Bone marrow haemophagocytosis indicates severe infection with severe acute respiratory syndrome coronavirus 2

• Published in: Histopathology 2021-04, Vol.78 (5), p.727-737
• Main Authors: Swoboda, Julia, Wittschieber, Daniel, Sanft, Juliane, Kleemann, Sandra, Elschner, Stefan, Ihle, Hannah, Hubig, Michael, Pletz, Mathias W, Mall, Gita, Gassler, Nikolaus
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Autopsy; Bone marrow; Bone Marrow - pathology; Bone Marrow - virology; CD163 antigen; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - pathology; COVID-19 - virology; Female; haemophagocytic lymphohistiocytosis; Hemophagocytic syndrome; Hospitalization; Humans; Immunohistochemistry; Inflammation; Light microscopy; Lymphohistiocytosis, Hemophagocytic - complications; Lymphohistiocytosis, Hemophagocytic - pathology; Lymphohistiocytosis, Hemophagocytic - virology; Male; Middle Aged; Morphology; Morphometry; Patients; SARS-CoV-2 - physiology; SARS‐CoV‐2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Vertebrae
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/his.14281

Possible Relationship between SARS‐CoV‐2 infection, bone marrow haemophagocytosis and accelerated deterioration of COVID‐19. Aims Haemophagocytosis in the bone marrow of patients who have succumbed to coronavirus disease 19 (COVID‐19) has not been widely studied. The aims of the present study were to perform morphological analyses and morphometry of haemophagocytosis in the bone marrow of patients with severe COVID‐19, and to correlate the findings with the clinical course of the disease. Methods and results In this single‐centre study performed at the University Hospital Jena, bone marrow specimens of 15 deceased patients who had experienced a severe course of COVID‐19 were sampled from the vertebral column during autopsy. Slides of the bone marrow were stained with routine stains or immunohistochemically, and further examined for haemophagocytosis by the use of light microscopy. To substantiate the morphological findings, additional slides were stained for CD163 and morphometry was performed. In all bone marrow samples, an increase in cellularity was found. Haemophagocytes with erythrophagocytosis were detected in 67% of the deceased patients. In tissues with low numbers of haemophagocytes or ill‐defined haemophagocytes, an increase in iron deposits was frequently seen. Morphological findings were then correlated with several important clinical data, and the HScore (probability of having a reactive hemophagocytic syndrome) was calculated to posthumously confirm the diagnosis of secondary haemophagocytic lymphohistiocytosis. The median duration of disease and the hospitalisation time were lower in patients with haemophagocytosis (n = 10) than in patients without haemophagocytosis (n = 5). In addition, patients with haemophagocytes showed increased inflammatory parameters 2–5 days prior to death, in contrast to patients without haemophagocytes. Conclusions Haemophagocytosis is a common finding in the bone marrow of deceased individuals with severe COVID‐19, and may indicate fatal severe acute respiratory syndrome coronavirus 2 infections.