key: cord-0779128-ynzye4em
authors: Zhang, Li; Zhai, Hui; Ma, Shasha; Chen, Jiasheng; Gao, Yu
title: Efficacy of therapeutic plasma exchange in severe COVID‐19 patients
date: 2020-05-26
journal: Br J Haematol
DOI: 10.1111/bjh.16890
sha: cb18ced7d191f0a445ee8c818d0ae721054dc8ca
doc_id: 779128
cord_uid: ynzye4em

Coronavirus disease 2019 (COVID‐19) could lead to a sharp increase in the levels of inflammatory cytokines. We report the efficacy of therapeutic plasma exchange in severe COVID‐19 patients with acute respiratory distress syndrome. The results suggested TPE could be used as a strategy to attenuate circulating cytokines and inflammatory mediators.

Abstract: Coronavirus disease 2019 (COVID-19) could lead to a sharp increase in the levels of inflammatory cytokines. We report the efficacy of therapeutic plasma exchange in severe patients with acute respiratory distress syndrome. The results suggested TPE could be used as a strategy to attenuate circulating cytokines and inflammatory mediators.

This article is protected by copyright. All rights reserved

At the end of December 2019, an outbreak of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan China. After that, it became an emergency disease nationally and internationally (Paules, et al 2020) . COVID-19 could damage the respiratory system of patients, inducing symptoms of fever, cough and shortness of breath (Huang, et al 2020) . To date, there is no specific antiviral therapeutic agent or vaccine recommended for COVID-19. Although most of the patients a had good prognosis after receiving antiviral, antibiotic, and oxygen therapy, some severe patients developed acute respiratory distress syndrome, among whom would die of multiple organ failure . The cause of deterioration, rapid aggravation, and even death might be related to cytokine storm (also called as inflammatory storm). There is no clear evidence that any specific treatment could be useful for cytokine storm for COVID-19 patients. Here, we reported the efficacy of therapeutic plasma exchange (TPE) in three severe COVID-19 patients with acute respiratory distress syndrome. The results suggested that TPE could be used as a strategy to attenuate circulating cytokines and other inflammatory mediators. This study was approved by the institutional ethics board of the first affiliated hospital of Bengbu Medical

Three patients (male, aged 44, 55, and 64 years), with acute respiratory distress syndrome related to COVID-19 confirmed by qRT-PCR and chest CT were all patients receiving therapeutic plasma exchange in the first affiliated hospital of Bengbu Medical College from January 22, 2020 to March 4, 2020. Timelines of symptom onset, qRT-PCR testing, severe complications, plasma exchange, and outcomes of the three severe patients were shown in the Figure. Three patients were admitted to the hospital with fever, dry cough, fatigue, dizziness, and nausea. All three patients had received various antiviral treatment, including arbidol (200 mg three times daily) and interferon alpha-2b (atomization inhalation, 5 million units twice daily). However, despite initial antiviral treatment and other therapeutic interventions, all three patients developed respiratory distress with respiratory frequency ≥ 30/min, pulse oximeter oxygen saturation ≤ 93% at rest, or oxygenation index (PaO 2 /FiO 2 ) ≤ 300 mmHg. The lymphocyte counts of the patients were lower than the normal range of adults. In

This article is protected by copyright. All rights reserved contrast the contents of C-reactive protein, neutrophil count, lactate dehydrogenase, and interleukin 6 (IL-6) were significantly higher than the normal reference ranges.

The three severe patients were transferred to the first affiliated hospital of Bengbu Medical College (a designated hospital for the treatment of severe cases of . According to the suggestion of "Diagnosis and treatment plan of novel coronavirus pneumonia (Trial version 6)" drawn up by the National Health Commission of the People's Republic of China, therapeutic plasma exchange was used as an emergency treatment for these three severe COVID-19 patients. TPE was performed with a plasma separator multi-filtration system, and about 3000 ml of normal fresh-frozen plasma was exchanged for one person. Each patient received one treatment of TPE between 1 and 3 days after transferred to the designated hospital.

The PaO 2 /FiO 2 (mmHg) ranged from 93 to 178 at the time of 2 hours before plasma exchange and increased (improved) for all three patients within 24 hours after TPE (ranged from 259 to 319). As shown in Table, the PaO 2 /FiO 2 was significantly improved from an average of 146 to 293 (P = 0.0103). One day after the treatment, the values of CRP decreased more than > 70%, and the levels of IL-6 were also declined to the normal reference range. After treatment, the values of the neutrophilto-lymphocyte ratio (NLR) were significantly decreased. Four or five days after treatment, the patients all changed to receive the low-flow oxygen from high-flow oxygen. After one day with lowflow oxygen, all patients could breathe ambient air with no requirement of oxygen supplementation. About ten days later after TPE, all three patients had met the discharged criteria, including nucleic acid tests negative twice separated by at least 1day, having a normal temperature more than 3 days, showing resolved respiratory symptoms, and improved acute exudative lesions on chest computed tomography images. The lengths of hospital stay were 14, 15, and 22 days, respectively. The time from symptom onset to recovery ranged from 18 to 25 days.

At present, the main reason for the severity and continuous progress of COVID-19 might be cytokine storm (Mehta, et al 2020) , which also might be a reason to induce the terminal stage of Ebola virus disease (EVD) (Younan, et al 2017) and severe acute respiratory syndrome (SARS) (Chien, et al 2006) . In the clinic, anti-infective drugs, corticosteroid, nutritional support, artificial ventilation, and other non-specific combined treatment measures are often used for cytokine storm. However, clinical

This article is protected by copyright. All rights reserved evidence did not support that COVID-19 could benefit from corticosteroid treatment (Russell, et al 2020) . Therapeutic plasma exchange is effective for cytokine storm and is widely used in the treatment of a variety of severe and critical patients, such as pneumonia and respiratory failure from H1N1 influenza A virus (Patel, et al 2011) . In this study, the results from three severe cases suggested that TPE had an immediate effect on the treatment of the cytokine storm, which was similar to the previous research results (Hadem, et al 2014) . NLR was considered as an inflammatory marker that could reflect systemic inflammatory response, and the NLR values were found to increase significantly in patients with COVID-19 with severe disease (Fu, et al 2020) . In a conclusion, as an efficient and rapid method to remove the abnormally elevated inflammatory factors, to supplement albumin, to improve coagulation function, and to correct immune disorder, therapeutic plasma exchange might be a rescue therapy in a severe COVID-19 patient with acute respiratory distress syndrome and cytokine storm.

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