Management of hyperinflammation in COVID-19 patients

In response to SARS-CoV-2 infection, the immune system physiologically upregulates to try to clear the virus from the body; failure to compensate for this inflammatory response with an anti-inflammatory response leads to dysregulation of the immune system that ultimately leads to a situation of uncontrolled hyperinflammation called cytokine storm. This cytokine storm can cause ARDS or multi-organ failure leading to patient death. This review exposes the different mechanisms of the inflammatory response in COVID-19 infection and the therapeutic options to treat this process

Prognostic value of proadrenomedullin in severe sepsis and septic shock patients with community-acquired pneumonia

Principles: Midregional proadrenomedullin (proADM) is a novel biomarker with potential prognostic utility in patients with community-acquired pneumonia. The aim of this study was to investigate the value of proADM levels for severity assessment and outcome prediction in severe sepsis and septic shock due to CAP. Methods: Prospective observational study including 49 patients admitted to ICU with both a clinical and radiologic diagnosis of pneumonia and fulfilling criteria for severe sepsis or septic shock. The prognostic accuracy of proADM levels was compared with those of pneumonia severity index and of procalcitonin (PCT) and C-reactive protein (CRP). Results: 49 patients with severe sepsis or septic shock due to CAP were included in the study. Mortality was 24.5% for ICU and 34.7% for hospital mortality. In all cases proADM values at ICU admission were pathological (considering normal proADM levels <4 nmol/L). ProADM consistently rose as PSI class advanced from II to V (p = 0.02). Median proADM levels were higher (p <0.01) in hospital non-survivors 5.0 (1.9-10.1) nmol/L vs. survivors 1.7 (1.3-3.1) nmol/L. These differences were also significant with respect to ICU mortality. The receiver-operating characteristic curve for proADM yielded an AUC of 0.72; better than the AUC for PCT and CRP (0.40 and 0.44 respectively) and similar to PSI (0.74). Conclusions: In our study MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients.Funding / potential competing interests: Borja Suberviola has received remuneration for lectures on the topic of inflammation markers by BRAHMS Iberia, Spain. BRAHMS Iberia had no influence on study design, data analysis, or final preparation of this manuscript

Prognostic value of plasma pentraxin 3 levels in patients with septic shock admitted to intensive care

Objective: To evaluate the usefulness of a new marker, pentraxin, as a prognostic marker in septic shock patients. Materials and methods: Single-centre prospective observational study that included all consecutive patients 18 years or older who were admitted to the intensive care unit (ICU) with septic shock. Serum levels of procalcitonin (PCT), C reactive protein (CRP) and pentraxin (PTX3) were measured on ICU admission. Results: Seventy-five septic shock patients were included in the study. The best predictors of inhospital mortality were the severity scores: SAPS II (AUC = 0.81), SOFA (AUC = 0.79) and APACHE II (AUC = 0.73). The ROC curve for PTX3 (ng/mL) yielded an AUC of 0.70, higher than the AUC for PCT (0.43) and CRP (0.48), but lower than lactate (0.79). Adding PTX3 to the logistic model increased the predictive capacity in relation to SAPS II, SOFA and APACHE II for in-hospital mortality (AUC 0.814, 0.795, and 0.741, respectively). In crude regression models, significant associations were found between in-hospital mortality and PTX3. This positive association increased after adjusting for age, sex and immunosuppression: adjusted OR T3 for PTX3 = 7.83, 95% CI 1.35?45.49, linear P trend = 0.024. Conclusion: Our results support the prognostic value of a single determination of plasma PTX3 as a predictor of hospital mortality in septic shock patients

The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure

Immunoglobulines; Sèpsia; SupervivènciaInmunoglobulinas; Sepsis; SupervivenciaImmunoglobulins; Sepsis; SurvivalBackground Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. Methods This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA ≥ 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan–Meier and multivariate logistic regression analysis. Results ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality. Conclusions Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities.Funding was provided by SACYL (Grant No. BOCYL-D-26072010), Instituto de Salud Carlos III (Grant Nos. EMER 07/050, PI12-01815)