key: cord-0820441-8ez7ai94 authors: Vincent, Jean-Louis title: COVID-19: it is all about sepsis date: 2021-01-25 journal: Future microbiology DOI: 10.2217/fmb-2020-0312 sha: 215a7b48ce015f295048cb3c109fd0b596fec07c doc_id: 820441 cord_uid: 8ez7ai94 nan Is using the word sepsis for COVID-19 patients just a question of semantics? No, the implications of calling this sepsis are important. First, this dysregulated host response explains why antiviral therapies, including remdesivir, have not been found to be very effective in COVID-19 patients who have become critically ill. On the other hand, immunomodulation with corticosteroids and tocilizumab are valid therapeutic approaches in some patients, and other options will follow. Second, the recognized importance of thrombotic coagulopathy, reinforced by the common occurrence of pulmonary embolism [15] , supports administration of heparin in patients hospitalized with COVID-19. Third, in all patients with sepsis, restoration and maintenance of adequate oxygen delivery to the organs is of paramount importance. The excessive focus on lung edema early in the pandemic initially resulted in liberal use of diuretics, with a secondary decrease in cardiac output and limitation of oxygen delivery. Cardiac involvement can cause severe myocardial depression and pulmonary embolism can cause obstructive shock. Hence, any clinical sign of altered tissue perfusion and/or even a slight increase in blood lactate levels should be an alarm signal to act to improve tissue perfusion. Depending on the individual's hemodynamic status, this may be achieved by administering intravenous fluid, giving dobutamine as an inotropic agent to increase cardiac output or giving red blood cell transfusions [16] . Recognizing COVID-19 as 'sepsis' can also encourage development of therapeutic approaches that target the host response. Unfortunately, too many trials have not attempted to characterize the pathophysiological alterations present in the study patients, yet an excessive host response can be characterized by specific signatures (high Creactive protein, high ferritin levels, high IL-6 levels, etc.). Increasingly the role of genetic factors in influencing the immune response, including the availability of interferons, is also being highlighted [17, 18] . In developing trials for treatments in COVID-19, we should be careful not to repeat the errors made when conducting trials of anticytokine treatments in sepsis, in which large heterogeneous populations were included rather than targeting those most likely to respond to the therapy under investigation [19] . Trials of immunomodulating therapies that only enroll COVID-19 patients who have hypoxemia as a unique abnormality are doomed to fail; patients need rather to be characterized according to their immune phenotypes. Instead of attempting to find a 'one size fits all' approach to therapy, the time has come to individualize management [20] . Patients with sepsis form a very heterogeneous population and even patients with more specific, COVID-19 sepsis can have multiple characteristics. Careful characterization of these patients can enable the most appropriate treatment to be selected on an individual basis. Financial & competing interests disclosure Adapting to an unprecedented scenario: surgery during the COVID-19 outbreak Laparoscopy at all costs? 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This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.