Publications by authors named "Jan Van Elslande"

13 Publications

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Delayed diagnosis and treatment of extreme hypertriglyceridemia due to rejection of a lipemic sample.

Biochem Med (Zagreb) 2021 Jun 15;31(2):021002. Epub 2021 Apr 15.

Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.

Introduction: Most laboratories routinely determine haemolysis, icterus and lipemia indices to identify lipemic samples and reject potentially affected results. Hypertriglyceridemia is the most common cause of lipemia and severe hypertriglyceridemia (≥ 11.3 mmol/L) is a major risk factor of acute pancreatitis.

Laboratory Analysis: A 56-year-old woman attended the outpatient clinic for a follow-up visit 1 month after a kidney transplantation. Her immunosuppressive therapy consisted of corticosteroids, cyclosporine, and mycophenolic acid. The routine clinical chemistry sample was rejected due to extreme lipemia. The comment "extreme lipemic sample" was added on the report, but the requesting physician could not be reached. The Cobas 8000 gave a technical error (absorption > 3.3) for the HIL-indices (L-index: 38.6 mmol/L) which persisted after high-speed centrifugation. The patient was given a new appointment 2 days later. The new sample was also grossly lipemic and gave the same technical error (L-index: 35.9 mmol/L).

What Happened: The second sample was manually diluted 20-fold after centrifugation to obtain a result for triglycerides within the measuring range (0.10-50.0 mmol/L). Triglycerides were 169.1 mmol/L, corresponding to very severe hypertriglyceridemia. This result was communicated to the nephrologist and the patient immediately recalled to the hospital. She received therapeutic plasma exchange the next day and did not develop acute pancreatitis.

Main Lesson: This case illustrates the delicate balance between avoiding the release of unreliable results due to lipemia and the risk of delayed diagnosis when results are rejected. Providing an estimate of the degree of hypertriglyceridemia might be preferable to rejecting the result.
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http://dx.doi.org/10.11613/BM.2021.021002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047784PMC
June 2021

Estimated half-life of SARS-CoV-2 anti-spike antibodies more than double the half-life of anti-nucleocapsid antibodies in healthcare workers.

Clin Infect Dis 2021 Mar 8. Epub 2021 Mar 8.

Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1093/cid/ciab219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989510PMC
March 2021

Longitudinal follow-up of IgG anti-nucleocapsid antibodies in SARS-CoV-2 infected patients up to eight months after infection.

J Clin Virol 2021 03 18;136:104765. Epub 2021 Feb 18.

Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address:

Background: Most SARS-CoV-2 infected patients develop IgG antibodies within 2-3 weeks after symptom onset. Antibody levels have been shown to gradually decrease in the first months after infection, but few data are available at six months or later.

Methods: A retrospective multi-center study was performed using 652 samples of 236 PCR-confirmed SARS-CoV-2 infected patients from 2 Belgian University hospitals. Patients were included if at least two samples were available (range 2-7 samples); including at least one sample collected 30 days or later after first positive PCR (range 0-240 days). Of those 236 patients, 19.1 % were classified as mild/asymptomatic (mild) and 80.9 % as moderate to critical (severe). IgG anti-nucleocapsid antibodies (anti-N) were measured using the Abbott Architect immunoassay.

Results: 22.2 % of mild and 2.6 % of severe COVID-19 cases never seroconverted (p < 0.001). Of the mild patients who seroconverted 0-59 days after PCR; 18.8 %, 40.0 % and 61.1 % were seronegative in the windows 60-119 days, 120-179 days and 180-240 days after PCR, respectively. In severe patients, these numbers were 1.9 %, 10.8 % and 29.4 % respectively (p < 0.05 each). Antibody levels were significantly higher in severe patients compared to mild patients in each 60 day window (p < 0.001 each).

Conclusions: SARS-CoV-2 anti-N IgG antibody levels steadily decreased after 2 months up to 8 months post PCR. Of severe COVID-19 patients, 70.6 % remained positive up to eight months after infection. Antibody levels were significantly lower in mild SARS-CoV-2 infected patients and 61.1 % became seronegative within 6 months after the first positive PCR.
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http://dx.doi.org/10.1016/j.jcv.2021.104765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891078PMC
March 2021

Immunoassays for anti-SARS-CoV-2 antibodies: recent insights.

Lancet Infect Dis 2021 05 30;21(5):e120. Epub 2020 Oct 30.

Clinical Department of Laboratory Medicine and National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, 3000 Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30846-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833516PMC
May 2021

Added value of anti-SARS-CoV-2 antibody testing in a Flemish nursing home during an acute COVID-19 outbreak in April 2020.

Acta Clin Belg 2020 Oct 18:1-6. Epub 2020 Oct 18.

Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium.

Objectives: To examine the added value of anti-SARS-CoV-2 antibody testing in a nursing home during an acute COVID-19 outbreak. RT-PCR is the gold standard, but can be false-negative.

Methods: 119 residents and 93 staff members were tested with RT-PCR test and/or a rapid IgM/IgG test. Of these participants, 176 had both tests, 24 only RT-PCR, and 12 only IgM/IgG in the period April 14 to 16 April 2020.

Results: 40 (34%) residents and 11 (13%) staff were PCR-positive. Using a rapid IgM/IgG test, 17 (17%) residents and 18 (20%) staff were positive for IgM and/or IgG (IgM/IgG). Thirty-two PCR-positive residents had an IgM/IgG test: 9 (28%), 11 (34%), and 13 (41%) were positive for IgM, IgG, and IgM/IgG. Ten PCR-positive staff had an IgM/IgG test: 3 (30%), 6 (60%), and 6 (60%) were positive for IgM, IgG, and IgM/IgG. Additional IgM/IgG tests were performed in 9 residents 11 to 14 days after the positive RT-PCR test. Of those, 7 (78%) tested positive for IgM/IgG. When retested 3 weeks later, the 2 remaining residents also tested positive. Of the 134 PCR-negative participants who had an IgM/IgG test, 15 were positive for IgM/IgG (8% of the 200 participants tested with RT-PCR).

Conclusions: During an acute outbreak in a nursing home, 26% of residents and staff were PCR-positive. An additional 8% was diagnosed using IgM/IgG antibody testing. The use of RT-PCR alone as the sole diagnostic method for surveillance during an acute outbreak is insufficient to grab the full extent of the outbreak.
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http://dx.doi.org/10.1080/17843286.2020.1834285DOI Listing
October 2020

Münchhausen Syndrome: A Case Report of an Unusual Cause of Vitamin K Antagonist Intoxication.

A A Pract 2020 Apr;14(6):e01189

Department of Cardiovascular Sciences, University Hospitals Leuven, Leuven, Belgium.

Psychiatric disorders must be considered in the differential diagnosis of patients presenting to the emergency department with unexplainable somatic symptoms. Physicians should be aware of Münchhausen syndrome as a possible diagnosis. A 46-year-old female patient presented at the emergency department with signs of coagulopathy. She denied taking any anticoagulant drugs as well as rat poison. Urine toxicology revealed the presence of vitamin K antagonists (VKAs). After an extensive workup, she was diagnosed with Münchhausen syndrome. Intentional intoxication with VKA is rare.
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http://dx.doi.org/10.1213/XAA.0000000000001189DOI Listing
April 2020

Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs.

Clin Microbiol Infect 2020 Nov 31;26(11):1557.e1-1557.e7. Epub 2020 Jul 31.

Clinical Department of Laboratory Medicine and National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address:

Objectives: The aim was to determine the antibody response against SARS-CoV-2 spike protein and nucleoprotein using four automated immunoassays and three ELISAs for the detection of total Ig antibodies (Roche) or IgG (Abbott, Diasorin, Snibe, Euroimmun, Mikrogen) in COVID-19 patients.

Methods: Sensitivity and dynamic trend to seropositivity were evaluated in 233 samples from 114 patients with moderate, severe or critical COVID-19 confirmed with PCR on nasopharyngeal swab. Specificity was evaluated in 113 samples collected before January 2020, including 24 samples from patients with non-SARS coronavirus infection.

Results: Sensitivity for all assays was 100% (95% confidence interval 83.7-100) 3 weeks after onset of symptoms. Specificity varied between 94.7% (88.7-97.8) and 100% (96.1-100). Calculated at the cut-offs that corresponded to a specificity of 95% and 97.5%, Roche had the highest sensitivity (85.0% (79.8-89.0) and 81.1% (76.6-85.7), p < 0.05 except vs. Abbott). Seroconversion occurred on average 2 days earlier for Roche total Ig anti-N and the three IgG anti-N assays (Abbott, Mikrogen, Euroimmun) than for the two IgG anti-S assays (Diasorin, Euroimmun) (≥50% seroconversion day 9-10 vs. day 11-12 and p < 0.05 for percent seropositive patients day 9-10 to 17-18). There was no significant difference in the IgG antibody time to seroconversion between critical and non-critical patients.

Discussion: Seroconversion occurred within 3 weeks after onset of symptoms with all assays and on average 2 days earlier for assays detecting IgG or total Ig anti-N than for IgG anti-S. The specificity of assays detecting anti-N was comparable to anti-S and excellent in a challenging control population.
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http://dx.doi.org/10.1016/j.cmi.2020.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834107PMC
November 2020

Comparison of the diagnostic performance with whole blood and plasma of four rapid antibody tests for SARS-CoV-2.

Clin Chem Lab Med 2020 09;58(10):e197-e199

Clinical Department of Laboratory Medicine and National Reference Center for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1515/cclm-2020-0817DOI Listing
September 2020

A case of severe pseudohyperkalaemia due to muscle contraction.

Biochem Med (Zagreb) 2020 Jun;30(2):021004

Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.

Introduction: Severe hyperkalaemia is a serious medical condition requiring immediate medical attention. Before medical treatment is started, pseudohyperkalaemia has to be ruled out.

Case Description: A 10-month old infant presented to the emergency department with fever and coughing since 1 week. Routine venous blood testing revealed a severe hyperkalaemia of 6.9 mmol/L without any indication of haemolysis. Reanalysis of the plasma sample confirmed the hyperkalaemia (7.1 mmol/L). Based on these results, the clinical pathologist suggested to perform a venous blood gas analysis and electrocardiogram (ECG) which revealed a normal potassium of 3.7 mmol/L and normal ECG, ruling out a potentially life-treating hyperkalaemia. The child was diagnosed with pneumonia. The paediatrician had difficulty to perform the first venous blood collection due to excessive movement of the infant during venipuncture. The muscle contractions of the child in combination with venous stasis most probably led to a local increase of potassium in the sampled limbs. The second sample collected under optimal preanalytical circumstances had a normal potassium. Since muscle contraction typically does not cause severe hyperkalaemia, other causes of pseudohyperkalaemia were excluded. K-EDTA contamination and familial hyperkalaemia were ruled out and the patient did not have extreme leucocytosis or thrombocytosis. By exclusion a diagnosis of pseudohyperkalaemia due to intense muscle movement and venous stasis was made.

Conclusion: This case suggests that intense muscle contraction and venous stasis can cause severe pseudohyperkalemia without hemolysis. Once true hyperkalemia has been ruled out, a laboratory work-up can help identify the cause of pseudohyperkalaemia.
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http://dx.doi.org/10.11613/BM.2020.021004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271752PMC
June 2020

Laboratory information system requirements to manage the COVID-19 pandemic: A report from the Belgian national reference testing center.

J Am Med Inform Assoc 2020 08;27(8):1293-1299

Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.

Objective: The study sought to describe the development, implementation, and requirements of laboratory information system (LIS) functionality to manage test ordering, registration, sample flow, and result reporting during the coronavirus disease 2019 (COVID-19) pandemic.

Materials And Methods: Our large (>12 000 000 tests/y) academic hospital laboratory is the Belgian National Reference Center for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We have performed a moving total of >25 000 SARS-CoV-2 polymerase chain reaction tests in parallel to standard routine testing since the start of the outbreak. A LIS implementation team dedicated to develop tools to remove the bottlenecks, primarily situated in the pre- and postanalytical phases, was established early in the crisis.

Results: We outline the design, implementation, and requirements of LIS functionality related to managing increased test demand during the COVID-19 crisis, including tools for test ordering, standardized order sets integrated into a computerized provider order entry module, notifications on shipping requirements, automated triaging based on digital metadata forms, and the establishment of databases with contact details of other laboratories and primary care physicians to enable automated reporting. We also describe our approach to data mining and reporting of actionable daily summary statistics to governing bodies and other policymakers.

Conclusions: Rapidly developed, agile extendable LIS functionality and its meaningful use alleviates the administrative burden on laboratory personnel and improves turnaround time of SARS-CoV-2 testing. It will be important to maintain an environment that is conducive for the rapid adoption of meaningful LIS tools after the COVID-19 crisis.
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http://dx.doi.org/10.1093/jamia/ocaa081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197526PMC
August 2020

UPLC-MS/MS method for determination of retinol and α-tocopherol in serum using a simple sample pretreatment and UniSpray as ionization technique to reduce matrix effects.

Clin Chem Lab Med 2020 04;58(5):769-779

Clinical Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.

Background Our goal was to develop a simple, rapid and precise ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the determination of retinol and α-tocopherol in serum. Currently published LC-MS/MS methods either require complex extraction procedures (liquid-liquid or solid-phase) or do not meet desirable specifications for imprecision in serum (coefficient of variation [CV] <6.8% and 6.9%, respectively). Methods Sample preparation consisted of a simple protein precipitation with ethanol and acetonitrile. Stable isotope-labeled internal standards (IS) and a homemade calibration curve were used for quantification. The analysis was performed using an Acquity I-class Xevo TQ XS LC-MS/MS. Chromatographic runtime was 6.0 min using a reversed phase gradient elution. UniSpray (US) as an ionization technique was compared to electrospray ionization (ESI). Analytical validation included matrix effect, recovery and trueness compared to National Institute of Standards and Technology (NIST) standards and United Kingdom National External Quality Assessment Service (UK NEQAS) samples. Results Intra- and inter-run CVs were <4.9% for retinol and <1.7% for α-tocopherol, both complying with desirable specifications for imprecision. Bias compared to NIST standards was <3.1% for both compounds. The method was linear over the entire tested range. The lower limit of quantification (LLOQ) with US was lower than with ESI for both retinol (0.022 vs. 0.043 mg/L) and α-tocopherol (0.22 vs. 0.87 mg/L). Matrix effects were not significant (<15%) for retinol. However, for α-tocopherol matrix effects of on average 54.0% were noted using ESI, but not with US. Conclusions We developed a fast, precise and accurate UPLC-MS/MS method for the determination of retinol and α-tocopherol in human serum using a single-step sample pretreatment. Ionization using US eliminated the matrix effects for α-tocopherol.
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http://dx.doi.org/10.1515/cclm-2019-1237DOI Listing
April 2020

The sudden death of the combined first trimester aneuploidy screening, a single centre experience in Belgium.

Clin Chem Lab Med 2019 Oct;57(11):e294-e297

Clinical Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium, Phone: 003216347015, Fax: 003216347931.

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http://dx.doi.org/10.1515/cclm-2019-0231DOI Listing
October 2019
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