Bone marrow haematopoiesis in patients with COVID‐19

Aims Severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) infection broadly affects organ homeostasis, including the haematopoietic system. Autopsy studies are a crucial tool for investigation of organ‐specific pathologies. Here we perform an in‐depth analysis of the impact of severe coronavirus disease 2019 (COVID‐19) on bone marrow haematopoiesis in correlation with clinical and laboratory parameters. Methods and results Twenty‐eight autopsy cases and five controls from two academic centres were included in the study. We performed a comprehensive analysis of bone marrow pathology and microenvironment features with clinical and laboratory parameters and assessed SARS‐CoV‐2 infection of the bone marrow by quantitative polymerase chain reaction (qPCR) analysis. In COVID‐19 patients, bone marrow specimens showed a left‐shifted myelopoiesis (19 of 28, 64%), increased myeloid–erythroid ratio (eight of 28, 28%), increased megakaryopoiesis (six of 28, 21%) and lymphocytosis (four of 28, 14%). Strikingly, a high proportion of COVID‐19 specimens showed erythrophagocytosis (15 of 28, 54%) and the presence of siderophages (11 of 15, 73%) compared to control cases (none of five, 0%). Clinically, erythrophagocytosis correlated with lower haemoglobin levels and was more frequently observed in patients from the second wave. Analysis of the immune environment showed a strong increase in CD68+ macrophages (16 of 28, 57%) and a borderline lymphocytosis (five of 28, 18%). The stromal microenvironment showed oedema (two of 28, 7%) and severe capillary congestion (one of 28, 4%) in isolated cases. No stromal fibrosis or microvascular thrombosis was found. While all cases had confirmed positive testing of SARS‐CoV‐2 in the respiratory system, SARS‐CoV‐2 was not detected in the bone marrow by high‐sensitivity PCR, suggesting that SARS‐CoV‐2 does not commonly replicate in the haematopoietic microenvironment. Conclusions SARS‐CoV‐2 infection indirectly impacts the haematological compartment and the bone marrow immune environment. Erythrophagocytosis is frequent and associated with lower haemoglobin levels in patients with severe COVID‐19.