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EDITORIAL
Year : 2020  |  Volume : 24  |  Issue : 2  |  Page : 51-54
 

Antibody testing in the context of COVID-19 and return to work


Global Medical and Occupational Health, Unilever and Non-Executive Independent Director, Apollo Hospitals Enterprise Limited, Mumbai, India

Date of Submission18-Jul-2020
Date of Acceptance25-Jul-2020
Date of Web Publication19-Aug-2020

Correspondence Address:
Dr. T Rajgopal
MD., DPH., DIH., DNB., FFOM (London)., FFOM (Ireland) Vice President, Global Medical and Occupational Health, Unilever & Non-Executive Independent Director, Apollo Hospitals Enterprise Limited.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijoem.IJOEM_276_20

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How to cite this article:
Rajgopal T. Antibody testing in the context of COVID-19 and return to work. Indian J Occup Environ Med 2020;24:51-4

How to cite this URL:
Rajgopal T. Antibody testing in the context of COVID-19 and return to work. Indian J Occup Environ Med [serial online] 2020 [cited 2020 Sep 22];24:51-4. Available from: http://www.ijoem.com/text.asp?2020/24/2/51/292612




COVID-19 has been labelled as global pandemic by the WHO, and as of early July 2020 it has affected 11 million individuals across the world and has led to 525,000 deaths.[1] It has posed an unprecedented challenge to Governments and public health scientists across the world, to control it.

While China was the first to open its country for routine activities, over the past month or so a few other countries have started to reopen in a phased manner. Examples include South Korea, New Zealand, Singapore, and now many countries in Europe. As workplaces open, employers are looking for answers on what measures they need to take while bringing employees back to work. [Figure 1] is a snapshot of the current burden of COVID-19 in some of the countries which have opened up.[2]
Figure 1: Showing the daily new confirmed COVID-19 cases per million people as a seven day rolling average

Click here to view


These countries have very low or negligible levels of community transmission and have allowed offices to function.

One of the hotly contested area is the belief that antibody testing will offer a clue about who are immune and who are not and thereby help bringing in employees faster to work—especially in countries which went through massive infections, plateaued and then have shown declining trends in infections and fatalities.

To understand any utility of these tests one should have an idea about the interpretation of these tests.

The first detectible serology marker is total antibody, followed by IgM and IgG, with a median seroconversion time of 15, 18, and 20 day post-exposure (d.p.e) or 9, 10, and 12 days post-onset of symptoms. Seroconversion was first detected at 7 d.p.e in 98.9% of the patients and viral load declined as antibody levels increased.[3]

A recent report by Long et al. has mentioned that within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion to IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. In this study, the proportion of patients with positive virus-specific IgG reached 100% approximately 17–19 days after symptom onset, while the proportion of patients with positive virus-specific IgM reached a peak of 94.1% approximately 20–22 days after symptom onset.[4]


  Reliability of Antibody Testing Top


Recent research[5] is showing that over 99.5% of the symptomatic COVID-19 patients develop antibodies to the SARS-CoV-2 spike protein. The time taken for IgG antibodies to develop range from 7 to 50 days from the onset of symptoms and 5 to 49 days from the symptom resolution. The median time taken to reach highest antibody titres are 24 days from symptom onset and 15 days from system resolution. These findings show that the optimum timeframe[6] to use antibody testing is at least 4 weeks after onset of symptoms or 2 weeks after symptom resolution.[7]

Shoreland Travax[8] reports that the U.S. FDA published a performance assessment of antibody tests that reviews for adequately robust antibody tests; correlation with immunity is pending further data. The SARS-CoV-2 IgG test (Abbott Diagnostics) and the Elecsys Anti-SARS-CoV-2 IgG test (Roche) both have sensitivity and specificity over 99.5% and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack (Ortho-Clinical Diagnostics, Inc.) and Anti-SARS-CoV-2 ELISA IgG test (EUROIMMUN US Inc.) have positive and negative predictive values above 99.5%. In a performance assessment by Public Health England, the Roche test had a specificity of 100%, and sensitivity was 87.7% 21 days after symptom onset and 100% more than 40 days after. The Abbott test had a specificity of 99.6%, with a sensitivity of 93.9% at 14 days after symptom onset. Other tests in the market have lower degrees of sensitivity and specificity and hence will have less positive predictive values.

Antibody tests are potentially useful to detect previous infection but should never be used alone for the detection of active infection in an ill or asymptomatic person.

The timeline in the development of antibodies to the coronavirus 2 is depicted in Figure 2.

For any judgement pertaining to exposure and actions to be taken based on reviewing both the test for the virus (PCR) and the test for antibodies (IgM and IgG), it would be useful to refer to Table 1.


  WHO Position Testing on the Use of Antibody Testing Top


Recently the WHO has come out with the following guideline with respect to Antibody testing:[9]

“There is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection. At this point in the pandemic, there is not enough evidence about the effectiveness of antibody-mediated immunity to guarantee the accuracy of an “immunity passport” or “risk-free certificate.” People who assume that they are immune to a second infection because they have received a positive test result may ignore public health advice. The use of such certificates may therefore increase the risks of continued transmission. As new evidence becomes available, WHO will update this scientific brief.”

In India, Public Health Authorities[10] mainly use antibody testing in hot spots using a mix of RT-PCR and antibody testing in line with ICMR guidelines.[11]


  CDC Recommendation on the Use of Antibody Testing Top


The CDC has recently updated its guidance on the use of antibody testing. Their key recommendations are:[12]

  • In general, a positive antibody test is presumed to mean a person has been infected with SARS-CoV-2, the virus that causes COVID-19, at some point in the past. It does not mean they are currently infected.
  • Antibodies start developing within 1–3 weeks after infection.
  • Until scientists get more data on whether antibodies protect against reinfection with this virus, everyone should continue to take steps to protect themselves and others, including staying at least 6 feet away from other people outside of their home (social distancing), even if they have had a positive antibody test.
  • People who wear personal protective equipment (PPE) at work should continue to wear PPE, even if they test positive for antibodies to the virus.
  • Antibody test results should not be used to determine if someone can return to work.


The American Society of Microbiologyhas the following guidance on when and when not to use antibody testing[13]

When COVID-19 Serology Testing Should Be Used

  • The primary application of serology testing is the identification of individuals who have previously been infected with SARS-CoV-2. This knowledge can be used to guide epidemiology and seroprevalence studies, as well as facilitate contact tracing.
  • Serological tests may also be used to identify potential convalescent plasma donors and to evaluate the immune response to candidate vaccines.


When COVID-19 Serology Testing Should not be used

  • Serology testing should not be used to diagnose acute or recent cases of COVID-19.
  • At this point in time, serology tests cannot be used to definitively determine if a patient has developed protective immunity.



  Conclusion Top


For mildly ill patients, shedding of viral RNA from saliva and nasopharyngeal secretions is at peak value on the day of symptom onset, remains high for approximately 6 days, declines significantly in the second week of illness, and usually ceases by day 14, but may continue for 21 days. No culturable virus has been detected for longer than 8 days after symptom onset.[14] This indicates that doing any antibody test would not pick up active cases when they are most likely to be transmitting infection and are also ill, thereby negating the use of antibody tests to aid clinical decision making.
Table 1: Interpreting Antigen and Antibody tests[8]

Click here to view
Table 2: Health Questionnaire to assess Return to Work

Click here to view


The WHO criteria for return to work is based on the following criteria (WHO does not advocate antibody testing)[15]

  • For symptomatic patients: 10 days after symptom onset, plus at least 3 additional days without symptoms (including without fever and without respiratory symptoms)
  • For asymptomatic cases: 10 days after positive test for SARS-CoV-2.


For example, if a patient had symptoms for 2 days, then the patient could be released from isolation after 10 days + 3 = 13 days from date of symptom onset; for a patient with symptoms for 14 days, the patient can be discharged (14 days + 3 days =) 17 days. Countries may choose to continue to use testing as part of the release criteria. If so, the recommendation of two negative PCR tests at least 24 h apart can be used.

The Infectious Diseases Society of America (IDSA) also cautions against the use of Antibody testing to draw conclusions on the levels of protection (immunity) being offered by antibodies against COVID-19.[16]

The Faculty of Occupational Medicine (UK) have the following observation pertaining to antibody testing. “Presence of antibody may suggest past or present infection with COVID-19 but does not reliably confirm future immunity and does not replace a need for workplace risk assessment and control.”[17]

For employers in countries which are opening up, when employees come back to work, depending on the local legislations in these countries it might be useful to determine return to work on the basis of a health questionnaire rather than interpreting any antibody tests. An example of a health questionnaire is given in the following table.

The ICMR has called for rapid antigen testing which promises an earlier diagnosis of infection. This test requires trained personnel, special rooms, full infection control practices including complete PPE to swab the patient but there is no need for special equipment or laboratory settings. The results are available in 15 min. Though the official page of the recommended antigen test kit claims the sensitivity at 84% and specificity at 99% based on a single trial,[19] the results from the 2 validation centres in India[20] puts a range of 50.6% to 84% for sensitivity. In the worst case, this translates to about 50% of false negatives. ICMR recommends that all antigen test positives are considered positives and all symptomatic negatives should be confirmed by RT-PCR and all asymptomatic negatives are declared negative. However, not all COVID-19 affected individuals develop symptoms.[21] Many people pass through the infection period without developing symptoms.[22],[23] Therefore, given the additional resources required, the low sensitivity and the unpredictable symptomatology of the disease, the rapid antigen test should be viewed with caution.

To summarize:

  1. Antibody tests should not be used as a means of determining return to work.
  2. International professional bodies like the WHO, CDC, Infectious Diseases Society of America as also the Faculty of Occupational Medicine have all cautioned against the use of Antibody tests as a proxy for determining immunity to COVID-19.
  3. The use of antigen testing is to be viewed with caution in the workplace setting.


Acknowledgement

I thank Dr Ramnik Parikh, Emeritus Member, International Commission on Occupational Health (ICOH) for his support in developing the graphics for [Figure 2]. I also acknowledge the critical review of this manuscript by Prof. Mary Dias of the Department of Microbiology at St. John's Medical College.
Figure 2: Schematic representation of the detection of antigen and antibodies to COVID- 19*
*PCR test positives are more likely to be detected once symptoms start


Click here to view




 
  References Top

1.
COVID-19 Dashboard by the centre for systems science and engineering (CSSE) at Johns Hopkins University (JHU). Available from: https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b48e9ecf6. [Last accessed on 2020 Jul 04].  Back to cited text no. 1
    
2.
3.
Lou B, Li T, Zheng S, Su Y, Li Z, Liu W, et al. Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset. medRxiv 2020. doi: 10.1101/2020.03.23.20041707.  Back to cited text no. 3
    
4.
Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020;26:845-8.  Back to cited text no. 4
    
5.
Zhao R, Li M, Song H, Chen J, Ren W, Feng Y, et al. Early detection of SARS-CoV-2 antibodies in COVID-19 patients as a serologic marker of infection. Clin Infect Dis 2020:ciaa523. doi: 10.1093/cid/ciaa523.  Back to cited text no. 5
    
6.
La Marca A, Capuzzo M, Paglia T, Roli L, Trenti T, Nelson SM. Testing for SARS-CoV-2 (COVID-19): A systematic review and clinical guide to molecular and serological in-vitro diagnostic assays. Reprod Biomed Online 2020:S1472-6483 (20) 30318-7. doi: 10.1016/j.rbmo. 2020.06.001.  Back to cited text no. 6
    
7.
Lisboa Bastos M, Tavaziva G, Abidi SK, Campbell JR, Haraoui LP, Johnston JC, et al. Diagnostic accuracy of serological tests for covid-19: Systematic review and meta-analysis. BMJ 2020;370:m2516. doi: 10.1136/bmj.m2516.  Back to cited text no. 7
    
8.
Evidence of Earlier Infection: Antibody Testing. Available from: https://www.travax.com/library/coronaviruses/events/coronavirus-disease-2019#diagnosis. [Last accessed on 2020 Jul 02].  Back to cited text no. 8
    
9.
“Immunity Passports” in the context of COVID-19. Scientific Brief. WHO. 24th April 2020.  Back to cited text no. 9
    
10.
Rajgopal T. COVID-19: Epidemiology and public health aspects. Indian J Community Med 2020;45:111-6.  Back to cited text no. 10
  [Full text]  
11.
ICMR: Advisory to start rapid antibody based blood test for COVID-19 (D.O. No. EC D/COVID -19/202 0 dated 4th April 2020).  Back to cited text no. 11
    
12.
Using Antibody Tests for COVID-19. Updated May 28, 2020. Available from: https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests.html. [Last accessed on 2020 Jun 10].  Back to cited text no. 12
    
13.
American Society for Microbiology. Available from: https://www.asm.org/Articles/2020/May/COVID-19-Serology-Testing-Explained. [Last accessed on 2020 May 30].  Back to cited text no. 13
    
14.
Available from: https://www.travax.com/library/coronaviruses/events/coronavirus-disease-2019#transmission. [Last accessed on 2020 Jul 05].  Back to cited text no. 14
    
15.
WHO. Criteria for releasing COVID-19 patients from isolation. Scientific Brief. 17th June 2020.  Back to cited text no. 15
    
16.
IDSA COVID-19 Antibody Testing Primer. Infectious Diseases Society America. Updated 4th May 2020.  Back to cited text no. 16
    
17.
Implications for Occupational Health Practice in Relation to Testing for Covid-19. Faculty of Occupational Medicine. London 4th May2020.  Back to cited text no. 17
    
18.
Coronavirus Disease 2019. (COVID-19). Symptoms of Coronavirus. CDC. Centers for Disease Control andPrevention.  Back to cited text no. 18
    
19.
SD Biosensor. STANDARD Q COVID-19 Ag. 2020. Available from: http://sdbiosensor.com/xe/product/7672. [Last accessed on 2020 Jul 15].  Back to cited text no. 19
    
20.
Indian Council of Medical Research. Advisory on Use of Rapid Antigen Detection Test for COVID-19. 2020.  Back to cited text no. 20
    
21.
Arons MM, Hatfield KM, Reddy SC, Kimball A, James A, Jacobs JR, et al. Presymptomatic SARS-CoV-2 infections and transmission in a skilled nursing facility. N Engl J Med 2020;382:2081-90.  Back to cited text no. 21
    
22.
World Health Organization (WHO). Coronavirus disease 2020 (COVID-19): Situation report, 73. World HealthOrganization.  Back to cited text no. 22
    
23.
World Health Organization (WHO). Transmission of SARS-CoV-2: Implications for infection prevention precautions. 2020.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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