Cytokine storm may play an important role in the pathophysiol. of COVID-19. IL-6 and TNF-a serum levels are associated with early death in community-acquired pneumonia patients. As part of explorative tests on patients participating in a clin. trial the authors measured baseline cytokine levels Millipore technol. to IL-6 amongst other cytokines on COVID-19 pos., hospitalized patients (n = 60). The authors report IL-6 that is mildly elevated, however, a small percentage of patients have very high levels of IL-6. Furthermore, excessive IL-6 plasma levels correlate with mortality. The authors explore the genetic landscape of IL-6 region in association to COVID-19 outcomes. The authors have conducted whole-genome sequencing on 60 participants. The authors explore the role of genetic regulatory variants affecting baseline IL-6 levels specifically in COVID-19 patients. The authors provide results of common known IL6 variant previously associated with pneumonia, rs1800795 as well as report novel variants detected in the authors' study patients. IL6-174 G/C (rs1800795) is a gene polymorphism in the promoter of the IL-6 gene. It has been previously reported in relation to serum IL6 in Egyptian children with community-acquired pneumonia. Interestingly in the authors' study the minor allele seems to correlate with mortality. It is a common variant with a global MAF of 0.68 (higher in males and large allelic differences between East Asian and European (0.55)). Looking at mortality 2 of the 3 people having the minor hom, died, as shown on Table 1. The minor allele for this variant would then be a risk locus significantly associated with higher mortality and perhaps a biomarker of need of earlier intervention. The authors have also inspected WGS samples from the authors' COVID-19 patients for the presence of LOF IL6 variants and the authors do not report any such variants in this study cohort. Furthermore, the authors conducted an anal. of modifiers of serum IL6 level on a set of Covid-19 pos. whole-genome sequencing samples. The authors have directly tested the association between variants in the IL6 and IL6R region and IL6 plasma levels. Linear regression corrected for PCs and covariates identified a strong significant signal within IL6R region, specifically rs7525477. The minor allele associated with higher IL6 levels is shown on Figure 1. Furthermore, the variant is a significant eQTL for expression of TDRD10 in the lung tissue, a gene associated previously associated with IL6R level. The authors believe that careful examination and interpretation of the IL-6 levels can help determine the patient population with the most robust clin. response to IL-6 inhibition.