Hypoalbuminemia in COVID‐19: assessing the hypothesis for underlying pulmonary capillary leakage

  1. M. A. Wu
  2. T. Fossali
  3. L. Pandolfi
  4. L. Carsana
  5. D. Ottolina
  6. V. Frangipane
  7. R. Rech
  8. A. Tosoni
  9. G. Lopez
  10. A. Agarossi
  11. C. Cogliati
  12. F. Meloni
  13. B. Marchini
  14. M. Nebuloni
  15. E. Catena
  16. R. Colombo

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Abstract

Background

Since the first observations of patients with COVID‐19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet.

Objective

We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial–endothelial barrier.

Methods

One hundred seventy‐four COVID‐19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied.

Results

Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL‐8) and interleukin 10 (IL‐10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID‐19 and compared with postmortem findings in a control group (bacterial pneumonia‐ARDS and H1N1‐ARDS). ICU patients had lower serum albumin than IMW patients [20 (18–23) vs 28 (24–33) g L −1 , P  < 0.001]. Serum albumin was lower in more compromised groups (lower PaO 2 ‐to‐FiO 2 ratio and worst chest X‐ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL‐8 and IL‐10 levels in BALF. Electron microscopy examinations of eight out of ten COVID‐19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells.

Conclusion

Hypoalbuminaemia may serve as severity marker of epithelial–endothelial damage in patients with COVID‐19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID‐19 and might be a potential therapeutic target.

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  1. Version published to 10.1111/joim.13208
  2. ScreenIT

    SciScore for 10.1101/2020.05.17.20104877: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Research and data collection protocols were approved by the Institutional Review Board (Comitato Etico di Area 1).
    Consent: Written informed consent was obtained by survivors and waived in all others.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data were analysed with Graphpad Prism version 8.4.1.
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, we are aware that our study has also some limitations. First, it is retrospective, and our findings will need confirmation in prospective studies. Moreover, we propose a pathophysiological model which necessarily needs validation, i.e. in animal studies. In conclusion, hypoalbuminemia is a frequent finding in COVID-19 patients and is linked to the severity of lung injury. It might depend on the complex interplay between direct viral effects and the hyperinflammatory host reaction, which lead to endothelial dysfunction and capillary leak syndrome. Further research is needed to get deeper insights into the mechanisms leading to this condition, and to identify new potential therapeutic targets to mitigate or even avoid endothelial dysfunction.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.05.17.20104877v1 on medRxiv