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

  1. Luca Cegolon
  2. Behzad Einollahi
  3. Yunes Panahi
  4. Sina Imanizadeh
  5. Mohammad Rezapour
  6. Mohammad Javanbakht
  7. Mohammad Nikpouraghdam
  8. Hassan Abolghasemi
  9. Giuseppe Mastrangelo

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Abstract

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.

Aims

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.

Methods

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.

Results

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 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.

Conclusions

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.

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  1. Version published to 10.3389/fnut.2022.809823
  2. ScreenIT

    SciScore for 10.1101/2021.04.19.21255657: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: According to above selection criteria, COVID-19 patients were broken down as shown in figure 1: Ethical statement: This study was approved by the Ethical Committee of Baqiyatallah University of Medical Sciences (IR.BMSU.REC.1398435; IRCT registration number: IRCT20080901001165N58; Registration date: 2020-05-27) [17].
    Consent: All ethical guidelines for studies on human subjects were carefully observed and informed consent was obtained from study participants.
    Sex as a biological variablenot detected.
    RandomizationStudy design: This single-centered retrospective observational controlled - yet not randomized - study enrolled 73 inpatients from Baqiyatallah Hospital in Tehran (Iran),4 March and 20 May 2020.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    In STATA commands, “stand” specifies that the effects are expressed as standardized (or beta) coefficients that make comparisons easy by ignoring the independent variable’s scale of units, while “vce(oim)” is the default and specifies how the standard errors are calculated.
    STATA
    suggested: (Stata, RRID:SCR_012763)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: All patients underwent measure of creatinine, blood urea nitrogen, white blood cells, lymphocytes, neutrophils, hemoglobin, and platelet the day of hospital admission and on day 3, day 6, and last day of hospitalization; whereas levels of c-reactive protein (CRP), lactate dehydrogenase, creatine phosphokinase, erythrocyte sedimentation rate, alanine aminotransferase and aspartate transaminase were assessed only the first and last day of hospital stay. By contrast, ferritin, d-dimers, serum il-6 level, SOFA score and APACHE II score were not available. The latter parameters, together with PiO2/FiO2, oxygen saturation, respiratory rate, lymphocyte count, neutrophil–lymphocyte ratio, CRP and lactate dehydrogenase, have critical cutoffs for decision making onto whether initiating TPE in COVID-19 patients according to a group of physicians from different parts of the world with extensive expertise in clinical apheresis and critical care [20]. Therefore, the diagnosis of CRS could be uncertain. However, the lack of data cannot be a major limitation because, on one hand, assessing all parameters may not be necessary to start, stop or refrain from TPE and single or multiple combinations of these parameters can be used to assess eligibility for TPE and subsequent responses [20]; and, on the other hand, all 73 patients were affected by severe COVID-19 pneumonia with evidence of hypoxemia (respiratory rate > 30/minute or partial pressure of oxygen on arterial blood gas less...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.04.19.21255657v3 on medRxiv
  4. Version published to 10.1101/2021.04.19.21255657v1 on medRxiv
  5. Version published to 10.1101/2021.04.19.21255657v2 on medRxiv