The title of this article raises the question on the role of the clinical chemistry laboratory in the management of patients with COVID-19; with this article being an AACC Academy Scientific short, the short answer is yes. As recently reviewed by Lippi and Plebani (1), the clinical chemistry laboratory plays a role in diagnosis, staging, prognostication, monitoring, and epidemiological surveillance. Although the bulk of molecular diagnostic testing for the COVID-19 virus (i.e., SARS-CoV-2) typically falls under the microbiology department, clinical chemists have been called upon to assist with validating, automating, and expanding previously semi-automated processes. The emerging utility of molecular diagnostic and serology testing for patients with COVID-19 has been nicely summarized by Feng and Wang in another Scientific Short in April this year (2).
Outside of molecular testing, there has been much interest in serological testing (2-4). In Canada, the Canadian Society of Clinical Chemists (CSCC) in collaboration with the Canadian Public Health Laboratory Network, the Association of Medical Microbiology and Infectious Disease Canada, the Canadian Association for Clinical Microbiology and Infectious Diseases and the COVID-19 Immunity Task Force published a joint paper on serology testing in the Canadian Medical Association Journal (CMAJ) in August 2020 (3). The key takeaway from this article was that the clinical indications for serological testing in health care settings are limited, with a minor role in routine clinical care at this time (3). It is not yet known whether presence of SARS-CoV-2 antibodies reflects effective and durable immunity that can appropriately guide an individual’s activities or care during this pandemic (3). Rather, serological testing is focused at the population level for sero-surveillance studies to determine disease prevalence overtime across different demographics and regions. This publication was followed by a guidance document by the CSCC special interest group on COVID-19, which provided recommendations to harmonize the implementation of SARS-CoV-2 serology testing, including test naming, reporting, and interpretation, and included a section on the utility of SARS-CoV-2 serology testing in the pediatric population (e.g., multisystem inflammatory syndrome in children; MIS-C) as well as a brief overview of point-of-care serology testing (4).
So what about the “common clinical chemistry” tests, the ones that were available before the pandemic in 2019? Here, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has posted a list of laboratory tests for managing patients with COVID-19, which, in addition to hematological parameters, includes common chemistry tests such as C-reactive protein (CRP), albumin and lactate dehydrogenase (LD), as well as more esoterictests such as procalcitonin (5). In this case, test results are used to assess organ involvement and disease severity and to predict morbidity and mortality risk. Chemistry markers can be used independently or in combination with others as a clinical risk score (6). Clinical scores, such as CURB-65, A-DROP, and the 4C Mortality Score, incorporate patient demographics, symptoms, and laboratory test results to aid in patient risk stratification at hospital presentation (7). Both CURB-65, which includes confusion, urea, respiratory rate, blood pressure, and age, and A-DROP, which includes age, urea or dehydration, oxyhemoglobin saturation or partial oxygen pressure, confusion, and systolic blood pressure, have been validated for predicting mortality risk in community acquired pneumonia and have been applied to COVID-19 management to varying degrees. The 4C Mortality Score, which includes age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea, and CRP, is specific to the management of COVID-19 and is able to discriminate between high and low mortality risk with a higher area under the curve as compared to CURB-65 and A-DROP (7). Specifically, a 4C Mortality Score ≥15 yielded a positive predictive value of 62% for death while a 4C Mortality Score ≤3 provided a negative predictive value of 99% (7). With several proposed risk scores, it remains to be determined how well they compare (6-8).
Although they have the potential to aid clinical decision making, risk scores are not without their limitations. Models have been developed retrospectively using readily available laboratory results. For example, the investigators of the 4C Mortality score could not assess scores that included LD, as this analyte is not routinely measured on hospital admission in the United Kingdom (7). Accordingly, powerful clinical chemistry tests, such as cardiac troponin, may have been excluded from models, which has been observed for some studies in patients with COVID-19 (9). It is important to understand how variability of testing at admission may impact the selection of variables chosen to include in the model. Fine-tuned clinical risk scores are anticipated as more data emerges regarding patient outcomes and long-term risks. Here, the role of clinical chemists will be needed to ensure utmost quality is maintained not only in testing the specific analytes but also in mitigating errors, thus further cementing the role of the clinical chemistry laboratory in the detection, monitoring, and management of COVID-19 patients.
- Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med. 2020;58(7):1063-1069.
- Feng S, Wang P.What Diagnostic Tests Are Available to Help Combat COVID-19?AACC Academy Scientific Shorts April 8, 2020. https://www.aacc.org/science-and-research/scientific-shorts/2020/what-diagnostic-tests-are-available-to-help-combat-covid19
- Van Caeseele P; Canadian Public Health Laboratory Network, Bailey D; Canadian Society of Clinical Chemists, Forgie SE; Association of Medical Microbiology and Infectious Disease Canada, Dingle TC; Canadian Association for Clinical Microbiology and Infectious Diseases, Krajden M; COVID-19 Immunity Task Force. SARS-CoV-2 (COVID-19) serology: implications for clinical practice, laboratory medicine and public health. CMAJ. 2020 Aug 24;192(34):E973-E979.
- Bailey D, Konforte D, Barakauskas VE, Yip PM, Kulasingam V, Abou El Hassan M, Beach LA, Blasutig IM, Catomeris P, Dooley KC, Gong Y, Kavsak P, Randell EW, Robinson JL, Shaw J, Taher J, White-Al Habeeb N. Canadian Society of Clinical Chemists (CSCC) Interim Consensus Guidance for Testing and Reporting of SARS-CoV-2 Serology. Clin Biochem. 2020 Oct 5:S0009-9120(20)30844-4.
- Kavsak PA, de Wit K, Worster A. Clinical chemistry tests for patients with COVID-19 - important caveats for interpretation. Clin Chem Lab Med. 2020 Jun 25;58(7):1142-1143.
- Kavsak PA, de Wit K, Worster A. Emerging key laboratory tests for patients with COVID-19. Clin Biochem. 2020 Jul;81:13-14.
- Knight SR, Ho A, Pius R, Buchan I, Carson G, Drake TM, Dunning J, Fairfield CJ, Gamble C, Green CA, Gupta R, Halpin S, Hardwick HE, Holden KA, Horby PW, Jackson C, Mclean KA, Merson L, Nguyen-Van-Tam JS, Norman L, Noursadeghi M, Olliaro PL, Pritchard MG, Russell CD, Shaw CA, Sheikh A, Solomon T, Sudlow C, Swann OV, Turtle LC, Openshaw PJ, Baillie JK, Semple MG, Docherty AB, Harrison EM; ISARIC4C investigators. Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score. BMJ. 2020 Sep 9;370:m3339.
- Liang W, Liang H, Ou L, Chen B, Chen A, Li C, Li Y, Guan W, Sang L, Lu J, Xu Y, Chen G, Guo H, Guo J, Chen Z, Zhao Y, Li S, Zhang N, Zhong N, He J; China Medical Treatment Expert Group for COVID-19. Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. JAMA Intern Med. 2020 Aug 1;180(8):1081-1089.
- Kavsak PA, Hammarsten O, Worster A, Smith SW, Apple FS. Cardiac Troponin Testing in Patients with COVID-19: A Strategy for Testing and Reporting Results. Clinical Chemistry, accepted manuscript.