key: cord-278620-mezsjdyb
authors: Choy, Kay W.
title: An urgent call to clinicians and researchers: 2020 acuity required when assessing and reporting laboratory abnormalities in COVID‐19
date: 2020-07-12
journal: Intern Med J
DOI: 10.1111/imj.14883
sha: 
doc_id: 278620
cord_uid: mezsjdyb

nan

An urgent call to clinicians and researchers: 2020 acuity required when assessing and reporting laboratory abnormalities in COVID-19

The current outbreak of coronavirus 2019 (COVID-19) calls for actionable information to be published as soon as possible in the interest of public health. There is a surge in literature reviews and meta-analyses summarising the roles of routine laboratory markers in assessing disease severity and guiding treatment in COVID-19. A closer look at the literature reveals some shortcomings in the reporting and interpretation of laboratory results. When discussing the management of liver injury in COVID-19, Zhang et al. provided a summary of patients with abnormal liver aminotransferases from several recent studies and discussed several possible mechanisms for liver injury. 1 Bangash et al. later reminded readers of the significance of the liver abnormalities reported in these studies, that, although the prevalence of elevated aminotransferases and bilirubin in patients faring worst was at least double that of others, clinically significant liver injury is uncommon (even when most severely ill patients are selected). 2 In addition, Bangash et al. noted that several studies have reported elevated levels of creatine kinase and lactate dehydrogenase or myoglobin.

Aminotransferase elevations do not necessarily arise from liver alone; COVID-19 infection might induce a myositis similar to that observed in severe influenza infections. 2 As study authors compare the significance of laboratory marker results between intensive care unit (ICU) and non-ICU groups, severe and less severe disease groups, or survivors and non-survivors, in addition to assessment of statistical significance of a marker between the two groups, the biological (and analytical) variation of the marker should be considered as well as the biological significance of the value difference.

A meta-analysis of four studies on the role of procalcitonin in patients with severe COVID-19 shows that increased procalcitonin values (above the normal reference limit) are associated with nearly fivefold higher risk of severe SARS-CoV-2 infection (odds ratio (OR), 4.76; 95% confidence interval (CI), 2.74-8.29). 3 A closer look at these four papers found that while Huang et al. [4] [5] [6] [7] It would be more informative to know the analytical methods used and, provided there is no significant between-method biases, to consider a common reference interval; alternatively, the degree of procalcitonin elevation may correlate with disease severity in COVID-19.

The analytical method details are scarce in much recent literature on COVID-19. This makes it challenging to adopt, apply or compare published results to the local settings. The European Federation of Clinical Chemistry and Laboratory Medicine and the European Union of Medical Specialists Joint Working Group on Guidelines have suggested a checklist to ensure that all relevant laboratory issues should be addressed for clinical decision making. 8 It includes sample type and handling, method-ology, limits of detection and quantification, analytical and biological variations (reference change values). 8 I call on clinicians and researchers to consider the preanalytical, analytical and post-analytical aspects of laboratory testing when reviewing or publishing laboratory results in this COVID-19 pandemic.

Liver injury in COVID-19: management and challenges

COVID-19 and the liver: little cause for concern

Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis

Clinical characteristics of coronavirus disease 2019 in China

Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Critical review of laboratory investigations in clinical practice guidelines: proposals for the description of investigation

Diagnostic testing for gestational diabetes mellitus during the COVID-19 pandemic: an opportunity to revisit glucose-based testing Advice on diagnostic testing for gestational diabetes mellitus (GDM) during the COVID-19 pandemic was recently provided by the Australasian Diabetes in Pregnancy Society and the Australian Diabetes Society. 1 For women at low risk for GDM, an alternative method of testing for GDM involves an initial fasting blood glucose (FBG) and subsequent oral glucose tolerance test (OGTT) (75 g oral glucose load) for women with FBG 4.7-5.0 mmol/L; FBG of >5.0 mmol/L is diagnostic of GDM. OGTT is not indicated if FBG is <4.7 mmol/L.The pre-analytical and analytical variations for glucosebased testing should be considered. A major source of preanalytical error is loss of glucose from blood specimens through glycolysis. 2 Glucose is lost from whole blood samples at a rate of 5-7% per hour at room temperature. 2 Preanalytical loss of glucose poses a threat to the diagnostic sensitivity of glucose-based testing for GDM. The most commonly used blood collection tube for glucose is sodiumfluoride-based and it is widely used to inhibit glycolysis but it is inadequate. Sodium-fluoride does not stop glycolysis for the first 2 h or more after sample collection, and during the first 60-90 min, the loss of glucose proceeds at the same rate with or without sodium-fluoride. 2 The American Diabetes Association (ADA) guideline on laboratory testing in diabetes recommends that samples be immediately immersed in ice slurry and analysed within 30 min of collection. 2 This is difficult to achieve in routine patient care and is not always followed in GDM testing. The diagnostic criteria for GDM were based on the Hyperglycaemia and Adverse Pregnancy Outcome study, which had strict protocol for glucose sample handling. 2 In a study by Daly et al., implementation of ADA glucose sample handling recommendations resulted in a 2.7-fold increased detection of GDM compared with usual hospital practices. 3 When studying the impact of handling fluoride-oxalate samples at room temperature in rural and remote Australia, Jamieson et al. estimated a 62% underdiagnosis of GDM compared to fluoride-oxalate samples on ice slurry. 4 Fluoride-citrate-EDTA (ethylenediaminetetraacetic acid) tubes virtually inhibit glycolysis and have been recommended to replace sodium-fluoride-containing tubes. 2 However, these tubes are not universally available and the costs are significantly higher.The biological variations of FBG and OGTT should not be overlooked. Chai et al. examined the impact of