Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients

IF 9 2区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of Internal Medicine Pub Date : 2024-03-27 DOI:10.1111/joim.13783

Andreas Barratt-Due, Kristin Pettersen, Tuva Børresdatter-Dahl, Jan Cato Holter, Renathe H. Grønli, Anne Ma Dyrhol-Riise, Tøri Vigeland Lerum, Aleksander Rygh Holten, Kristian Tonby, Marius Trøseid, Ole H. Skjønsberg, Beathe Kiland Granerud, Lars Heggelund, Anders Benjamin Kildal, Camilla Schjalm, Trond Mogens Aaløkken, Pål Aukrust, Thor Ueland, Tom Eirik Mollnes, Bente Halvorsen, NOR-Solidarity study groupThe Norwegian SARS-CoV-2 study group

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引用次数: 0

Abstract

Background

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.

Methods

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 (PO₂/FiO₂ ratio <26.6 kPa) and/or admission to intensive care unit, 60-day total mortality and pulmonary pathology after 3 months.

Findings

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.

Conclusion

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.

Abstract Image

查看原文本刊更多论文

SARS-CoV-2 感染者住院期间补体激活升级与 60 天内死亡风险升高有关。

背景：补体系统是先天性免疫的上游识别系统，在感染SARS-CoV-2后被激活。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 急性期的补体激活情况、恢复后的持续情况以及与疾病严重程度相关的动态变化：方法：我们从两组住院的 COVID-19 患者（n = 457）中采集了连续血样。测量了住院期间（入院第 3-5 天和第 7-10 天）、3 个月和 1 年后的全身补体激活产物，包括经典/选择蛋白（C4d）、替代性补体激活产物（C3bBbP）、普通补体激活产物（C3bc）和终末途径补体激活产物（TCC 和 C5a）。住院期间的激活水平和时间曲线与定义为呼吸衰竭的疾病严重程度（PO2/FiO2 比值结果）有关：与健康对照组相比，住院期间TCC、C4d、C3bc、C3bBbP和C5a显著升高。重症患者的 TCC 和 C4d 水平明显更高（p 结论：COVID-19 患者在住院期间表现出较高的血红蛋白水平：COVID-19 住院患者表现出明显而持久的全身补体激活。可通过加强风险分层和密切监测院内补体激活产物的变化来实现系统的最佳目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Internal Medicine 医学-医学：内科

CiteScore

22.00

自引率

0.90%

发文量

176

审稿时长

4-8 weeks

期刊介绍： JIM – The Journal of Internal Medicine, in continuous publication since 1863, is an international, peer-reviewed scientific journal. It publishes original work in clinical science, spanning from bench to bedside, encompassing a wide range of internal medicine and its subspecialties. JIM showcases original articles, reviews, brief reports, and research letters in the field of internal medicine.