Cremoni Marion, Cuozzo Sébastien, Martinuzzi Emanuela, Barbosa Susana, Ben Hassen Nadia, Massa Filippo, Demonchy Elisa, Durand Matthieu, Thaunat Olivier, Esnault Vincent, Le Quintrec Moglie, Caillard Sophie, Glaichenhaus Nicolas, Sicard Antoine
Department of Nephrology Dialysis and Transplantation, Pasteur 2 Hospital, Nice University Hospital, 06001 Nice, France.
Clinical Research Unit Côte d'Azur (UR2CA), University Côte d'Azur, 06200 Nice, France.
Viruses. 2022 Mar 5;14(3):542. doi: 10.3390/v14030542.
Kidney transplant (KT) recipients are at increased risk of developing severe forms of COVID-19. Little is known about the immunological mechanisms underlying disease severity in these patients receiving T-cell targeting immunosuppressive drugs. We investigated the relationship between T cell responsiveness at the beginning of the infection and the risk of subsequent progression to respiratory failure. We performed a multicentric prospective study in KT recipients with a positive RT-PCR COVID-19 test and only mild symptoms at inclusion. Blood samples were collected at baseline in a cell culture system containing T cell stimuli. We assessed T cell responsiveness by computing the ratio between the levels of Th1, Th2, Th17 and Treg cytokines produced after polyclonal stimulation and the number of blood lymphocytes. We then used an unsupervised classification approach to stratify patients into low and high T cell responders and a penalized logistic regression to evaluate the association between T cell responsiveness and progression to severe pneumonia. Forty-five patients were included. All patients who progressed to severe pneumonia (24.4%, n = 11) were low T cell responders at baseline ( = 0.01). In multivariate analysis, low T cell responsiveness at baseline was the main risk factor for subsequent progression to severe pneumonia. This study provides novel insights into the mechanisms underlying COVID-19 severity in organ transplant recipients and data of interest to clinicians managing immunosuppressive drugs in these patients.
肾移植（KT）受者感染重症 COVID-19 的风险增加。对于这些接受靶向 T 细胞免疫抑制药物治疗的患者，疾病严重程度背后的免疫机制知之甚少。我们研究了感染初期 T 细胞反应性与随后进展为呼吸衰竭风险之间的关系。我们对 RT-PCR COVID-19 检测呈阳性且纳入时仅有轻微症状的 KT 受者进行了一项多中心前瞻性研究。在含有 T 细胞刺激物的细胞培养系统中于基线时采集血样。我们通过计算多克隆刺激后产生的 Th1、Th2、Th17 和 Treg 细胞因子水平与血淋巴细胞数量的比值来评估 T 细胞反应性。然后，我们使用无监督分类方法将患者分为低 T 细胞反应者和高 T 细胞反应者，并使用惩罚逻辑回归来评估 T 细胞反应性与进展为重症肺炎之间的关联。共纳入 45 名患者。所有进展为重症肺炎的患者（24.4%，n = 11）在基线时均为低 T 细胞反应者（P = 0.01）。在多变量分析中，基线时低 T 细胞反应性是随后进展为重症肺炎的主要危险因素。本研究为器官移植受者中 COVID-19 严重程度的潜在机制提供了新见解，也为管理这些患者免疫抑制药物的临床医生提供了有价值的数据。
