In its most simple terms, sepsis is life threatening infection. Its pathophysiology is quite complex and not entirely understood, but results of targeted therapeutics have been largely disappointing. TPE offers a promising, less-targeted therapy, and a single prospective clinical trial demonstrated a trend toward improved survival with adjunct TPE [7]. Others have reported similar favorable outcomes including improved survival and decreased need for vasopressor support [8]. Prior to COVID, our group considered TPE on a case to case basis for patients meeting ASFA criteria of sepsis with multiple organ failure, and retrospectively observed a favorable clinical response [9]. Given the shared pathophysiology, we postulated that TPE may play a role in certain cases of severe COVID-19 infection and began to utilize TPE on a case to case basis in March 2020 with some success [10].

Our patient is unique in that she manifested two separate shock states, both due to SARS-CoV-2 infection. Many of the earliest reports in COVID-19 describe cardiac involvement, presenting in various ways, although the pathophysiology is not entirely understood and is likely multifactorial. Notably, autopsy reports have not definitively confirmed myocarditis and most available data suggests that the acute myocardial depression is due to the profound inflammatory response [11]. Outside COVID, stress-induced cardiomyopathy has been shown to be the direct result of high levels of epinephrine on ventricular myocardium [12]. While several cases of self-resolving Takotsubo in the setting of COVID-19 have been reported, Faqihi reported a case of reverse Takotsubo cardiomyopathy in fulminant COVID-19 with cytokine storm that resolved following TPE [13]. Our patient’s initial instability was due to refractory cardiogenic shock despite mechanical circulatory support (MCS), inotropic/vasopressor support, and CRRT. Her exam and PAC values demonstrated ongoing cardiogenic shock while laboratory values were consistent with hyperinflammation and coagulopathy consistent with cytokine storm. Extrapolating from the data above, we felt that she might benefit from TPE. Indeed, her hemodynamics quickly improved, inflammatory biomarkers decreased, and cardiac function returned to normal following TPE (Table 1). After her initial improvement, she again worsened with development of sepsis and multiple organ dysfunction. Again, her illness appeared to be driven by cytokine storm and after an additional round of TPE she improved clinically. While many laboratory values are missing/incomplete, the available biomarker response suggests abatement of the cytokine storm with TPE on both occasions (Table 2). These trends - both clinical and laboratory – add to the existing data associating cytokine storm with severe illness, and a potential role for TPE.

Despite the temporal relationship to TPE, it is impossible to know whether our patient would have improved without TPE. Furthermore, the sepsis that subsequently developed after the initial TPE may have been result of the net response to TPE originally. Some clinicians have expressed concern about the possible net negative immunologic effects of TPE [14], and certainly this cannot be refuted or proven in our case. While safety of TPE in sepsis has been reported, the net effect of treatment should be investigated in a prospective manner to standardize monitoring and safety. Additionally, clinical features and/or laboratory values that suggest cytokine storm are highly variable. Threshold abnormalities for certain markers have been associated with poor outcomes [15], but the clinical impact of various treatments including TPE is uncertain. It is also unclear whether decreases in these values signifies clinical improvement and “successful” use of said treatments.

A case report in real time islimited and should not be used to change clinical practice but these results should be noted. As SARS-CoV-2 continues to mutate, critical illness is certain to some degree. Targeted therapies are likely to evolve and change with time, but TPE may continue to offer a temporizing intervention that may prevent host-mediated damage in response to infection. While the significance of the biomarker trend is uncertain, the favorable hemodynamic response has been demonstrated rather consistently and may be particularly useful in the case of catecholamine induced stress cardiomyopathy. Our case offers an exciting anecdotal outcome while generating hypotheses for further clinical research.