Our study characterized longitudinally the influence of CD, identified by echocardiography (LV or RV dysfunction), on LUS findings during moderate-to-severe COVID-19 pneumonia. CD+ patients presented fewer LUS pathologic findings than CD− patients in the upper part of the right hemithorax, but the LUS scores were not different between groups. Furthermore, there was a better correlation between LUS scores and P/F ratio in CD− than in CD+ patients during the hospital stay. However, the clinical condition of CD+ patients was more severe, as they had a worse P/F ratio, more ICU admission, and required IMV more frequently than CD− patients. [26]

SARS-CoV 2 infection promotes a systemic inflammatory response [11]. In an advanced stage, a cytokine storm may progress with myocardial injury, manifested by heart failure and symptomatic CD. CD has been already reported to occur after acute SARS-COV 2 infection [24]. In our study, CD detected with FoCUS was present without previous cardiovascular disease despite a high prevalence of cardiovascular risk factors in COVID-19 patients, as has already been reported [13, 24, 25]. In our study, only coronary artery disease, heart failure, cardiomyopathy, and arrhythmias were considered cardiovascular disease (i.e., six patients).

About half of the patients in this study showed CD, with LV and biventricular dysfunction in 43% and 24%, respectively. A similar percentage of CD patients with COVID-19 pneumonia was found by Lazzeri and colleagues (2021) [13] evaluated by increased RV/LV ratio in non-survivors than in survivors. A comprehensive echocardiographic study also found a similar frequency of CD in COVID-19 pneumonia [28]. Furthermore, Li and colleagues (2021) [31] found RV dysfunction in 27 out of 89 patients with cardiovascular disease and without elevation of cardiac biomarkers. In addition, a significant increase in cardiac biomarkers has been reported in only 30% of hospitalized COVID-19 patients [29] with established cardiovascular disease [29,30,31].

Pulmonary vasoconstriction with thrombotic vessel changes occurs during SARS-CoV 2 infection contributing to increased pulmonary systolic arterial pressure [6, 12, 27], although it may not occur due to low afterload stress in non-ventilated patients. [27] Another potential explanation is that patients hospitalized with COVID-19 had coronary heart disease before infection with SARS-CoV-2. [31]. However, in one series, the total percentage of patients with known coronary heart disease was 10.6%, and only 29.3% of those with elevated troponins had a history of known coronary heart disease [30]. Therefore, other potential mechanisms are likely to have a role in cardiac injury [30].

In our study, both groups showed a high interquartile range of the N-terminal prohormone of brain natriuretic peptide, surpassing the lower cutoff to exclude CD in patients with acute dyspnea [34]. Taking into account such data, we could hypothesize that an unbalanced pro-inflammatory milieu, rather than a direct cytopathic effect on myocytes, would lead to a cardio-depressor effect as in sepsis [34]. However, only half of our cohort showed CD. We hypothesized that some patients might develop a myocarditis-like injury, resulting from either direct infection of the cardiac myocytes or infection of non-myocytes [32]. In fact, an association was recently described [32] between the immunological trait and CD in severe COVID-19 pneumonia [33]. This could also explain the increase in cardiac function across time points simultaneously with the solving COVID-19 infection. [35]

Chest X-ray is a first-choice imaging modality for evaluating patients with respiratory distress, but lacks sensitivity for diagnosing COVID-19 pneumonia [35,36,37,38]. In our study, we used the British Society of Thoracic Imaging guidelines for categorizing chest radiographs [17]. Our results showed a similar sensitivity to identify classic COVID-19 pneumonia features in about half of the patients. Literature reports support our data [36, 37]. Classic COVID-19 chest X-rays findings increased throughout the hospital stay, which could be explained by the time needed for neutrophil and macrophage alveolar infiltration establishing a radiological opacity [38].

LUS is a useful first tool in an emergency setting to help diagnose COVID-19 pneumonia, distinguishing mild from severe forms of acute respiratory distress syndrome [10, 39,40,41], and monitoring disease progression [7, 9, 12, 42,43,44,45,46]. The presence of bilateral B-lines, white lung areas with patchy peripheral distribution and sparing areas is the most suggestive LUS picture of COVID-19 [41]. Furthermore, LUS showed good agreement between confluent B-lines and subpleural consolidations findings with computed tomography in identifying ground-glass opacity and peripheral consolidations on lung parenchyma, respectively[4, 5, 39,40,41,42,43,44,45]. Moreover, such knowledge is based on a daily increase of LUS by intensivists compared with the pre-COVID-19 era [47].

In our patients, the most common finding was bilateral pleural thickening followed by B-lines and consolidations in the lower part of the thorax. Patients in the CD+ group showed fewer pleural irregularities and subpleural consolidations if not requiring IMV, with an overall sparing of the upper part of the right hemithorax than patients in the CD− group. Similar COVID-19 pneumonia LUS findings have been already reported [13, 33], but none described LUS specifically concerning CD, nor their evolution with treatment during the hospital stay. In our cohort, LUS findings prevalence improved along with successive time points, predominantly in CD− patients, consistent with other patients’ series [13, 46]. In contrast, non-survivors showed an increase in the number of consolidations at D10.

Cardiogenic pulmonary edema can present in LUS as regular homogeneous B-lines in continuous regions of the lung parenchyma [14, 15]. These findings are differentiated from the typical pattern of progressive bilateral loss of alveolar aeration in moderate-to-severe COVID-19 pneumonia, starting from isolated B-lines to confluent B-lines and consolidation findings [20, 22, 39, 41]. In our data, CD+ patients were associated with worse clinical condition than CD− patients, as they required IMV more frequently and had significantly lower P/F ratios. However, despite the high prevalence of LV dysfunction in our sample, the presence of B-lines was not higher in CD+ than CD− patients. Such findings may suggest a predominance of pneumonic alveolar edema. Ultrasound cardiogenic alveolar edema is reflected by the presence of homogenous B-lines in lung regions with low ventilation–perfusion ratio [15] (i.e., lower lung regions), sparing the upper thorax regions, as shown by our data.

LUS score in COVID-19 pneumonia patients correlated with prognosis [7, 9, 10, 12, 46]. LUS score is calculated to demonstrate lung involvement and alveolar destruction [9, 10, 46, 48]. Some B-line signs may be related only to COVID-19 pneumonia [39]. In our study, we based our score on the progressive loss of aeration described in pneumonia [20, 39, 48]. However, we discriminated between subpleural and lobar consolidations as the most relevant finding [10, 38, 43] due to their contribution to uneven alveolar ventilation–perfusion [8, 25, 27]. Our data showed that LUS scores obtained at D1 predicted the P/F ratio when using comprehensive cohort data. As reported in the literature, such findings were more pronounced in CD− patients during their hospital stay [42, 46]. In CD+ patients, we found no correlation between LUS scores and the P/F ratio until D10. Such results and the fewer LUS findings and their distribution in CD+ patients may be explained by the predominant presence of cardiogenic alveolar edema. On the other hand, CD+ patients requiring IMV had significantly higher LUS scores than CD+ patients not requiring IMV, which the predominant presence of pneumonia-related findings may explain.