B Cell Depletion and Signs of Sepsis Acquired Immunodeficiency in Bone Marrow and Spleen of COVID-19 Deceased

Ihlow, Jana; Michaelis, Edward; Greuel, Selina; Heynol, Verena; Lehmann, Annika; Radbruch, Helena; Meinhardt, Jenny; Miller, Florian; Herbst, Hermann; Corman, Victor Max; Westermann, Jörg; Bullinger, Lars; Horst, David; von Brünneck, Ann-Christin; Elezkurtaj, Sefer

OBJECTIVES: In COVID-19, the adaptive immune response is of considerable importance and detailed cellular immune reactions in the hematological system of patients with severe SARS-CoV2-infection are yet to be clarified. METHODS: Here, we provide a morphologic characterization of both bone marrow (BM) and spleen (SPL) in 11 COVID-19 deceased with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden. RESULTS: In the BM, we found activation and left shift in at least 55% of patients, which was mirrored by anemia and granulocytic immaturity in the peripheral blood as well as thromboembolic events. In the setting of abscess-forming superinfection of COVID-19 pneumonia, we found signs of sepsis acquired immunodeficiency. Furthermore, we observed a severe B cell loss in the BM and/or SPL in 64 % of COVID-19 patients, which was reflected by lymphocytopenia in the blood. These findings were associated with higher pulmonary SARS-CoV-2 load and only marginally decreased T cells as compared to patients with B cell preservation. CONCLUSIONS: Our results suggest that sepsis-related immunodeficiency might aggravate the progress of COVID-19. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, that might impede the humoral immune response to SARS-CoV-2.