Secondary haemophagocytic lymphohistiocytosis in COVID-19: correlation of the autopsy findings of bone marrow haemophagocytosis with HScore

Abstract

BackgroundSecondary haemophagocytic lymphohistiocytosis (sHLH) is characterised by a hyper activation of immune system that leads to multiorgan failure. It is suggested that excessive immune response in patients with COVID-19 could mimic this syndrome. Some COVID-19 autopsy studies have revealed the presence of haemophagocytosis images in bone marrow, raising the possibility, along with HScore parameters, of sHLH.AimOur objective is to ascertain the existence of sHLH in some patients with severe COVID-19.MethodsWe report the autopsy histological findings of 16 patients with COVID-19, focusing on the presence of haemophagocytosis in bone marrow, obtained from rib squeeze and integrating these findings with HScore parameters. CD68 immunohistochemical stains were used to highlight histiocytes and haemophagocytic cells. Clinical evolution and laboratory parameters of patients were collected from electronic clinical records.ResultsEleven patients (68.7%) displayed moderate histiocytic hyperplasia with haemophagocytosis (HHH) in bone marrow, three patients (18.7%) displayed severe HHH and the remainder were mild. All HScore parameters were collected in 10 patients (62.5%). Among the patients in which all parameters were evaluable, eight patients (80%) had an HScore >169. sHLH was not clinically suspected in any case.ConclusionsOur results support the recommendation of some authors to use the HScore in patients with severe COVID-19 in order to identify those who could benefit from immunosuppressive therapies. The presence of haemophagocytosis in bone marrow tissue, despite not being a specific finding, has proved to be a very useful tool in our study to identify these patients.

Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19)

“…Hemophagocytosis in the bone marrow has been reported in most of the MITS cases conducted in Spain [ 54 ], and has also been observed in a few complete autopsies in patients with COVID-19 [ 65 , 67 , 68 ]. This finding has also been reported in the spleen and the lymph nodes [ 65 , 67 , 68 ]. Hemophagocytosis (in spleen and lymph nodes) was also reported in a pediatric MITS case in Brazil [ 50 ].…”

Case Report: Secondary Hemophagocytic Lymphohistiocytosis (sHLH) and Candida auris Fungemia in Post-acute COVID-19 Syndrome: A Clinical Challenge

“…There are case reports of SARS-CoV-2-induced sHLH diagnosed antemortem (11)(12)(13)(14)(15) and postmortem (1,(16)(17)(18)(19) while the illness is/was ongoing, as shown in Table 2B. However, the literature is sparse about COVID-19 recovered cases developing sHLH (8)(9)(10), as shown in Table 2B.…”

Haemophagocytic lymphohistiocytosis after ChAdOx1 nCoV-19 vaccination

“…HLH has been reported as a consequence of SARS-CoV-2 infection, and there is some evidence that sHLH is underdiagnosed in severe COVID-19 illness. 4 Both lead to a hyperinflammatory syndrome and a severe cytokine storm with elevated ferritin levels being associated with poor outcomes in COVID-19 and sHLH. 5 This underpins the finding that the IL-6 inhibitor tocilizumab improves outcomes in patients hospitalised with COVID-19.…”