Prolonged international normalized ratio values are associated with COVID-19 severity and mortality

Objectives:
D-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. Therefore, this review article has been conducted.

Are prolonged international normalized ratio (INR) values associated with COVID-19 severity and mortality?

Study design:
This review article included 38 studies with 7,440 COVID-19 patients with low disease severity or survivor status during follow up (50% males, mean age 57 years) and 2,331 with high severity or non-survivor status (60% males, mean age 69 years).

No publication bias was detected with the Begg's [p = 0.15] or the Egger's [p = 0.12] t-tests. However, the trim-and-fill method identified seven potential missing studies to add to the left side of the funnel plot to ensure symmetry.

Results and conclusions:
The investigators found the international normalized ratio was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status [SMD = 0.60, 95% CI = 0.42 to 0.77, p 0.001, I2 = 90.2%, p 0.001]. Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified.

The investigators found, in meta-regression, the SMD of the international normalized ratio was significantly associated with C-reactive protein [p = 0.048] and D-dimer [p = 0.001].

The investigators concluded prolonged international normalized ratio (INR) values are associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.

Original title:
INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression by Zinellu A, Paliogiannis P, [...], Mangoni A.

Link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292100/

Additional information of El Mondo:
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In healthy people an INR of 1.1 or below is considered normal.