Severe COVID-19 is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in COVID-19 patients. We found that neutrophils from severe COVID-19 patients express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2 and show a strong association with platelets. Production of CXCL8 correlated with plasmatic concentrations of LDH and D-dimer. Whole blood assays revealed that neutrophils from severe COVID-19 patients show a clear association with IgG immune complexes. Moreover, we found that sera from severe patients contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-SARS-CoV-2 IgG antibodies from severe patients displayed a higher pro-inflammatory profile compared with antibodies from mild patients. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils worsening the course of COVID-19.

High salt (NaCl) concentrations are found in a number of tissues under physiological and pathological conditions. Here, we analyzed the effects induced by high salt on the function of human neutrophils. The culture of neutrophils in medium supplemented with high salt (50 mM NaCl) for short periods (30-120 min) inhibited the ability of conventional agonists to induce the production of IL-8 and the activation of respiratory burst. By contrast, exposure to high salt for longer periods (6-18 h) resulted in the activation of neutrophils revealed by the production of high levels of IL-8, the activation of the respiratory burst, and a marked synergistic effect on the production of TNF-α induced by LPS. Increasing osmolarity of the culture medium by the addition of sorbitol or mannitol (100 mM) was shown to be completely unable to stimulate neutrophil responses, suggesting that high sodium but not an increased osmolarity mediates the activation on neutrophils responses. A similar biphasic effect was observed when the function of monocytes was analyzed. Short term exposure to high salt suppressed IL-8 and TNF-α production induced by LPS while culture for longer periods triggered the production of IL-8 but not TNF-α in the absence of LPS stimulation. Contradictory results have been published regarding how high salt modulates neutrophil function. Our results suggest that the modulation of neutrophil function by high salt is strongly dependent on the exposure time.