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Healthy control individuals, n = 10 patients who were paucisymptomatic (pauci), n = 10 patients with pneumonia (pneumo), n = 31–34 patients with ARDS, n = 26–28. b, Concentration of C5a desArg in plasma of HC and patients with COVID-19. 1a), consistent with previous studies, which show higher titres of anti-SARS-CoV-2 antibodies in patients with severe COVID-19 4.Ī, Concentrations of CRP, IL-6, CCL4, CCL2 and CXCL9 in plasma from healthy control individuals (HC) and patients with COVID-19. The ability of plasma from patients to neutralize the SARS-CoV-2 virus was also correlated with disease severity (Extended Data Fig. These results confirmed previous observations of the ‘cytokine storm’ that develops in patients with severe COVID-19 3. We focused on molecular pathways that could block the overt inflammation associated with ARDS.ĭisease severity was associated with an increase in the amounts of plasma C-reactive protein (CRP) and inflammatory cytokines-such as interleukin-6 (IL-6), and the chemokines CCL4 (macrophage inflammatory protein-1β), CCL2 (monocyte chemoattractant protein 1) and CXCL9 (monokine induced by interferon-γ)-that are produced by and act on myeloid cells (Fig. We therefore monitored immune parameters in a cohort of 82 individuals: 10 healthy control individuals, 10 patients with COVID-19 who were paucisymptomatic, 34 patients with pneumonia and 28 patients with ARDS due to SARS-CoV-2 infection (Supplementary Table 1). In particular, given the urgent need for effective treatments for pneumonia in patients with COVID-19, the elucidation of the immune responses that occur during the course of COVID-19 could lead to the repurposing of approved immunomodulatory drugs and candidate drugs that have already been tested in clinical trials. A detailed characterization of the immune responses that occur during disease progression from mild to severe forms is therefore important for understanding the ways in which we can manipulate immunity to propose new therapies. The immune system has a dual role in the pathology of COVID-19, contributing to both virus elimination and the development of ARDS 2. Most patients with COVID-19 have only a few mild symptoms, but about 15% of patients progress to severe pneumonia, and about 5% develop acute respiratory distress syndrome (ARDS), for which effective therapeutic strategies are urgently required 2. These results suggest that blockade of the C5a–C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a–C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes 1. Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic 1.