In a recent study posted to the Research Square* preprint server and under consideration at Scientific Reports, researchers evaluated the survival benefit conferred by plasma exchange therapy (PLEX) in patients with severe coronavirus disease 2019 (COVID-19) and cytokine-storm syndrome.
Background
Study: Therapeutic Plasma Exchange: Impact on Survival in Patients With Covid-19. Image Credit: creativeneko/Shutterstock
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
The adverse outcomes of COVID-19 include cytokine storm syndrome and acute respiratory distress syndrome (ARDS). These disorders develop as a result of increased levels of pro-inflammatory mediators that damage the pulmonary alveolar endothelium. Both these conditions lead to significant COVID-19-associated mortality.
PLEX therapy involves eliminating sizeable plasma volumes (PV) and replacing them with fluids such as albumin and fresh frozen plasma (FFP). This exchange removes the pro-inflammatory molecules effectively, thereby reducing COVID-19-associated hyper-inflammation. To this end, PLEX helps restore host immune responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections.
About the study
In the present study, the researchers assessed the efficacy of PLEX therapy in improving survival in critical COVID-19 and associated cytokine storm syndrome patients.
The study population comprised 16 to 65-year-old hospitalized COVID-19 patients diagnosed between April 2020 to August 2020 on the basis of computed tomography (CT) radiological features established by the Radiological Society of North America (RSNA) and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
The ARDS patients demonstrated elevated levels of C reactive protein (CRP) >60 mg/L, interleukin-6 (IL-6) >40 pg/mL, erythrocyte sedimentation rate (ESR) >40 m/s or ferritin >500 ng/mL. In these patients, the lymphocyte count was reduced (<1.0 x10/L). Individuals with IL-6 levels exceeding 40 pg/mL, lymphopenia, and elevation in several inflammatory markers were diagnosed with the cytokine-storm syndrome. Patients with active bleeding, hypofibrinogenemia <80 mg/dL, thrombocyte count <50,000 cells, and sequential organ failure assessment (SOFA) scores <11 points were excluded from this clinical trial.
A total of 20 patients received two sessions of PLEX therapy along with standard therapy, whereas 40 patients received only standard therapy. PLEX therapy involved replacing one-and-a-half times the circulating PV with 3% albumin and two FFP units that were transfused towards completion of each PLEX session. The second PLEX session was performed two days after the initial session. Standard therapy involved the use of azithromycin, chloroquine, supplementary oxygen, dexamethasone, intravenous immunoglobulin, or tocilizumab. The PLEX group participants received immunoglobulin and tocilizumab before plasmapheresis.
Blood was collected from the patients’ pre and post both PLEX sessions to estimate cytokine levels. Additionally, one day prior to the first PLEX session and ten days post-second PLEX session, the affected lung volumes were measured by CT pulmonary volume determination.
The primary outcome was mortality within 60 days of PLEX therapy, whereas the secondary outcomes were reduction in the pro-inflammatory biomarkers and hospital stay, changes in SOFA and national early warning (NEWs-2) scores, and mechanical ventilation requirements.
Results
PLEX group patients had an average age of 47 years. About 85% of the patients were men, with the most prevalent comorbidity being obesity (80%). These patients had increased IL-6 and ferritin with lower platelet counts compared to controls. The first PV exchange was performed within an average of five days. The average time from the first clinical symptom to PLEX was 12 days, and the average volume exchange in PLEX therapy was 4.46 liters.
PLEX therapy reduced 60-day mortality from 50% (standard therapy) to 20% irrespective of variability in patient demographics and drug regimens used. Additionally, PLEX therapy significantly decreased NEWs-2 and SOFA scores and serum levels of pro-inflammatory mediators. Moreover, PLEX therapy increased lymphocyte counts and decreased affected lung volumes.
However, it had no significant effect on the mechanical ventilation needs and the ratio of oxygen saturation to the fraction of inspired oxygen (SatO2/FiO2). Notably, PLEX therapy increased the hospital stay for severe COVID-19 patients. In the control group, the levels of pro-inflammatory molecules and pulmonary indicators worsened.
In five patients who received PLEX therapy, hypotension was observed and treated with noradrenaline infusions or/and fluid bolus. Additionally, four patients developed secondary gram-negative bacterial infections such as pneumonia and empyema a week after the last PLEX session. However, these adverse events were not significant.
Conclusion
The study findings showed that PLEX therapy improved survival in severe COVID-19 patients. Plasmapheresis decreased the 60-days mortality and efficiently cleared pro-inflammatory mediators without significant adverse events. Thus, PLEX therapy could be highly beneficial in severe COVID-19 patients.
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Article Revisions
- May 12 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
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