Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019.

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.

Post intensive care syndrome in survivors of COVID-19 who required mechanical ventilation during the third wave of the pandemic: A prospective study.

BACKGROUND: Post intensive care syndrome is defined as the presence of any impairment affecting the physical, psychiatric, or cognitive domains as a result of critical illnesses. OBJECTIVES: To explore functional, cognitive and psychological outcomes at 30 days post hospital discharge among survivors of COVID-19-associated acute respiratory distress syndrome, who required mechanical ventilation. METHODS: Prospective cohort study. We included adult patients with COVID-19-associated acute respiratory distress syndrome, invasively ventilated in two ICUs in Buenos Aires. We measured functional, cognitive and psychological impairments with Barthel index, Montreal Cognitive Assessment test, Patient Health Questionnaire-9 and General Anxiety Disorder-7. Primary outcome was post-intensive care syndrome. Secondary outcome was mortality at 60 days. RESULTS: We admitted 40 patients, median age was 69 (60-75) and mostly male (75%). Mortality at 60 days was 37%. Cox regression analysis identified diabetes and Apache II as independent predictors of mortality. Out of 22 patients studied, 14 (64%) developed PICS after discharge. With a physical, cognitive and psychological impairment in 64%, 41% and 32% of patients, respectively. Obesity, days of mechanical ventilation, Apache II, vasopressors use, delirium duration and cumulative midazolam dose were associated with functional dependence. CONCLUSIONS: We identified a high prevalence of functional, cognitive and mental impairment at 30 days after hospital discharge in COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated. The physical domain was the most frequently affected. These findings suggest the need for long-term follow-up of this population.