Low blood sodium increases risk and severity of COVID-19: a systematic review, meta-analysis and retrospective cohort study

  1. Yi Luo
  2. Yirong Li
  3. Jiapei Dai

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Abstract

Background Novel coronavirus (SARS-CoV-2) infects human lung tissue cells through angiotensin-converting enzyme-2 (ACE2), and the body sodium is an important factor for regulating the expression of ACE2. Through a systematic review, meta-analysis and retrospective cohort study, we found that the low blood sodium population may significantly increase the risk and severity of SARS-CoV-2 infection. Methods We extracted the data of serum sodium concentrations of patients with COVID-19 on admission from the articles published between Jan 1 and April 28, 2020, and analyzed the relationship between the serum sodium concentrations and the illness severity of patients. Then we used a cohort of 244 patients with COVID-19 for a retrospective analysis. Results We identified 36 studies, one of which comprised 2736 patients.The mean serum sodium concentration in patients with COVID-19 was 138.6 mmol/L, which was much lower than the median level in population (142.0). The mean serum sodium concentration in severe/critical patients (137.0) was significantly lower than those in mild and moderate patients (140.8 and 138.7, respectively). Such findings were confirmed in a retrospective cohort study, of which the mean serum sodium concentration in all patients was 137.5 mmol/L, and the significant differences were found between the mild (139.2) and moderate (137.2) patients, and the mild and severe/critical (136.6) patients. Interestingly, such changes were not obvious in the serum chlorine and potassium concentrations. Conclusions The low sodium state of patients with COVID-19 may not be the consequence of virus infection, but could be a physiological state possibly caused by living habits such as low salt diet and during aging process, which may result in ACE2 overexpression, and increase the risk and severity of COVID-19. These findings may provide a new idea for the prevention and treatment of COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2020.05.18.20102509: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    There exist two limitations in this study. The data from the systematic review and meta-analysis were mainly extracted from the observational studies in a preprint form due to an unexpected, fast and short-period SARS-CoV-2 pandemic, which would not allow the research works to be published immediately through a traditional review way. However, it could be recognized that the standardization and automatic detection methods for serum electrolytes used in the modern hospitals could ensure the reliability of extracted data from the identified studies. In addition, for the retrospective cohort analysis, although a small cohort of 59 non-COVID-19 inpatients as control have provided very useful control data, however, it would be benefit to our conclusion if a normal control population matched with age and sex, etc.; during the SARS-CoV-2 epidemic period. In conclusion, we found that people with low serum sodium (hyponatremia) may be related to the susceptibility of SARS-CoV-2 infection and the development of severity of disease. This finding may provide an important idea to prevent the widespread prevalence of this virus or even other types of coronavirus, and to treat the patients. In the epidemic stage, it may be of great significance to properly provide enough sodium intake or maintain blood sodium at a reasonable level for the susceptible population in order to reduce the virus infection, and treat patients through therapeutic sodium supplementation (such as infusion) to prevent...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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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  2. Version published to 10.1101/2020.05.18.20102509v1 on medRxiv