Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 29;11(9):1166.
doi: 10.3390/antibiotics11091166.

Mid-Regional Pro-Adrenomedullin as a Prognostic Factor for Severe COVID-19 ARDS

Etienne de Montmollin  1   2 , Katell Peoc'h  3   4 , Mehdi Marzouk  2 , Stéphane Ruckly  1 , Paul-Henri Wicky  2 , Juliette Patrier  2 , Pierre Jaquet  2 , Romain Sonneville  1   2 , Lila Bouadma  1   2 , Jean-François Timsit  1   2
Affiliations

Mid-Regional Pro-Adrenomedullin as a Prognostic Factor for Severe COVID-19 ARDS

Etienne de Montmollin et al. Antibiotics (Basel). .

Abstract

Mid-regional proadrenomedullin (MR-proADM) protects against endothelial permeability and has been associated with prognosis in bacterial sepsis. As endothelial dysfunction is central in the pathophysiology of severe SARS-CoV-2 infection, we sought to evaluate MR-proADM both as a prognostic biomarker and as a marker of bacterial superinfection. Consecutive patients admitted to the ICU for severe SARS-CoV-2 pneumonia were prospectively included and serum was bio-banked on days 1, 3, and 7. MR-proADM levels were measured blindly from clinical outcomes in batches at the end of follow-up. Among the 135 patients included between April 2020 and May 2021, 46 (34.1%) had died at day 60. MR-proADM levels on days 1, 3, and 7 were significantly higher in day-60 non-survivors. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve (0.744, p < 0.001) of day-1 MR-proADM compared favorably with the AUC ROC curve of day-1 procalcitonin (0.691, p < 0.001). Serial MR-proADM measurements on days 3 and 7 may add prognostic information. After adjusting for CRP, LDH, and lymphocyte values, day-1 MR-proADM remained significantly associated with day-60 mortality. MR-proADM concentrations were significantly higher in patients with respiratory superinfections (on days 3 and 7) and bloodstream infections (on days 1, 3, and 7) than in patients without infection. Our results suggest that MR-proADM is a good predictor of outcome in severe SARS-CoV-2 infection and could be a useful tool to assess bacterial superinfection in COVID-19 patients.

Keywords: ARDS; COVID-19; Mid-regional Pro-adrenomedullin; SARS-CoV-2; biomarker; prognosis; superinfection.

PubMed Disclaimer

Conflict of interest statement

The authors received a research grant from Thermo Fisher to perform the study. Outside of the study, J.-F.T. declares a participation to the boards of Merck, Pfizer, BD, Gilead and Paratek, and lecture fees for Pfizer, Shionogi, BD and Merck.

Figures

Figure 1
Figure 1
(a) MR-proADM concentrations according to day-60 survival; (b) ROC curves for day-60 survival of MR-proADM on days 1, 3, and 7. * p < 0.05.
Figure 2
Figure 2
Survival curves according to a cut-point of 1 nmol/L of MR-proADM on day 1.
Figure 3
Figure 3
ROC curves of the association of day-60 mortality with various biomarkers on day 1 and the SOFA score. Abbreviations: MR-proADM, Mid-regional proadrenomedullin; SOFA, Sequential Organ Failure Assessment; CRP, C-reactive protein.
Figure 4
Figure 4
(a) MR-proADM concentrations according to the occurrence of pneumonia on days 1, 3, and 7. (b) MR-proADM concentrations according to the occurrence of pneumonia on days 1, 3, and 7. Abbreviations: MR-proADM, Mid-regional proadrenomedullin. * p < 0.05.
See this image and copyright information in PMC

References

    1. WHO Coronavirus (COVID-19) Dashboard. [(accessed on 22 August 2022)]. Available online: https://covid19.who.int.
    1. COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators Clinical Characteristics and Day-90 Outcomes of 4244 Critically Ill Adults with COVID-19: A Prospective Cohort Study. Intensive Care Med. 2021;47:60–73. doi: 10.1007/s00134-020-06294-x. - DOI - PMC - PubMed
    1. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S., Mehra M.R., Schuepbach R.A., Ruschitzka F., Moch H. Endothelial Cell Infection and Endotheliitis in COVID-19. Lancet. 2020;395:1417–1418. doi: 10.1016/S0140-6736(20)30937-5. - DOI - PMC - PubMed
    1. Bonaventura A., Vecchié A., Dagna L., Martinod K., Dixon D.L., Van Tassell B.W., Dentali F., Montecucco F., Massberg S., Levi M., et al. Endothelial Dysfunction and Immunothrombosis as Key Pathogenic Mechanisms in COVID-19. Nat. Rev. Immunol. 2021;21:319–329. doi: 10.1038/s41577-021-00536-9. - DOI - PMC - PubMed
    1. Calabretta E., Moraleda J.M., Iacobelli M., Jara R., Vlodavsky I., O’Gorman P., Pagliuca A., Mo C., Baron R.M., Aghemo A., et al. COVID-19-induced Endotheliitis: Emerging Evidence and Possible Therapeutic Strategies. Br. J. Haematol. 2021;193:43–51. doi: 10.1111/bjh.17240. - DOI - PMC - PubMed