Background Activation of the vasopressin system plays a key role for the maintenance of osmotic, cardiovascular and stress hormone homeostasis during disease. We investigated levels of copeptin, the C-terminal segment of the vasopressin prohormone, that mirrors the production rate of vasopressin in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We measured levels of copeptin on admission and after 3/4, 5/6 and 7/8 days in 74 consecutive hospitalized adult COVID-19 patients and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n=876) and acute or chronic bronchitis (n=371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. Results Median admission copeptin levels in COVID-19 patients were almost 4-fold higher in non-survivors compared to survivors (49.4 pmol/L (IQR 24.9-68.9 pmol/L) vs. 13.5 pmol/L (IQR 7.0-26.7 pmol/L) resulting in an age and gender-adjusted odds ratio of 7.0 (95%CI 1.2 to 40.3), p<0.03 for mortality. Higher copeptin levels in non-survivors persisted during the short-term follow-up. Compared to the control group patients with acute/chronic bronchitis and pneumonia, COVID-19 patients did not have higher admission copeptin levels. Conclusions A pronounced activation of the vasopressin system in COVID-19 patients is associated with an adverse clinical course in COVID-19 patients. This finding, however, is not unique to COVID-19 but similar to other types of respiratory infections. .

No abstract

Objectives Risk stratification in patients with infection is usually based on the Sequential Organ Failure Assessment-Score (SOFA score). Our aim was to investigate whether the vasoactive peptide mid-regional pro-adrenomedullin (MR-proADM) improves the predictive value of the SOFA score for 30-day mortality in patients with acute infection presenting to the emergency department (ED). Methods This secondary analysis of the prospective observational TRIAGE study included 657 patients with infection. The SOFA score, MR-proADM, and traditional inflammation markers were all measured at time of admission. Associations of admission parameters and 30-day mortality were investigated by measures of logistic regression, discrimination analyses, net reclassification index (NRI), and integrated discrimination index (IDI). Results MR-proADM values were higher in non-survivors compared with survivors (4.5 ± 3.5 nmol/L vs. 1.7 ± 1.8 nmol/L) with an adjusted odds ratio of 26.6 (95% CI 3.92 to 180.61, p=0.001) per 1 nmol/L increase in admission MR-proADM levels and an area under the receiver operator curve (AUC) of 0.86. While the SOFA score alone revealed an AUC of 0.81, adding MR-proADM further improved discrimination (AUC 0.87) and classification within predefined risk categories (NRI 0.075, p-value <0.05). An admission MR-proADM threshold of 1.75 nmol/L provided the best prognostic accuracy for 30-day mortality; with a sensitivity of 81% and a specificity of 75%, and a negative predictive value of 98%. Conclusions MR-proADM improved the mortality risk stratification in patients with infection presenting to the ED beyond SOFA score alone and may further improve initial therapeutic site-of-care decisions. Trial registration ClinicalTrials.gov NCT01768494. Registered January 15, 2013.

Objective: Systemic infections and sepsis lead to a strong activation of the vasopressin system, which is pivotal for stimulation of the endocrine stress response and in addition has vasoconstrictive and immunomodulatory effects. Our aim was to assess the significance of the vasopressor system through measurement of C-terminal proAVP (copeptin) regarding mortality prediction in a large prospective cohort of patients with systemic infection. Design and Methods: This secondary analysis of the observational cohort TRIAGE study included consecutive, adult, medical patients with an initial diagnosis of infection seeking emergency department care. We used multivariable regression analysis to assess associations of copeptin levels in addition to the sequential organ failure assessment (SOFA) score with 30-day mortality. Discrimination was assessed by calculation of the area under the curve (AUC). Results: Overall, 45 of 609 (7.4%) patients with infection died within 30 days. Non-survivors had a marked upregulation of the vasopressin system with a more than 4-fold increase in admission copeptin-levels compared to non-survivors (199.9 ± 204.7 vs. 46.6 ± 77.2 pmol/L). In a statistical model copeptin was significantly associated with mortality (adjusted odds ratio of 1.04, 95% CI 1.01 to 1.07, p=0.002). Regarding discrimination, copeptin alone showed an AUC of 0.82, while adding copeptin to the SOFA score significantly improved its prognostic ability (AUC 0.83 vs. 0.86, p=0.027). Conclusion: Activation of vasopressin system mirrored by an increase in copeptin levels provided significant information regarding mortality risk and improved the SOFA score for prediction of sepsis mortality. Trial registration: ClinicalTrials.gov NCT01768494. Registered January 9, 2013

No abstract

No abstract