This is a retrospective, unicentric, and observational study.

Hospital Universitario y Politécnico la Fe has two critical care units for adults; a 36-bed medical critical care unit (MCCU) carried by intensivists and a 36-bed surgical critical care unit (SCCU) carried by anaesthesiologists in which patients recovering from surgery or severe trauma are admitted. Due to SARS-CoV-2 pandemics COVID-19 patients were also admitted to the SCCU once all MCCU beds were occupied.

MCCU has a rapid response service (RRS) that daily evaluates patients admitted to the ward and identifies those who, due to a high NEWS score punctuation, would be eligible for admission to the unit.12 During the SARS-CoV-2 pandemic, the RRS was reinforced with a second physician. Patient admission to the MCCU was guided by the major/minor ATS/IDSA criteria for severe community pneumonia.13

All consecutive SARS-CoV-2 positive patients (≥18 years old) admitted to our MCCU were included in the study. A confirmed case of COVID-19 was defined by a positive result on a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of a specimen collected from airway secretion or from a nasopharyngeal swab.14 The first patient was admitted on the 16th of March and the last one on the 9th of April 2020. Patients were followed until hospital discharge or death; study follow-up was closed 3rd of June. Patients were distinguished between those with clinical pneumonia due to SARS-CoV-2 and those who were admitted to MCCU because of other disease unrelated to SARS-CoV-2 positivity. Patients in whom ARDS diagnosis, management and prognosis could not be evaluated due to treatment withdrawal or very early death at CCU admission (<6hours) were excluded from the final analysis.

We obtained demographic data, coexisting conditions information, data on clinical symptoms or signs at CCU admission and follow-up, and laboratory and radiological results during CCU stay. All laboratory and radiological assessments were performed at responsible physician discretion. COVID-19 treatments and life support measures were recorded.

Bacterial co-infection at hospital admission was assessed. Nosocomial infection and multi-drug resistant bacteria (MDRB) colonization was proactively sought during CCU stay according to a pre-established infection control program including weekly MDRB surveillance cultures.15 Infections due to opportunistic microorganisms were prospectively discarded in those patients with prolonged invasive mechanical ventilation (≥ one week) and signs or symptoms of respiratory or infectious deterioration of unclear origin.

Acute respiratory distress syndrome (ARDS) was defined as acute-onset hypoxemia (ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) <300) with bilateral pulmonary opacities on chest imaging not explained by congestive heart failure. ARDS patients who required invasive mechanical ventilation were managed agreeing to the guidelines with a protective ventilation (tidal volume ≤6ml/Kg, plateau pressure <30 cmH2O and driving pressure <15 cmH2O) and rescue therapies when necessary (prone position, recruitment manoeuvres, nitric oxide (NO) and/or extracorporeal membrane oxygenation (ECMO)).16

Nosocomial infections diagnosis was established according to the Centers for Disease Control criteria.17 Invasive pulmonary aspergillosis was diagnosed according to EORTC criteria modified by Blot et al for critically ill patients.18 CMV reactivation was identified by a clinical picture of sepsis/pneumonia besides the presence of>400 copies/ml in plasma or positive PCR in bronchoalveolar lavage.19 HSV pneumonia was diagnosed in the absence of other aetiology besides positivity for HSV PCR in alveolar fluid.20

Descriptive statistics were used to summarize the results; reported as means and standard deviations or medians and interquartile ranges, as appropriate. Categorical variables were expressed as counts and percentages. Categorical variables were compared using the Chi square test. Comparison of numerical variables was performed with the Mann–Whitney U test. The statistical significance was set at 0.05 (95% confidence interval). Analysis was performed with SPSS 16.0.

The study was approved by our hospital Ethical Committee and informed consent was waived due to the retrospective nature of the study.

During the study period 573 patients were admitted to hospital for COVID-19 (at present 351 (61%) had been discharged, 88 (15%) had died and 150 (26%) remain hospitalized). Seventy-four (13%) patients were admitted to CCU; 58 to medical CCU and 16 to surgical CCU. Six patients were admitted to MCCU because of a disease unrelated to SARS-COV-2 positivity and therefore were excluded from the analysis. Four patients were initially admitted to MCCU and were suffering respiratory failure, but due to do not resuscitate orders (DNRO) supportive treatment was withdrawn because of the following situations: patient admitted because of traumatic brain injury who developed irreversible brain damage, patient with malignant hemopathy non-responding to quemotherapy, patient with severe co-morbidities who was not intubated and patient with irreversible post-anoxic encephalopathy due to cardiorespiratory arrest after iatrogenic haemopericardium. Three patients died in less of 6hours because of haemorrhagic shock, fulminant myocarditis and non-responding asthma crisis respectively; ARDS diagnosis and management could not be evaluated and therefore these patients were not included. And one SDRA patient was RT-PCR negative in four different determinations and COVID-19 diagnosis was finally obtained by means of immunoglobulin assay (positive IgM and IgG followed by negative IgM/positive IgG); this patient was excluded from the analysis. Therefore, data concerning 44 patients admitted to MCCU under the care of intensivist will be presented in this study (Figure 1).

Figure 1.

COVID-19 patients treated in the hospital during the study period.

Demographic and clinical characteristics are depicted in Table 1. Most patients were male (n 32, 72.7%), mean age was 61.5 [53.2-67]. Arterial hypertension (23, 52.3%), dyslipidaemia (16, 36.4%) and diabetes (6, 13.6%) were the most frequent co-morbidities. Time in days between the onset of symptoms and hospital admission was 6.5 [5-8] and between hospital admission and MCCU admission was 2 [0-4]. SAPS3 punctuation was 50 [43.5-59].

Laboratory findings at MCCU admission are shown in Table 2. Inflammatory biomarkers were elevated in most patients. However, only 8 patients (18.2%) presented with IL6 above 200 pg/ml. Five patients (11.4%) had procalcitonin (PCT) higher than 1ng/ml although none bacterial co-infection could be demonstrated in these patients. C-reactive protein (CRP) had a more homogeneous behaviour, all patients had values above the normal range and only 7 (16%) were below 100mg/l. Ferritin was available only in four patients. Albumin below or equal to 3g/dl was present in 8 patients (18.2%).

Lymphopenia (≤1000 cell/mm3) was detected in most of the patients (86.4%, n 38); severe lymphopenia (≤500 cell/mm3) occurred in 7 patients (16%). Thrombocytopenia (≤150.000 cell/mm3) was present in 7 patients but only one case had less than 100.000 cell/mm3. Augmented D-dimers (≥500 ng/ml) occurred in 28 patients (63.6%) but only 3 cases (6.8%) were higher than 3.000 ng/ml.

All patients had a bilateral diffuse infiltrate on the initial chest radiograph. Median PaO2:FiO2 ratio was 83 [60.6-117].

Almost all patients were treated with chloroquine and azithromycine (100% and 95.5% respectively). Other treatments directed towards the virus are depicted in Table 3. Immunomodulation was attempted in all patients except two (95.5%); steroids in 35 cases (79.5%) (≥1mg/Kg/day in 93.2% of all treated patients), tocilizumab in 36 cases (81.8%) and baricitinib in 4 cases (9%). All patients were under prophylactic low molecular weight heparin and only two received therapeutic anticoagulant treatment due to the presence of an aortic prosthetic valve and to the development of a venous thrombosis related to the presence of a central catheter.

Thirty-four patients needed invasive mechanical ventilation (77.3%); of them 13 (38%) were intubated the same day they were admitted to the MCCU and 21 (67.8%) were intubated after a median of 2 [1-2] days of delay. Not intubated patients and those with a delay until intubation were supported with high flow nasal cannula (HFNC). None patient received non-invasive mechanical ventilation.

Among ventilated patients all coupled with moderate-severe ARDS definition (PaO2/FiO2 <200). All mechanically ventilated patients received protective ventilation. Prone-position ventilation was performed in 33 patients (97%) (median of 3 sessions [2-5] per patient) achieving an improvement in oxygenation in all patients (at least temporarily), recruitment manoeuvres were realized in 25 patients (73.5%) and nitric oxide was administered to 7 patients (20.6%). Extracorporeal membrane oxygenation (ECMO) was used in 3 cases (8.8%); 2 veno-venous systems and 1 veno-arterial system because of heart failure.

Norepinephrine was used in 28 patients (63.6%) because of hypotension unresponsive to fluid administration (and avoiding fluid overload in SDRA context) but none of them attended with serum lactate> 2 mmol/l.

Only one patient under VA-ECMO needed extracorporeal renal replacement. However 36% of our patients (n 16) coupled with AKIN stage 1 criteria due to urine output <0.5ml/Kg during 6hours. All patients responded to fluid administration and none of them progressed to more severe AKIN stages.

None bacterial co-infection could be demonstrated at hospital or ICU admission.

ICU-nosocomial infection was detected 16 times in 13 patients (29.5%). Ventilator-associated pneumonia (VAP) was the most common infection; 8 of 34 ventilated patients (23.5%). Ventilated-associated tracheobronchitis (TAVM) was diagnosed in 1 patient (2.9%). Catheter-related bacteraemia (CRB) occurred in three patients (6.8%) and primary bacteremia in one patient (2.3%). Most common aetiologies were: Pseudomonas aeruginosa (n 7; 46.7%), Staphylococcus aureus (n 3; 20%) and Escherichia coli (n 1; 6.7%). Opportunistic infections were diagnosed in 5 patients; 4 cases of HSV pneumonia (one of them co-infecting with CMV) and 1 pulmonary invasive aspergillosis.

At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27] and hospital length of stay was 28 days [19-39]. Mortality at study closing was 20,5% (n 9). All deaths occurred in CCU after a median of 17 days [12-24]. If we include all COVID19 patients (SARS-CoV-2 positive without disease and patients with DNRO) mortality will rise to 28% (16 deaths in 57 patients).

Mechanical ventilation duration for the 34 ventilated patients was 16 days [11-28]. All ventilated patients were treated with neuromuscular blockers for a median of 5 days [3-14]. Tracheostomy was performed in ten patients (29.4%) after a median of 21 days [19.3-23.5]. Five patients (14.7%) presented spontaneous pneumothorax during mechanical ventilation. Mortality among ARDS ventilated patients was 26.5%. Death in ventilated patients occurred after a median of 17 days [12-24].

Four patients (9%) required readmission to the MCCU after discharge. Three of them presented haemorrhagic shock related with anticoagulation treatment and were managed with arterial embolization. The fourth patient was readmitted because of respiratory worsening due to pulmonary fibrosis secondary to ARDS and finally died.