CORONA (COre ultRasOund of covid in iNtensive care & Acute medicine) Study: National Service Evaluation of Lung and Heart Ultrasound in Intensive Care Patients with Suspected or Proven COVID-19

: Background: Combined Lung Ultrasound (LUS) and Focused UltraSound for Intensive Care heart (FUSIC heart - formerly Focused Intensive Care Echocardiography, FICE) can aid diagnosis, risk stratification and management in COVID-19. However, data on its application and results are limited to small studies in varying countries and hospitals. This United Kingdom (UK) national service evaluation study assessed how combined LUS and FUSIC Heart were used in COVID-19 Intensive Care Unit (ICU) patients during the first wave of the pandemic. Method:

transfer to a central database.

Results:
372 studies were performed on 265 patients. There was a small but significant relationship between LUS score >8 and 30-day mortality (OR 1.8). Progression of score was associated with an increase in 30-day mortality (OR 1.2). 30-day mortality was increased in patients with right ventricular (RV) dysfunction (49.4% vs 29.2%). Severity of LUS score correlated with RV dysfunction (p < 0.05). Change in management occurred in 65% of patients following a combined scan.

Conclusions:
In COVID-19 patients there is an association between lung ultrasound score severity, RV dysfunction and mortality identifiable by combined LUS and FUSIC Heart.
The use of 12point LUS scanning resulted in similar risk score to 6-point imaging in the majority of cases.
Our findings suggest that serial combined LUS and FUSIC Heart on COVID-19 ICU patients may aid in clinical decision making and prognostication. A data capture tool based on standardised point-of-care imaging protocols was provided.
LUS findings could be recorded in a maximum of 14 predefined anatomical zones. Clinicians recorded whether a 6-point, 12-point or 14-point approach had been undertaken. A semiquantitative severity score was recorded at each anatomical location.
• Score 0: A-lines or < 2 B lines (normal aeration) • Score 1: ≥ 2 well-spaced B-lines (moderate loss of aeration) • Score 2: Coalescent B lines +/-small consolidations < 1cm (severe loss of aeration) • Score 3: Tissue like pattern +/-frank consolidation +/-small consolidations > 1cm (complete loss of aeration) Summated LUS severity score was approach dependent -in the case of 6-point imaging it was between 0-18. Presence of pleural effusion was recorded, and a subjective assessment of the pleura for each lung recorded as normal or abnormal.
Bedside transthoracic echocardiography data collection tool was derived from the FUSIC Heart protocol. This involved visual assessment for LV and RV dilatation and function. The presence of ventricular dilatation was recorded as a binary variable. Ventricular dysfunction was defined as either a dilated or visually impaired left or right ventricle. Advanced, quantitative measurements of dilatation and functional impairment were recorded in some studies.
The indication for imaging and any immediate change of management was recorded.
Patient outcome was recorded at 30-days after the imaging study.

Statistics
Analysis was performed using the R statistical software. Normally distributed continuous variables are described using mean and standard deviation and non-normally distributed continuous variables are described using median value and interquartile range. Count data is described as proportions with 95% confidence intervals.
Logistic regression was used to explore the relationship between LUS, the PCR result and 30day outcomes. Some patients had repeated imaging obtained. The relationship between severity score and mortality was undertaken on the initial scan. Primary analysis was restricted to scans performed within 7 days of admission to the intensive care unit. Invasive mechanical ventilation (IMV) was being provided to 320 (86.0%) patients at the time of imaging. Non-invasive respiratory support was being provided to 24 (6.5%) patients The distribution of 6-point scores stratified by the interval between admission and imaging is provided in Figure 1A. The distribution of scores was asymmetric with skew towards higher scores. The distribution of scores was broadly similar when stratified by the interval between ICU admission and scan. The median score using the 6-point protocol was 11 (8-13 IQR). Ultrasound severity scores obtained utilising a 12-point protocol were compared to the 6-point score derived from the same study..

Lung involvement and mortality
There was an association between the severity of lung involvement (as assessed by 6point severity score within 7 days of admission) and 30-day mortality (adjusted OR 1.1 95%CI 1.0 -1.2).
. The discriminatory performance of the ultrasound severity score to predict 30-day mortality was poor (AUC 0.58). The observed 30-day mortality associated within quartiles of lung severity score stratified by the time interval between ICU admission and the initial thoracic imaging study is shown in Figure 4A.

Paired studies
Comparisons were made between the initial studies and a second study taken at a later time point in the 71 cases where serial studies were recorded. The median interval between the initial and second study was 4 days (IQR 3-5). There was no statistical difference in mean score comparing the initial and later study (mean 9.0 SD 3.6 vs 9.3 SD 3.8, p value = 0.6). The trajectory of lung severity scores between scans is provided in Fig. 5A. A unit increase in lung severity score was associated with a small increase in 30-day mortality in a model adjusted for the time interval between imaging studies (adjusted OR 1.2 95%CI 1.0-1.5, p value = <0.05).

Discussion
This service evaluation is the first national study of its kind at the time of publication. It included patients admitted with respiratory failure during the COVID-19 pandemic from 12 different UK trusts. Patient demographics from this cohort closely matched ICNARC data 22 , indicating that we studied a generalizable sample.
T here was a mean time to scan of 2 days from ICU admission, and only 39.5% of patients received two or more scans. Serial scan data in our study and other papers have shown increased mortality with worsening lung scores 23 . This suggests that there is currently suboptimal provision for serial ICU PoCUS services across the trusts involved and potentially nationwide.
However, i n our evaluation, combined LUS and FUSIC Heart were performed in 89.5% of total patients enrolled. This indicates that, even in severely critically ill COVID-19 patients, combined LUS and FUSIC Heart were deliverable alongside the high intensity ICU clinical workload across the trusts. Maximum benefit of an ICU POCUS service would more likely be achieved with serial scanning of patients with subsequent changes in management rather than a focused scan done on ICU admission alone.
The correlation between 12-point and 6-point scores supports the role of the 6-point LUS protocol in ICU patients 24   The combination of these two imaging modalities, LUS and FUSIC Heart, in COVID-19 patients at ICU admission (or ideally before) provides dynamic clinical information and informs the complex interactions between the heart and lungs and the effects, if any, of therapeutic intervention. It is therefore crucial to the overall management of this condition.

Limitations
Service evaluation methodology provides insight into how LUS and FUSIC Heart are utilised in the delivery of routine care at the expense of a defined study protocol which ensures consistency in approach. Based on the observational methodology, the results should be interpreted within the constraints and limitations of a service evaluation study.
There was considerable variation in the time to first imaging study and intervals between studies. Including scans performed in the initial 7 days from ICU admission introduces a degree of survivor bias. The use of a semi-quantitative score may be an oversimplification of a fundamentally subjective assessment. The salient information which dictated changes may not have been captured within the ordinal scale used.
This is an evaluation of a service that for most was set up de novo to meet the needs of the pandemic. This may explain some of the discrepancies in the results. It seems less likely that a patient admitted to the ICU with severe respiratory failure due to COVID-19 pneumonitis had a lung score of zero, which may reflect issues with PoCUS sonographers' training or reporting.
In this study, 86% of patients were being mechanically ventilated. The ICNARC data from 1 September2020 to 30 April 2021* reports 30.6% of patients were mechanically ventilated within the first 24 hours. Therefore, caution needs to be taken with regard to interpreting the results in this study, as significantly more patients were mechanically ventilated compared to current practice. in this study, 6.5% of patients were receiving NIV; LUS and FUSIC Heart scanning in these patients are of equal importance and, indeed, may influence management changes such as escalation of care and decision to prone.
It is important to note that RV assessment is more challenging than first appreciated. If the left ventricle is hyperdynamic, one may expect the right to be in a similar state. The fact that the right merely appeared to be 'normally' functioning may actually represent dysfunction at this stage in context. The basic level of training has enabled a larger number of patients to have an assessment scan. However, the trade-off is that subtle echo signs such as apical RV dilatation or early systolic dysfunction may have not been appreciated as this would have required an advanced skill set not reliably available on ICUs.
This raises questions around 'quantity versus quality' -is it better to provide a screening service where most patients have a scan or is it desirable to have a detailed analysis in a few, sicker patients? This question is beyond the scope of this study and requires further investigation to understand the optimum way to organise a PoCUS service.

Conclusions
Our service evaluation suggests that serial, combined LUS and FUSIC Heart can perform an