Elevated plasma IL-6 and CRP levels are associated with adverse clinical outcomes and death in critically ill SARS-CoV-2 patients: inflammatory response of SARS-CoV-2 patients

Abstract

Background SARS coronavirus 2 (SARS-CoV-2) is responsible for high morbidity and mortality worldwide, mostly due to the exacerbated inflammatory response observed in critically ill patients. However, little is known about the kinetics of the systemic immune response and its association with survival in SARS-CoV-2+ patients admitted in ICU. We aimed to compare the immuno-inflammatory features according to organ failure severity and in-ICU mortality. Methods Six-week multicentre study (N = 3) including SARS-CoV-2+ patients admitted in ICU. Analysis of plasma biomarkers at days 0 and 3–4 according to organ failure worsening (increase in SOFA score) and 60-day mortality. Results 101 patients were included. Patients had severe respiratory diseases with PaO2/FiO2 of 155 [111–251] mmHg), SAPS II of 37 [31–45] and SOFA score of 4 [3–7]. Eighty-three patients (83%) required endotracheal intubation/mechanical ventilation and among them, 64% were treated with prone position. IL-1β was barely detectable. Baseline IL-6 levels positively correlated with organ failure severity. Baseline IL-6 and CRP levels were significantly higher in patients in the worsening group than in the non-worsening group (278 [70–622] vs. 71 [29–153] pg/mL, P < 0.01; and 178 [100–295] vs. 100 [37–213] mg/L, P < 0.05, respectively). Baseline IL-6 and CRP levels were significantly higher in non-survivors compared to survivors but fibrinogen levels and lymphocyte counts were not different between groups. After adjustment on SOFA score and time from symptom onset to first dosage, IL-6 and CRP remained significantly associated with mortality. IL-6 changes between Day 0 and Day 3–4 were not different according to the outcome. A contrario, kinetics of CRP and lymphocyte count were different between survivors and non-survivors. Conclusions In SARS-CoV-2+ patients admitted in ICU, a systemic pro-inflammatory signature was associated with clinical worsening and 60-day mortality.

Lenzilumab Efficacy and Safety in Newly Hospitalized Covid-19 Subjects: Results From the Live-Air Phase 3 Randomized Double-Blind Placebo-Controlled Trial

“…In subjects with CRP<150 mg/L and < 85 years old, lenzilumab improved SWOV by nearly 3-fold and was accompanied by a 2.17-fold improvement in mortality as well as a 36% improvement in time to recovery. Given that CRP is a readily available, routinely measured biomarker of systemic inflammation, with prognostic value affirmed in this and other trials 11,12 , it can clearly be used to clinically identify a phenotype of COVID-19 disease that best responds to lenzilumab treatment.…”

“…CRP was analyzed as it is a marker of systemic inflammation, routinely used clinically and known to be proportionally elevated with the severity of COVID-19 disease. 11-13 In this trial, 77% of subjects with an evaluable CRP, had a baseline value <150 mg/L and 74% had a baseline CRP value <150 mg/L and age<85. The CRP analysis clearly demonstrated that CRP less than 150 mg/L was associated with best likelihood of achieving SWOV and clearly differentiated emerging hyperinflammation from full-blown CS.…”

“…CRP levels greater than 100 mg/L upon hospital admission are one of the strongest predictors of critical illness, even more so than age greater than 75 years or other comorbid conditions associated with COVID-19. 11,12 Subjects with CRP above 150 mg/L are defined as experiencing COVID-19-associated hyperinflammation (COV-HI) and are at risk of escalated respiratory support or death 13 . CRP is a readily available and cost-effective biomarker that can be used to delineate the state of COV-HI, help to identify subjects with emerging CS, and predict the need for early intervention to prevent or reduce progression to IMV and intensive care.…”

Potential SARS-CoV-2 Immune Correlates of Protection in Infection and Vaccine Immunization

“…The signature includes interleukin-10 and interleukin-6, which could anticipate subsequent clinical progression [63]. In severe COVID-19 patients, a systemic pro-inflammatory signature, including elevated plasma IL-6 and C-reactive protein (CRP) levels, was associated with clinical worsening and 2-month mortality [64].…”

Markers of immune activation and inflammation in individuals with post-acute sequelae of SARS-CoV-2 infection

“…Multidisciplinary efforts are underway to characterize the epidemiology, natural history, and biology of this condition [4,5], but there is limited biological information regarding its predictors and correlates. Inflammation during early infection has been associated with adverse outcomes, particularly in those who were hospitalized with COVID-19 [1,2,[6][7][8][9][10]. Emerging data suggest that inflammation related to acute SARS-CoV-2 infection can persist for weeks to months [11,12].…”