Hemophagocytosis of the Hilar Pulmonary Lymph Nodes Is a More Sensitive Indicator of the Severity of COVID-19 Disease than Bone Marrow Hemophagocytosis

Abstract

In systemic hyper-inflammation, as in severe COVID-19 disease, there are pronounced disorders of the hematological and lymphatic systems with prognostically relevant hemophagocytosis of the bone marrow. The current work aimed to address the importance of hemophagocytosis in the lymph nodes of patients with severe COVID-19 disease. From 28 patients who died of severe COVID-19 infection, samples of the vertebral bone marrow and lymph nodes from the cervical, hilar, para-aortic, mesenteric and inguinal locations were morphologically and immunohistologically (CD163, CD68, CD61, CD71, CD3, CD20, CD138) examined for the possible presence of hemophagocytosis. In the single-center study at the University Hospital Jena, a total of 191 hemophagocytes were found in the bone marrow and a total of 780 hemophagocytes in the lymph nodes in a standardized area of 21,924 mm2 per tissue sample. With 370 hemophagocytes, hilar lymph nodes were most frequently affected (370/780; 47.44%; 95%-CI: [43.94, 50.95]), followed by cervical lymph nodes (206/780; 26.41%; 95%-CI: [23.41, 29.59]), para-aortic lymph nodes (125/780; 16.03%; 95%-CI: [13.58, 18.73]) and inguinal/mesenteric lymph nodes (79/780; 10.13%; 95%-CI: [8.155, 12.4]). Based on the standard area (21,924 mm2), the difference in the number of hemophagocytes in the bone marrow and in the hilar lymph nodes was statistically significant (p < 0.05), while this did not apply to the lymph nodes from the other locations. In fatal COVID-19 disease, hemophagocytosis is particularly found in the hilar lymph nodes and is therefore a better indicator of the severity of the disease than hemophagocytosis in the bone marrow. The findings provide some evidence for the concept of compartmentalized human host responses to life-threatening infections.