Fig. 1.
Distribution of ICU admissions, corresponding variant predominance across different waves, and mortality throughout the pandemic. Abbreviations: ICU, intensive care unit.
Table 1.
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 |
[i] All data are expressed as n (%), unless otherwise defined. Abbreviations: N, number of patients; IQR, interquartile range; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment; COPD, chronic obstructive pulmonary disease; MV, mechanical ventilation; HFNC, high flow nasal cannula; ICU, intensive care unit; CRRT, continuous renal replacement therapy; LOS, length of stay.
Table 2.
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 |
[i] Data are expressed as median (IQR). Abbreviations: ICU, intensive care unit; N, number of patients; WBC, white blood cell; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; hs-cTnI, high sensitivity cardiac troponin I; CRP, C-reactive protein; PEEP, positive end expiratory pressure.
Fig. 2.
Kaplan-Meier survival curves among the four waves. Abbreviations: ICU-LOS, intensive care unit-length of stay.
Table 3.
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 |
Fig. 3.
Distribution of age quartiles in non-survivors among the four waves.
Fig. 4.
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.
Table 4.
Log Rank pairwise comparisons between the age quartiles for each pandemic wave
| Age quartiles | 1 | 2 | 3 | 4 | |||||
|---|---|---|---|---|---|---|---|---|---|
| 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 | |||