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. 2023 Oct;83(4):582-590.
doi: 10.1111/his.14969. Epub 2023 Jun 14.

Bone marrow haematopoiesis in patients with COVID-19

Ewerton Marques-Maggio  1   2 , Umberto Maccio  1 , Alexandra Marx  3 , Serena Galli  4 , Nathalie Schwab  5 , Angela Frank  5 , Baptiste Hamelin  5 , Zsuzsanna Varga  1 , César Nombela-Arrieta  4 , Kirsten D Mertz  5 , Alexandre Pa Theocharides  4 , Viktor H Koelzer  1
Affiliations

Bone marrow haematopoiesis in patients with COVID-19

Ewerton Marques-Maggio et al. Histopathology. 2023 Oct.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; autopsy; haematology; pathology.

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