Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawai'i at Manoa, Honolulu, HI, United States.
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School Medicine, University of Hawai'i at Manoa, Honolulu, HI, United States.
Front Immunol. 2022 Dec 15;13:1076724. doi: 10.3389/fimmu.2022.1076724. eCollection 2022.
Low-density granulocytes (LDGs) are a distinct subset of neutrophils whose increased abundance is associated with the severity of COVID-19. However, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on LDG levels and phenotypic alteration remain unexplored.
Using participants naïve to SARS-CoV-2 (NP), infected with SARS-CoV-2 with no residual symptoms (NRS), and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC), we compared LDG levels and their phenotype by measuring the expression of markers for activation, maturation, and neutrophil extracellular trap (NET) formation using flow cytometry.
The number of LDGs was elevated in PPASC compared to NP. Individuals infected with SARS-CoV-2 (NRS and PPASC) demonstrated increased CD10 and CD16 subset counts of LDGs compared to NP group. Further characterization of LDGs demonstrated that LDGs from COVID-19 convalescents (PPASC and NRS) displayed increased markers of NET forming ability and aggregation with platelets compared to LDGs from NP, but no differences were observed between PPASC and NRS.
Our data from a small cohort study demonstrates that mature neutrophils with a heightened activation phenotype remain in circulation long after initial SARS-CoV-2 infection. Persistent elevation of markers for neutrophil activation and NET formation on LDGs, as well as an enhanced proclivity for platelet-neutrophil aggregation (PNA) formation in COVID-19 convalescent individuals may be associated with PPASC prognosis and development.
低密度粒细胞（LDG）是中性粒细胞的一个独特亚群，其丰度增加与 COVID-19 的严重程度相关。然而，严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染对 LDG 水平和表型改变的长期影响仍未被探索。
我们使用对 SARS-CoV-2 无感染史（NP）、无残留症状感染 SARS-CoV-2（NRS）和有慢性肺部症状感染 SARS-CoV-2（PPASC）的参与者，通过流式细胞术测量激活、成熟和中性粒细胞胞外陷阱（NET）形成标志物的表达来比较 LDG 水平及其表型。
与 NP 相比，PPASC 中的 LDG 数量升高。与 NP 组相比，感染 SARS-CoV-2 的个体（NRS 和 PPASC）的 LDG 中 CD10 和 CD16 亚群计数增加。对 LDG 的进一步特征分析表明，与 NP 组的 LDG 相比，COVID-19 恢复期患者（PPASC 和 NRS）的 LDG 显示出增强的 NET 形成能力和与血小板聚集的标志物，而在 PPASC 和 NRS 之间未观察到差异。
我们从小队列研究中获得的数据表明，初始 SARS-CoV-2 感染后很长时间，具有高度激活表型的成熟中性粒细胞仍在循环中。LDG 上的中性粒细胞激活和 NET 形成标志物持续升高，以及 COVID-19 恢复期个体中血小板-中性粒细胞聚集（PNA）形成的增强倾向，可能与 PPASC 的预后和发展有关。
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