Therapeutic plasma exchange in life-threatening COVID-19 and associated cytokine release syndrome

Background Cytokine release syndrome (CRS) plays a pivotal role in the pathophysiology and progression of Coronavirus disease-2019 (COVID-19). Therapeutic plasma exchange (TPE) by removing the pathogenic cytokines is hypothesized to dampen CRS. Objective To evaluate the outcomes of the patients with COVID-19 having CRS being treated with TPE compared to controls on the standard of care. Methodology Retrospective propensity score-matched analysis in a single centre from 1st April to 31st July 2020. We retrospectively analyzed data of 280 hospitalized patients developing CRS initially. PSM was used to minimize bias from non-randomized treatment assignment. Using PSM 1:1, 90 patients were selected and assigned to 2 equal groups. Forced matching was done for disease severity, routine standard care and advanced supportive care. Many other Co-variates were matched. Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of viral clearance on Polymerase chain reaction testing. Results After PS-matching, the selected cohort had a median age of 60 years (range 32–73 in TPE, 37–75 in controls), p = 0.325 and all were males. Median symptoms duration was 7 days (range 3–22 days’ TPE and 3–20 days controls), p = 0.266. Disease severity in both groups was 6 (6.6%) moderate, 40 (44.4%) severe and 44 (49%) critical. Overall, 28-day survival was significantly superior in the TPE group (91.1%), 95% CI 78.33–97.76; as compared to PS-matched controls (61.5%), 95% CI 51.29–78.76 (log rank 0.002), p<0.001. Median duration of hospitalization was significantly reduced in the TPE treated group (10 days vs 15 days) (p< 0.01). CRS resolution time was also significantly reduced in the TPE group (6 days vs. 12 days) (p< 0.001). In 71 patients who underwent TPE, the mortality was 0 (n = 43) if TPE was done within the first 12 days of illness while it was 17.9% (deaths 5, n = 28 who received it after 12th day (p = 0.0045). Conclusion An earlier use of TPE was associated with improved overall survival, early CRS resolution and time to discharge compared to SOC for COVID-19 triggered CRS in this selected cohort of PS-matched male patients from one major hospital in Pakistan.

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Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy

Blood ◽

10.1182/blood.2019001463 ◽

2019 ◽

Vol 134 (24) ◽

pp. 2149-2158 ◽

Cited By ~ 42

Author(s):

Rebecca A. Gardner ◽

Francesco Ceppi ◽

Julie Rivers ◽

Colleen Annesley ◽

Corinne Summers ◽

...

Keyword(s):

T Cell ◽

Acute Lymphocytic Leukemia ◽

Negative Impact ◽

Lymphocytic Leukemia ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Car T Cell ◽

Car T ◽

Antileukemic Effect ◽

Life Threatening

Gardner et al report that early intervention with tocilizumab and steroids at the first signs of mild cytokine release syndrome (CRS) following CD19 chimeric antigen receptor (CAR) T-cell infusion for B-cell acute lymphocytic leukemia reduces the development of life-threatening severe CRS without having a negative impact on antileukemic effect.

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Therapeutic plasma exchange in adult critically ill patients with life-threatening SARS-CoV-2 disease: A pilot study

Journal of Critical Care ◽

10.1016/j.jcrc.2020.07.001 ◽

2020 ◽

Vol 60 ◽

pp. 328-333 ◽

Cited By ~ 7

Author(s):

Fahad Faqihi ◽

Abdulrahman Alharthy ◽

Mohammed Alodat ◽

Demetrios J. Kutsogiannis ◽

Peter G. Brindley ◽

...

Keyword(s):

Pilot Study ◽

Plasma Exchange ◽

Critically Ill ◽

Critically Ill Patients ◽

Therapeutic Plasma Exchange ◽

Life Threatening

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Life-threatening COVID-19 presenting as stroke with antiphospholipid antibodies and low ADAMTS-13 activity, and the role of therapeutic plasma exchange: A case series

SAGE Open Medical Case Reports ◽

10.1177/2050313x20964089 ◽

2020 ◽

Vol 8 ◽

pp. 2050313X2096408

Author(s):

Abdulrahman Alharthy ◽

Fahad Faqihi ◽

Abdullah Balhamar ◽

Ziad A Memish ◽

Dimitrios Karakitsos

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Plasma Exchange ◽

Plasma Volume ◽

Antiphospholipid Antibodies ◽

Rescue Therapy ◽

Antiviral Treatment ◽

Case Series ◽

Therapeutic Plasma Exchange ◽

Life Threatening

We present a case series of three patients with COVID-19 who were admitted to our intensive care unit due to acute respiratory distress syndrome, brain infarction, pulmonary embolism, and antiphospholipid antibodies. We applied therapeutic plasma exchange on all cases. On intensive care unit admission, all patients had low (<10) Glasgow Coma Scale, and central nervous imaging showed multiple brain infarctions. COVID-19 was confirmed by reverse transcriptase polymerase chain reaction assays. Patients underwent rescue therapeutic plasma exchange using the Spectra OptiaTM Apheresis System (Terumo BCT Inc., USA), which operates with acid-citrate dextrose anticoagulant as per Kidney Disease Improving Global Outcomes 2019 guidelines. A dose of 1.5 plasma volume was used for the first dose and then 1 plasma volume daily for a total of five doses. Plasma was replaced with Octaplas LG® (Octapharma AG, USA), which is an artificial fresh frozen plasma product that has undergone viral inactivation by prion reduction technology. We administered ARDS-net/prone positioning ventilation, empiric antiviral treatment, therapeutic anticoagulation, and intensive care unit supportive care. Laboratory tests showed lymphocytopenia; elevated levels of D-dimer, fibrinogen, total bilirubin, C-reactive protein, lactate dehydrogenase, and ferritin; as well as low levels of ADAMTS-13 activity and antibody. Serology tests depicted positive IgM and IgG antiphospholipid antibodies (anti-cardiolipin and anti-β2-glycoprotein I antibodies). No side effects of therapeutic plasma exchange were recorded. After the completion of therapeutic plasma exchange, patients improved clinically and gradually recovered neurologically (after 27–32 days). To conclude, in life-threatening COVID-19, especially when immune dysregulation features such as antiphospholipid antibodies exist, therapeutic plasma exchange could be an effective rescue therapy.

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Current concepts in the diagnosis and management of cytokine release syndrome

Blood ◽

10.1182/blood-2014-05-552729 ◽

2014 ◽

Vol 124 (2) ◽

pp. 188-195 ◽

Cited By ~ 957

Author(s):

Daniel W. Lee ◽

Rebecca Gardner ◽

David L. Porter ◽

Chrystal U. Louis ◽

Nabil Ahmed ◽

...

Keyword(s):

Treatment Algorithm ◽

Interferon Γ ◽

Therapeutic Benefit ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Cell Therapies ◽

Patients At Risk ◽

Life Threatening ◽

Circulating Levels ◽

Important Cytokine

Abstract As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly important. Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome. However, because early and aggressive immunosuppression could limit the efficacy of the immunotherapy, current approaches seek to limit administration of immunosuppressive therapy to patients at risk for life-threatening consequences of the syndrome. This report presents a novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of CRS based on severity. The goal of our approach is to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of CRS.

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Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis

Cell Death and Differentiation ◽

10.1038/s41418-021-00866-0 ◽

2021 ◽

Cited By ~ 1

Author(s):

Chiara Musiu ◽

Simone Caligola ◽

Alessandra Fiore ◽

Alessia Lamolinara ◽

Cristina Frusteri ◽

...

Keyword(s):

Inflammatory Responses ◽

Myeloid Cells ◽

Constitutive Expression ◽

Multiple Organ ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Pathogen Invasion ◽

Organ Failures ◽

Inflammatory State ◽

Life Threatening

AbstractInflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state.

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Critical Care COVID-19 Patient with a Picture of Thrombotic Thrombocytopenic Purpura

European Journal of Case Reports in Internal Medicine ◽

10.12890/2020_002143 ◽

2020 ◽

Author(s):

Rehab AL-Ansari ◽

Mohanad Bakkar ◽

Leena Abdalla ◽

Khaled Sewify

Keyword(s):

Mechanical Ventilation ◽

Critical Care ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Kidney Injury ◽

Therapeutic Plasma Exchange ◽

Thrombocytopenic Purpura ◽

Threatening Condition ◽

Life Threatening

Background: Thrombotic thrombocytopenic purpura (TTP) is an uncommon haematological disease which can occur at any age and may present with COVID-19. This case describes a COVID-19 complication associated with a presentation resembling TTP. Case description: A 51-year-old man who had received a kidney transplant and was on immunosuppressant medication, was admitted to a critical care unit with severe COVID-19 pneumonia/acute respiratory distress syndrome (ARDS) which required intubation, mechanical ventilation and inotropic support. The course was complicated by the classic pentad of thrombocytopenia, intravascular haemolysis, acute kidney injury, neurological symptoms and fever, which prompted the diagnosis of probable TTP. After five sessions of therapeutic plasma exchange, the patient’s general status improved, he was weaned off mechanical ventilation and his renal panel and haemolytic markers normalized. Conclusion: TTP is a life-threatening condition which requires urgent management with therapeutic plasma exchange. This case highlights some possible complications of COVID-19 generally and in immunocompromised patients specifically. The potential role of plasma exchange in COVID-19 patients without a positive diagnosis of TTP (the so-called ‘TTP resembling presentation’) is an area of further research.

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