Cytokine Profiles Before and After Immune Modulation in Hospitalized Patients with COVID-19

Abstract

We describe the cytokine profiles of a large cohort of hospitalized patients with moderate to critical COVID-19, focusing on IL-6, sIL2R, and IL-10 levels before and after receiving immune modulating therapies, namely, tocilizumab and glucocorticoids. We also discuss the possible roles of sIL2R and IL-10 as markers of ongoing immune dysregulation after IL-6 inhibition. We performed a retrospective chart review of adult patients admitted to a tertiary care center with moderate to critical SARS-CoV-2 infection. Disease severity was based on maximum oxygen requirement during hospital stay to maintain SpO2 > 93% (moderate, 0-3 L NC; severe, 4-6 L NC or non-rebreather; critical, HFNC, NIPPV, or MV). All patients were treated using the institution's treatment algorithm, which included consideration of tocilizumab for severe and critical disease. The most common cytokine elevations among all patients included IL-6, sIL2R, IFN-γ, and IL-10; patients who received tocilizumab had higher incidence of IL-6 and sIL2R elevations. Pre-tocilizumab IL-6 levels increased with disease severity (p = .0151). Both IL-6 and sIL2R levels significantly increased after administration of tocilizumab in all severity groups; IL-10 levels decreased in severe (p = .0203), but not moderate or critical, patients after they received tocilizumab. Cluster analysis revealed association between higher admission IL-6, sIL2R, and CRP levels and disease severity. Mean IL-6, sIL2R, and D-dimer were associated with mortality, and tocilizumab-treated patients with elevated IL-6, IL-10, and D-dimer were more likely to also receive glucocorticoids. Accessible clinical cytokine panels may be useful for monitoring response to treatment in COVID-19. The increase in sIL2R post-tocilizumab, despite administration of glucocorticoids, may indicate the need for combination therapy in order to modulate more than one hyperinflammatory pathway in COVID-19. We also discuss the role of cytokines as potential biomarkers for use of adjunct glucocorticoid therapy.Keywords COVID-19 . SARS-CoV-2 . cytokine release syndrome . interleukin-2 receptor (soluble) . interleukin-10 . tocilizumab . glucocorticoids . cytokine profile . cytokine panel

Severe COVID-19 infection is associated with aberrant cytokine production by infected lung epithelial cells rather than by systemic immune dysfunction

“…By day 10 post-symptom onset, 44 of 45 evaluable patients had detectable anti-Spike and anti-RBD total Ig (Figure 1b). IgG titers to Spike and RBD persisted through the acute phase of infection (day [10][11][12][13][14][15][16][17][18][19], recovery (day , and into late recovery (day 60 -120), whereas IgM titers started to decline in the recovery phase, as expected (Figure 1c). There was a corresponding increase in the frequency of antibody-producing plasmablasts, class switched IgD neg B cells, and T follicular helper cells (Tfh) by day 9 (Fig 1d).…”

Encephalopathy and Cytotoxic Lesion of the Corpus Callosum Associated with Cytokine Storm in COVID-19: A Case Report

“…in our patient have provided evidence of cytokine storming and T-cell activation in the pathogenesis of COVID-19 related encephalopathy and CLOCCs. Indeed, several studies have shown a positive association of IL-6 and sIL2R levels with the disease severity, at least in adult patients with COVID-19 [14,15]. Notably, our patient recovered well following the immunomodulatory therapy, not requiring cytokine antagonists such as Tocilizumab.…”

Tocilizumab-Induced Unexpected Increase of Several Inflammatory Cytokines in Critically Ill COVID-19 Patients: The Anti-Inflammatory Side of IL-6

“…Although the mechanisms leading to inflammation in COVID-19 are still poorly understood, immunomodulatory agents have rapidly been proposed and included into various clinical trials, most of them focused on IL-1b, -6, -8, and TNF-a (6,9,14). Azmy et al suggested that TCZ was unable to calm the inflammatory storm focusing on increased IL-10 and IL-2 receptor levels in patients receiving TCZ (2). However, the profile of a large panel of cytokines immediately after TCZ administration is yet unknown.…”