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

Background and Objectives: Due to the poor prognosis and the very high mortality rate associated with severe SARS-CoV-2 infections, various regimens have been tried to stop the evolution of the inflammatory cascade, such as immunomodulatory therapy and plasma clearance of the acute phase reactants involved. Therefore, the objective of this review was to analyze the effects of using therapeutic plasma exchange (TPE), also known as plasmapheresis, on the inflammatory markers of critically ill COVID-19 patients admitted to the intensive care unit (ICU). Materials and Methods: A thorough scientific database search was performed, and it included a review of articles published on PubMed, Cochrane Database, Scopus, and Web of Science from the beginning of the COVID-19 pandemic in March 2020 until September 2022 that focused on the treatment of SARS-CoV-2 infections using plasma exchange for patients admitted to the ICU. The current study included original articles, reviews, editorials, and short or special communications regarding the topic of interest. Results: A total of 13 articles were selected after satisfying the inclusion criterion of three or more patients enrolled with clinically severe COVID-19 that were eligible for TPE. From the included articles, it was observed that TPE was used as a last-resort salvage therapy that can be regarded as an alternative treatment method when the standard management for these patients fails. TPE significantly decreased the inflammatory status as measured by Interleukin-6 (IL-6), C-reactive protein (CRP), lymphocyte count, and D-dimers, as well as improving the clinical status measured with PaO2/FiO2 and duration of hospitalization. The pooled mortality risk reduction after TPE was 20%. Conclusions: There are sufficient studies and evidence to show that TPE reduces inflammatory mediators and improves coagulation function and the clinical/paraclinical status. Nevertheless, although it was shown that TPE decreases the severe inflammatory status without significant complications, the improvement of survival rate remains unclear.

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

Aim: Therapeutic plasma exchange (TPE) is a frequently discussed treatment modality in severe coronavirus disease 2019 (COVID-19) patients. It requires an apheresis device and experienced personnel for the application. In this study, we aimed to reveal the characteristics and clinical outcomes of adult patients with COVID-19 who experienced TPE. Material(s) and Method(s): Adult patients who had undergone TPE in our apheresis unit were retrospectively analyzed and COVID-19-positive cases were included in the study. All the medical information about the cases was obtained from the electronic database and technical details of the procedures were gathered from apheresis unit records. Result(s): A total of 80 patients with a median age of 60 (19-85) years were included in the study. Severe pneumonia was present in 98.8% (n=79) of the cases. More than three-quarters of the patients had lymphopenia, critically elevated C-reactive protein (CRP), and D-dimer, and 41.0% (n=32) had high ferritin. The median length of stay in the intensive care unit was 26 (5-124) days. The mortality rate observed on the 14th and 28th days following the TPE procedure was 51.3% (n=41) and 75.0% (n=60), respectively. High ferritin level, multiple organ failure (MOF), and intubation were parameters found to be associated with mortality in the multivariate analysis. Conclusion(s): The mortality rate observed in patients with COVID-19 who underwent TPE in our study was similar to the cases in the literature without the procedure, while it has been shown that high ferritin levels, intubation, and the presence of MOF increase the risk of mortality.Copyright © 2023, Duzce University Medical School. All rights reserved.

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

Coronavirus disease (COVID)-19 is characterised in particular by vascular inflammation with platelet activation and endothelial dysfunction. During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. This procedure consists in replacing the inflammatory plasma by fresh frozen plasma from healthy donors and is often used to remove pathogenic molecules from plasma (autoantibodies, immune complexes, toxins, etc.). This study uses an in vitro model of platelet-endothelial cell interactions to assess changes in these interactions by plasma from COVID-19 patients and to determine the extent to which TPE reduces such changes. We noted that exposure of an endothelial monolayer to plasmas from COVID-19 patients post-TPE induced less endothelial permeability compared to COVID-19 control plasmas. Yet, when endothelial cells were co-cultured with healthy platelets and exposed to the plasma, the beneficial effect of TPE on endothelial permeability was somewhat reduced. This was linked to platelet and endothelial phenotypical activation but not with inflammatory molecule secretion. Our work shows that, in parallel to the beneficial removal of inflammatory factors from the circulation, TPE triggers cellular activation which may partly explain the reduction in efficacy in terms of endothelial dysfunction. These findings provide new insights for improving the efficacy of TPE using supporting treatments targeting platelet activation, for instance.

Renal Thrombotic Microangiopathy: A Review.

Thrombotic microangiopathy (TMA), a pathological lesion observed in a wide spectrum of diseases, is triggered by endothelial injury and/or dysfunction. Although TMA lesions are often accompanied by clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury, renal-limited forms of TMA are not infrequently encountered in clinical practice. The presence of renal-limited manifestations can be diagnostically challenging, often delaying the initiation of targeted therapy. Prompt investigation and empirical treatment of TMA is warranted to reduce associated morbidity and mortality. Major advances have been made with respect to the pathophysiology of primary TMA entities, with the subsequent development of novel diagnostic tools and lifesaving therapies for diseases like thrombotic thrombocytopenic purpura and complement-mediated TMA. This article will review the clinical presentation and pathologic hallmarks of TMA involving the kidney, and the disease-specific mechanisms that contribute to the endothelial injury that characterizes TMA lesions. Diagnostic approach and both empirical and disease-specific treatment strategies will be discussed, along with the potential role for emerging targeted disease-specific therapies.

Comparison of outcomes and costs of extracorporeal blood purification therapies in critically ill COVID-19 patients.

INTRODUCTION: Plasmapheresis and hemoperfusion are used against cytokine release syndrome in COVID-19. This study aims to compare their outcomes, costs, and side-effects. METHODS: Survival, costs and side-effects were compared in intensive care unit (ICU) patients receiving plasmapheresis (n = 49), hemoperfusion (n = 20), or none (n = 107), followed until death or discharge. RESULTS: Plasmapheresis survival time was higher than hemoperfusion or controls (HR = 0.764, p = 0.397 and HR = 0.483, p = 0.002, respectively), although the latter diminished after controlling for age and disease severity (p = 0.979). There was no significant difference in ICU costs for plasmapheresis and hemoperfusion (p = 0.738) while both costed more than controls (both p < 0.001). Hypocalcemia and thrombocytopenia incidence did not differ between two groups (p = 0.124 and p = 0.389, respectively) while being higher than controls in plasmapheresis (both p < 0.001) and hemoperfusion (p < 0.001 and p = 0.056, respectively). CONCLUSION: Plasmapheresis and hemoperfusion do not differ significantly in patient survival, ICU costs and side-effects with a higher incidence of hypocalcemia and thrombocytopenia compared witcontrols.

Effects of convalescent plasma infusion on the ADAMTS13-von Willebrand factor axis and endothelial integrity in patients with severe and critical COVID-19.

Background: Convalescent plasma infusion (CPI) was given to patients with COVID-19 during the early pandemic with mixed therapeutic efficacy. However, the impacts of CPI on the ADAMTS13-von Willebrand factor (VWF) axis and vascular endothelial functions are not known. Objectives: To determine the impacts of CPI on the ADAMTS13-VWF axis and vascular endothelial functions. Methods: Sixty hospitalized patients with COVID-19 were enrolled in the study; 46 received CPI and 14 received no CPI. Plasma ADAMTS13 activity, VWF antigen, endothelial syndecan-1, and soluble thrombomodulin (sTM) were assessed before and 24 hours after treatment. Results: Patients with severe and critical COVID-19 exhibited significantly lower plasma ADAMTS13 activity than the healthy controls. Conversely, these patients showed a significantly increased VWF antigen. This resulted in markedly reduced ratios of ADAMTS13 to VWF in these patients. The levels of plasma ADAMTS13 activity in each patient remained relatively constant throughout hospitalization. Twenty-four hours following CPI, plasma ADAMTS13 activity increased by ∼12% from the baseline in all patients and ∼21% in those who survived. In contrast, plasma levels of VWF antigen varied significantly over time. Patients who died exhibited a significant reduction of plasma VWF antigen from the baseline 24 hours following CPI, whereas those who survived did not. Furthermore, patients with severe and critical COVID-19 showed significantly elevated plasma levels of syndecan-1 and sTM, similar to those found in patients with immune thrombotic thrombocytopenic purpura. Both syndecan-1 and sTM levels were significantly reduced 24 hours following CPI. Conclusion: Our results demonstrate the relative deficiency of plasma ADAMTS13 activity and endothelial damage in patients with severe and critical COVID-19, which could be modestly improved following CPI therapy.

Assessing the Outcomes of Patients with Severe SARS-CoV-2 Infection after Therapeutic Plasma Exchange by Number of TPE Sessions.

The high mortality risk in severe SARS-CoV-2 infections is tightly correlated to the extreme elevation of inflammatory markers. This acute accumulation of inflammatory proteins can be cleared using plasma exchange (TPE), commonly known as plasmapheresis, although the available data on performing TPE in COVID-19 patients is limited regarding the optimal treatment protocol. The purpose for this study was to examine the efficacy and outcomes of TPE based on different treatment methods. A thorough database search was performed to identify patients from the Intensive Care Unit (ICU) of the Clinical Hospital of Infectious Diseases and Pneumology between March 2020 and March 2022 with severe COVID-19 that underwent at least one session of TPE. A total of 65 patients satisfied the inclusion criteria and were eligible for TPE as a last resort therapy. Of these, 41 patients received 1 TPE session, 13 received 2 TPE sessions, and the remaining 11 received more than 2 TPE sessions. It was observed that IL-6, CRP, and ESR decreased significantly after all sessions were performed in all three groups, with the highest decrease of IL-6 in those who received >2 TPE sessions (from 305.5 pg/mL to 156.0 pg/mL). Interestingly, there was a significant increase in leucocyte levels after TPE, but there was no significant difference in MAP changes, SOFA score, APACHE 2 score, or the PaO2/FiO2 ratio. The ROX index was significantly higher among the patients who underwent more than two TPE sessions, with an average of 11.4, compared to 6.5 in group 1 and 7.4 in group 2, which increased significantly after TPE. Nevertheless, the mortality rate was very high (72.3%), and the Kaplan-Meier analysis identified no significant difference in survival according to the number of TPE sessions. TPE can be used as last resort salvage therapy that can be regarded as an alternative treatment method when the standard management of these patients fails. It significantly decreases the inflammatory status measured via IL-6, CRP, and WBC, as well as demonstrating an improvement of the clinical status measured via PaO2/FiO2, and duration of hospitalization. However, the survival rate does not seem to change with the number of TPE sessions. Based on the survival analysis, one session of TPE as last resort treatment in patients with severe COVID-19 proved to have the same effect as repeated TPE sessions of 2 or more.

Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam.

BACKGROUND AND OBJECTIVES: Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS: We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS: Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS: Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.

Efficacy of therapeutic plasma exchange in patients with severe COVID-19: A systematic review and meta-analysis.

We conducted this systematic review and meta-analysis to evaluate the existing evidence and to quantitatively synthesise evidence on the impact of therapeutic plasma exchange (TPE) on severe COVID-19 patients. This systematic review and meta-analysis protocol was prospectively registered on PROSPERO (CRD42022316331). We systemically searched six electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, clinicaltrial.gov, and Cochrane Central Register of Controlled Trials) from inception until 1 June 2022. We included studies comparing patients who received TPE versus those who received the standard treatment. For risk of bias assessment, we used the Cochrane risk of bias assessment tool, the ROBINS1 tool, and the Newcastle Ottawa scale for RCTs, non-RCTs, and observational studies, respectively. Continuous data were pooled as standardized mean difference (SMD), and dichotomous data were pooled as risk ratio in the random effect model with the corresponding 95% confidence intervals (CI). Thirteen studies (one randomized controlled trials (RCT) and 12 non-RCTs) were included in the meta-analysis, with a total of 829 patients. There is a moderate-quality evidence from one RCT that TPE reduces the lactic dehydrogenase (LDH) levels (SMD -1.09, 95% CI [-1.59 to -0.60]), D-dimer (SMD -0.86, 95% CI [-1.34 to -0.37]), and ferritin (SMD -0.70, 95% CI [-1.18 to -0.23]), and increases the absolute lymphocyte count (SMD 0.54, 95% CI [0.07-1.01]), There is low-quality evidence from mixed-design studies that TPE was associated with lower mortality (relative risk 0.51, 95% CI [0.35-0.74]), lower IL-6 (SMD -0.91, 95% CI [-1.19 to -0.63]), and lower ferritin (SMD -0.51, 95% CI [-0.80 to -0.22]) compared to the standard control. Among severely affected COVID-19 patients, TPE might provide benefits such as decreasing the mortality rate, LDH, D-dimer, IL-6, and ferritin, in addition to increasing the higher absolute lymphocyte count. Further well-designed RCTs are needed.

Bradycardia unresponded to atropin testing was successfully treated with therapeutic plasma exchange in a patient with severe COVID-19 complicated by Guillain-Barré syndrome: A case report.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an alarming situation worldwide for the past 2 years. The symptoms of coronavirus disease 2019 (COVID-19) are not only confined to the respiratory system but also affect a multitude of organ systems. Bradycardia associated with Guillain-Barré syndrome (GBS) is a rare autonomic and peripheral neurological complication of COVID-19. In this case report, we present the case of a 26-year-old man diagnosed with bradycardia associated with GBS after contracting COVID-19. Initially, this patient had the classical symptoms of COVID-19 and was hospitalized in the intensive care unit (ICU) for acute respiratory distress syndrome (ARDS). Then, he developed weakness in the lower extremities, diminished tendon reflexes, a loss of sensation without sphincter muscle disorders, and bradycardia. His bradycardia did not respond to atropine. The patient was treated concurrently with a high-flow nasal cannula, systemic corticosteroids, anticoagulation, and therapeutic plasma exchange (TPE) for COVID-19-induced ARDS, bradycardia, and GBS. His ARDS and bradycardia improved after the first cycle of TPE and medical treatment. After three cycles of TPE, the patient progressively recovered his muscle strength in the lower limbs and regained peripheral sensation. He was discharged from the hospital in stable condition after 4 weeks of hospitalization and was followed up after 6 months for cardiorespiratory and neurological complications. This case report elucidates the potential difficulties and challenges that physicians may encounter in diagnosing and treating COVID-19-induced bradycardia and GBS during the pandemic outbreak. However, the patient outcomes with the treatment combining the conventional treatment with therapeutic plasma exchange seem to be optimistic.

Effects of therapeutic plasma exchange on a cohort of patients with severe coronavirus infection: real world evidence from Brazil.

Introduction: The therapeutic plasma exchange (TPE) controls the systemic cytokine level and might improve the immune response in patients with severe Coronavirus (COVID-19) infection. To date, in developing countries, no study has explored the effectiveness and risk factors in a population with severe COVID-19 exposed to the TPE. Method: We described the risk factors associated with survival rates higher than 28 days and length of stay (LOS) in the intensive care unit (ICU) shorter than 15 days. Severe COVID-19 cases treated with TPE were included, from August 2020 to June 2021. Survival analysis with Kaplan-Meier curves, log-rank tests and multivariate logistic regressions were conducted to assess patient-related factors that could predict a higher survival rate and the ICU LOS. Results: A total of 99 patients with severe COVID-19 who had received TPE were followed during their hospital stay and for 28 days after discharge. The sample was composed of men (63%) aged 56 ±â€¯16 years. The overall survival rate at 28 days was 80%. The ICU LOS (p = 0.0165) and mechanical ventilation (MV) (p = 0.00008) were considered factors that could increase the risk of death. Patient-related factors that influenced the 28-day mortality were the smoking status (OR = 5.8; 95%CI 1.5, 22) and history of oncologic or non-malignant hematologic diseases (OR = 5.9; 95%CI 1.2, 29). Conclusion: Patients with severe COVID-19 exposed to the TPE were associated with a 20% risk of death in a 28-day observation window, appearing to be lower than previous treatments. Active smoking, cancer and immunosuppressive conditions should be considered as relevant variables to be controlled in future trials on the TPE and COVID-19.

COVID-19-associated transverse myelitis treated by therapeutic plasma exchange: A case report.

BACKGROUND: Transverse myelitis (TM) is a very uncommon condition in children which can be associated with viral infections. Acute TM cases have been reported after Coronavirus disease 2019 (COVID-19) infection during the pandemic. CASE REPORT: We report a child with TM related to severe acute respiratory syndrome coronavirus 2, who was successfully treated with therapeutic plasma exchange (TPE). Inability to walk and urinary retention were the central nervous system symptom. Spinal magnetic resonance imaging revealed signal changes in the spinal cord. Her neurological symptoms worsened despite receiving IVIG and high-dose steroids for the first 3 d. We performed 10 TPE sessions with 5% albumin replacement and the neurological symptoms rapidly improved. CONCLUSION: We demonstrated that a child diagnosed with acute TM related to COVID-19 infection, was successfully treated with TPE.

Efficacy of Therapeutic Plasma Exchange in Severe Acute Respiratory Distress Syndrome in COVID-19 Patients from the Western Part of Romania.

Background and Objectives: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has surprised the medical world with its devastating effects such as severe acute respiratory distress syndrome (ARDS) and cytokine storm, but also with the scant therapeutic solutions which have proven to be effective against the disease. Therapeutic plasma exchange (TPE) has been proposed from the very beginning as a possible adjuvant treatment in severe cases. Our objective was to analyze the evolution of specific biological markers of the COVID-19 disease before and one day after a therapeutic plasma exchange session, how a change in these parameters influences the patient's respiratory status, as well as the impact of TPE on the survival rate. Materials and Methods: In this retrospective study, we include 65 patients with COVID-19 admitted to the intensive care unit department of our hospital between March 2020 and December 2021, and who received a total of 120 sessions of TPE. Results: TPE significantly reduced the following inflammation markers (p < 0.001): interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, ferritin, and erythrocyte sedimentation rate. This procedure significantly increased the number of lymphocytes and decreased D-dimers levels (p = 0.0024). TPE significantly improved the PaO2/FiO2 ratio (p < 0.001) in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 100). Survival was improved in intubated patients who received TPE. Conclusions: TPE involved the reduction in inflammatory markers in critical patients with COVID-19 disease and the improvement of the PaO2/FiO2 ratio in patients with severe ARDS and had a potential benefit on the survival of patients with extremely severe COVID-19 disease.

Immune-mediated thrombotic thrombocytopenic purpura in a Jehovah's Witness - Effectiveness of incorporating extracorporeal immunoadsorption to caplacizumab, steroids and rituximab.

We report the case of a Jehovah's Witness adolescent patient with immune-mediated thrombotic thrombocytopenic purpura after SARS-Cov2 infection successfully treated without therapeutic plasma exchange (TPE) using caplacizumab, corticosteroids, rituximab, and extracorporeal immunoadsorption (EIA). Further patients for whom TPE is not an option might benefit from this approach.

Efficacy of therapeutic plasma exchange and convalescent plasma therapy in moderate-to-severe COVID-19 patients

Background: Coronavirus disease 2019 (COVID-19) has emerged as a global health catastrophe since its first reported cases in late December 2019. Critically ill COVID-19 patients have been related to cytokine storms leading to acute respiratory distress syndrome and high mortality rates. Therapeutic plasma exchange (TPE) and convalescent plasma (CP) therapy improve clinically by removing inflammatory cytokines excess and using passive antibody-containing blood, respectively. This study aimed to evaluate TPE and CP treatment for moderate-to-severe COVID-19 infection.Method: The patients were randomly divided into TPE group (n = 10), CP group (n = 11), and control group (n = 10). This 1-week quasi-experimental study with a pretest-post-test control group design was conducted in the Intensive Care Unit (ICU) of Dr. Moewardi General Hospital and Universitas Sebelas Maret (UNS) Hospital. The study comparison between groups included blood gas analysis profile (pH, base excess, PaCO2, PaO2, hematocrit, HCO3, total CO2, SaO2), FiO2, P/F ratio, COVID-19 severity, and D-dimer. The paired t-test was used to analyze every group's pretest-post-test mean difference. One-way ANOVA was performed to analyze the mean difference across the three groups. SPSS version 22.0 for Windows was used to perform statistical analyses.Result: TPE and CP groups showed significant clinical-laboratory improvement than control (p > 0.05). Furthermore, high clinical-laboratory improvement tendency was observed in CP therapy than TPE.Conclusion: The use of TPE and CP in moderate-to-severe COVID-19 patients has been related to improving clinical -laboratory outcomes.

Analysis of first apheresis services in Ghana-Greater Accra Regional Hospital.

Background: At the combined American Society for Apheresis (ASFA) annual meeting and World Apheresis Association (WAA) Congress in 2014, it was observed that there were significant disparities with regard to the access of apheresis services within and across developing countries, with only few of such facilities available in Africa; notably South Africa and Nigeria. In 2019, Bone Marrow Transplantation (BMT) Unit-Ghana, acquired an apheresis machine. By the collaboration between BMT-Ghana, the Greater Accra Regional Hospital (GARH) and the Ministry of Health (Ghana), apheresis services is now available in Ghana. The aim of this paper is to present an analysis of apheresis services so far in Ghana. Method: A 12-month period from 2019 to 2021 was examined (less the period of the COVID-19 outbreak when the Unit was virtually at a standstill). The electronic database and hard copies of documented activities were analysed. Basic information on demographics and procedure types and counts was used. Results: The retrospective study encompassed data of 43 patients. Two (2) patients came from the West Africa sub-region (Nigeria and Cameroon) with the rest from 6 out of the 14 regions of Ghana (Greater Accra, Western, Central, Eastern, Ashanti, Volta). The essential nature of the apheresis services being the first in Ghana, brought patients as far as 315 km from the hinterlands to the Unit. Ages ranged from 2-52 years with a mean of 16.3 ± 15.3 years. Slightly more females (n = 23, 53%) received services than males (n = 20, 47%). Eighty-six percent (n = 37, 86%) of the patients were sickle cell patients referred to the Unit. Red Blood Cell exchange (RBCx) accounted for 87% (n = 40), of the 46 procedure counts followed by Continuous Mononuclear Cell Collection (CMNC) (n = 4, 9%) and lastly, Therapeutic Plasma Exchange (TPE) (n = 2, 4%). Conclusion: Ghana can now be counted among African countries offering apheresis services and the GARH is acknowledged as the only hospital in the country with this facility, thus improving patient care significantly.

Cardiovascular Outcomes in Children with Multisystem Inflammatory Syndrome Treated with Therapeutic Plasma Exchange.

BACKGROUND: Multisystem inflammatory syndrome in children is a new, rare, post-infectious complication of SARS-CoV-2 infection in children. The aim of this study was to display the role of therapeutic plasma exchange on cardiovascular outcomes in children with multisystem inflammatory syndrome. METHODS: This study included children who met the diagnostic criteria for multisystem inflammatory syndrome and who were admitted to the intensive care unit. This is a prospective single-center study conducted between August 2020 and September 2021. Subjects had cardiac involvement which was defined as elevated troponin I, abnormal electrocardiographic and echocardiographic findings. Patients were followed by a pediatric cardiologist throughout the intensive care unit stay and after discharge for 12 months. Patients were divided into two groups which received therapeutic plasma exchange and which did not. RESULTS: 38 children were included in this study. There were 16 patients in the no plasma exchange group and 22 patients in the plasma exchange group. The two groups were similar in age, sex, leucocyte, thrombocyte count, neutrophil percentage, hemoglobin, C-reactive protein, erythrocyte sedimentation rate, alanine aminotransferase, albumin, ferritin, fibrinogen, D-dimer, IL-6, troponin I, number of electrocardiographic abnormalities and patients with mitral valve regurgitation detected at admission (p > 0.05). There was no significant difference between the two groups in terms of duration of normalization of electrocardiographic abnormalities and disappearance of mitral valve regurgitation (p > 0.05). Duration of normalization of troponin I (2, IQR 1-4, versus 5, IQR 3-9 days; p = 0.044) and length of hospital stay (7, IQR 6-10, versus 13, 8-20 days; p = 0.001) was longer in the plasma exchange group. CONCLUSIONS: We did not observe any significant improvement in children having undergone plasma exchange as compared to children who did not. On the opposite, their length of hospital stay and time to troponin I normalisation were even longer. Some baseline differences in cardiac attainment severity may partly explain this finding.

Role of therapeutic plasma exchange in the management of COVID-19-induced cytokine storm syndrome.

The risk of mortality in patients with coronavirus disease 2019 (COVID-19) is largely related to an excessive immune response, resulting in a hyperinflammatory and hypercoagulable condition collectively referred to as cytokine storm syndrome (CSS). Management of critically ill patients with COVID-19 has included attempts to abate this process, prevent disease progression, and reduce mortality. In this context, therapeutic plasma exchange (TPE) offers an approach to eliminate inflammatory factors and cytokines, offset the pathologic coagulopathy, and reduce the CSS effects. The aim of this review is to analyze available data on the use of TPE for the treatment of CSS in patients with COVID-19. Systematic searches of PubMed, Scopus and COVID-19 Research were conducted to identify articles published between March 1, 2020 and May 26, 2021 reporting the use of TPE for the treatment of COVID-19-induced CSS. A total of 34 peer-reviewed articles (1 randomized controlled trial, 4 matched case-control series, 15 single-group case series, and 14 case reports), including 267 patients, were selected. Despite the low evidence level of the available data, TPE appeared to be a safe intervention for critically ill patients with COVID-19-induced CSS. Although inconsistencies exist between studies, they showed a general trend for decreased interleukin-6, C-reactive protein, ferritin, D-dimer, and fibrinogen levels and increased lymphocyte counts following TPE, supporting the immunomodulatory effect of this treatment. Moreover, TPE was associated with improvements in clinical outcomes in critically ill patients with COVID-19. While TPE may offer a valuable option to treat patients with COVID-19-induced CSS, high-quality randomized controlled clinical trials are needed to confirm its potential clinical benefits, feasibility, and safety. Moreover, clear criteria should be established to identify patients with CSS who might benefit from TPE.

Integrated therapeutic plasma exchange and traditional Chinese medicine treatment in a patient with severe COVID-19: A case report.

This report presents the case of a 59-year-old man with severe COVID-19 that gradually progressed to cytokine release syndrome and then acute respiratory distress syndrome; he was successfully treated via integration of therapeutic plasma exchange and traditional Chinese medicine. The patient initially presented with a sore throat, severe muscle aches, productive cough and fever. On the worsening of symptoms, remdesivir was administered. However, as the symptoms continued to worsen and a cytokine release syndrome was suspected, oxygen was provided through a high-flow nasal cannula (50 L/min) and therapeutic plasma exchange was performed to prevent worsening of the acute respiratory distress syndrome. On the same day, a course of traditional Chinese medicine was introduced in consultation with the infectious house staff. The patient's symptoms gradually improved; the levels of C-reactive protein and D-dimers reduced, and the patient was weaned to a simple oxygen mask and eventually to room air. This is the first reported case of the integration of these treatments. Together, they prevented the patient from requiring intubation, played a role in cytokine management, and also improved the clinical symptoms, including productive purulent sputum, cough, frequent stool passage and intermittent fever, with no adverse effects. As a result, the patient was discharged within two weeks of the integration of these treatments. Therefore, the integration of therapeutic plasma exchange and traditional Chinese medicine is an effective therapy for patients with severe COVID-19.

The Successful Recovery of a Critically Ill COVID-19 Patient, Following the Combination of Therapeutic Plasma Exchange and Convalescent Plasma Transfusion: A Case Report.

With an intricate symptom pattern involving a dysregulated host response to infection, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe inflammation and cytokine storms, acute respiratory distress syndrome, coagulopathy, multi-organ failure, and finally death. The uniqueness of this case report lies in the nature of the therapeutic intervention performed. While numerous studies are available on both the use of therapeutic plasma exchange in coronavirus disease 2019 (COVID-19) patients and convalescent plasma transfusion as separate treatment methods, there is very little information regarding the combination of these procedures. We present the case of a 52-year-old male, unvaccinated for COVID-19, who tested positive on reverse transcriptase polymerase chain reaction for SARS-CoV-2 for the first time and presented in the emergency room with fever, chills, severe cough, tachypnea, tachycardia, and dyspnea that started two days before presentation. Upon rapid assessment, the patient showed signs of acute respiratory failure, so it was decided to transfer the patient to the intensive care unit, COVID-19 ward, after preliminary radiological examination. For the next 24 days, the patient was stationed in the intensive care unit, where he was closely monitored and treated. Invasive mechanical ventilation was required following the initial worsening of his respiratory status. We performed therapeutic plasma exchange on the first day of his stay in the intensive care unit, and immediately after the procedure, the patient was transfused with 500 mL of convalescent plasma from healthy donors. The patient's condition improved over the next few days, which led to the cessation of mechanical ventilation and, after treating the superinfection, the patient was discharged home, making a full recovery. The early initiation of therapeutic plasma exchange followed by transfusion of convalescent plasma in severe and critical forms of COVID-19 may reduce the risk of the progression of the disease and ultimately reduce the risk of negative outcomes in a selected group of patients.