Lagedal Rickard, Eriksson Oskar, Sörman Anna, Huckriede Joram B, Kristensen Bjarne, Franzén Stephanie, Larsson Anders, Bergqvist Anders, Alving Kjell, Forslund Anders, Persson Barbro, Ekdahl Kristina N, Garcia de Frutos Pablo, Nilsson Bo, Nicolaes Gerry A F, Lipcsey Miklos, Hultström Michael, Frithiof Robert
Department of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, 752 36 Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, 752 36 Uppsala, Sweden.
J Clin Med. 2022 Jun 14;11(12):3419. doi: 10.3390/jcm11123419.
the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival.
All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure.
A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively.
In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.
解释新型冠状病毒肺炎（COVID-19）临床结局差异的病理生理机制尚未完全阐明。本研究旨在调查重症COVID-19患者的抗体反应与炎症、器官衰竭及30天生存率的关系。
纳入2020年3月至9月期间在瑞典一家三级重症监护病房（ICU）住院、经PCR确诊为COVID-19且签署知情同意书的所有患者。收集人口统计学资料、重复的血液样本及器官功能指标。检测血浆中抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）抗体（IgM、IgA和IgG），并将其与患者结局以及炎症和器官衰竭的生物标志物进行关联分析。
前瞻性纳入115例患者（中位年龄62岁，77%为男性）。所有患者均出现严重呼吸功能障碍，59%接受有创通气治疗。所有纳入患者的30天死亡率为22.6%。与抗体阳性患者相比，ICU入院时血浆中任何抗SARS-CoV-2抗体均为阴性的患者30天死亡率更高。IgM阳性患者无ICU、无呼吸机、无肾脏替代治疗及无血管活性药物治疗的天数更多。IgA抗体浓度与简化急性生理学评分第3版（SAPS3）及最高序贯器官衰竭评估（SOFA）评分均呈负相关，IgM水平与SAPS3呈负相关。抗体水平低于检测限的患者在第1天血浆细胞外组蛋白水平较高，肾脏和心脏生物标志物水平升高，但无炎症增加、补体激活或细胞因子释放的迹象。校正年龄后，IgM和IgG抗体阳性仍与30天生存率增加相关，比值比（OR）分别为7.1（1.5 - 34.4）和4.2（1.1 - 15.7）。
在需要重症监护的重症COVID-19患者中，抗体反应不佳与器官衰竭、全身组蛋白释放及30天死亡率增加相关。
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