Characterisation of the pro-inflammatory cytokine signature in severe COVID-19

Abstract

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19.

Higher levels of IL-1ra, IL-6, IL-8, MCP-1, MIP-3α, MIP-3β, and fractalkine are associated with 90-day mortality in 132 non-immunomodulated hospitalized patients with COVID-19

“…Some cytokines, such as TNF-α and IL-10, have been associated with COVID-19 severity and mortality in other studies [ 16 , 37 , 38 ], but was not found to be significantly different between survivors and non-survivors after Bonferroni correction in our study. Infliximab, a TNF-α inhibitor, was shown to lower 28-day mortality in a selected group of patients with COVID-19, suggesting a role of TNF-α in the pathogenesis of more severe COVID-19 [ 39 ].…”

Neurological Complications of COVID-19 Vaccination: A Case Report of Generalized Convulsive Status Epilepticus

“…First hypothesis is that the virus or vaccine may trigger an autoimmune response that targets the brain, leading to inflammation and neuronal injury [13]. COVID-19 infection and vaccination-associated GCSE have showed the elevated levels of pro-inflammatory cytokines in their cerebrospinal fluid [14]. Second hypothesis is that the virus or vaccine may induce an allergic reaction that results in cerebral edema and seizures [15].…”

Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?

“…In 118 hospitalized COVID-19 patients (78% considered severe), 0.11 pg./mL median IL-1β was measured in plasma. In 44 healthy controls 0.10 pg./mL was observed with no difference in levels determined between COVID-19 patients and controls ( Hawerkamp et al, 2023 ). Serum IL-1β was measured in 46 COVID-19 patients in intensive care (median 0.35 pg./mL), in 30 COVID-19 patients not in intensive care (median 0.32 pg./mL), and in 24 healthy volunteers (median IL-1β 0.11 pg./mL).…”

“…This imprecision, combined with the advent of multiplex assay platforms that can simultaneously measure up to 100 molecules in blood ( Kupcova Skalnikova et al, 2020 ) has resulted in conflicting reports enumerating molecules relevant for linking sepsis to inflammation. A sampling of COVID-19 reports list blood levels for 20 ( Hawerkamp et al, 2023 ), 27 ( Huang et al, 2020 ), 35 ( Mudd et al, 2020 ), 48 ( Tjan et al, 2021 ), or 53 ( Herr et al, 2021 ) molecules. These quantifications include molecules thought to be pro-inflammatory like IL-1 and TNF, anti-inflammatory cytokines such as IL-6 and IL-10, interferons, chemokines, soluble cell receptors, complement components, ferritin, tumor markers, the acute-phase protein CRP, procalcitonin, and chitinase 3-like 1 (YKL-40).…”