Lung involvement in macrophage activation syndrome and severe COVID-19: results from a cross-sectional study to assess clinical, laboratory and artificial intelligence–radiological differences

Abstract

ObjectivesTo evaluate the clinical pictures, laboratory tests and imaging of patients with lung involvement, either from severe COVID-19 or macrophage activation syndrome (MAS), in order to assess how similar these two diseases are.MethodsThe present work has been designed as a cross-sectional single-centre study to compare characteristics of patients with lung involvement either from MAS or severe COVID-19. Chest CT scans were assessed by using an artificial intelligence (AI)-based software.ResultsTen patients with MAS and 47 patients with severe COVID-19 with lung involvement were assessed. Although all patients showed fever and dyspnoea, patients with MAS were characterised by thrombocytopaenia, whereas patients with severe COVID-19 were characterised by lymphopaenia and neutrophilia. Higher values of H-score characterised patients with MAS when compared with severe COVID-19. AI-reconstructed images of chest CT scan showed that apical, basal, peripheral and bilateral distributions of ground-glass opacities (GGOs), as well as apical consolidations, were more represented in severe COVID-19 than in MAS. C reactive protein directly correlated with GGOs extension in both diseases. Furthermore, lymphopaenia inversely correlated with GGOs extension in severe COVID-19.ConclusionsOur data could suggest laboratory and radiological differences between MAS and severe COVID-19, paving the way for further hypotheses to be investigated in future confirmatory studies.

Haemophagocytic syndrome and COVID-19

“…In the view of the limitations for applying the standard HLH criteria, most studies have used the HScore, a classification score developed specifically for secondary, and especially malignancy associated, HLH in adults, that does not include any cytokine-related criteria [ 3 ]; a HScore > 169 has a sensitivity of 93% and a specificity of 86% for a HLH diagnosis. In studies searching for HLH in severe COVID-19 patients, there were 17 (4%) out of 428 patients that had a score > 169 [ 33 , 34 , 37 , 41 , 42 ] (Table 2 ) , while in the individual reported cases summarised in Table 3 , 7 (12%) had a score equal or higher than 169. The use of HScore for COVID-19 patients has been questioned after highlighting some limitations regarding temperature, leukopenia (the score does not distinguish between neutropenia and lymphocytopenia), and the lack of published data on hypertriglyceridaemia, splenomegaly, hepatomegaly and BM haemophagocytosis, and therefore, some authors recommend against their use due to a potential lack of sensitivity [ 35 ].…”

“…Among biochemical parameters, the typical triad of abnormalities in HLH includes hypertriglyceridaemia, hypofibrinogenaemia and hyperferritinaemia. Triglyceride levels are not usually measured in the standard of care of patients with COVID-19, and in studies focused on investigating HLH-related features in COVID-19, 90/975 (9%) patients showed hypertriglyceridaemia (Table 2 ) [ 33 – 35 , 37 , 38 ], and one study has reported no significant differences for mean TG levels between non-severe and severe COVID-19 patients [ 44 ]. In addition, the use of tocilizumab should always be discarded as a potential cause of hypertriglyceridaemia in patients with COVID-19 [ 45 , 46 ].…”

“…However, some COVID-19 patients with a progressive severe disease may develop hypofibrinogenaemia preceding the development of severe disorders like disseminated intravascular coagulation (DIC) or HLH [ 47 ]. The frequency of hypofibrinogenaemia in COVID-19 reported in several studies is 1.3% [ 33 – 35 , 37 – 39 ], although in severe COVID-19 patients (admitted in the ICU, non-survivors), the frequency raised to 28–30% [ 48 , 49 ], and most patients with hypofibrinogenaemia fulfilled the International Society on Thrombosis and Haemostasis (ISTH) diagnostic criteria for DIC [ 48 ]. Finally, hyperferritinaemia is a frequent laboratory abnormality detected in COVID-19 patients, although most large series expressed the values as a mean, with only two reported categorised results with a frequency of raised ferritin levels in 45–78% of cases using different thresholds for defining hyperferritinaemia [ 33 , 50 , 51 ].…”

Cytokine Storm in Coronavirus Disease 2019 and Adult-Onset Still’s Disease: Similarities and Differences

“…The cardinal target organ of COVID-19 is the lung, causing an acute respiratory distress syndrome. Recently, Ruscitti et al conducted a study to compare the difference of clinical manifestation, laboratory tests, and radiological imaging in patients with lung involvement between severe COVID-19 and MAS secondary to AOSD (71). More patients in the COVID-19 group presented with ground-glass opacities (GGOs) compared with those in the group of MAS secondary to AOSD.…”

SARS–CoV-2 Mediated Hyperferritinemia and Cardiac Arrest: Preliminary Insights

“…Severe COVID-19 may be considered part of the (heavy:light:heavy) HLH chain spectrum due to overlapping clinical features 75 , 76 . However, both laboratory and radiological differences between secondary HLH and severe COVID-19, which did not appear as part of the HLH spectrum, exist [77] . For better understanding, readers are invited to read the articles references here.…”