Associations and prognostic accuracy of electrolyte imbalances in predicting poor COVID-19 outcome: a systematic review and meta-analysis
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Abstract
Background
Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value.
Objectives
To systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome.
Methods
PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR+, LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed.
Results
We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR=2.08, 95%CI=1.48-2.94, I 2 =93%, N=8), hypernatremia (OR=4.32, 95%CI=3.17-5.88, I 2 =45%, N=7) and hypocalcemia (OR=3.31, 95%CI=2.24-4.88, I 2 =25%, N=6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR+ 4.0, PPV=55%, AUC=0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV=87%, AUC=0.71). Overall quality of evidence ranged from very low to moderate.
Conclusion
Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.
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SciScore for 10.1101/2021.11.19.21266563: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding Study Selection, Data Extraction, Risk of Bias Assessment and Quality of Evidence: Two authors independently selected relevant studies, extracted key data and assessed risk of bias in a blinded manner using the online platform Rayyan.[31] We accepted observational studies published as full-length articles in peer-reviewed journals that reported the associations of electrolyte imbalances in patients diagnosed with COVID-19 that were either higher (e.g. hypernatremia) or lower (e.g. hyponatremia) than the normal physiological range. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentenc… SciScore for 10.1101/2021.11.19.21266563: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding Study Selection, Data Extraction, Risk of Bias Assessment and Quality of Evidence: Two authors independently selected relevant studies, extracted key data and assessed risk of bias in a blinded manner using the online platform Rayyan.[31] We accepted observational studies published as full-length articles in peer-reviewed journals that reported the associations of electrolyte imbalances in patients diagnosed with COVID-19 that were either higher (e.g. hypernatremia) or lower (e.g. hyponatremia) than the normal physiological range. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources 30] Search Strategy: We searched three databases (PubMed, Embase and Cochrane Library) from inception till 22nd May 2021 using search terms related to COVID-19 and electrolyte imbalances concerning the electrolytes sodium, calcium, potassium, magnesium, chloride and phosphate (Supplemental Methods). PubMedsuggested: (PubMed, RRID:SCR_004846)Embasesuggested: (EMBASE, RRID:SCR_001650)Cochrane Librarysuggested: (Cochrane Library, RRID:SCR_013000)We conducted all analyses using RevMan (version 5.4), Stata (version 17) and RStudio (version 1.4) using the meta package (version 4.18). RevMansuggested: (RevMan, RRID:SCR_003581)RStudiosuggested: (RStudio, RRID:SCR_000432)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:Limitations: Firstly, there were insufficient studies looking at the same outcome and same electrolyte imbalance for a statistically-powered meta-regression and funnel plot for the assessment of publication bias. We were unable to conduct some meaningful subgroup analyses to explain heterogeneity, but this potentially could be explained by the differing impacts of the pandemic on different healthcare systems globally, as well as their varying management strategies. This may be confirmed using future studies for subgroup analyses stratified by country or region. Secondly, participants may be admitted with differing COVID-19 baseline severities, with some being admitted directly to the ICU with an already severe infection. We are unable to discern this group from those that deteriorated after admission, potentially introducing a source of bias as participants who are severely infected will be more prone to having a poor outcome. Nonetheless, we mitigated this by marking down the study’s representativeness on the NOS scale. Thirdly, our results do not allow us to interpret the causality of the association as it is unclear whether the electrolyte imbalances further aggravate participants with COVID-19 or whether its just a general indication of poor health. Furthermore, the temporal sequence between COVID-19 diagnosis and the presence of electrolyte imbalances is hard to establish. Studies also did not monitor the progression of these imbalances throughout the length of hospital ...
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.
Results from scite Reference Check: We found no unreliable references.
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