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The spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to respiratory failure and death of patients [1]. Severely affected patients may develop a cytokine storm-like clinical syndrome with multi-organ failure and a mortality rate of up to 90% [2]. Recently, it has been suggested that plasma exchange (PE) may positively influence this unfavorable course [3].
Here we report on five COVID-19 patients with a median age of 67 years who were admitted to the medical intensive care unit of Heidelberg University Hospital due to respiratory failure. Patients who had received at least one PE until May 15, 2020, were considered for analysis with clinical follow-up until June 15, 2020. Prophylactic antibiotic (piperacillin/tazobactam), antimycotic (caspofungin), and antiviral/immunomodulatory therapy (hydroxychloroquine or maraviroc) was initiated in all patients upon admission according to center practice. Additional treatments that were administered in some distance to PE are given in Table 1. During the course of the disease, patients developed vasopressor-dependent circulatory shock and/or persistent refractory fever (> 40.5 °C) together with increased interleukin 6 levels compatible with the cytokine storm-like clinical syndrome. In addition, all patients had multi-organ failure with acute respiratory distress syndrome (ARDS, 4 severe, 1 moderate) and acute kidney injury of at least KDIGO stage 2. A single PE with a median of 3.39 L of fresh frozen plasma was initiated in all patients followed by one additional treatment in patients 1, 3, and 5. During the PE, striking reduction of inflammatory markers C-reactive protein (− 47%, P = 0.0078) and interleukin 6 (− 74%, P = 0.0078), as well as significant reduction of ferritin (− 49%, P = 0.0078), LDH (− 41%, P = 0.0078), and D-dimer (− 47%, P = 0.016) were observed (Fig. 1a–e). Due to circulatory shock, four patients received vasopressor treatment at the start of the PE that could be substantially reduced during treatment (− 71%, P = 0.031, Fig. 1h). Biochemical and clinical improvement continued over the following days together with an increase in the oxygenation index in 4 out of 5 patients (Fig. 1i). These improvements were achieved with only 1 to 2 PE, which might be a possible indication of a direct pathophysiological influence of PE on the COVID-19-associated cytokine storm-like clinical syndrome. Three of the 5 most critically ill patients are alive, while a 71-year-old male and a 76-year-old female patient died after the therapy was limited due to persistent severe ARDS.
Table 1
Patient characteristics and treatment
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Age (years)
53
71
62
76
67
Sex
Male
Male
Male
Female
Female
Comorbidities
No
CAD, s/p CABG, schizophrenia, depression
Atrial fibrillation, hypertension
Diabetes, hypertension, s/p stroke
Diabetes, hypertension, CKD stage V*, obesity stage II
Antibiotic therapy during the course of the disease
Extubated and spontaneous breathing, discharged from hospital
Died
Extubated and spontaneous breathing, discharged from hospital
Died
Extubated and spontaneous breathing, discharged from hospital
*Not yet on dialysis, #representing center practice for critically ill COVID-19 patients at the time of treatment
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It has been suggested that a cytokine storm-like clinical syndrome may be responsible for a significant proportion of COVID-19-associated patient deaths [4]. PE improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes. Further studies to test whether (repeated) PE can alter the course of critically ill COVID-19 patients are clearly indicated.
Acknowledgements
Not applicable.
Ethics approval and consent to participate
Biochemical and clinical parameters were collected under the ethics vote S148/2020 of the Ethics Committee of Heidelberg University, and informed consent was retrieved from legal representatives of the patients.
Consent for publication
Informed consent was retrieved from legal representatives of the patients.
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Competing interests
The authors declare that they have no competing interests.
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