Background: Current testing of symptomatic patients for SARS-CoV-2 involves the use of nucleic acid amplification tests, also known as genetic, RNA or PCR to detect viral RNA. The initial use of point-of-care (POC) antibody tests, also known as serological tests in the management of SARS-CoV-2 infection was limited. In this review, we determine the significance of POC antibody serological tests and explore their possible role in the diagnosis and management of patients infected with SARS-CoV-2 virus.
Methods: A literature search was conducted in Google Scholar, PubMed, and Embase, and supplemented by searching the Center for Disease Control (CDC), and the Infectious Diseases Society of America (IDSA) websites. We identified 7 articles published in the last 6 months pertaining to the keywords. The sensitivity and specificity of the IgG/IgM antibody tests obtained from these studies were compared and used to determine the clinical importance of the rapid diagnostic antibody test in SARS-CoV-2 infection.
Results: Through the literature review, it was found that POC diagnostic antibody tests can be used as an adjuvant with the nucleic acid amplification tests in determining both active and post-exposure antibodies. These rapid antibody IgG/IgM tests had high sensitivity, the ability of a test to correctly identify those with the disease, and high specificity, the ability of the test to correctly identify those without the disease.
Conclusion: Emerging studies indicate the importance of POC antibody serological testing as an important diagnostic tool in the current SARS-CoV-2 pandemic. Considering the limitations of the molecular methods of testing, POC antibody tests can help reduce dependency on the molecular assays of testing when used in conjunction with them

Balcom, Dawn

Sheikh, Daniya

Tripathi, Nishita

English

Background: Current testing of symptomatic patients for SARS-CoV-2 involves the use of nucleic acid amplification tests, also known as genetic, RNA, or polymerase chain reaction (PCR), to detect viral RNA. The initial use of point of care (POC) antibody tests, also known as serological tests, in the management of SARS-CoV-2 infection was limited. In this review, we determine the significance of POC antibody serological tests and explore their possible role in the diagnosis and management of patients infected with the SARS-CoV-2 virus.
Methods: A literature search was conducted in Google Scholar, PubMed, and Embase, supplemented by searching the Centers for Disease Control and Prevention (CDC) and Infectious Diseases Society of America (IDSA) websites. We identified seven articles published in the last six months pertaining to our search. The sensitivity and specificity statistics of IgG/IgM antibody tests obtained from these studies were compared and used to determine the clinical importance of rapid diagnostic antibody tests for SARS-CoV-2.
Results: Through the literature review, it was found that POC diagnostic antibody tests can be used as an adjuvant with nucleic acid amplification tests in determining both active and post-exposure antibodies. These rapid antibody IgG/IgM tests had high sensitivity—the ability of a test to correctly identify those with the disease—and high specificity, the ability of a test to correctly identify those without the disease.
Conclusion: Emerging studies indicate the importance of POC antibody serological testing as a diagnostic tool in the current SARS-CoV-2 pandemic. Considering the limitations of the molecular methods of testing, POC antibody tests can help reduce dependency on molecular assays when used in conjunction with them

University of Louisville

University of Louisville Journal of Respiratory InfectionsBRIEF REVIEWULJRI | https://doi.org/10.18297/jri/vol4/iss1/70 1AbstractBackground: Current testing of symptomatic patients for SARS-CoV-2 involves the use of nucleic acid amplification tests, also known as genetic, RNA or PCR to detect viral RNA. The initial use of point-of-care (POC) antibody tests, also known as serological tests in the manage-ment of SARS-CoV-2 infection was limited. In this review, we determine the significance of POC antibody serological tests and explore their possible role in the diagnosis and management of patients infected with SARS-CoV-2 virus.Methods: A literature search was conducted in Google Scholar, PubMed, and Embase, and supplemented by searching the Center for Disease Control (CDC), and the Infectious Diseases Society of America (IDSA) websites. We identified 7 articles published in the last 6 months per-taining to the keywords. The sensitivity and specificity of the IgG/IgM antibody tests obtained from these studies were compared and used to determine the clinical importance of the rapid diagnostic antibody test in SARS-CoV-2 infection.Results: Through the literature review, it was found that POC diagnostic antibody tests can be used as an adjuvant with the nucleic acid amplification tests in determining both active and post-exposure antibodies. These rapid antibody IgG/IgM tests had high sensitivity, the ability of a test to correctly identify those with the disease, and high specificity, the ability of the test to correctly identify those without the disease.Conclusion: Emerging studies indicate the importance of POC antibody serological testing as an important diagnostic tool in the current SARS-CoV-2 pandemic. Considering the limitations of the molecular methods of testing, POC antibody tests can help reduce dependency on the molecular assays of testing when used in conjunction with them.IntroductionIgG and IgM are among the different types of antibodies produced during an immuno-logical response to a pathogen. Detection of IgM in the body indicates a recent infection while the presence of IgG indicates a prior exposure to the same pathogen or a chronic infection. The two major antigenic targets of severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) virus against which antibodies are detected are spike glycoprotein (S) and nucleocapsid phosphoprotein (N). As per CDC, SARS-CoV-2 infection is unusual as there is simultaneous appearance of both IgG and IgM antibodies in the serum within 2-3 weeks after the onset of illness. Therefore, detection of IgM without IgG is uncom-mon during this timeframe. [1] Studies indicate that serological tests can detect the pres-ence of SARs-CoV-2 IgG and IgM antibodies as early as day 4 after symptom onset, how-ever, antibodies could be also be detected in the middle and later course of the disease. [2] Most patients seroconvert around 7-11 days post-exposure to the virus. [3] One study found that the IgM antibodies initially increased followed by a decline while the IgG antibody levels stabilized over time. IgG antibody levels were also found to double after the PCR resulted negative. [4] Another study found that the average levels of IgM and IgA antibodies increased within 6-8 days from the onset of symptoms. Compared to the IgM antibody, IgA antibody showed persistently higher levels for the whole observation period, with a peak level at 20-22 days. [5] The detection of the antibodies collectively at Recommended Citation:Tripathi, Nishita; Sheikh, Daniya; and Balcom, Dawn (2020). “The Role of Rapid Diagnostic Point of Care IgG/IgM Antibody Tests in the Diagnosis of SARS-CoV-2 Infection,” The University of Louisville Journal of Respiratory Infections: Vol. 4, Iss. 1, Article 70. Received Date: September 4, 2020Accepted Date: November 4, 2020Published Date: November 23, 2020Copyright: © 2020 The author(s). This origi-nal article is brought to you for free and open access by ThinkIR: The University of Louis-ville’s Institutional Repository. For more infor-mation, please contact thinkir@louisville.edu. This article is distributed under the terms of the Creative Commons Attribution 4.0 Internation-al License (CC BY 4.0), which permits unre-stricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding Source: The author(s) received no specific funding for this work.Conflict of Interest: All authors declared no conflict of interest in relation to the main objec-tive of this work.The Role of Rapid Diagnostic Point of Care IgG/IgM Antibody Tests in the Diagnosis of SARS-CoV-2 InfectionNishita Tripathi1*, MD; Daniya Sheikh1, MD; Dawn Balcom1, DNP1 Division of Infectious Diseases, University of Louisville School of Medicine, Louisville, KY, USA*nishita.tripathi@louisville.eduULJRI | https://doi.org/10.18297/jri/vol4/iss1/70 2ULJRI The Role of Rapid Diagnostic Point of Care IgG/IgM Antibody Tests in the Diagnosis of SARS-CoV-2 Infectionthe time when the PCR becomes negative implied that they may have a role in the clearance of the virus. [2] While one study linked the appearance of antibodies with the severity of the disease, another study revealed that it may be inde-pendent of the clinical course of the disease. [6] It was also found that high antibody levels may help in the progression of the infection as high viral load lead to strong extra-follicular B cell stimulation leading to rapid antibody production which doesn’t follow the sequential change from IgM to IgG. Such antibodies stimulate cytokine storm which has been implicated in acute lung injury associated with COVID-19 infection. [6] Many patients were found to be seropositive within the course of illness for more than 30 days. [2] However, a negative serological test does not exclude COVID-19 infection as many patients were found to be seronegative during the early course of the infection. [4] Hence the results of these serological assays may be inconclusive during the early course of the disease.The CDC categorizes antibody tests into two broad categories: 1) Binding antibody detection tests and 2) neutralizing antibody tests. While the use of neutralizing antibody tests has not been approved by the US-FDA, the binding antibody tests are widely employed in the detection of the IgG and IgM antibodies. These tests detect the presence of different types of antibodies against different components of the SARS-CoV-2 virus using purified proteins of the virus. Specific reagents are used to identify individual antibody types such as IgG, IgM, and IgA. These tests are further classified into point-of-care tests (POC) such as lateral flow immunochromatography assays (LFIA) and laboratory-based tests such as Enzyme-linked immunosorbent assay (ELISA) and chemiluminescent assay (CIA). POC tests are performed at the time and place of patient care such as the patient’s bedside or the physician’s office. These tests use lateral flow devices to detect IgG or IgG and IgM or total antibody in serum, plasma, whole blood, saliva. While the POC tests can be per-formed in a field setting, lab-based tests require trained laboratorians and a specialized setting. IgG/IgM rapid tests are the two available point of care, qualitative antibody detection tests. [1] The current recommendations by CDC heavily depend upon the use of reverse transcriptase polymerase chain reaction (RT-PCR) for the qualitative detection of SARS-CoV-2 viral nucleic acid for the diagnosis and the management of the COVID-19. In the wake of the increasing emergence of challenges and limitations of the molecular tests, the importance of rapid diagnostic antibody tests has increased, and their role is being rapidly explored. [7] In our review, we explore the role of the POC antibody tests.MethodsFor our article, literature contained in Google Scholar, PubMed,  and Embase, as well as websites for the Center for Disease Control (CDC) and the Infectious Diseases Society of America (IDSA) database, was searched using combina-tions of keywords ‘SARS-CoV-2’, ‘coronavirus’, ‘COVID-19 pandemic’, ‘health care workers’, ‘molecular test’, ‘diagnos-tic tests’, ‘serological tests’ and their variants. The articles used for the review were published within the last 6 months (December 2019 to June 2020).ResultsSeven studies were eligible for inclusion in this review. All the included studies used immunochromatography method of POC IgG/IgM antibody test. The tests were conducted on blood or plasma or serum samples. Spicuzza et al, Ying et al, Zhengtu et al, Dohla et al, and Choe et al used combined IgG/IgM antibody kit and divided patients in two groups. [8-12] One group had patients who tested positive for SARS-CoV-2 using RT-PCR while the second group had patients who were suspected of having COVID-19 infection, but tested negative on an RT-PCR. Hoffman et al conducted the study by dividing their patients in a similar manner, but they used rapid IgG-IgM detection test which detected IgG and IgM antibody separately. [13] While Xiang et also used rapid IgG-IgM antibody detection kit detecting the anti-bodies separately, they tested patients diagnosed with a positive viral RT-PCR in both groups. [14] They tested one of the groups with laboratory-based ELISA antibody test while the other group was tested using the rapid IgG-IgM POC antibody test. These studies calculated the sensitivities and specificities of the test, which can be seen in Table 1.ULJRI | https://doi.org/10.18297/jri/vol4/iss1/70 3ULJRI The Role of Rapid Diagnostic Point of Care IgG/IgM Antibody Tests in the Diagnosis of SARS-CoV-2 InfectionS.no Author Title Result Summary1 Spicuzza et alReliability and usefulness of a rapid IgM-IgG antibody test for the diagnosis of SARS-CoV-2 infection: A preliminary report. Sample size-37           Sensitivity=82.6%         Specificity=92.8%In patients presenting with a discrepancy between the clinical/radiological feature and the molecular test, the rapid antibody detection might be an additional element helping the clinician to make a correct diagnosis2 Xiang et alDiagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2Sample size-179       Sensitivity- 85% (77/90)        Specificity- 91% (8/89)The sensitivity and specificity of the IgG/IgM combined test kit is adequate, with short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contribute to its competence for mass testing. At the current stage, it cannot replace SARA-CoV-2 nucleic acid RT-PCR, but it can serve as a complementary option with RT-PCR.3 Yan et alEvaluation of Enzyme-linked Immunoassay and Colloidal Gold Immunochromatographic Assay kit for detection of novel coronavirus (SARS-CoV-2) causing an outbreak of pneumonia (COVID 19)Sample size-154              Sensitivity- 82(75/91)     Specificity- 100% (35/35)Although ELISA and GICA are simple, fast, and safe, the results can be used for clinical reference4 Hoffman et alEvaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2Sample size - 153        Sensitivity- Ig M: 69% (20/29)             Ig G-99% (27/29)         Specificity- Ig M-100% (124/124)         Ig G- 99%(123/124)The test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first few weeks after infection.5 Zhengtu et alDevelopment and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosisSample size-397           Sensitivity- 89% (352/397)             Specificity- 91% (12/128) The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories6 Dohla et alRapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivitySample size-49                 Sensitivity- 36.4%           Specificity- 90% Rapid antibody test have low sensitivity and is not recommended for community screening.7 Choe et alDiagnostic performance of immunochromatography assay forrapid detection of IgM and IgG in coronavirus disease 2019 Sample size- 149           Sensitivity- 93% (95% CI: 84.1-97.6)        Specificity- 96.2% (95% CI: 89.3-99.2)The immunochromatography-based COVID-19 IgG/IgM rapid test is a useful and practical diagnostic assay for practical diagnostic assay for detection of COVID-19, especially in the presence of IgM or IgG antibodies.Table 1. Studies considered for our review.DiscussionIt was observed that the overall sensitivity and specificity of these antibody tests was high except for Dohla et al. The antibody tests also yielded high sensitivity and specificity for the detection of individual IgG/IgM antibodies. The re-sults indicate that these tests could play a very important role in diagnosis of SARS-CoV-2 infection when used in con-junction with the molecular tests. The rapid diagnostic POC test could be preferred over the laboratory-based antibody test. Hence, the rapid diagnostic IgG/IgM antibody tests can be used in conjunction with the molecular test. These tests are faster, less expensive, easy to use, accessible to staff without lab training and are higher specificity versus the laboratory-based antibody test. [4,2,15] These antibody tests have also been found to be beneficial in diagnosing pa-tients with a prolonged clinical course. They can be used to diagnose patients with a prolonged course of illness, who get a false negative result on the PCR. [2] They can diagnose patients who have recovered from a prior asymptomatic infection. These asymptomatic patients may have a positive IgG, a negative IgM, a negative molecular test with no prior history of COVID-19 infection. [16] POC antibody tests can also be used for contact tracing, serological surveillance at local, regional, state, and national levels. They can identify possibly immune patients and individuals who could be a source of therapeutic or prophylactic neutralizing antibodies and vaccine trials. [15,17] However, the use of these assays cannot be used to determine immune status in individuals until the presence, durability and duration of immunity is established. [1]ULJRI | https://doi.org/10.18297/jri/vol4/iss1/70 4ULJRI The Role of Rapid Diagnostic Point of Care IgG/IgM Antibody Tests in the Diagnosis of SARS-CoV-2 InfectionReferences 1. 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The Role of Rapid Diagnostic Point of Care IgG/IgM Antibody Tests in the Diagnosis of SARS-CoV-2 Infection

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The role of rapid diagnostic point of care IgG/IgM antibody tests in the diagnosis of SARS-CoV-2 infection

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