Background
COVID-19 patients can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation (IMV). Since interleukin-6 (IL-6) is a relevant cytokine in ARDS, the blockade of its receptor with Tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19.
Objective
To determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ.
Methods
Retrospective observational study performed in hospitalized patients diagnosed of COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with pre- and post-administration of TCZ. Multivariable logistic and linear regressions, and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio (PaO
2
/FiO
2
) or mortality.
Results
One hundred and forty-six patients were studied, predominantly male (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels>30 pg/ml was the best predictor for IMV (OR:7.1; p<0.001). Early administration of TCZ was associated with improvement of oxygenation (PaO
2
/FiO
2
) in patients with high IL-6 (p=0.048). Patients with high IL-6 not treated with TCZ showed high mortality (HR: 4.6; p=0.003), as well as those with low IL-6 treated with TCZ (HR: 3.6; p=0.016). No relevant serious adverse events were observed in TCZ-treated patients.
Conclusion
Baseline IL-6>30 pg/ml predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administration.
COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8–22.6] for Roche, OR 10.3 [3.6–29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13–23.57] for TFS viremia and HR = 7.09 [3.3–14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.
Background
Early Kinetics of SARS‐CoV‐2 viral load (VL) in plasma determined by quantitative RT‐PCR was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort.
Methods
Prospective observational single‐centre study including consecutive adult patients hospitalised with COVID‐19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT‐PCR was performed to assess SARS‐CoV‐2 VL. The main outcomes were in‐hospital mortality, admission to the Intensive Care Unit (ICU) and their combination (Poor Outcome).
Relevant Viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalised COVID‐19 patients from April 2021‐May 2022, in which plasma samples were collected according to clinical criteria.
Results
Prospective cohort: 57 patients were included. RV was defined as at least a two‐fold increase in VL within ≤2 days or a VL>300 copies/mL, in the first week. Patients with RV (N=14; 24.6%) were more likely to die than those without RV (35.7% vs 0%), needed ICU admission (57% vs 0%) or had Poor Outcome (71.4% vs 0%), (p<0.001 for the three variables)
Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU‐admission [OR 5.6 (95%CI,2.1‐15.1); p=0.001], mortality [OR 13.5 (95%CI,6.3‐28.7); p<0.0001] and Poor Outcome [OR 11.2 (95%CI,5.8‐22); p<0.0001]
Conclusion
Relevant SARS‐CoV‐2 viremia in the first week of hospitalisation was associated with higher in‐hospital mortality, ICU admission, and Poor Outcome.
Findings observed in the prospective cohort were confirmed in a larger validation cohort.
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