Karina Karina, Christoffel Louis Martin, Novariani Rita, Rosadi Imam, Rosliana Iis, Rosidah Siti, Sobariah Siti, Fatkhurohman Novy, Puspitaningrum Nurlaela, Hertati Yuli, Afini Irsyah, Ernanda Difky, Widyastuti Tias, Sulaeha A D, Zakiyah Alfida, Aini Noor, Krisandi Grady, Andrew Hubert
Klinik Hayandra, Yayasan Hayandra Peduli, Jl. Kramat VI No. 11, Jakarta, Indonesia.
HayandraLab, Yayasan Hayandra Peduli, Jl. Kramat VI No. 11, Jakarta, Indonesia.
Scientifica (Cairo). 2021 Jul 8;2021:9427978. doi: 10.1155/2021/9427978. eCollection 2021.
Elevated concentration of proinflammatory cytokines followed by hyperinflammation is one of the hallmarks of severe and critical COVID-19. In the short term, this may result in ARDS and lung injury; subsequently, this may cause pulmonary fibrosis-a disease with poor prognosis-in the long run. Among the cytokines, interleukin-1 (IL-1) is one of the most overexpressed in COVID-19. We speculate that administration of intravenous activated autologous platelet-rich plasma (aaPRP), which contains interleukin-1 receptor antagonist (IL-1RA), would lower IL-1 levels and benefit the severe and critical COVID-19 patients.
After acquiring ethical clearance, we recruited 12 adult COVID-19 patients of both sexes from the Koja Regional Hospital (Jakarta, Indonesia) ICU. After selection, seven patients were included and divided into two groups, severe and critical. In addition to three doses of aaPRP, both groups received the same treatment of antiviral, steroid, and antibiotics. Quantification of plasma IL-1 levels was performed by beads multiplex assay a day before the first aaPRP administration and a day after the second and third aaPRP administration. PaO/FiO ratio and lung injury scores were evaluated a day before and a day after each aaPRP administration.
Severe and critical patients' initial plasma IL-1 concentration was 4.71 pg/mL and 3.095 pg/mL, respectively. After 2 treatments with aaPRP, severe patients' plasma IL-1 concentration decreased 12.48 pg/mL, while critical patients' plasma IL-1 concentration increased to 18.77 pg/mL. Furthermore, after 3 aaPRP treatments, significant amelioration of patients' PaO/FiO ratio from 71.33 mmHg at baseline to 144.97 mmHg was observed ( < 0.05). However, no significant improvement in lung injury score was observed in severe and critical groups. All severe patients and one critical patient recovered.
The use of aaPRP may prevent pulmonary fibrosis in severe COVID-19 patients through the reduction of patients' plasma IL-1 concentration and the amelioration of PaO/FiO ratio.
促炎细胞因子浓度升高继而引发过度炎症是重症和危重症 COVID-19 的特征之一。短期内,这可能导致急性呼吸窘迫综合征(ARDS)和肺损伤;从长期来看,这可能会引发肺纤维化,一种预后不良的疾病。在细胞因子中,白细胞介素-1(IL-1)是 COVID-19 中表达最为过度的因子之一。我们推测,静脉注射含有白细胞介素-1 受体拮抗剂(IL-1RA)的自体活化富血小板血浆(aaPRP),会降低 IL-1 水平,并使重症和危重症 COVID-19 患者受益。
获得伦理批准后,我们从印度尼西亚雅加达科贾地区医院重症监护病房招募了 12 名成年 COVID-19 患者,男女不限。筛选后,7 名患者被纳入并分为两组,重症组和危重症组。除了三剂 aaPRP 外,两组均接受相同的抗病毒、类固醇和抗生素治疗。在首次注射 aaPRP 前一天以及第二次和第三次注射 aaPRP 后一天,通过磁珠多重检测法对血浆 IL-1 水平进行定量。在每次注射 aaPRP 前一天和后一天评估 PaO/FiO 比值和肺损伤评分。
重症和危重症患者的初始血浆 IL-1 浓度分别为 4.71 pg/mL 和 3.095 pg/mL。经过 2 次 aaPRP 治疗后,重症患者的血浆 IL-1 浓度下降了 12.48 pg/mL,而危重症患者的血浆 IL-1 浓度升至 18.77 pg/mL。此外,经过 3 次 aaPRP 治疗后,观察到患者的 PaO/FiO 比值从基线时的 71.33 mmHg 显著改善至 144.97 mmHg(<0.05)。然而,重症组和危重症组的肺损伤评分均未观察到显著改善。所有重症患者和 1 名危重症患者康复。
使用 aaPRP 可能通过降低患者血浆 IL-1 浓度和改善 PaO/FiO 比值来预防重症 COVID-19 患者发生肺纤维化。