COVID-19-associated Cytokine Release Syndrome and Autologous Conditioned Serum: A Hypothesis

Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic causing death worldwide, particularly in individuals with comorbidities or in the elderly population. The increased pro-inflammatory cytokines in patients with severe COVID-19 can be considered macrophage activation syndrome or a cytokine storm. It has been reported that an autocrine loop of interleukin (IL) 1 beta (IL-1β) over-secretion leads to a cytokine storm of IL-6, IL-18, ferritin, interferon-gamma, etc. from macrophages. Several features of COVID-19, such as the cytokine profile including pro-inflammatory cytokine levels, subsets of immune cells, serological markers, and clinical symptoms resemble a cytokine storm commonly triggered by viral infections. Although the pathophysiology and management of severe COVID-19 remains uncertain, the use of an easily obtained autologous anti-inflammatory cocktail, termed autologous conditioned serum (ACS), can be hypothesized. ACS consists of a variety of anti-inflammatory cytokines, including mainly IL-1 receptor antagonist (IL-1Ra; as much as 140-fold greater than plasma), and several growth factors. Post-mortem findings of COVID-19 patients reveal that the main pathological events are localized to the alveoli. Therefore, administering ACS via the same pathway as the viral trigger may have a positive impact on treatment. ACS should be discussed for the management of COVID-19 to target and lessen the overactive immune response while still allowing time for the host immune system to clear the virus. To balance the cytokine storm, it could be suggested to administer ACS by the same pathway as the viral trigger, using a nebulizer to directly reach the most intensely affected location: the alveoli.