The paradoxical effect of IL-6 and implications for the use of Tocilizumab in Covid-19 patients

Abstract In the context of the current SARS-CoV-2 pandemic, patients affected by chronic obstructive pulmonary disease (COPD) should be more vulnerable to Covid-19, whereas they seem to be protected against severe Covid-19. That paradox has important practical implications for the use of the drug Tocilizumab in Covid-19. Interleukin-6 (IL-6) orchestrates the so-called cytokine storm leading to the Acute Respiratory Distress Syndrome (ARDS), the life-threatening condition that is responsible for Covid-19 deaths. However, IL-6 has a paradoxical effect in many viral infections. For pathogens such as HIV and Hepatitis B for example, mild elevations of IL-6 show a protective effect whereas high elevations show a toxic effect and are associated with higher mortality (e.g. they promote progression to AIDS in HIV patients). IL-6 can be therefore considered as being both a pro-inflammatory and an anti-inflammatory cytokine. Several studies have shown that severe COPD is associated with extremely-high levels of IL-6, whereas mild COPD is associated with mild elevations of IL-6. It is plausible that the chronic, mildly-elevated concentrations of IL-6 found in mild COPD patients is protective against the deterioration of Covid-19, as it is the case for other viral diseases. That may explain why COPD is surprisingly an uncommon comorbidity in Covid-19 intensive care units. This may have an important practical implication for the treatment of Covid-19 patients: our hypothesis is that Tocilizumab must be used exclusively in patients with an ongoing cytokine storm. Otherwise, an early use of Tocilizumab can be harmful, especially in patients affected by COPD or other conditions with mildly-elevated IL-6.