The scenario that Cunningham et al. [1] describe relates more to loss of function in the immune system or what is termed “perforinopathies”. In Fig. 3A of our article [3] we included the monogenic perforinopathies where there may be complete absence of perforin pathway machinery and where failure to clear virus leads to T-cell expansion that drives macrophage activation in what is termed primary HLH. Cunningham et al. [1] point out a scenario where high levels of IL-6 is associated with diminished T-cell perforin expression in experimental settings. Therefore, it is suggested that anti-IL6R blockade may help augment cytotoxicity of CD8+ T-cells and NK-cells consequent to IL-6 reduction. However, in other experimental studies IL-6 deficiency was associated with the different scenario of impaired viral clearance [5]. Given that the COVID-19 infection disables early type 1 interferon expression [6] then inhibition of the “second wave” of cytokines including IL-6 may be disadvantageous. As summarized in our article, it is conceivable that the pleiotrophic actions of IL-6 in the context of pleiotrophic viral interactions with the immune system may actually favour viral persistence in some models where IL-6 level elevation could be beneficial [7]. Registry data from over 16,000 tocilizumab treated rheumatoid arthritis cases showed an increased risk of bacterial infection but no evidence for an increased risk of viral infection in humans, suggesting that IL-6 reduction is not linked to the emergence of previously known common viral infections.