Guironnet-Paquet Aurelie, Hamzeh-Cognasse Hind, Berard Frederic, Cognasse Fabrice, Richard Jean Christophe, Yonis Hodane, Mezidi Mehdi, Desebbe Olivier, Delannoy Bertrand, Demeret Sophie, Marois Clemence, Saheb Samir, Le Quoc Viet, Schoeffler Mathieu, Pugliesi Paul Simon, Debord Sophie, Bastard Paul, Cobat Aurélie, Casanova Jean Laurent, Pescarmona Rémi, Viel Sébastien, Nicolas Jean François, Nosbaum Audrey, Vocanson Marc, Hequet Olivier
Apheresis Unit, Etablissement Français du Sang Auvergne-Rhône-Alpes, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL), Pierre Bénite, France.
International Center for Infectiology Research (CIRI), Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM), U1111, Lyon, France.
Front Immunol. 2025 Jan 17;15:1492672. doi: 10.3389/fimmu.2024.1492672. eCollection 2024.
Immunological disturbances (anti-type I IFN auto-antibody production, cytokine storm, lymphopenia, T-cell hyperactivation and exhaustion) are responsible for disease exacerbation during severe COVID-19 infections.
In this study, we set up a prospective, randomised clinical trial (ClinicalTrials.gov ID: NCT04751643) and performed therapeutic plasma exchange (TPE) in severe COVID-19 patients in order to decrease excess cytokines and auto-antibodies and to assess whether adding TPE to the standard treatment (ST, including corticosteroids plus high-flow rate oxygen) could help restore immune parameters and limit the progression of acute respiratory distress syndrome (ARDS).
As expected, performing TPE decreased the amount of anti-type I IFN auto-antibodies and improved the elimination or limited the production of certain inflammatory mediators (IL-18, IL-7, CCL2, CCL3, etc.) circulating in the blood of COVID-19 patients, compared to ST controls. Interestingly, while TPE did not influence changes in ARDS parameters throughout the protocol, it proved more effective than ST in reversing lymphopenia, preventing T-cell hyperactivation and reducing T-cell exhaustion, notably in a fraction of TPE patients who had an early favourable respiratory outcome. TPE also restored appropriate numbers of CD4+ and CD8+ T-cell memory populations and increased the number of circulating virus-specific T cells in these patients.
Our results therefore indicate that the addition of TPE sessions to the standard treatment accelerates immune cell recovery and contributes to the development of appropriate antiviral T-cell responses in some patients with severe COVID-19 disease.
免疫紊乱（抗I型干扰素自身抗体产生、细胞因子风暴、淋巴细胞减少、T细胞过度激活和耗竭）是导致重症新型冠状病毒肺炎（COVID-19）感染期间疾病加重的原因。
在本研究中，我们开展了一项前瞻性随机临床试验（ClinicalTrials.gov标识符：NCT04751643），对重症COVID-19患者进行治疗性血浆置换（TPE），以减少过量的细胞因子和自身抗体，并评估在标准治疗（ST，包括皮质类固醇加高流量吸氧）基础上加用TPE是否有助于恢复免疫参数并限制急性呼吸窘迫综合征（ARDS）的进展。
正如预期的那样，与ST对照组相比，进行TPE可减少抗I型干扰素自身抗体的量，并改善COVID-19患者血液中某些炎症介质（IL-18、IL-7、CCL2、CCL3等）的清除或减少其产生。有趣的是，虽然在整个方案中TPE并未影响ARDS参数的变化，但事实证明，TPE在逆转淋巴细胞减少、预防T细胞过度激活和减少T细胞耗竭方面比ST更有效，特别是在一部分呼吸结局早期良好的TPE患者中。TPE还恢复了适当数量的CD4+和CD8+T细胞记忆群体，并增加了这些患者循环中病毒特异性T细胞的数量。
因此，我们的结果表明，在标准治疗中增加TPE疗程可加速免疫细胞恢复，并有助于一些重症COVID-19疾病患者产生适当的抗病毒T细胞反应。
