COVID-19: more than a cytokine storm

 

COVID-19: more than a cytokine storm

 

by Giovanni Riva, Vincenzo Nasillo, Enrico Tagliafico, Tommaso Trenti, Patrizia Comoli and Mario Luppi 

 

Critical Care volume 24, Article number: 549 (2020)

 

In these first months of coronavirus disease-19 (COVID-19) pandemic, a mainstream pathogenetic hypothesis, likely stemming from early clinico-therapeutic observations, has been suggesting that severe COVID-19 may represent a sort of hyperimmune disorder, akin, in particular, to secondary hemophagocytic lymphohistiocytosis (sHLH) and macrophage activation syndrome (MAS) [1,2,3]. In this view, COVID-19-associated cytokine storm, with elevated plasma levels of IL-6, IL-1, and TNF-α, as well as ferritin and other inflammatory biomarkers, has been considered as a typical sign of sHLH/MAS, but the other “key feature” of COVID-19—the progressive lymphopenia with T cell exhaustion [4,5,6]—has largely been neglected. Of note, both CD4+ and CD8+ T lymphocytes were found to be remarkably decreased in severe cases (median 177.5 and 89.0 × 106/L, respectively), when compared to moderate ones (median 381.5 and 254.0 × 106/L, respectively), thus suggesting T cell lymphopenia may constitute a potential prognostic marker to be included in the monitoring of COVID-19 patients [4]. Frequencies of IFN-γ-producing CD4+ T cells (i.e., cytotoxic Th1 subset) tended to be lower in severe than in moderate illness (median 14.1% versus 22.8%, respectively), possibly indicating a progressive skew of the Th1/Th2 balance toward a tolerogenic response [4]. In addition, the percentages of both memory Th cells and regulatory T cells were found to decrease in severe cases [5].