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

Abstract

Background Identifying patients with COVID‐19 disease who will deteriorate can be useful to assess whether they should receive intensive care, or whether they can be treated in a less intensive way or through outpatient care. In clinical care, routine laboratory markers, such as C‐reactive protein, are used to assess a person's health status. Objectives To assess the accuracy of routine blood‐based laboratory tests to predict mortality and deterioration to severe or critical (from mild or moderate) COVID‐19 in people with SARS‐CoV‐2. Search methods On 25 August 2022, we searched the Cochrane COVID‐19 Study Register, encompassing searches of various databases such as MEDLINE via PubMed, CENTRAL, Embase, medRxiv, and ClinicalTrials.gov. We did not apply any language restrictions. Selection criteria We included studies of all designs that produced estimates of prognostic accuracy in participants who presented to outpatient services, or were admitted to general hospital wards with confirmed SARS‐CoV‐2 infection, and studies that were based on serum banks of samples from people. All routine blood‐based laboratory tests performed during the first encounter were included. We included any reference standard used to define deterioration to severe or critical disease that was provided by the authors. Data collection and analysis Two review authors independently extracted data from each included study, and independently assessed the methodological quality using the Quality Assessment of Prognostic Accuracy Studies tool. As studies reported different thresholds for the same test, we used the Hierarchical Summary Receiver Operator Curve model for meta‐analyses to estimate summary curves in SAS 9.4. We estimated the sensitivity at points on the SROC curves that corresponded to the median and interquartile range boundaries of specificities in the included studies. Direct and indirect comparisons were exclusively conducted for biomarkers with an estimated sensitivity and 95% CI of ≥ 50% at a specificity of ≥ 50%. The relative diagnostic odds ratio was calculated as a summary of the relative accuracy of these biomarkers. Main results We identified a total of 64 studies, including 71,170 participants, of which 8169 participants died, and 4031 participants deteriorated to severe/critical condition. The studies assessed 53 different laboratory tests. For some tests, both increases and decreases relative to the normal range were included. There was important heterogeneity between tests and their cut‐off values. None of the included studies had a low risk of bias or low concern for applicability for all domains. None of the tests included in this review demonstrated high sensitivity or specificity, or both. The five tests with summary sensitivity and specificity above 50% were: C‐reactive protein increase, neutrophil‐to‐lymphocyte ratio increase, lymphocyte...