Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Highlights-Thoracic anesthesiologists might be involved in the perioperative care of patients suspected to have or diagnosed COVID-19 who might undergo thoracic surgery during the acute or convalescence phases of the disease.-Caution should be exercised when securing the airway and performing lung separation (if required), through vigilant donning/doffing of personal protection equipment (PPE), planning ahead, team briefing, proper preparations, systematic approach, and debriefing.-Lung separation / isolation should be individualized using either bronchial blockers or double lumen tubes according to the patient"s status and postoperative care plan.-Optimum PPE donning should be maintained during surgery and anesthesia. One lung ventilation could be challenging in this group of patients.-The anesthesiologists should discuss the feasibility of extubating the patient following thoracic surgery, and procedures for postoperative care andtransferring the patient to the isolation wards or intensive care unit.Abstract 110 words, Manuscript 4935 words Running

In patients after CABG surgery who were ventilated with low tidal volumes, SVV enabled prediction of fluid responsiveness and assessment of the haemodynamic effects of volume loading.

Full author information is available at the end of the article Greet Van den Berghe, Alexander Wilmer, Rik Gosselink and Greet Hermans have equally contributed. The members of the COVID-19 consortium are listed in "Acknowledgements".