To the Editor,
The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has recently posted a list of laboratory tests for monitoring patients with COVID-19 (IFCC Information Guide on COVID-19; published Thursday, March 26: https://www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19/). Besides hematology (i.e. complete blood count) and coagulation (i.e. d-dimer and prothrombin time), the list also includes specific clinical chemistry tests for the biochemical monitoring of patients with COVID-19, which are supported by the initial clinical course of patients from Wuhan, China . These tests have also been recently highlighted in Clinical Chemistry and Laboratory Medicine  (Table 1). Importantly, the original list omits blood gas panels as well as urea, with the latter needed for the CURB-65 community-acquired pneumonia severity score used in the emergency setting . We have added these tests to the list and have provided important caveats for the interpretation of these tests as preanalytical, analytical and postanalytical issues can affect interpretation.
Clinical chemistry tests for patients with COVID-19 in the emergency setting (modified from the IFCC list and ref. ).
|Clinical chemistry tests||Lab value direction for unfavorable prognosis in patients with COVID-19||Preanalytical, analytical and postanalytical caveats for interpretation|
|Tests widely available as STAT at hospital laboratories|
|Albumin||Decreased||There are two main types of albumin assays: bromocresol green reports higher concentrations than bromocresol purple|
|Lactate dehydrogenase (LD)||Increased||Preanalytical factors such as handling via pneumatic tube systems and in vitro hemolysis may cause elevations|
|Alanine aminotransferase (ALT)||Increased||Sex-specific reference intervals should be used|
|Aspartate aminotransferase (AST)||Increased||Can be elevated from many different tissues and factors, such as in vitro hemolysis, may cause elevations|
|Total bilirubin||Increased||Photosensitive, so testing should not be delayed, used in SOFA score|
|Creatinine||Increased||eGFR by CKD-EPI equation would be a useful adjunct, used in SOFA score|
|C-reactive protein (CRP)||Increased||There are two main types of assays, hs-CRP and CRP; both assays are appropriate for acute phase response|
|Cardiac troponin||Increased||There are two main types of assays, hs-cTn and cTn; both assays are appropriate for detecting myocardial injury, with hs-cTn testing preferred for risk stratification|
|Urea||Predicted to be increased||Used for CURB-65 score|
|Blood gas panel||Predicted to have increased and decreased levels for many different tests||Many blood gas analyzers provide pH, pO2, pCO2, bicarbonate, glucose, lactate, free calcium, Na, K, Cl. Testing needs to be performed promptly|
|Tests that may not be available at hospital laboratories|
|Ferritin||Increased||May not be available for STAT testing|
|Procalcitonin||Increased||Is not available in all hospitals|
|Cytokines (IL-6)||Increased||Is not available in all hospitals and many tests are for research use|
Briefly, for clinical chemistry tests related to liver function, there are preanalytical, analytical and postanalytical variables that can influence test interpretation , , , , , . Both aspartate aminotransferase (AST) and lactate dehydrogenase (LD) results can be affected by preanalytical factors such as pneumatic tube system transportation and in vitro hemolysis which will result in higher levels , . For transportation via pneumatic tube systems, careful validation and monitoring of the system for force and acceleration may mitigate these effects, even when hemolysis is not present , . Bilirubin is photosensitive and alanine aminotransferase (ALT) should be interpreted based on sex-specific reference intervals for both the pediatric and adult populations , . Albumin levels are affected by the analytical method used to generate the results (e.g. bromocresol green versus bromocresol purple) , . Here, the bromocresol green method for albumin measurement is less specific than the bromocresol purple method and binds other proteins. This effect is most noticeable at low concentrations; thus, physicians need to be mindful of this if comparing results from different laboratories, especially with low albumin levels , .
Of the inflammatory-related clinical chemistry tests listed, C-reactive protein (CRP) is more widely available at hospitals and in the emergency setting. Both high-sensitivity CRP (hs-CRP) and CRP can be used for the detection of an acute phase response. Finally, both cardiac troponin and high-sensitivity cardiac troponin (hs-cTn) can identify myocardial injury with hs-cTn superior for identifying low-risk individuals . Importantly, survivors of COVID-19 at admission had a median hs-cTnI level of 3 ng/L ; as such low hs-cTn levels, in combination with other algorithms, may be helpful in this setting , , .
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Dr. Kavsak has received grants/reagents/consultant/advisor/ honoraria from several diagnostic companies, including Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche Diagnostics and Siemens Healthcare Diagnostics. McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular biomarker field. Dr. de Wit has received a research grant from Bayer.
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