Objective: While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Methods: Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Results: Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched whereas all other parameters returned to baseline. Conclusion: Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcome.

中文翻译：

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区分轻中度 COVID-19 的潜伏期和急性疾病阶段

目标：虽然许多研究已经比较了重度和轻度至中度 COVID-19 患者对 SARS-CoV-2 的免疫反应，但纵向轨迹仍然很少。因此，我们着手分析来自轻度至中度患者的系列血液样本，以确定不同疾病进展阶段的免疫状况。方法：22 名 COVID-19 患者在确诊或入院后 7 天内接受连续静脉穿刺。进行流式细胞术以分析外周血免疫细胞组成及其活化，以及血浆细胞因子和 SARS-CoV-2 特异性免疫球蛋白的水平。健康供体作为对照。结果：整合浆母细胞和 SARS-CoV-2 特异性抗体的动力学可以定义早期 COVID-19 的三个疾病阶段。孵育阶段的特点是促炎单核细胞和终末分化的细胞毒性 T 细胞急剧增加。后者与 IP-10 浓度升高显着相关。早期急性感染的特点是 PD-1+ 细胞毒性 T 细胞、浆母细胞和病毒特异性抗体滴度增加。在晚期急性感染期间，未成熟的中性粒细胞富集，而所有其他参数返回到基线。结论：我们的研究结果将有助于确定对于改进新的抗病毒和抗炎疗法必不可少的里程碑，并且还可以告知临床医生优化治疗和预防致命结果。孵育阶段的特点是促炎单核细胞和终末分化的细胞毒性 T 细胞急剧增加。后者与 IP-10 浓度升高显着相关。早期急性感染的特点是 PD-1+ 细胞毒性 T 细胞、浆母细胞和病毒特异性抗体滴度增加。在晚期急性感染期间，未成熟的中性粒细胞富集，而所有其他参数返回到基线。结论：我们的研究结果将有助于确定对于改进新的抗病毒和抗炎疗法必不可少的里程碑，并且还可以告知临床医生优化治疗和预防致命结果。孵育阶段的特点是促炎单核细胞和终末分化的细胞毒性 T 细胞急剧增加。后者与 IP-10 浓度升高显着相关。早期急性感染的特点是 PD-1+ 细胞毒性 T 细胞、浆母细胞和病毒特异性抗体滴度增加。在晚期急性感染期间，未成熟的中性粒细胞富集，而所有其他参数返回到基线。结论：我们的研究结果将有助于确定对于改进新的抗病毒和抗炎疗法必不可少的里程碑，并且还可以告知临床医生优化治疗和预防致命结果。后者与 IP-10 浓度升高显着相关。早期急性感染的特点是 PD-1+ 细胞毒性 T 细胞、浆母细胞和病毒特异性抗体滴度增加。在晚期急性感染期间，未成熟的中性粒细胞富集，而所有其他参数返回到基线。结论：我们的研究结果将有助于确定对于改进新的抗病毒和抗炎疗法必不可少的里程碑，并且还可以告知临床医生优化治疗和预防致命结果。后者与 IP-10 浓度升高显着相关。早期急性感染的特点是 PD-1+ 细胞毒性 T 细胞、浆母细胞和病毒特异性抗体滴度增加。在晚期急性感染期间，未成熟的中性粒细胞富集，而所有其他参数返回到基线。结论：我们的研究结果将有助于确定对于改进新的抗病毒和抗炎疗法必不可少的里程碑，并且还可以告知临床医生优化治疗和预防致命结果。