To the editor
Since the appearance of the coronavirus disease 2009 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in December 2019, the COVID-19 has spread throughout the world, occurring in forming several peaks in waves. We read with interest the recent article published by Saito et al.,1 where they compared the severity and characteristics of the first and second waves in Japan. In Spain we have seen three waves: a first wave during March-April 2020, a second wave during September-November 2020, and a third wave during January-February 2021. There are very few articles comparing clinical characteristics of COVID-19 patients between the different waves.1, 2, 3 The objective of the present study was to compare clinical characteristics, treatments administered, and the evolution of critically ill COVID-19 patients during the three waves suffered in an Intensive Care Unit (ICU) in the northwestern of Spain.
We prospectively evaluated patients admitted to the Clinical University Hospital of Santiago, Spain, in the three waves, with laboratory-confirmed COVID-19 disease who had severe acute respiratory distress syndrome (ARDS) needing ICU admission. The following information were collected in all patients: age, sex, comorbidities, inflammatory biomarkers, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, PaO2/FiO2, ICU treatments, prone position (PP) sessions, need of mechanical ventilation (MV), duration of ICU admission and ICU outcomes. Data was presented as number (percentage), and mean ± standard deviations or median and interquartile range as appropriate considering variable distribution. Chi-square and Wilcoxon rank-sum test were used to test for differences between categorical or numeric variables. Descriptive statistics were calculated, non-parametric tests were used for comparison of groups. Data were analysed using SPSS program (v. 22.0). The study protocol was approved by the ethics committee of Galicia (code No. 2020-184), and all participating subjects provided informed consent.
A total of 89 ICU patients with ARDS by Covid-19 were included. Demographic details and treatments are summarized in Table 1 . Contrary to the first wave, higher proportion of patients in the second and third wave were not intubated, receiving high flow nasal oxygen (HFNO) or noninvasive mechanical ventilation (NIMV) (Table 1). In the third wave more patients were treated with corticosteroids compared with fist wave (100% vs 80%, p = 0.007) and in more patients were used awake prone positioning compared with first wave (91% vs 45%, p=<0.001) and second wave (91% vs 56%, p = 0.001). In patients who needed MV, the duration between ICU admission and tracheal intubation was longer during the third wave compared with the first wave. Nosocomial infections, complications, duration of ICU admission and mortality were similar in the three waves (Table 1).
Table 1.
Demographics, clinical characteristics, treatments, and outcomes of COVID-19 patients admitted in ICU during the three waves.
| Demographics | First Wave (1)N = 20 | Second Wave (2)N = 23 | Third Wave (3)N = 46 | P value(1 vs. 2) | P value(1 vs 3) | P value (2 vs 3) |
|---|---|---|---|---|---|---|
| Age, mean (SD) | 64.85 (12.39) | 69.57 (12.44) | 65.02 (12.42) | 0.188 | 0.840 | 0.108 |
| Male sex, No. (%) | 11 (55.0) | 16 (69.6) | 34 (73.9) | 0.324 | 0.130 | 0.703 |
| BMI, mean ± SD, | 29.99 (4.93) | 30.30 (5.9) | 30.88 (7.53) | 0.733 | 0.983 | 0.619 |
| Coexisting conditions, No. (%) | ||||||
| Hypertension | 9 (45.0) | 14 (60.9) | 23 (50.0) | 0.298 | 0.709 | 0.393 |
| Hyperlipidemia | 9 (45.0) | 9 (39.1) | 23 (50.0) | 0.697 | 0.709 | 0.393 |
| Diabetes | 4 (20.0) | 6 (26.1) | 10 (21.7) | 0.728 | 0.999 | 0.687 |
| Asthma | 1 (5.0) | 3 (13.0) | 3 (6.5) | 0.610 | 0.999 | 0.393 |
| Chronic obstructive pulmonary disease | 3 (15.0) | 1 (4.3) | 4 (8.7) | 0.323 | 0.425 | 0.658 |
| Heart disease | 5 (25.0) | 4 (17.4) | 4 (8.7) | 0.711 | 0.116 | 0.426 |
| Obesity (BMI ≥ 30 Kg m − 2) | 6 (30.0) | 14 (60.9) | 18 (39.1) | 0.067 | 0.479 | 0.088 |
| Cancer | 2 (10.0) | 5 (21.7) | 4 (8.7) | 0.420 | 0.999 | 0.148 |
| Trasplant | 1 (5.0) | 2 (8.7) | 3 (6.5) | 0.999 | 0.999 | 0.999 |
| Not comorbidity | 4 (20.0) | 1 (4.3) | 3 (6.5) | 0.167 | 0.189 | 0.999 |
| Home treatments, No. (%) | ||||||
| ACE inhibitors | 4 (20.0) | 0 (0.0) | 1 (2.2) | 0.039 | 0.027 | 0.999 |
| Antiplatelets | 0 (0.0) | 5 (21.7) | 7 (15.2) | 0.051 | 0.092 | 0.517 |
| Statins | 5 (25.0) | 10 (43.5) | 28 (60.9) | 0.205 | 0.007 | 0.171 |
| Laboratory parameters, median (IR) | ||||||
| Lymphocyte count, /µL | 510(277–670) | 560 (320–720) | 500 (297–665) | 0.770 | 0.928 | 0.765 |
| Lactate dehydrogenase, U/L, | 635 (341–901) | 437 (329–561) | 567(381–794) | 0.051 | 0.748 | 0.027 |
| D-dimer, ng/mL, | 1064(692–1834) | 1000 (454–4114) | 968 (679–3781) | 0.644 | 0.978 | 0.693 |
| C-reactive protein, mg/L. | 14 (13–25) | 5 (3–19) | 11 (6–18) | 0.008 | 0.040 | 0.140 |
| Procalcitonin | 0.13 (0.10–0.67) | 0.21 (0.07–0.77) | 0.13 (0.07–0.25) | 0.457 | 0.111 | 0.460 |
| Serum Ferritin, µg/L | 864 (561–1592) | 951 (455–1612) | 1048 (472–1616) | 0.770 | 0.999 | 0.770 |
| ICU Medical treatments, No. (%) | ||||||
| Lopinavir-ritonavir | 20 (100.0) | 0 (0.0) | 0 (0.0) | <0.001 | <0.001 | – |
| Hydroxychloroquine | 20 (100.0) | 0 (0.0) | 0 (0.0) | <0.001 | <0.001 | – |
| Remdesivir | 1 (5.0) | 8 (34.8) | 7 (15.2) | 0.024 | 0.418 | 0.063 |
| Tocilizumab | 8 (40.0) | 4 (17.4) | 21 (45.7) | 0.099 | 0.671 | 0.021 |
| Anakinra | 0 (0.0) | 4 (17.4) | 3 (6.5) | 0.111 | 0.548 | 0.211 |
| Corticosteroids | 16 (80.0) | 21 (91.3) | 46 (100.0) | 0.393 | 0.007 | 0.108 |
| Anticoagulant intermediate dose | 8 (40.0) | 8 (34.8) | 14 (30.4) | 0.724 | 0.449 | 0.715 |
| Anticoagulant high dose | 10 (50.0) | 15 (65.2) | 30 (65.2) | 0.313 | 0.245 | 0.999 |
| Characteristics during ICU admission | ||||||
| APACHE II, median (IR) | 16 (13–10) | 14 (10–20) | 14 (12–17) | 0.625 | 0.109 | 0.740 |
| Time from illness onset to ICU admission, days median (IR) | 11 (10–14) | 9 (7–11) | 9 (5–11) | 0.033 | 0.002 | 0.506 |
| PaO2:FiO2 ratio at ICU admission, median (IR) | 113 (85–144) | 95 (68–123) | 92 (69–106) | 0.219 | 0.009 | 0.624 |
| Patients needing mechanical ventilation (MV), No. (%) | 14 (70.0) | 6 (26.1) | 18 (39.1) | 0.004 | 0.021 | 0.284 |
| Duration between ICU admission and MV, days, median (IR) | 0 (0–1) | 2 (0 −4) | 5 (2–9) | 0.091 | <0.001 | 0.066 |
| Duration of MV, days, median (IR) | 13 (8–25) | 13 (7–26) | 14 (9–17) | 0.968 | 0.722 | 0.871 |
| Patients treated with VMNI or HFNO. No. (%) | 4 (20.0) | 19 (82.6) | 44 (95.7) | <0.001 | <0.001 | 0.090 |
| Use of awake prone positioning, No. (%) | 9 (45.0) | 13 (56.5) | 42 (91.3) | 0.451 | <0.001 | 0.001 |
| Use of intubated prone positioning, No. (%) | 12 (85.7) | 4 (66.7) | 13 (72.2) | 0.549 | 0.426 | 0.9999 |
| Patients needing tracheostomy, No. (%) | 5 (25.0) | 1 (4.3) | 9 (19.6) | 0.081 | 0.745 | 0.148 |
| Nosocomial infection, No. (%) | 9 (45.0) | 5 (21.7) | 14 (30.4) | 0.104 | 0.254 | 0.446 |
| Pneumothorax. No. (%) | 2 (10.0) | 1 (4.3) | 3 (6.5) | 0.590 | 0.635 | 0.999 |
| Renal replacement therapy, No. (%) | 1 (5.0) | 0 (0.0) | 4 (8.7) | 0.465 | 0.999 | 0.293 |
| Length of ICU stay, days, median (IR) | 15 (6–31) | 12 (6–22) | 10 (6–21) | 0.421 | 0.258 | 0.637 |
| ICU mortality, No. (%) | 5 (25.0) | 4 (17.4) | 10 (21.7) | 0.711 | 0.759 | 0.760 |
Date are number (percentage (%)), median (interquartile range (IR)); ICU: Intensive Care Unit; COPD, chronic obstructive pulmonary disease; ACE: Angiotensin-converting-enzyme inhibitors; APACHE II: Acute Physiology and Chronic Health Evaluation II, BMI: Body mass index;; VMNI: noninvasive mechanical ventilation; HFNO: High flow nasal oxygen; FiO2: inspired oxygen fraction.
In conclusion, we observed that during the third wave there was a tendency to use corticosteroids,4 NIMV, HFNO, and awake PP, with lower use of MV compared with first wave. A limitation of the study is that present study only included patients admitted of one hospital. Thus, the results may not reflect the experience and results in hospital of other regions. Multicenter studies with a greater number of patients will be able to confirm whether there is a trend towards less use of MV and whether this may influence the decrease in the incidence of nosocomial infections, complications associated with MV, length of stay in the ICU and mortality.
Summary statement
During the third wave there was a tendency to use corticosteroids, NIMV, HFNO, and awake PP, with lower use of MV compared with first wave.
Funding statement
No funding provided.
Support
Support was provided solely from institutional and departmental sources.
CRediT authorship contribution statement
Manuel Taboada: Conceptualization, Writing – original draft, Data curation, Writing – review & editing. Mariana González: Writing – original draft, Data curation, Writing – review & editing. Antía Alvarez: Writing – original draft, Data curation, Writing – review & editing. María Eiras: Writing – original draft, Data curation, Writing – review & editing. Jose Costa: Writing – original draft, Data curation, Writing – review & editing. Julián Álvarez: Writing – original draft, Data curation, Writing – review & editing. Teresa Seoane-Pillado: Formal analysis, Data curation, Writing – original draft, Writing – review & editing.
Acknowledgments
The authors thank all physicians and nurses of the Hospital Clínico Universitario Santiago de, Compostela. Spain.
References
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