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Introduction

Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and this disease originally emerged in Wuhan, China in December 2019, as a cluster of patients with pneumonia (1). A global outbreak of the disease occurred in the subsequent months, leading to the COVID-19 pandemic in 2020(2).

Patients with COVID-19 present with a variety of symptoms, including fever, cough, dyspnea, fatigue, myalgia, headache, anosmia, nausea, vomiting and diarrhea. The most severe complications of the disease include pneumonia, acute respiratory distress syndrome, shock, acute kidney and liver injury, myocarditis, thromboembolic events and neurological disorders (3,4). Elderly patients and patients with underlying conditions, such as hypertension, diabetes and cardiovascular disease, exhibited an increased risk of developing severe COVID-19 (3-5).

COVID-19 also exerted a significant effect on the mental health of patients. During the early stages of the pandemic, numerous affected countries implemented quarantine measures to prevent viral spread. However, the subsequent reduction of physical activity exerted a negative effect on the psychological well-being of patients (6). Notably, results of a previous study revealed that adapted physical activity prevented COVID-19 disease progression and aided in rehabilitation following the disease, leading to positive psychological outcomes in patients (7).

During the first year of the pandemic, the number of patients with COVID-19 that required hospitalization increased, due to a lack of vaccinations and specific targeted therapies (3,5). As a result, the COVID-19 pandemic exerted a significant effect on healthcare systems worldwide (5,8). Certain countries, such as Italy, were particularly affected by the disease and the requirement for additional beds in hospitals and intensive care units was increased (9).

Following the first year of the pandemic, bed availability for patients with COVID-19 decreased, placing a burden on healthcare systems. A high percentage of patients admitted to hospital with COVID-19 exhibited underlying comorbidities that required prolonged hospitalization and bed requirements continued to increase until after the severe phase of the disease had passed. Notably, these patients remained in COVID-19 hospital wards, as a negative SARS-CoV-2 PCR test result was required for transferal to a non-COVID-19 hospital ward. The incidence of hospital-acquired SARS-CoV-2 infection also increased during this period and patients undergoing surgery were transferred to COVID-19 wards, regardless of symptom severity. This was also the case for patients with COVID-19 who were transferred to hospital from other healthcare locations, such as nursing homes, as they were unable to return to these without a negative PCR test. Thus, the requirement for hospital beds for patients with COVID-19 was crucial and the impact on healthcare systems was evident.

According to Eurostat, Greece accounted for 418 available hospital beds per 10,0000 inhabitants in 2019(10). At the beginning of the COVID-19 pandemic, the Greek Government implemented several measures to support healthcare systems. These measures included restrictions in public movement, guidelines outlining the number of days in quarantine required for patients with COVID-19 and the development of COVID-19 units. The majority of these units included previous medical and surgical hospital wards that were dedicated to patients with COVID-19. Private hospitals were not involved in the care of hospitalized patients with COVID-19; however, these hospitals contributed to the care of patients without the disease, through the provision of beds to support the increasing requirements of public hospitals.

In the present study, data was obtained from a middle-step COVID-19 Unit in a secondary care hospital in the region of Western Attica, between October 2020 and June 2021. The present study aimed to validate the role of a supportive department when healthcare systems were under pressure of the COVID-19 pandemic. The present study also aimed to assess the effectiveness of the middle-step unit, which may exhibit potential in future pandemics. Thus, patient outcomes, including time to hospital discharge, referral back to the referring hospital or death and the length of hospital stay were evaluated. Patient demographics, comorbidities and clinical characteristics were also examined in the present study.

Materials and methods

In the region of Western Attica, five central general hospitals provided wards exclusively for patients with COVID-19 (Attikon General University Hospital of Athens, General Hospital of Nikaia, Agios Panteleimon, Asklipieio Voulas General Hospital, Thriasio General Hospital of Elefsina and Tzaneio General Hospital of Piraeus). At baseline, 180 hospital beds were provided and the number of available COVID-19-specific hospital beds was adjusted according to the number of COVID-19 cases at each timepoint. Notably, during peaks of the COVID-19 pandemic, a total of ~420 hospital beds were available in the five reference hospitals.

To overcome the limited number of COVID-19-specific hospital beds, a novel middle-step COVID-19 Unit was created in a secondary care hospital in the region of Western Attica. The middle-step unit of the Agia Varvara hospital was founded in the first year of the pandemic and patients with COVID-19 were accepted and transferred to the Unit, following referrals from COVID-19 wards of the five general hospitals of the region. The rationale was to support the referral hospitals, through the acceptance of patients with non-severe COVID-19, patients who could not be discharged until a quarantine period was completed, or patients with underlying diseases that could not be transferred to medical or surgical wards prior to a negative PCR test. Notably, the unit included new hospital beds and did not include previously existing wards that had been converted to COVID-19-specific wards. In total, the unit had a capacity of 35 beds, which increased to 55 during the peaks of the pandemic. Medical staff working in the unit consisted of three Consultant Respiratory Physicians, three Consultant General Internal Medicine Physicians, one Consultant Cardiologist, one Consultant Surgeon, one Consultant Anesthetist and three General Internal Medicine Registrars.

Inclusion criteria was as follows: Confirmed COVID-19 via a SARS-CoV-2 PCR test; at least two days of hospitalization prior to unit transfer; no signs of progressive severe COVID-19; and hemodynamic stability with oxygen requirements of ≤40% fraction of inhaled oxygen (FiO2). Patients with concomitant underlying conditions that required prolonged hospitalization following the acute phase of COVID-19 infection, who also exhibited a positive SARS-CoV-2 PCR test, were also accepted to the unit. Deteriorating patients that could not be managed at the unit or in secondary care were referred back to the original referring hospital.

The protocol of the present study was approved by the Ethics Committee of Attikon University Hospital (ethics approval no. 121/03-03-2021) and complied with the guidelines of the Declaration of Helsinki.

In the current study descriptive statistical analysis was performed. Categorical variables are presented as n (%), whereas numerical variables are presented as mean ± standard deviation or median [interquartile ranges (IQR)] for normally distributed and skewed data, respectively. In this way data were present on the median number of days between admission and discharge from the unit and the number of patients that were discharged home, returned to the referring hospital or succumbed. Furthermore, a random sample of 401 patients were examined regarding Charlson Comorbidity Index (11), frequency of hypertension, diabetes mellitus, background of coronary artery disease, heart failure, history of atrial fibrillation, cancer, history of connective tissue disease, dementia, chronic obstructive pulmonary disease, asthma and idiopathic pulmonary fibrosis. The present study also analyzed the prevalence of fever, anosmia, anorexia, cough, dyspnea, fatigue, headache, diarrhea or other gastrointestinal symptoms and partial arterial pressure for oxygen/FiO2 on admission in this random sample. Finally, it examined the incidence of new-onset infection, pulmonary embolism, deep vein thrombosis, new cardiovascular events, acute kidney injury and acute liver injury during hospitalization. Data were analyzed using SPSS 17.0 for Windows (SPSS Inc.).

Results

Between October 2020 and June 2021, the mean weekly admissions for the five general hospitals in the Western Attica region was 225 and the mean weekly discharges was 197. The mean number of admissions per hospital was 98 for the Attikon General University Hospital of Athens; 51 for the General Hospital of Nikaia, Agios Panteleimon; 34 for the Asklipieio Voulas General Hospital; 27 for the Thriasio General Hospital of Elefsina; and 46 for the Tzaneio General Hospital of Piraeus.

In addition, the COVID-19 Unit of the Agia Varvara Hospital had a total of 631 admissions. The median age of patients was 69 years (IQR, 56-81) and 316 (50.1%) patients were male. In total, 83 (13.15%) patients were nursing home residents prior to hospital admission. All patients were managed and treated according to the guidelines of the National Public Health Organization (12). The median number of days between admission and discharge from the unit was 6 (IQR, 4-13). In total, 539/631 patients (85.4%) were discharged, 57 patients (9%) were referred back to the referring hospitals for further management and 35 patients (5.6%) succumbed (Table I).

Table I Overall patient admissions, discharges, repatriations and deaths at the middle-step COVID-19 Unit in different time periods.

Table I

Overall patient admissions, discharges, repatriations and deaths at the middle-step COVID-19 Unit in different time periods.

Period	Admissions Agia Varvara Covid-19 Unit	Discharges Agia Varvara Covid-19 Unit	Repatriations Agia Varvara Covid-19 Unit	Deaths Agia Varvara Covid-19 Unit
10/2020-12/2020	146	106	10	14
01/2021-03/2021	293	235	30	11
04/2021-5/2021	192	198	17	10
Total, n (%)	631 (100.0)	539 (85.4)	57 (9.0)	35 (5.6)

[i] Data are presented as n (%).

Data was also obtained from a random sample of 401 patients with COVID-19. The median Charlson Comorbidity Index score was 4 (IQR, 2-5). In addition, 196 patients (48.9%) had hypertension, 103 patients (25.7%) had diabetes mellitus, 36 patients (9%) had a background of coronary artery disease, 36 patients (9%) had heart failure, 48 patients (12%) had a known history of atrial fibrillation, 13 patients (3.2%) had cancer, 8 patients (2%) had a known history of connective tissue disease, 96 patients (23.9%) had dementia, 25 patients (6.2%) had chronic obstructive pulmonary disease, 18 patients (4.5%) had asthma and one patient (0.2%) had a known history of idiopathic pulmonary fibrosis (Table II).

Table II Comorbidities of 401 study participants.

Table II

Comorbidities of 401 study participants.

Variable	Value
Charlson Comorbidity Indexa	4 (2-5)
Hypertension, n (%)	196 (48.9)
Diabetes mellitus, n (%)	103 (25.7)
Coronary artery disease, n (%)	36 (9.0)
Heart failure, n (%)	36 (9.0)
Atrial fibrillation, n (%)	48 (12.0)
Malignancy, n (%)	13 (3.2)
Connective tissue disease, n (%)	8 (2.0)
Dementia, n (%)	96 (23.9)
Chronic Obstructive Pulmonary Disease (COPD), n (%)	25 (6.2)
Asthma, n (%)	18 (4.5)
Idiopathic pulmonary fibrosis, n (%)	1 (0.2)

[i] ^aData are presented as median (IQR).

In addition, 302 patients (75.3%) presented with fever, nine patients (2.3%) presented with anosmia, 38 patients (9.5%) presented with anorexia, 138 patients (34.4%) presented with a cough, 140 patients (34.9%) presented with dyspnea, 109 patients (27.3%) presented with fatigue, 33 patients (8.3%) presented with a headache and 72 patients (18%) presented with diarrhea or other gastrointestinal symptoms. The median paO2/FiO2 on admission to the COVID-19 Unit was 328 (IQR, 283-371; Table III). During hospitalization, 75 patients (18.7%) experienced a new-onset infection, three patients (0.7%) experienced pulmonary embolism, two patients (0.5%) experienced deep vein thrombosis, 35 patients (8.7%) experienced new cardiovascular events, 36 patients (9%) experienced acute kidney injury and three patients (0.7%) experienced acute liver injury (Table IV).

Table III Presenting symptoms of 401 study participants.

Table III

Presenting symptoms of 401 study participants.

Variable	Value
Fever, n (%)	302 (75.3)
Anosmia, n (%)	9 (2.3)
Anorexia, n (%)	38 (9.5)
Cough, n (%)	138 (34.4)
Dyspnea, n (%)	140 (34.9)
Fatigue, n (%)	109 (27.3)
Headache, n (%)	33 (8.3)
Gastrointestinal symptoms, n (%)	72 (18.0)
PaO2/FiO2a	328 (283-371)

[i] ^aData are presented as median (IQR). PaO₂, partial arterial pressure for oxygen; FiO₂, fraction of inhaled oxygen.

Table IV Events during hospitalization of 401 study participants.

Table IV

Events during hospitalization of 401 study participants.

Variable	Value
New onset infection, n (%)	75 (18.7)
Pulmonary embolism, n (%)	3 (0.7)
Deep vein thrombosis, n (%)	2 (0.5)
Cardiovascular events, n (%)	35 (8.7)
Acute kidney injury, n (%)	36 (9.0)
Acute liver injury, n (%)	3 (0.7)

Based on observations of the COVID-19 unit of the Agia Varvara Hospital during the pandemic, an algorithm for implementing a middle-step unit was proposed. According to the algorithm, patients presenting with respiratory symptoms at the central general hospital should first undergo a validated test to confirm the diagnosis of the specific respiratory infection. Following confirmation of respiratory infection, disease severity should be assessed. Notably, disease severity is assessed according to hemodynamic stability; a requirement for oxygen of ≤40% FiO2; acute type II respiratory failure; underlying conditions requiring specialist care, in the context of a central general hospital; and complications of respiratory infection that required specialist care, in the context of a central general hospital. According to the aforementioned assessment, patients with severe disease should remain under the care of the central general hospital. Patients with non-severe disease should be referred to the middle-step unit. Following patient transferal to the middle-step unit, appropriate management and treatment will be initiated. Subsequently, a reassessment of patient status can take place. If the patient is clinically stable or improving, they will continue hospitalization in the middle-step unit. If the patient is fit for discharge and there are no ongoing issues requiring medical or surgical care at a central general hospital, they will be discharged. If the patient fit for discharge presents with underlying conditions that require medical or surgical care at a central general hospital, they should be referred back to the central general hospital. If the patient requires inotropes or oxygen of >40% FiO2, has developed type II respiratory failure that cannot be managed with non-invasive ventilation, or has developed complications associated with respiratory infection that cannot be managed in the context of a middle-step unit, they will be referred back to the central general hospital (Fig. 1).

Figure 1 Proposed algorithm for the assessment and referral to a middle-step unit.

Discussion

In the present study, incorporation of a specialized middle-step unit contributed to a decrease in workload in the central general hospitals observed. During peaks of the pandemic between January and March 2021, the number of available beds and the number of admissions to the COVID-19 Unit of the Agia Varvara Hospital were increased by ~2-fold. This increased bed availability for patients with and without COVID-19 in the central general hospitals.

Results of the present study demonstrated that the middle-step unit provided adequate care to patients with a variety of different backgrounds, comorbidities and symptoms. They also demonstrated that in patients with COVID-19, hypertension was the most frequent comorbidity and fever, dyspnoea and cough were the most frequent symptoms of disease. Notably, these results were comparable with those observed in previous studies (13,14). In addition, the length of hospital stay in the middle-step unit was reduced, compared with results obtained from previous studies (13,14). However, the acceptance of patients from central hospitals after at least two days of hospitalization in the referring hospital may have affected these results.

Notably, the middle-step unit was operating in the early stages of the pandemic. In this period, specific targeted treatment options and vaccines were yet to be developed (15,16). Thus, patient outcomes may not be reflective of the entire duration of the pandemic. However, results of the present study demonstrated that incorporation of a middle-step unit may exhibit potential in future pandemics, when no vaccines or specific targeted treatments are available.

A previous study discussed proposals for future pandemics, based on the outcomes of the COVID-19 pandemic, focusing on therapeutic strategies (17). An additional previous study examined the efficacy of mobile cabin hospitals that were opened in public in the early stages of the pandemic (18). By contrast, the present study introduced a middle-step unit within secondary care, with resources, staff and medical supplies readily available. In addition, mobile cabin hospitals excluded elderly patients and patients with pre-existing conditions (18). However, the middle-step unit described in the present study accepted elderly patients and patients with comorbidities and the proposed algorithm may improve patient outcomes. Thus, the middle-step unit exhibited potential in future pandemics.

The present study possessed limitations. Notably, bed management was observed in the healthcare system of a specific region, while each healthcare system may possess different dynamics and resources. However, limited bed availability is often observed during pandemics. Therefore, the middle-step unit proposed in the present study exhibited potential as a viable solution to reduce workload within healthcare systems. In addition, the number of available beds and daily patient transfers to the unit fluctuated during different time periods, in accordance with the overall admissions to hospitals in the region. Notably, the number of available beds and staff recruitment was adjusted in the unit during peaks of the pandemic. Patients were also transferred from central hospitals to the unit using ambulance services. Despite the requirement for additional resources, the increase in bed availability for patients with severe infection at the central hospitals was beneficial.

In conclusion, the middle-step unit exhibited potential in increasing bed availability and reducing workload within the healthcare system during peaks of the COVID-19 pandemic. Thus, the proposed model exhibits potential in reducing healthcare system workload, supporting specialist management and optimizing patient outcomes during future pandemics.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The data generated in the present study may be requested from the corresponding author.

Author's contributions

GV, AP, VA, DK, DB, SP, EM and SL contributed to the conception, drafting and critical revisions of the manuscript. GV, AP, VA and SL contributed to the acquisition, analysis and interpretation of data. GV, VA and SL confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

The study protocol was approved by the Ethics Committee of Attikon University Hospital (approval no. 121/03-03-2021) and complied with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all patients included in the present study.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References