Clinical, Radiologic Differences Observed Between Lung Involvement in Macrophage Activation Syndrome and Severe COVID-19

Researchers assessed clinical and laboratory data of patients with lung involvement in macrophage activation syndrome and severe COVID-19.

There are laboratory and radiologic differences between lung involvement in macrophage activation syndrome (MAS) and severe coronavirus disease 2019 (COVID-19), according to study results published in Annals of the Rheumatic Diseases.

Previous studies have hypothesized that COVID-19 may belong to the spectrum of hemophagocytic lymphohistiocytosis (HLH) because of the overlapping clinical features of MAS and COVID-19. In the present study, researchers sought to assess the laboratory and clinical similarities between patients with MAS and severe COVID-19.

Patients with clinician-diagnosed MAS were retrospectively selected for the study from a hospital database in Italy. Patients with MAS were matched with consecutive patients with laboratory-confirmed COVID-19 who had been admitted to the intensive or subintensive care units at the same hospital. Laboratory readings and chest computed tomography (CT) scans were obtained from medical records. An artificial intelligence-based software was used to assess chest scans. Researchers compared laboratory and radiologic data between patient groups.

The study cohort included 10 patients with MAS (mean age, 56.20±10.58 years; 60% men) and 47 patients with severe COVID-19 (mean age, 66.27±13.98 years; 75% men). All patients with MAS and COVID-19 presented with fever and dyspnea. Compared with patients with COVID-19, patients with MAS had lower platelet counts (121.90±36.34 vs 254.53±19.51 109/L; P =.043) and higher ferritin levels (4888.83±1131.49 vs 1207.17±171.66 ng/mL; P =.010). Patients with MAS vs severe COVID-19 also had higher H-scores (201.9±15.3 vs 88.8±48.3; P <.0001), suggesting greater immunoreactivity. Compared with the MAS cohort, the COVID-19 cohort was characterized by lower lymphocyte counts (2.61±0.58 vs 1.02±0.09 103/mL; P =.005) and higher neutrophil counts (4.08±0.55 vs 8.98±2.32 103/mL; P =.044).

On CT scan, all patients with COVID-19 compared with 60% of those with MAS presented with ground-glass opacities (P =.028). In artificial intelligence-reconstructed images, the extension of consolidation was higher in the COVID-19 than MAS cohort (353.31±122.19 vs 227.26±65.91 cm3; P =.014). Higher C-reactive protein levels were associated with the extension of lung opacities in both the MAS (P =.031) and COVID-19 (P =.020) groups. In patients with COVID-19 only, lymphocyte levels were inversely correlated with the extension of ground glass opacities (P =.008).

These data show that while some clinical overlap was apparent between patients with MAS and those with severe COVID-19, significant laboratory and radiologic differences were also observed.

“[COVID-19] did not appear as being part of the HLH spectrum.” the researchers concluded. They added that the laboratory and radiological differences between MAS and severe COVID-19 may “help physicians to differentiate these patients in spite of overlapping clinical pictures.”


Ruscitti P, Bruno F, Berardicurti O, et al. 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. Ann Rheum Dis. Published online July 21, 2020. doi:10.1136/annrheumdis-2020-218048