Skip to main content
  • 7 Nikola Pašić Sq., 4th Fl., 11000 Belgrade
  • info@smj.rs

logo LKS

Case report

Limitations of rapid serological testing for SARS-CoV-2 in non-vaccinated patients in acute cardiac care

Mihajlo Viduljević1, Marija Polovina1,2, Milika Ašanin1,2, Igor Mrdović1,2
  • Cardiology Department, University Clinical Center of Serbia, Belgrade, Serbia
  • Faculty of Medicine, University of Belgrade, Serbia

ABSTRACT

In December 2019 in the city of Wuhan, in China, the first cases of infection caused by the new SARS-CoV-2 virus appeared, and later on, the disease caused by this virus was named COVID-19. Shortly after this, on March 11th, 2020, the WHO characterized COVID-19 as a global pandemic. The symptoms of COVID-19 and acute cardiovascular disorders (e.g., heart failure, pulmonary embolism or myocardial ischemia) frequently overlap, which poses a challenge for the establishing of a differential diagnosis in clinical practice. Rapid serological tests, which detect IgM and IgG classes of antibodies for SARS-CoV 2, have been developed with the primary purpose of screening the population’s immunological response to the SARS-CoV-2 virus. However, rapid serological tests are often used outside their original purpose, i.e., for the triage of possibly infected, non-vaccinated individuals, because they offer quick results, which may be particularly relevant in emergency settings. If serological testing is used to guide the admission of non-vaccinated patients with acute cardiovascular disorders to either an isolation unit for suspected COVID-19 positive individuals, or to hospital facilities for non-infected patients, it is important to recognize its limitations, in order to reduce the risk of false-positive or false-negative results. Hence, appropriate patient selection and cautious test interpretation is necessary to avoid misdiagnosis. The aim of this paper is to illustrate how serological testing may be used as a screening tool to inform the management of non-vaccinated patients with acute cardiovascular disorders requiring urgent hospital admission. As an illustration, we describe two clinical situations, in which serological testing produced meaningful results.


INTRODUCTION

In December 2019 in the city of Wuhan, in China, the first cases of infection caused by the new SARS-CoV-2 virus were registered, and later on, the disease caused by this virus was named COVID-19 [1]. Shortly after this, on March 11th, 2020, the WHO characterized COVID-19 as a global pandemic. The typical clinical presentation includes bilateral interstitial pneumonia; however, many patients also develop acute respiratory distress syndrome (ARDS) or multiorgan involvement. In particular, individuals with cardiovascular diseases have a twice to threefold higher risk of adverse outcomes, as compared to patients without comorbidities [2].

The symptoms of COVID-19 and acute cardiovascular disorders (e.g., heart failure, pulmonary embolism or myocardial ischemia) frequently overlap, which poses a challenge for the establishing of a differential diagnosis in clinical practice, especially in emergency settings. The confirmation of COVID-19 infection requires a positive antigen test or a positive reverse transcriptase polymerase chain reaction (RT-PCR) test of nasopharyngeal secretions, as standard diagnostic methods [3]. Rapid antigen testing was not available in most healthcare settings during the best part of 2020. With regard to RT-PCR testing, it may take a considerable amount of time to obtain the results. Occasionally, patients with a negative test result may be SARS-CoV-2 carriers, with delayed development of viral shedding (false- negative test), thus posing a threat for the spreading of the virus. Rapid serological tests, which detect IgM and IgG classes of antibodies for SARS-CoV-2, have been developed with the main purpose of screening the population for immunological response to SARS-CoV-2 [4]. However, rapid serological tests have often been used during 2020 outside their original purpose, for the triage of possibly infected individuals, because they offer quick results, which may be particularly relevant in emergency settings. The aim of this paper is to illustrate how serological testing may be used as a screening tool to inform the management of non-vaccinated patients with acute cardiovascular disorders requiring urgent hospital admission.

As an illustration, we describe two clinical situations, in which serological testing produced meaningful results.

The first case is a 76-year-old male presenting with high fever (38.6 °C) and dyspnea for 10 days before admission. The patient had a history of cardiomyopathy and signs of heart failure (S3 gallop, bilateral lung rales, hepatomegaly, lower extremity edema), but also, he had been in contact with a COVID-19 positive family member 12 days before admission, and he had not been vaccinated for SARS-CoV 2. Although he was diagnosed with decompensated heart failure, positive IgM antibodies for SARS-CoV-2 indicated admission to an isolation unit, and COVID-19 was subsequently confirmed with a positive RT-PCR test.

The second case is a 79-year-old male presenting with dyspnea, low-grade fever (37.4 °C), stabbing chest pain, which had begun three days before admission, and a negative epidemiological survey for COVID-19, also non-vaccinated. He was diagnosed with pulmonary embolism, but computed tomography (CT) scanning also revealed extensive bilateral ground-glass opacities, suspicious of COVID-19 pneumonia. The patient tested negative for SARS-CoV-2 IgM antibodies but was, nevertheless, admitted to the isolation unit, due to high clinical suspicion of COVID-19, which was subsequently confirmed with a positive RT-PCR test.

DISCUSSION

If serological testing is used (when rapid antigen testing is not available) to guide the admission of non-vaccinated patients with acute cardiovascular disorders to either an isolation unit for suspected COVID-19 positive individuals, or to hospital facilities for non-infected patients, it is important to recognize its limitations in reducing the risk of false-positive or false-negative results. Hence, only tests with high sensitivity and specificity should be used for this purpose. The test used in our institution has a reported sensitivity of 87% and a specificity of 100% for detecting the IgM class of antibodies, whilst the sensitivity and specificity for detecting the IgG class of antibodies is 96% and 98%, respectively.

PREVENTING FALSE-NEGATIVE TEST RESULTS

Priority should be given to non-vaccinated patients with high pretest probability, i.e., high likelihood of having the COVID-19 infection and of producing a detectable number of antibodies, which takes approximately one to three weeks from infection [5]. This point is well illustrated by the first clinical situation described above, where the epidemiological data were compelling, and sufficient time had elapsed to allow antibody detection.

For patients with low pretest probability, as in the second case described above (i.e., presenting within the first 7-10 days after symptom onset, with unclear exposure data), serological testing may be futile, yielding false-negative results. In this situation, an orthogonal testing algorithm should be employed. This implies the sequential use of two independent tests (SARSCoV-2 antigen detection in nasopharyngeal secretions or RT-PCR testing) to validate serological findings. In our case, the patient was admitted to an isolation unit based on clinical suspicion, and orthogonal testing with the use of RT-PCR to confirm COVID-19 was employed. It is of note that this approach allowed both appropriate clinical management and the prevention of in-hospital spread of the SARS-CoV-2 infection.

PREVENTING FALSE-POSITIVE TEST RESULTS

Although serological tests are considered to have high sensitivity and specificity for SARS-CoV-2, exceptionally, false-positive results in non-vaccinated patients may occur. Available data are scarce, but the data that does exist suggest that, in patients with a moderate to high titer of the rheumatoid factor, IgM antibodies for SARS-CoV-2 can test false-positive, presumably due to antibody cross-reactivity [6]. In the same way, cases of cross-reactivity with serological tests for dengue fever and Kawasaki disease have been described [7],[8]. These rare, but clinically relevant situations, need to be considered when interpreting test results.

CONCLUSION

In conclusion, the diagnostic validity of serological tests in non-vaccinated patients depends on the pretest probability and the likelihood of producing a detectable number of antibodies. Hence, if serological testing is used to guide hospital admission, appropriate patient selection and cautious test interpretation is necessary to avoid misdiagnosis. Furthermore, RT-PCR remains the gold standard for confirming COVID-19.

  • Conflict of interest:
    None declared.

Informations

Volume 2 No 3

September 2021

Pages 302-305
  • Keywords:
    COVID-19, triage, false-positive, false-negative, misdiagnosis
  • Received:
    28 June 2021
  • Revised:
    24 July 2021
  • Accepted:
    28 July 2021
  • Online first:
    30 September 2021
  • DOI:
  • Cite this article:
    Viduljević M, Polovina M, Ašanin M, Mrdović I. Limitations of rapid serological testing for SARS-CoV-2 in non-vaccinated patients in acute cardiac care. Serbian Journal of the Medical Chamber. 2021;2(3):302-5. doi: 10.5937/smclk2-32938
Corresponding author

Marija Polovina
Cardiology Department, University Clinical Center of Serbia
Faculty of Medicine, University of Belgrade
8 Koste Todorovića Street, 11000 Belgrade, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


  • 1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England Journal of Medicine. 2020;382(8):727-33.[CROSSREF]

    2. Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020.[CROSSREF]

    3. Sharfstein JM, Becker SJ, Mello MM. Diagnostic Testing for the Novel Coronavirus. JAMA. 2020;323(15):1437-8.[CROSSREF]

    4. Caini S, Bellerba F, Corso F, Díaz-Basabe A, Natoli G, Paget J, et al. Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications. Euro Surveill. 2020;25(23).[CROSSREF]

    5. Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antibody tests for identification of current and past infection with SARSCoV-2. The Cochrane Database of Systematic Reviews. 2020;6(6):Cd013652.[CROSSREF]

    6. Wang Q, Du Q, Guo B, Mu D, Lu X, Ma Q, et al. A Method to Prevent SARS-CoV-2 IgM False Positives in Gold Immunochromatography and Enzyme-Linked Immunosorbent Assays. J Clin Microbiol. 2020;58(6).[CROSSREF]

    7. Yan G, Lee CK, Lam LTM, Yan B, Chua YX, Lim AYN, et al. Covert COVID-19 and false-positive dengue serology in Singapore. Lancet Infect Dis. 2020;20(5):536.[CROSSREF]

    8. To KK, Chua GT, Kwok KL, Wong JS, Au DCY, Lam YY, et al. False-positive SARS-CoV-2 serology in 3 children with Kawasaki disease. Diagn Microbiol Infect Dis. 2020;98(3):115141.[CROSSREF]


REFERENCES

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England Journal of Medicine. 2020;382(8):727-33.[CROSSREF]

2. Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020.[CROSSREF]

3. Sharfstein JM, Becker SJ, Mello MM. Diagnostic Testing for the Novel Coronavirus. JAMA. 2020;323(15):1437-8.[CROSSREF]

4. Caini S, Bellerba F, Corso F, Díaz-Basabe A, Natoli G, Paget J, et al. Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications. Euro Surveill. 2020;25(23).[CROSSREF]

5. Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antibody tests for identification of current and past infection with SARSCoV-2. The Cochrane Database of Systematic Reviews. 2020;6(6):Cd013652.[CROSSREF]

6. Wang Q, Du Q, Guo B, Mu D, Lu X, Ma Q, et al. A Method to Prevent SARS-CoV-2 IgM False Positives in Gold Immunochromatography and Enzyme-Linked Immunosorbent Assays. J Clin Microbiol. 2020;58(6).[CROSSREF]

7. Yan G, Lee CK, Lam LTM, Yan B, Chua YX, Lim AYN, et al. Covert COVID-19 and false-positive dengue serology in Singapore. Lancet Infect Dis. 2020;20(5):536.[CROSSREF]

8. To KK, Chua GT, Kwok KL, Wong JS, Au DCY, Lam YY, et al. False-positive SARS-CoV-2 serology in 3 children with Kawasaki disease. Diagn Microbiol Infect Dis. 2020;98(3):115141.[CROSSREF]

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England Journal of Medicine. 2020;382(8):727-33.[CROSSREF]

2. Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020.[CROSSREF]

3. Sharfstein JM, Becker SJ, Mello MM. Diagnostic Testing for the Novel Coronavirus. JAMA. 2020;323(15):1437-8.[CROSSREF]

4. Caini S, Bellerba F, Corso F, Díaz-Basabe A, Natoli G, Paget J, et al. Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications. Euro Surveill. 2020;25(23).[CROSSREF]

5. Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Spijker R, Taylor-Phillips S, et al. Antibody tests for identification of current and past infection with SARSCoV-2. The Cochrane Database of Systematic Reviews. 2020;6(6):Cd013652.[CROSSREF]

6. Wang Q, Du Q, Guo B, Mu D, Lu X, Ma Q, et al. A Method to Prevent SARS-CoV-2 IgM False Positives in Gold Immunochromatography and Enzyme-Linked Immunosorbent Assays. J Clin Microbiol. 2020;58(6).[CROSSREF]

7. Yan G, Lee CK, Lam LTM, Yan B, Chua YX, Lim AYN, et al. Covert COVID-19 and false-positive dengue serology in Singapore. Lancet Infect Dis. 2020;20(5):536.[CROSSREF]

8. To KK, Chua GT, Kwok KL, Wong JS, Au DCY, Lam YY, et al. False-positive SARS-CoV-2 serology in 3 children with Kawasaki disease. Diagn Microbiol Infect Dis. 2020;98(3):115141.[CROSSREF]


© All rights reserved. Medical Chamber of Serbia.

To top