Here, we summarize macrophage activation syndrome and its possible contribution to COVID-19, and cytokine targeted attempts in severe COVID-19 cases.
Macrophage responses associated with COVID-19: A pharmacological perspective
Here we discuss the potential underlying basis for the impact of SARS-CoV-2 on macrophages, both direct and indirect, and potential therapeutic targets. These include granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 6 (IL-6), interferons, and CXCL10 (IP-10).
Hemophagocytic lymphohistiocytosis (HLH)
Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic
HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment.
COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate
Children presenting with moderate-severe COVID-19 and Kawasaki disease shock-like syndrome exhibit peripheral blood picture analogous to HLH. HScore, a validated tool to diagnose HLH, has been suggested to screen severe COVID-19 patients for cytokine storm. However, HScore faces certain limitations in this scenario. It may be more pragmatic to use ‘high D-dimer’ (> 3 µg/mL) instead of ‘low fibrinogen’ to facilitate early detection of cytokine storm. COVID-19 associated coagulopathy resembles hypercoagulable form of DIC with bleeding being rarely reported. Although the International Society on Thrombosis and Haemostasis (ISTH) interim guidance recommends low molecular weight heparin in all hospitalized patients, data is lacking in population below 14 years of age. However, in the presence of life-threatening thromboembolic event or symptomatic acro-ischemia, unfractionated heparin (UFH) should be used with caution.
HScore can be used as a complement to clinical decision for initiating immunosuppression. Children with moderate-to-severe COVID-19, especially those with documented thrombocytopenia or chilblains, should be regularly monitored for coagulopathy.
Hemophagocytic lymphohistiocytosis in a patient with COVID-19 treated with tocilizumab: a case report
COVID-19 may induce a hyperinflammatory clinical picture and in some cases develop into hemophagocytic lymphohistiocytosis. In our patient's case, therapeutic interleukin-6 blockade abrogated signs of hyperinflammation but did not seem to improve pulmonary function. Measurement of ferritin and C-reactive protein, as well as quantification of interleukin-6 on indication, should be performed in patients with severe COVID-19.
Edward Carmichael Aschoff (December 24, 1985 – December 24, 2019) was an American sports reporter
Aschoff died on his thirty-fourth birthday of hemophagocytic lymphohistiocytosis, a complication of pneumonia and underlying undiagnosed stage 4 Non-Hodgkin lymphoma. After his passing, the hospital received the final results from his lung biopsy. Unbeknownst to us, Edward had stage 4, non-Hodgkin’s lymphoma in his lungs.