Liver-spleen axis dysfunction in COVID-19

Table 4 Summary of the main studies reporting coronavirus disease 2019 related spleen dysfunction

Ref.	Country	Patients	Patients with spleen involvement, n (%)	Main findings
Feng et al[54]	China	6	6 (100)	ACE2 expression on tissue-resident CD169+ macrophages in spleen; viral NP antigen found in ACE2+ cells in spleen; direct damage of spleen tissue (lymph follicle depletion, splenic nodule atrophy, lymphocyte reduction, etc.)
Remmelink et al[55]	Belgium	17	11 (65)	SARS-CoV-2 RNA detected in spleen autopsy samples by RT-PCR assay
Sekulic et al[56]	United States	2	2 (100)	SARS-CoV-2 RNA detected at high level in spleen FFPE samples by RT-PCR assay
Han et al[58]	China	7356	NA	Expression of ACE2 in spleen tissue (lower than in other tissues), without difference according to sex
Li et al[59]	China	31	NA	Expression of ACE2 in spleen tissue (lower than in other tissues), without difference according to sex and age
Xu et al[60]	China	10	10 (100)	Decrease in spleen cell composition with decrease in lymphocyte components, white pulp atrophied, lymphoid follicles decreased or absent, increase in red pulp to white pulp ratio
Menter et al[61]	Switzerland	21	6 (29)	Acute splenitis and/or septic neutrophilic leucocytosis of the red pulp, suggesting vascular disfunction in patients with COVID-19
Lax et al[62]	Austria	11	10 (90)	White pulp atrophy due to lymphocyte depletion, areas of haemorrhage with acute or chronic congestion
Duarte-Neto et al[63]	Brazil	5	5 (100)	Lymphoid hypoplasia in 100%, red pulp haemorrhages in 60%, splenitis in 40%, extramedullary haematopoiesis in 50%, endothelial changes in 80%, vasculitis and arterial thrombus in 20%
Lenti et al[29]	Italy	63	55 (87.3)	IgM memory B cell depletion that correlates with increased mortality and superimposed infections
Kaneko et al[65]	United States	11	11 (100)	Loss of spleen germinal centres due to depletion of Bcl-6+ germinal centre B cells and Bcl-6+ germinal centre T follicular helper cells, resulting in a dysregulated humoral immune response

COVID-19: Coronavirus disease 2019; FFPE: Formalin-fixed paraffin-embedded; NA: Not available; NP: Nucleocapsid protein; RT-PCR: Real-time reverse-transcript polymerase chain reaction; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.