IL-10 and IL-12 (P70) Levels Predict the Risk of Covid-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Trial

Abstract

Background: Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients.Methods: The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome.Results: During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model.Conclusions: This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.

COVID‐19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances

“…The proinflammatory cytokines and chemokines, such as IL‐6, IL‐8, tumour necrosis factor (TNF), IL‐17, IL‐12, IL‐1, IP‐10, MCP‐1, and CCL5, were generally increased with higher BMI. 27 , 28 , 36 , 40 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 Furthermore, high levels of IL‐10, an anti‐inflammatory cytokine, appear to be a hallmark of hyperinflammation during severe SARS‐CoV‐2 infection, 57 , 58 and some studies included in this review observed that IL‐10 levels predict poor outcomes in COVID‐19 patients with obesity. 32 , 51 In an attempt to reduce the high COVID‐19 mortality rates due to a cytokine storm, intensive research is underway examining the use of anti‐inflammatory drugs.…”

NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial

“…Clinical comorbidities, particularly diabetes, hypertension, and obesity, have been associated with COVID-19 severity in several studies, as we discussed in a previous work [11]. A chest CT examination has also been proposed for the prediction of clinical outcomes of COVID-19 [23,24].…”

“…Cytokine levels of IL-6 and IL-10, which are markedly increased in patients with COVID-19, can elicit the upregulation of NKG2A expression, potentializing its inhibitory role [25]. We previously observed increased levels of these cytokines in hypertensive patients with COVID-19 progression to severe disease [11]. Cho et al showed that IL-6 and IL-10 enhanced CD94/NKG2A expression in naive CD8+ T cells [29], and different authors have demonstrated that higher levels of IL-10 are associated with increased NKG2A expression in viral infections [30][31][32].…”

“…A chest CT examination has also been proposed for the prediction of clinical outcomes of COVID-19 [23,24]. In our previous study, we demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19, and we proposed a biomarker-based approach to improve the prediction of this risk [11]. In this study, to improve the understanding of the associations of clinical variables and immune cell profiles with the risk of COVID-19 progression, we also used a forward stepwise predictive model, which combined immune cell subsets with clinical variables to predict the probability of progression to severe COVID-19.…”

“…Various subsets of immune cells such as B and T lymphocytes that are involved in innate and adaptive immune responses are implicated in vascular injury in hypertension [7]. Likewise, a dysregulated immune response has been described as a hallmark of severe COVID-19 and is associated with the progression to acute respiratory distress syndrome and death [8][9][10][11]. Thus, research groups have made significant efforts to determine the role of immune cells in COVID-19 [12][13][14].…”