbreviations: ICU-LOS, intensive care unit-length of stay.

Distribution of age quartiles in non-survivors among the four waves.

Kaplan-Meier survival curves of age quartiles a) in the overall cohort, b) in the first wave, c) in the second wave, d) in the third wave, and e) in the fourth wave. Abbreviations: ICU-LOS, intensive care unit-length of stay.

Laboratory findings and respiratory parameters on ICU admission

Total n=805	1st wave n=243		2nd wave n=300		3rd wave n=158		4th wave n=104		P value
Laboratory tests
WBC count, 109/L	9.6	(6.4–13.6)	10.3	(7.1–14.2)	11.8	(6.9–15.4)	11.6	(7.2–16.4)	0.04
Neutrophil count, 109/L	8.2	(5.1–12.1)	8.7	(6.0–12.6)	10.1	(5.8–13.7)	10.1	(6.3–14.7)	0.04
Lymphocyte count, 109/L	.80	(.55 –1.17)	.78	(.50–1.10)	.67	(.49–0.94)	.76	(.49–1.16)	0.08
NLR	9.7	(5.5–15.7)	12.2	(6.9–19.6)	13.1	(8.0–21.5)	13.4	(7.9–25)	0.001
Hemoglobin, g/dL	12.6	(11.4–13.7)	12.1	(10.3–13.7)	12.5	(10.9–13.7)	12.0	(10.3–13.4)	0.12
Platelet count, 109/L	236	(182–306)	247	(187–317)	239	(174–309)	239	(169–301)	0.71
Fibrinogen, mg/dL	600	(497–714	582	(485–701)	551	(481–679)	551	(385–687)	0.009
D-dimers, mg/L	1.3	(.7–2.6)	1.6	(.9–4.3)	1.5	(.8–3.4)	2.2	(1.0–7.2)	0.003
Ferritin, ng/mL	718	(278–1710)	628	(318–1941)	602	(286–1941)	491	(189–1328)	0.16
Albumin, g/dL	3.3	(2.9–3.6)	3.1	(2.9–3.5)	3.2	(2.8–3.6)	3.1	(2.7–3.5)	0.007
Sodium, mEq/L	139	(136–142)	140	(137–144)	140	(138–144)	141	(138–145)	0.001
Creatinine, mg/dL	.9	(.7–1.2)	.9	(.7–1.3)	.8	(.6–1.3)	.9	(.7–1.3)	0.80
AST, IU/L	44	(26–70)	37	(26–68)	35	(23–62)	35	(21–54)	0.08
ALT, IU/L	36	(21–54)	32	(19–56)	26	(16–500	30	(17–61)	0.09
LDH, IU/L	438	(333–610)	474	(357–643)	458	(348–629)	463	(302–591)	0.29
hs-cTnI, ng/L	18	(8–61)	24	(11–79)	24	(8–62)	39	(18–103)	0.001
Procalcitonin, ng/mL	.30	(.12–1.17)	.24	(.11–0.63)	.23	(.10–0.55)	.20	(.10–0.54)	0.19
CRP, mg/dL	12	(5–19)	11	(6–17)	9	(4–17)	9	(3–16)	0.04

Respiratory parameters
pH	7.39	(7.30–7.45)	7.33	(7.26–7.40)	7.34	(7.26–7.41)	7.29	(7.24–7.36)	0.001
PaCO2, mmHg	40	(33–47)	43	(35–51)	41	(36–47)	43	(37–52)	0.005
Bicarbonate, mEq/L	23	(20–26)	22	(19–24)	22	(20–24)	21	(19–24)	0.007
Lactate, mmol/L	1.6	(1.2–2.1)	1.6	(1.3–2.2)	1.6	(1.2–2.3)	1.8	(1.4–2.5)	0.04
PaO2/FiO2	123	(89–171)	114	(84–181)	137	(90–180)	138	(94–213)	0.17
Respiratory rate, breaths/min	24	(22–27)	25	(21–28)	25	(23–28)	25	(22–28)	0.22
Tidal volume, mL	480	(450–500)	460	(420–500)	450	(400–480)	450	(400–480)	0.001
PEEP, cm H2O	12	(10–15)	12	(10–15)	13	(10–15)	13	(10–16)	0.22
Plateau pressure, cm H2O	26	(24–29)	26	(24–28)	26	(23–28)	27	(24–28)	0.62
Driving pressure, cm H2O	13	(12–15)	12	(11–14)	12	(10–14)	12	(11–14)	0.10

Demographics, comorbidities, treatments and outcomes distribution among the four pandemic waves

Total n=805	1st wave n=243		2nd wave n=300		3rd wave n=158		4th wave n=104		P value
Demographics
Sex, male	176	(72)	200	(67)	100	(64)	71	(69)	0.28
Age, years, median (IQR)	67	(57–76)	68	(59–75)	65	5(0–76)	68	(56–76)	0.21

Severity scores
Charlson index, median (IQR)	3	(2–5)	3	(2–5)	3	(1–5)	3	(2–5)	0.08
APACHE II score, median (IQR)	13	(9–19)	15	(12–19)	14	(11–19)	15	(12–18)	0.004
SOFA score, median (IQR)	6	(2–9)	7	(6–9)	7	(5–8)	7	(6–8)	0.002

Comorbidities
Hypertension	101	(42)	131	(44)	58	(37)	40	(38)	0.50
Diabetes	65	(27)	82	(27)	33	(21)	24	(23)	0.42
Obesity	29	(12)	34	(11)	26	(16)	15	(14)	0.42
Cerebrovascular disease	65	(27)	71	(24)	34	(21)	32	(31)	0.32
COPD	25	(10)	51	(17)	18	(11)	12	(11)	0.10
Malignancy	18	(7)	35	(12)	16	(10)	16	(15)	0.14
Chronic kidney disease	15	(6)	31	(10)	13	(8)	6	(6)	0.26

Treatments
Remdesivir	78	(32)	163	(54)	90	(57)	60	(58)	0.001
Dexamethasone	150	(62)	260	(87)	143	(90)	84	(81)	0.001
Tocilizumab	0	(0)	2	(1)	14	(9)	20	(19)	0.001
MV on admission	131	(54)	249	(83)	116	(73)	92	(88)	0.001
HFNC on admission	75	(31)	41	(14)	38	(24)	4	(4)	0.001

Outcomes
ICU outcome, death	109	(45)	148	(50)	73	(46)	52	(50)	0.64
Hospital outcome, death	108	(47)	154	(61)	73	(50)	54	(63)	0.003
CRRT need	67	(28)	83	(28)	45	(28)	43	(41)	0.04
MV duration, days, median (IQR)	9	(0–17)	12	(5–26)	13	(4–27)	13	(6–25)	0.001
ICU LOS, days, median (IQR)	13	(7–23)	15	(8–31)	19	(9–36)	17	(9–31)	0.03

Log Rank pairwise comparisons between the age quartiles for each pandemic wave

	Age quartiles	1		2		3		4
	Age quartiles	Chi-Square	P value	Chi-Square	P value	Chi-Square	P value	Chi-Square	P value
Age quartiles				first wave
	1			0.062	0.803	1.732	0.188	14.845	0.000
	2	0.062	0.803			2.727	0.099	22.948	0.000
	3	1.732	0.188	2.727	0.099			11.988	0.001
	4	14.845	0.000	22.948	0.000	11.988	0.001

				second wave
	1			0.785	0.376	7.082	0.008	15.125	0.000
	2	0.785	0.376			4.591	0.032	12.535	0.000
	3	7.082	0.008	4.591	0.032			2.530	0.112
	4	15.125	0.000	12.535	0.000	2.530	0.112

				third wave
	1			0.005	0.941	7.056	0.008	9.876	0.002
	2	0.005	0.941			4.955	0.026	7.594	0.006
	3	7.056	0.008	4.955	0.026			0.03	0.863
	4	9.876	0.002	7.594	0.006	0.03	0.863

				fourth wave
	1			7.484	0.006	10.813	0.001	12.182	0.000
	2	7.484	0.006			0.459	0.498	1.944	0.163
	3	10.813	0.001	0.459	0.498			0.001	0.969
	4	12.182	0.000	1.944	0.163	0.001	0.969

Univariate and multivariate Cox proportional hazards models

	B	P-value	Odds Ratio	95% CI

				Lower	Upper
Univariate model
Wave 1st (reference)
Wave 2nd	−.067	.602	.935	.725	1.205
Wave 3rd	−.287	.062	.750	.555	1.015
Wave 4th	−.135	.430	.874	.625	1.221
Multivariate model
Sex	.070	.588	1.072	.833	1.381
SOFA score	.145	.000	1.157	1.106	1.209
Wave 1st (reference)
Wave 2nd	−.150	.297	.861	.650	1.140
Wave 3rd	−.208	.227	.812	.580	1.138
Wave 4th	−.160	.424	.852	.576	1.261
Hypertension	−.085	.467	.918	.729	1.156
Diabetes	−.153	.248	.858	.662	1.112
Obesity	.001	.996	1.001	.701	1.430
Cardiovascular disease	.244	.062	1.277	.988	1.651
COPD	.462	.002	1.588	1.178	2.141
Malignancy	.424	.010	1.529	1.109	2.107
Chronic kidney disease	.112	.568	1.118	.762	1.642
Remdesivir	−.215	.094	.807	.627	1.037
Dexamethasone	.122	.449	1.129	.824	1.547
Tocilizumab	−.734	.052	.480	.229	1.007
Age quartile 1st (reference)
Age quartile 2nd	.113	.596	1.119	.738	1.698
Age quartile 3rd	.608	.002	1.838	1.239	2.724
Age quartile 4th	.849	.000	2.337	1.580	3.455

DOI: https://doi.org/10.2478/jccm-2025-0036 | Journal eISSN: 2393-1817 | Journal ISSN: 2393-1809

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Language: English

Page range: 417 - 428

Submitted on: Feb 17, 2025

Accepted on: Jul 28, 2025

Published on: Oct 31, 2025

Published by: University of Medicine, Pharmacy, Science and Technology of Targu Mures

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

COVID-19,

pandemic waves,

SARS-CoV-2 variants,

ICU,

age,

Related subjects:

Internal medicine, other,

Surgery,

Surgery, other,

Anaesthesiology,

Emergency medicine and intensive-care medicine

© 2025 Stelios Kokkoris, Aikaterini Goufa, Dimitrios Tsilivarakis, Fotios Kavallieratos, Georgia Minatsi, Despoina Papadaki, Aikaterini Pranti, Spyros Zakynthinos, Anastasia Kotanidou, Christina Routsi, published by University of Medicine, Pharmacy, Science and Technology of Targu Mures
This work is licensed under the Creative Commons Attribution 4.0 License.

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Comparative analysis of COVID-19 critically ill patients across four pandemic waves in Greece

Figures & Tables

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Laboratory findings and respiratory parameters on ICU admission

Demographics, comorbidities, treatments and outcomes distribution among the four pandemic waves

Log Rank pairwise comparisons between the age quartiles for each pandemic wave

Univariate and multivariate Cox proportional hazards models

Paradigm

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