The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils.

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n = 20) or other viral (n = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/µL; p < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11bbright population consisted of 5.4% (CI95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11bbright cells comprised nearly half the population (42.21%, CI95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11bbright cells before activation (7.6%, CI95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11bbright fraction after activation (23.7%, CI95% = 18.5, 27.6; p < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue.

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Critical COVID-19 is thought to be associated with a hyper-inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID-19 patients. Therefore, a prospective study was performed on all patients with suspected COVID-19 presenting at the emergency room of a large academic hospital. Blood drawn within 2 d after hospital presentation was analyzed by point-of-care automated flow cytometry and compared with blood samples collected at later time points. COVID-19 patients did not exhibit neutrophilia or eosinopenia. Unexpectedly neutrophil activation markers (CD11b, CD16, CD10, and CD62L) did not differ between COVID-19-positive patients and COVID-19-negative patients diagnosed with other bacterial/viral infections, or between COVID-19 severity groups. In all patients, a decrease was found in the neutrophil maturation markers indicating an inflammation-induced left shift of the neutrophil compartment. In COVID-19 this was associated with disease severity.

An increase in CD62Ldim neutrophils precedes the development of pulmonary embolisms in COVID-19 patients.

OBJECTIVES: A high incidence of pulmonary embolism (PE) is reported in patients with critical coronavirus disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE. METHODS: We studied COVID-19 patients admitted to the ICU of our tertiary hospital between 19-03-2020 and 17-05-2020. Point-of-care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay. RESULTS: Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7-12) days. A significant increase in the immune-suppressive neutrophil phenotype CD16bright /CD62Ldim was observed on the day of ICU admission (P = 0.014) in patients developing PE compared to patients who did not. CONCLUSION: The increase in this neutrophil phenotype indicates that the increased number of CD16bright /CD62Ldim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID-19 patients.