Cegolon Luca, Einollahi Behzad, Panahi Yunes, Imanizadeh Sina, Rezapour Mohammad, Javanbakht Mohammad, Nikpouraghdam Mohammad, Abolghasemi Hassan, Mastrangelo Giuseppe
Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
Public Health Department, University Health Agency Giuliano-Isontina (ASUGI), Trieste, Italy.
Front Nutr. 2022 Feb 22;9:809823. doi: 10.3389/fnut.2022.809823. eCollection 2022.
There is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs and vaccines. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill patients with COVID-19 is still provisional, and further investigations are needed to confirm its eventual beneficial effects.
To assess the effect of TPE on the risk of mortality in patients with COVID-19-associated pneumonia, using three statistical procedures to rule out any threats to validity.
We therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with the diagnosis of COVID-19-associated pneumonia confirmed by real-time polymerase chain reaction (RT-qPCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir), and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 l of patients' plasma by a solution, 50% of normal plasma, and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint.
Deaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of structural equation modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name "severity"). Disease severity was lower (Wilkinson rank-sum test < 0.001) among patients with COVID-19 undergoing TPE (median: -2.82; range: -5.18; 7.96) as compared to those not receiving TPE (median: -1.35; range: -3.89; 8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as the covariate in Cox regression models. The univariate hazard ratio (HR) of 0.68 (95%CI: 0.26; 1.80; = 0.441) for TPE turned to 1.19 (95%CI: 0.43; 3.29; = 0.741) after adjusting for severity.
In this study sample, the lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than the TPE effects.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）存在新突变的风险，这可能使2019冠状病毒病（COVID-19）对包括抗病毒药物和疫苗在内的大多数治疗方法产生耐药性。关于治疗性血浆置换（TPE）用于治疗COVID-19重症患者的证据仍不确凿，需要进一步研究以证实其最终的有益效果。
采用三种统计方法排除对有效性的任何威胁，评估TPE对COVID-19相关性肺炎患者死亡风险的影响。
因此，我们进行了一项单中心回顾性观察性非安慰剂对照试验，纳入了来自伊朗德黑兰巴奇亚塔拉医院的73名住院患者，这些患者经鼻咽拭子实时聚合酶链反应（RT-qPCR）和高分辨率计算机断层扫描胸部扫描确诊为COVID-19相关性肺炎。这些患者被分为两组：第1组（30例患者）接受标准治疗（皮质类固醇、头孢曲松、阿奇霉素、泮托拉唑、羟氯喹、洛匹那韦/利托那韦），第2组（43例患者）接受上述治疗方案加TPE（用一种溶液置换患者2升血浆，该溶液含50%的正常血浆和50%的5%白蛋白），并根据不同时间表进行给药。随访时间为30天，全因死亡率为终点指标。
第2组死亡6例（14%），第1组死亡14例（47%）。然而，未接受TPE的患者中存在不同的有害风险因素，而非在干预组和对照组中平均分布。我们使用结构方程模型（STATA软件）算法将大量潜在混杂因素汇总为一个单一分数（用描述性名称“严重程度”表示）。与未接受TPE的患者（中位数：-1.35；范围：-3.89；8.84）相比，接受TPE的COVID-19患者疾病严重程度较低（威尔科克森秩和检验<0.001）（中位数：-2.82；范围：-5.18；7.96），这证实了治疗分配存在根据入院时COVID-19严重程度对患者进行选择的偏倚。在Cox回归模型中，以严重程度作为协变量进行混杂因素调整。调整严重程度后，TPE的单变量风险比（HR）为0.68（95%CI：0.26；1.80；P = 0.441）变为1.19（95%CI：0.43；3.29；P = 0.741）。
在本研究样本中，接受TPE的患者死亡率较低是由于COVID-19严重程度较低，而非TPE的作用。
