New review: Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID‐19 in people with SARS‐CoV‐2

Lab testing

How accurate are routine laboratory tests in predicting mortality and deterioration to severe or critical COVID‐19 in people with SARS‐CoV‐2?

What are routine laboratory tests?
Routine laboratory tests are a set of commonly performed blood tests that provide information about a patient's health status. These tests can be used to identify disease or monitor health.

What did we want to find out?
It is important to identify patients, presenting at a doctor's appointment at an outpatient service or at the emergency department who are at high risk of developing severe COVID‐19 disease or dying. It can help clinicians in deciding if the patients need hospitalisation. We wanted to know if routine laboratory tests were sufficiently accurate to predict mortality and deterioration in patients with confirmed SARS‐CoV‐2.

What did we do?
We searched for studies that assessed how well routine laboratory tests predict mortality and deterioration in patients with confirmed SARS‐CoV‐2. We included studies of any design and set anywhere in the world. Patients of any age or sex were included.

What we found
We found 64 studies that looked at 53 different routine laboratory tests. These studies assessed how well these tests could predict mortality, deterioration, or both. A total of 71,170 patients were included, of which 8169 (11.5%) patients died, and 4031 (5.7%) patients deteriorated to severe/critical disease. Adult patients were included in 31 studies, two studies reported on patients more than 60 years, two studies included a mix of children and adults, and one study included only children. Most studies were done in China, followed by Spain and Italy. All studies took place in hospitals.

'Sensitivity' and 'specificity' are often used to report the performance of tests. Sensitivity is the proportion of patients with the outcome (= mortality or deterioration) that are correctly detected by the test, and specificity is the proportion of people without the outcome that are correctly detected by the test. The closer the sensitivity and specificity of a test are to 100%, the more accurate the test is. To safely rule out patients who will not die or deteriorate, a high sensitivity of more than 90% is necessary. When four or more studies assessed the same tests, we pooled the data and analysed them together. We did not find any tests that were accurate enough to safely rule out a severe outcome, such as deterioration or death. We found five tests with both sensitivity and specificity exceeding 50%. Four of these laboratory tests indicate important inflammation in a SARS‐CoV‐2 infection. These four tests are C‐reactive protein, neutrophil‐to‐lymphocyte ratio, lymphocyte count, and lactate dehydrogenase. The fifth test, d‐dimer, reflects a state of increased blood clotting in a SARS‐CoV‐2 infection.

How reliable are the results?
We have low confidence in the evidence of this review, because there were important differences between the included studies, and it was, therefore, difficult to compare them. Sensitivity and specificity depend on where the cut‐off point is made between positive (indicative of disease) and negative (disease‐free). For some studies, the authors decided on the cut‐off value (for a test) before doing the test (less likely to create bias) and in others, they chose the cut‐off value after analysis of the test (more likely to be biassed).

Who do the results of this review apply to?
Routine laboratory tests can be performed at a doctor's appointment or at the emergency department. However, the included studies only assessed patients presenting to the hospital. We included patients with confirmed SARS‐CoV‐2 infection. Only one study reported on vaccinated patients, and we could not assess the effect of different SARS‐CoV‐2 variants of concern. Therefore, our results might not be representative for vaccinated patients or different variants of concern.

What does this mean?
These routine laboratory tests, linked to inflammation and blood clotting in patients with COVID‐19 disease, can be used for risk stratification to assess a patient. However, none of these tests performed well enough to safely rule out progression to severe or deadly disease. These tests might serve to assess the overall health status of the patient. To predict deterioration or mortality, a more comprehensive assessment, including clinical symptoms, radiological findings and patient's characteristics, may be considered.

How up‐to‐date is this review?
We searched for all COVID‐19 studies up to 25 August 2022.

 

De Rop L, Bos DAG, Stegeman I, Holtman G, Ochodo EA, Spijker R, Otieno JA, Alkhlaileh F, Deeks JJ, Dinnes J, Van den Bruel A, McInnes MDF, Leeflang MMG, Verbakel JY. Accuracy of routine laboratory tests to predict mortality and deterioration to severe or critical COVID‐19 in people with SARS‐CoV‐2. Cochrane Database of Systematic Reviews 2024, Issue 8. Art. No.: CD015050. DOI: 10.1002/14651858.CD015050.pub2. Access the full-text article here.

The editorial base of the Cochrane Infectious Diseases Group is funded by UK aid from the UK government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government's official policies.