COMPLEX IMMUNE DYSREGULATION IN COVID-19 PATIENTS WITH SEVERE RESPIRATORY FAILURE
2020
Proper management of COVID-19 mandates better understanding of disease pathogenesis The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF All SRF patients displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen (HLA)-DR expression accompanied by profound depletion of CD4-lymphocytes, CD19- lymphocytes and natural killer cells TNF? and IL-6 production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab;off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation
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