Amelioration of COVID‐19‐related cytokine storm syndrome: parallels to chimeric antigen receptor‐T cell cytokine release syndrome

Abstract

Coronavirus disease‐2019 (COVID‐19) severity appears to parallel the host immune response, with a subset of patients developing COVID‐19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID‐19,(2–5) and interleukin (IL)‐6 appears to play a central role in COVID‐19 related CSS.(6–8) Based on the success of IL‐6 receptor blockade for chimeric antigen receptor T‐cell therapy associated cytokine release syndrome (CAR T‐cell CRS), similar strategies using tocilizumab are being investigated in COVID‐19.

The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19

“…Although the host immune response to SARS-CoV-2 infection appears to be related to COVID-19 severity, 11 , 14 - 21 we did not demonstrate group differences in serum inflammatory cytokines within our subcohort. Biologically, this may reflect a lack of blood group effect, because the juncture at which blood group and disease severity intersect is putatively at the level of cell entry.…”

“…Our specific aims were to determine whether ABO blood group is associated with clinical indicators of COVID-19 severity (eg, mechanical ventilation, ventilator-free days, CRRT, length of intensive care unit [ICU] stay, and mortality) and to determine whether ABO blood group is associated with differences in serum biomarkers of organ dysfunction. Further, given the role of the host immune response as a potential determinant of COVID-19 severity, 11 , 14 - 21 we aimed to assess whether ABO blood type is related to the levels of serum inflammatory cytokines. We hypothesized that (1) that there would be a greater proportion of critically ill COVID-19 patients with blood group A or AB requiring mechanical ventilation and/or CRRT than those with blood group O or B, (2) clinical laboratory indices of multiorgan dysfunction would be elevated in patients with blood group A or AB compared with group O or B, and (3) serum inflammatory cytokines would be higher in critically ill COVID-19 patients with blood group A or AB compared with group O or B.…”

Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome

“…In the early days of COVID-19 in our own center, when IL-6 was being measured for research purposes rather than clinical care, we used the following criteria for COVID-CSS: 1) COVID-19 pneumonia requiring mechanical ventilation; 2) fever (maximum temperature > 38°C); 3) CRP > 100 mg/L; and 4) peak serum ferritin > 1000 μg/L. [13] Patients meeting these criteria had markedly elevated research serum IL-6 levels, median 91 pg/mL, interquartile range (IQR) 54-696 pg/mL (n=15). However, IL-6 does not always correspond to CRP (which is produced by hepatocytes in response to IL-6) or ferritin (which is a marker of macrophage activity).…”

A digital protein microarray for COVID-19 cytokine storm monitoring

“…5D). 22,35 Among patients who did not receive tocilizumab, we observed a large degree of variability in IL-6 levels, with a quarter of subjects having IL-6 <15 pg mL −1 , the median value of 106 pg m −1 , and the CV of 114%. Variability of TNF-α (CV 164%) and IL-1β (CV 193%) was driven by a small number of subjects with elevated levels.…”