On Therapeutic Plasma Exchange Against Severe COVID-19-Associated Pneumonia: An Observational Clinical Study

Abstract

BackgroundThere 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.AimsTo 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.MethodsWe 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.ResultsDeaths 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 p < 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; p = 0.441) for TPE turned to 1.19 (95%CI: 0.43; 3.29; p = 0.741) after adjusting for severity.ConclusionsIn 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.

Therapeutic Plasma Exchange in Adult Patients with COVID-19 and Severe Pneumonia: Single Center Experience of Eighty Patients

“…The mortality rate observed for the E a r l y A c c e s s patients who underwent TPE was 75.0% (n=60) on the 28 th day of the procedure in our study, and this rate is similar to the cases in which the procedure was not performed compared to the literature. As a matter of fact, it was also concluded in a similar observational study published in Iran that TPE could not reduce mortality rates (24). These findings contradict the literature reported on the effectiveness of TPE to date and needs to be confirmed by further observation and prospective studies (9, 25,26).…”

The Impact of Therapeutic Plasma Exchange on Inflammatory Markers and Acute Phase Reactants in Patients with Severe SARS-CoV-2 Infection

“…After filtering the matching studies, we included in this systematic review 13 articles that used TPE as treatment in adult patients with severe COVID-19 [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. The included articles are summarized in Table 1 .…”

“…The main outcomes extracted from the studied papers observed a total of 485 severely ill patients treated with TPE, with a mortality rate of 18.1% (72 patients). However, the mortality rate is arguably lower than in patients without TPE treatment because only six studies had a control group for comparison [ 19 , 22 , 27 , 28 , 29 , 30 , 31 ], and their results were not always statistically significant. However, the duration of ICU admission was reported as significantly lower than in control groups, averaging six days compared with fourteen days among controls.…”

The efficacy of therapeutic plasma exchange in COVID-19 patients on endothelial tightness in vitro is hindered by platelet activation

“…This procedure has already been used during the COVID-19 pandemic with inconsistent results. Indeed, some studies highlighted a beneficial outcome on mortality ( 28 ) and others an improvement in terms of clinical features ( 29 , 30 ) without any obvious impact on mortality ( 31 , 32 ). However, very few studies investigated cellular responses to TPE and were limited to sepsis ( 23 ).…”