Differences between the first and the second wave of critically ill COVID-19 patients admitted to the intensive care units.

Background: To compare the demographic characteristics and prognosis of patients admitted to the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19) pneumonia during the first wave (March-July) versus those admitted during the second wave (August-December).
Methods: Prospective, observational, descriptive cohort-study including patients admitted to the ICU for COVID-19 pneumonia during the first wave (March-July 2020) or the second wave (August-December). The demographic characteristics, comorbidities, treatments, complications, and mortality in both pandemic waves were studied.
Results: A total of 72 patients were included: Twenty-six admitted during the first wave and 46 during the second wave. Men were predominant in both waves: 61.5% versus 73.9%. The most frequently associated comorbidities in both periods were: arterial hypertension 65.4% versus 65.2%, diabetes mellitus 46.2% versus 34.8% and overweight, measured as (body mass index), 29.13 ± 3.38 versus 28.98 ± 4.25. More patients received noninvasive mechanical ventilation prior to invasive ventilation during the second wave (P < 0.01); the incidence of atelectasis and bronchial obstruction were lower during the second wave (P < 0.01 and P = 0.055 respectively); no further differences were observed in the occurrence of other complications. Conclusions: No significant differences were observed between the first and the second wave in the demographic characteristics or comorbidities of admitted patients. Blood hypertension, diabetes and overweight were remarkable risk factors. Improving our knowledge of the complications, these patients tend to develop was essential to reduce some of them, such as endotracheal tube obstruction or atelectasis, and to promote the use of noninvasive ventilation therapies. Copyright:

INTRODUCTION

Spain, like the rest of the world, faced several waves of coronavirus disease 2019 (COVID-19) during 2020. Consequently, the different treatments applied during admission to intensive care units (ICU) have been modified on the basis of a continuous analysis of the infection course.[123]

With the aim of offering quality care to critically ill patients while maintaining quality standards, the Spanish Society of Intensive Medicine, Critical Medicine and Coronary Units developed recommendations for healthcare professionals in charge of critically ill COVID-19 patients during the pandemic. These recommendations consisted of a contingency plan, ethical recommendations, guidelines on noninvasive ventilation systems and on critical care transport, all of which was necessary in a context of an overloaded health system and high need to redistribute resources and patients.[456]

In certain areas, the second wave was more severe than the first one. In addition, new variants of the virus appeared, like the so-called British strain (69/70 -deletion C N501Y C D614G) or the South African strain (E484K C N501Y C D614G), which showed changes in terms of viral transmissibility, virulence, clinical and epidemiological presentation, or efficiency of the vaccine.[7]

It could be assumed that the experience in diagnosis and treatment acquired during the first wave could contribute to improve the prognosis of critical COVID-19 patients admitted during the second wave.[89] Therefore, it is interesting to know, in a specific setting and in our case, in a specific ICU, the evolution of patients’ characteristics and prognosis after the modifications that were introduced in therapeutic protocols.

Background

To compare the characteristics and prognosis of patients admitted to our ICU for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 (reverse transcriptase polymerase chain reaction [RT-PCR] positive) during the first wave (from March to July 2020) versus those admitted during the second wave (August to December 2020).

METHODS

Design of the study

We conducted a prospective, observational, descriptive cohort-study with patients admitted for COVID-19-induced pneumonia in the ICU of the Complejo Hospitalario Universitario Insular Materno Infantil (Mother and Child University Hospital), which is equipped with 718 beds and is part of the public hospital network of the Canary Islands Health Service belonging to the Canary Islands Regional Health Administration. The ICU has 32 beds; the maximum occupancy rate for COVID-19 patients during the studied period was 56.25% (This study adheres to the STROBE guidelines).

Since the beginning of the pandemic, information was recorded from patients admitted with severe SARS-CoV-2 pneumonia (based on the WHO system), confirmed during admission. The whole study period was from March to December 2020; patients admitted from March to July 2020 were considered first wave, while those admitted from August to December were considered second wave. These periods were determined on the basis of the accumulated incidence/100,000 people in the last 14 days [Figure 1].

Figure 1

Accumulated incidence at 14 days per 100,000 habitants in the Canary Islands

COVID-19 diagnosis was based on the detection of viral ribonucleic acid in nasopharyngeal smear, through the RT-PCR test. The study included patients admitted to the ICU with a diagnosis of severe COVID-19 infection, defined as the presence of SARS, sepsis or septic shock.

Analyzed variables

Data were collected on patients’ demographic characteristics (age, sex, body mass index [BMI]), comorbidities at admission (arterial hypertension, chronic heart disease, dyslipidemia, diabetes mellitus, smoking habit, chronic obstructive pulmonary disease, cancer, liver disease, immunosuppression or pregnancy). In addition, the Charlson comorbidity index and the severity and organ failure indexes were calculated at the moment of admission, as measured by APACHE-II and SOFA.

The time lapse was measured in number of days, from the onset of COVID-19 symptoms to the day the patient visited the hospital, from patient's admission to hospital until admission to the ICU, total ICU stay and total hospital stay.

Recorded information on treatment included: number of patients who received noninvasive mechanical ventilation (NIMV), duration of NIMV before intubation, need for intubation and re-intubation, days with mechanical ventilation, administration of sedatives, muscle relaxant drugs or catecholamines, need to use the prone position and its duration in days, number of patients needing tracheotomy and administration of active humidification, corticosteroids or anticoagulant agents.

Recorded complications possible occurring during ICU stay included bronchial obstruction, cardiac arrhythmia, myocarditis, pneumothorax, atelectasis, prolonged delirium, prone position sores, acute renal failure, life-threatening hemorrhage, thromboembolism, and death.

Finally, we recorded hospital mortality and survival rates at 15, 30, 45, and 60 days after hospital discharge.

Ethical considerations

The project was approved by the Ethics Committee. A written informed consent waiver was granted due to the urgent need to collect data. The authors were in charge of analyzing and interpreting the data. Every patient from the database was assigned a code, in order to preserve anonymity.

Statistical analysis

Quantitative variables were described through mean, standard deviation, median and percentiles 25 and 75. Distribution normality was analyzed with the Kolmogorov−Smirnov test for sample size >50 or with the Shapiro−Wilk otherwise. Qualitative variables were described through frequencies and percentages. Survival analysis was conducted with the Kaplan−Meier test and the Log−Rank test to compare survival curves. P values lower than 0.05 were considered statistically significant. We used the statistical software R Core Team 2020, version 4.0.2 (statistical computing. R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

Patients’ characteristics at intensive care unit admission

A total of 72 patients admitted with severe COVID-19 were included: 26 during the first wave and 46 during the second wave. No significant differences were found in a comparison between both waves in terms of demographic characteristics, comorbidities or risk factors. Male patients were predominant in both waves, 61.5% versus 73.9%. The most frequently associated comorbidities, in both periods, were arterial hypertension (65.4% vs. 65.2%) and diabetes mellitus (46.2% vs. 34.8%). In addition, the mean BMI of admitted patients indicated overweight, 29.13 ± 3.38 versus 28.98 ± 4.25. The severity (APACHE and SOFA) and comorbidity rates at the time of admission were similar [Table 1].

Table 1

Demographic characteristics and comorbidities on admission.

	1st wave (n=26), n (%)	2nd Wave (n=46), n (%)	P
Age (years)	65.23±9.92	62±14.34	0.366
Gender (male)	16 (61.5)	34 (73.9)	0.298
BMI	29.13±3.38	28.98±4.25	0.859
Previous comorbidities, n (%)
Arterial hypertension	17 (65.4)	30 (65.2)	1
Previous heart disease	5 (19.2)	8 (18.2)	1
Diabetes	12 (46.2)	16 (34.8)	0.451
Dyslipidemia	10 (23.5)	28 (60.9)	0.087
Smoking	5 (19.2)	14 (30.4)	0.407
COPD	4 (15.4)	3 (6.5)	0.244
Liver disease	0	1 (2.2)	1
Cancer	1 (3.8)	7 (15.2)	0.244
Immunosuppression	3 (12)	5 (10.9)	1
Pregnancy	1 (3.8)	0	0.361
APACHE	14.2±4.1	17±8	0.164
SOFA	8.30±4.5	7±4	0.162
Charlson	2.96±1.56	3±2	0.656
Days onset of symptoms until hospital admission	8.19±4.69	5.29±2.83	0.011
Days from hospital admission to ICU	1.65±1.62	2.04±3.22	0.946
Days of ICU stay	22.62±15.26	17.48±13.02	0.197
Days of hospital stay	31.69±19.9	31.84±19.4	0.923

BMI: Body mass index, ICU: Intensive care units, COPD: Chronic obstructive pulmonary disease, APACHE: Acute physiology, age and chronic health evaluation, SOFA: Sequential organ failure assessment

Clinical management during intensive care unit stay

The protocols used at our hospital, were different between the first and the second waves, and were changed on the basis of therapeutic recommendations from the expert committee at the time. In particular, the treatment during the first wave included Lopinavir/Ritonavir and Chloroquine, while in the second wave, it was changed to Emtricitabine/Tenofovir and Remdesivir. Tocilizumab was administered in both waves, although it was more frequently used in the first than in the second one (differences not significant, P 0.053). The differences in the clinical management during intensive care unit stay was as shown in [Table 2].

Table 2

Differences in the treatment applied between the first and second waves

	1st wave (n=26), n (%)	2nd wave (n=46), n (%)	P
NIMV	1 (3.8)	23 (50)	<0.01
Hours of NIMV prior to intubation	5±0.98	46.26±4.8	<0.01
Orotracheal intubation	22 (84.61)	33 (73.33)	0.26
Reintubation	14 (53.8)	8 (17.4)	0.003
Mechanical ventilation days	19.02±14.48	13.43±13.92	0.073
Sedation	22 (84.6)	31 (67.4)	0.165
Neuromuscular blockade	22 (84.6)	28 (60.9)	0.061
Catecholamines	22 (84.6)	31 (67.4)	0.165
Prone positioning	12 (46.2)	23 (50)	0.809
Prone duration (days)	1.84±2.55	2.6±3.43	0.666
Active humidification	4 (18.2)	25 (57.8)	0.04
Corticosteroids	17 (65.4)	41 (89.1)	0.027
Anticoagulation	3 (11.5)	23 (50)	0.001
Tracheotomy	16 (61.5)	16 (34.8)	0.047
Percutaneous	11 (68.8)	14 (87.5)	0.394
Surgical	5 (31.2)	2 (12.5)
Mucolytics	13 (50)	31 (67)	0.208
Meduri	2 (8)	14 (30.4)	0.039

NIMV: Noninvasive mechanical ventilation

In the second wave, besides treatment modifications introduced following therapeutic recommendations of the expert committee, a significant increase was observed in the use of corticosteroids (P = 0.027), as well as in their use according to a Meduri protocol (P = 0.039).

Similarly, an increase was observed in the use of active humidification (P = 0.04) and in the establishment of anticoagulant therapy in patients with D-dimer > 3.000 mg/l (P = 0.001).

Patients in the first wave, visited the hospital later, from the onset of symptoms, than those in the second wave (P = 0.011); however, their stay in the hospital ward before being admitted to the ICU was not shorter (P = 0.946).

NIMV (including High Flow Nasal Cannula) prior to invasive one was more frequent during the second wave (P < 0.01). No differences were found in the need for invasive mechanical ventilation (P = 0.26) or in the number of days with mechanical ventilation (P = 0.073); consequently, no differences were found in the use of sedation, neuromuscular relaxant drugs, catecholamines or prone position (P = 0.809). The proportion of tracheotomy procedures was higher in the first wave (P = 0.047). These results were not associated to significant differences in the ICU stay between the first and the second waves (P = 0.197). Hospital stay was around 31 days in both waves, with no significant differences between them (P = 0.923).

Complications

Table 3 describes the differences in the observed complications between the first and the second wave: the incidence of atelectasis (P < 0.01) and bronchial obstruction were lower in the second wave (P = 0.055), while no significant differences were observed in the occurrence of other complications during the ICU stay.

Table 3

Analysis of the differences of the complications that appeared in the two epidemic waves

	1st wave (n=26), n (%)	2nd wave (n=46), n (%)	P
Bronchial obstruction	17 (77.27)	23 (50)	0.055
Cardiac arrhythmias	8 (30.8)	15 (32.6)	1
Myocarditis	0	2 (4.3)	0.532
Neumothorax	1 (3.8)	3 (6.5)	1
Atelectasis	18 (69.2)	11 (23.9)	<0.01
Delirium	13 (50)	18 (39.1)	0.459
Prone ulcers	6 (23.1)	15 (32.6)	0.433
Acute kidney failure	7 (26.9)	11 (23.9)	0.784
Massive hemorrhage	4 (15.4)	3 (6.5)	0.244
Thromboembolic complication	0	1 (2.2)	1
Exitus	5 (19.2)	6 (13)	0.511

Survival during intensive care unit and hospital stay

Figure 2 shows the Kaplan−Meier survival curves, where 60-day survival rates at the ICU or the hospital were similar in both waves.

Figure 2

Kaplan−Meier survival estimates during the 60 days at ICU or hospital admission of COVID-19 patients admitted during the first wave (red curve) and the second wave (blue curve)

DISCUSSION

Here, we present the first comparison between the two COVID-19 pandemic waves in the Canary Islands community. Patients’ demographic characteristics and severity upon admission did not differ between the first and the second wave, which makes the comparison of complications and prognosis more relevant. The fact that the study was carried out in only one healthcare unit contributes to the strength of the study, since the criteria used for tracheal intubation and clinical management were established by only one team of intensive care professionals.

The most frequently associated comorbidities in our COVID-19 patients were hypertension and diabetes mellitus. In a study including more than fifteen thousand patients from 150 Spanish hospitals, the prevalence of hypertension and diabetes mellitus were 50.9% and 19.4%, respectively, namely significantly lower than ours.[10]

This finding is in line with earlier studies that revealed differences between communities in adjusted diabetes prevalence, with lower rates in the north and center of Spain and higher rates in the south and east, as well as in the islands. Actually, the lowest prevalence corresponded to Castilla y LeɃn (4.51%) and the highest one to the Canary Islands (9.72%).[11] Furthermore, it has been demonstrated that a large proportion of deaths due to heart attack in the latter community may be attributed to diabetes (9.4; 95%CI 4.8−13.6).[12]

Both waves patients showed overweight, as measured by their BMI. Nutritional status is considered an indicator of health status and of the influence of diet on the immune system and predisposition to certain diseases. Particularly in COVID-19, some studies showed that patients with nutritional deficiencies evolved unfavorably.[13] Some authors highlight the fact that many studies consider obesity as a risk factor for the disease, but disregard nutritional status.[1415]

The experience acquired during the first wave may have contributed to change the ICU therapeutic protocols, in particular toward a greater use of corticosteroids at the time of admission and of noninvasive mechanical ventilation. The expert panel of the Surviving Sepsis Campaign Guidelines recommended systemic corticosteroids together with vein thromboprophylaxis for severely or critically ill COVID-19 patients.[16] Regarding ventilation, the clinical guidelines recommended early intubation in the first wave, but over time, the use of NIMV as the initial therapy proved beneficial for survival. Moreover, mortality was not higher among patients who needed intubation after NIMV than among those that needed to be intubated directly.[17]

Despite the greater number of COVID-19 patients admitted during the second wave, no increase in the complication rate or differences in mortality were observed between both waves (19% vs. 13%). Actually, the mortality rate remained low as compared to those described in the medical literature so far, which may reach almost 30%.[18] A better knowledge of possible complications enhanced our management of some of them, such as bronchial obstruction and the consequent development of atelectasis, which were found to decrease during the second wave.[19]

Apart from the sample size, this study has the limitation, like any observational study, of being subjected to some confusion and to the fact that any association between exposure and results should not be interpreted as causal.

In addition, the criteria used for ICU admission in our cohort may differ from those of other studies and may not represent the totality of the severely ill COVID-19 patient population.

CONCLUSIONS

No significant differences were found between the first and the second wave in the profile of patients admitted to our ICU for critical COVID-19, nor in their comorbidities, where hypertension, diabetes, and overweight remained predominant. A better knowledge of complications possibly affecting these patients was essential to reduce the occurrence of some of them, such as endotracheal tube obstruction, and to promote the use of NIMV therapies.

Research quality and ethics statement

This study was approved by the Institutional Review Board / Ethics Committee (Approval # CEI/CEIM 2020-231-1 COVID-19). A waiver of written informed consent was granted. The authors followed the applicable EQUATOR Network (http://www.equator-network.org/) guidelines, specifically the STROBE Guideline, during the conduct of this research project.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.