Department of Anesthesia and Intensive Care Medicine, Oslo University Hospital, Oslo, Norway.
Research Laboratory, Nordland Hospital Trust, Bodø, Norway.
J Intern Med. 2024 Jul;296(1):80-92. doi: 10.1111/joim.13783. Epub 2024 Mar 27.
The complement system, an upstream recognition system of innate immunity, is activated upon SARS-CoV-2 infection. To gain a deeper understanding of the extent and duration of this activation, we investigated complement activation profiles during the acute phase of COVID-19, its persistence post-recovery and dynamic changes in relation to disease severity.
Serial blood samples were obtained from two cohorts of hospitalized COVID-19 patients (n = 457). Systemic complement activation products reflecting classical/lectin (C4d), alternative (C3bBbP), common (C3bc) and terminal pathway (TCC and C5a) were measured during hospitalization (admission, days 3-5 and days 7-10), at 3 months and after 1 year. Levels of activation and temporal profiles during hospitalization were related to disease severity defined as respiratory failure (PO/FiO ratio <26.6 kPa) and/or admission to intensive care unit, 60-day total mortality and pulmonary pathology after 3 months.
During hospitalization, TCC, C4d, C3bc, C3bBbP and C5a were significantly elevated compared to healthy controls. Severely ill patients had significantly higher levels of TCC and C4d (p < 0.001), compared to patients with moderate COVID-19. Escalated levels of TCC and C4d during hospitalization were associated with a higher risk of 60-day mortality (p < 0.001), and C4d levels were additionally associated with chest CT changes at 3 months (p < 0.001). At 3 months and 1 year, we observed consistently elevated levels of most complement activation products compared to controls.
Hospitalized COVID-19 patients display prominent and long-lasting systemic complement activation. Optimal targeting of the system may be achieved through enhanced risk stratification and closer monitoring of in-hospital changes of complement activation products.
补体系统是先天免疫的上游识别系统，在 SARS-CoV-2 感染时被激活。为了更深入地了解这种激活的程度和持续时间，我们研究了 COVID-19 急性期、恢复期后以及与疾病严重程度相关的动态变化期间的补体激活谱。
我们从两批住院 COVID-19 患者（n=457）中采集了连续的血样。在住院期间（入院时、第 3-5 天和第 7-10 天）、3 个月和 1 年后，测量反映经典/凝集（C4d）、替代（C3bBbP）、共同（C3bc）和末端途径（TCC 和 C5a）的系统性补体激活产物。住院期间的激活水平和时间谱与疾病严重程度相关，疾病严重程度定义为呼吸衰竭（PO/FiO 比值<26.6kPa）和/或入住重症监护病房、60 天总死亡率和 3 个月后的肺部病理学。
与健康对照组相比，住院期间 TCC、C4d、C3bc、C3bBbP 和 C5a 明显升高。与中度 COVID-19 患者相比，严重疾病患者的 TCC 和 C4d 水平显著升高（p<0.001）。住院期间 TCC 和 C4d 水平升高与 60 天死亡率升高相关（p<0.001），C4d 水平还与 3 个月时的胸部 CT 变化相关（p<0.001）。在 3 个月和 1 年时，与对照组相比，我们观察到大多数补体激活产物的水平持续升高。
住院 COVID-19 患者表现出明显且持久的系统性补体激活。通过增强风险分层和更密切监测补体激活产物在住院期间的变化，可能实现对该系统的最佳靶向治疗。
