Neutrophil and Eosinophil Responses Remain Abnormal for Several Months in Primary Care Patients With COVID-19 Disease

B N Jukema; K Smit; M T E Hopman; C C W G Bongers; T C Pelgrim; M H Rijk; T N Platteel; R P Venekamp; D L M Zwart; F H Rutten; L Koenderman

doi:10.3389/falgy.2022.942699

Neutrophil and Eosinophil Responses Remain Abnormal for Several Months in Primary Care Patients With COVID-19 Disease

Front Allergy. 2022 Jul 27:3:942699. doi: 10.3389/falgy.2022.942699. eCollection 2022.

Authors

B N Jukema^{1

2}, K Smit³, M T E Hopman⁴, C C W G Bongers⁴, T C Pelgrim^{1

2}, M H Rijk³, T N Platteel³, R P Venekamp³, D L M Zwart³, F H Rutten³, L Koenderman^{1

2}

Affiliations

¹ Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
² Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
³ Department of General Practice, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
⁴ Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Abstract

Introduction: Neutrophil and eosinophil activation and its relation to disease severity has been understudied in primary care patients with COVID-19. In this study, we investigated whether the neutrophil and eosinophil compartment were affected in primary care patients with COVID-19.

Methods: COVID-19 patients, aged ≥ 40 years with cardiovascular comorbidity presenting to the general practitioner with substantial symptoms, partaking in the COVIDSat@Home study between January and April 2021, were included. Blood was drawn during and 3 to 6 months after active COVID-19 disease and analyzed by automated flow cytometry, before and after stimulation with a formyl-peptide (fNLF). Mature neutrophil and eosinophil markers at both time points were compared to healthy controls. A questionnaire was conducted on disease symptoms during and 3 to 6 months after COVID-19 disease.

Results: The blood of 18 COVID-19 patients and 34 healthy controls was analyzed. During active COVID-19 disease, neutrophils showed reduced CD10 (p = 0.0360), increased CD11b (p = 0.0002) and decreased CD62L expression (p < 0.0001) compared to healthy controls. During active COVID-19 disease, fNLF stimulated neutrophils showed decreased CD10 levels (p < 0.0001). Three to six months after COVID-19 disease, unstimulated neutrophils showed lowered CD62L expression (p = 0.0003) and stimulated neutrophils had decreased CD10 expression (p = 0.0483) compared to healthy controls. Both (un)stimulated CD10 levels increased 3 to 6 months after active disease (p = 0.0120 and p < 0.0001, respectively) compared to during active disease. Eosinophil blood counts were reduced during active COVID-19 disease and increased 3 to 6 months after infection (p < 0.0001). During active COVID-19, eosinophils showed increased unstimulated CD11b (p = 0.0139) and decreased (un)stimulated CD62L expression (p = 0.0036 and p = 0.0156, respectively) compared to healthy controls. Three to six months after COVID-19 disease, (un)stimulated eosinophil CD62L expression was decreased (p = 0.0148 and p = 0.0063, respectively) and the percentage of CD11b^bright cells was increased (p = 0.0083 and p = 0.0307, respectively) compared to healthy controls.

Conclusion: Automated flow cytometry analysis reveals specific mature neutrophil and eosinophil activation patterns in primary care patients with COVID-19 disease, during and 3 to 6 months after active disease. This suggests that the neutrophil and eosinophil compartment are long-term affected by COVID-19 in primary care patients. This indicates that these compartments may be involved in the pathogenesis of long COVID.

Keywords: SARS-CoV-2; activation; flow cytometry; granulocytes; long COVID; primary care.