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Antibody Testing

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Last reviewed: October 20, 2021

The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject.


Serologic tests for SARS-CoV-2 measure individuals’ antibody response to SARS-CoV-2 infection or to vaccination. Therefore, unlike nucleic acid amplification tests such as RT-PCR, which detect viral RNA, serologic assays do not directly detect pathogens but rather the immune response to their presence. Depending on the target, a positive serology result may indicate a current and/or past infection or evidence of vaccination. Prior infection generates antibodies against the SARS-CoV-2 nucleocapsid protein or the spike protein, while vaccination results exclusively in antibodies formed against the spike protein.  

Serologic tests are now widely available and vary in their sensitivity and specificity.  The use of serologic assays in SARS-CoV-2 require a general understanding of the dynamics of the immune response to infection and vaccination as well as specific knowledge of test characteristics.  

Dynamics of the immune response 

Antibodies are detectable approximately 1 to 2 weeks after the onset of infection (Guo, March 2020Zhao, March 2020Compeer, August 2020), with IgA, IgM and IgG rising in concert (CDC, August 2020). Levels of IgM and IgA begin to fall starting 2 to 3 weeks post-infection while IgG persists for longer. Exactly how long these antibodies stay detectable and in what populations is not fully known (Korte, August 2020Vabret, July 2020), though one study of a large cohort of individuals infected during the first wave in New York City showed high levels of anti-spike antibodies for up to 6 months (Wajnberg, December 2020).  

Due to the time it takes for antibodies to become detectable, serologic tests are not useful early in the course of illness for diagnosing COVID-19. In addition, most but not all patients with SARS-CoV-2 infection develop an antibody response, and so a negative serologic result does not exclude past infection.  

Test interpretation and the importance of prevalence 

To be useful, SARS-CoV-2 serologic tests require a specificity of >= 99.5% (CDC, August 2020IDSA, August 2020) due to the low prevalence of disease during non-epidemic periods. In general, the lower the prevalence, the higher the risk of false positives.  

Indications for testing 

Serology testing in SARS-CoV-2 infection may be useful for identifying symptomatic people suspected of long COVID/post COVID who may be beyond the period where viral RNA is detectable. Additionally, data from the RECOVERY trial suggests that those who are seronegative may benefit from monoclonal antibody treatment over those who are seropositive (RECOVERY Collaborative Group, June 2021 – preprint, not peer-reviewed). 

Impact of variants 

The impact of SARS-CoV-2 variants on the performance of serologic assays has not been fully defined. The majority of commercial assays are designed to detect antibodies to wildtype spike protein, therefore there is a theoretical risk that infection with a variant of concern or receipt of a vaccine targeting a variant spike protein may generate antibodies that would not be detected by these assays. However, to date there are no rigorous studies that have shown any impact of SARS-CoV-2 variants on the analytic or clinical sensitivity of currently-available antibody assays.

Use of serologies to assess protection 

There is currently not enough data to support the use of serologic testing for determining protection against primary or re-infection. This is because the antibody response against SARS-CoV-2 represents just one aspect of a complex immune response that is highly dynamic and includes components of innate immunity and virus-specific T-cell activity (Dan, February 2021). While many studies have shown positive associations between the level and quality of neutralizing antibody responses and protection from primary infection and re-infection, others have shown antibody levels to be associated with worse outcomes (Lucas, July 2021Garcia-Beltran, January 2021), suggesting that the relationship is complex and involves both the quality and dynamics of antibody production. Furthermore, while T-cells may play an important role in protection, FDA-approved assays evaluating SARS-CoV-2 specific T-cell responses are not in widespread use, as the clinical significance of testing is unknown. Additionally, the correlation between antibodies and T-cells generated in response to natural infection or immunization is likely to vary by patient population. A lack of antibodies does not necessarily mean that a patient is not protected, as a memory B-cell response generated from prior infection or vaccination may still confer protection upon re-exposure.  


Interim CDC guidance on the use of antibody tests for SARS-CoV-2 recommends against their use to diagnose acute SARS-CoV-2 infection due to their low sensitivity early in infection. However, they can be used to support the diagnosis in people with signs and symptoms of COVID-19 who are at least 7 days out from symptom onset or suffering from its long-term complications but have negative testing for viral RNA, such as RT-PCR. These include pediatric patients with multisystem inflammatory disorder.  

  • The impact of variants on the performance of serologic assays remains unknown. There is no role at this time for using qualitative or semi-quantitative antibody assays in determining whether an individual is adequately protected from infection.  

Key Literature


Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison (The National SARS-CoV-2 Serology Assay Evaluation Group, September 2020).

Overall, from four commercial SARS-CoV-2 antibody immunoassays tested, all assays achieved a sensitivity of at least 98% with thresholds optimized to achieve a specificity of at least 98% on samples taken 30 days or more post symptom onset. The authors note that even with such sensitivity and specificity, thousands of additional incorrect diagnoses can occur if millions of tests are done in large populations; at a 10% seroprevalence, the Siemens assay would generate an estimated 2800 total errors per million tests, while the DiaSorin assay at a rate of 16 700 total errors per million tests. Community prevalence of disease and individual patient characteristics must be taken into account when interpreting results.

Study population:

  • Four SARS-CoV-2 antibody assays: SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA), LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy), Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland), SARS-CoV-2 Total assay (Siemens, Munich, Germany), and a novel 384-well ELISA (the Oxford immunoassay).
  • Sensitivity and specificity was derived from 976 pre-pandemic blood samples and 536 blood samples from patients with laboratory-confirmed SARS-CoV-2 infection (collected at least 20 days post symptom onset).

Primary endpoint:

  • To investigate the performance of 4 high-throughput commercial SARS-CoV-2 antibody immunoassays and a novel 384-well ELISA.

Key findings:

  • The Abbott assay sensitivity was 92.7% (95% CI 90.2–94.8) and specificity was 99.9% (99.4–100%); the DiaSorin assay sensitivity was 95.0% (92.8–96.7) and specificity was 98.7% (97.7–99.3); the Oxford immunoassay sensitivity was 99.1% (97.8–99.7) and specificity was 99.0% (98.1–99.5); the Roche assay sensitivity was 97.2% (95.4–98.4) and specificity was 99.8% (99.3–100); and the Siemens assay sensitivity was 98.1% (96.6–99.1) and specificity was 99.9% (99.4–100%).


  • Limited by sample volumes, especially given the constraints imposed by dead volume requirements for liquid handling, and unable to do repeat analyses.
  • Subgroup analysis by timing of collection or disease severity was constrained by small numbers and larger studies would be of value.
  • The sample did not include children, and likely under-represented certain ethnic minority groups
  • Characteristics of the patient population from which the samples were derived were not , including characteristics that could affect serology results, such as immune compromised status


Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset (Lou, May 2020).

Overall, in patients with COVID-19, serology testing provided an important complement to RNA testing in the later stages of illness. 

Study population: 

  • 80 hospitalized patients with PCR-confirmed COVID-19 in China; 26 patients with severe COVID-19. 
  • The incubation period was 0-23 days with a median of 5 days (IQR, 2–10 days). 

Primary endpoint: 

  • Determine the impact of total antibody (Ab), IgM, and IgG levels in patients with COVID-19 using the Wantai SARS-CoV-2 Ab ELISA.  

Key findings: 

  • The seroconversion rates for Ab, IgM and IgG were 98.8%, 93.8% and 93.8%, respectively.  
  • Seroconversion time since exposure was significantly longer for patients with a long incubation period than for those with a short incubation period (21 d vs. 13 d, p<0.001). 
  • The first detectible serology marker was Ab, followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 days post-exposure or 9, 10 and 12 days post-symptom onset, respectively.  
  • Antibody levels increased rapidly 6 days post-exposure, and were accompanied by a decline in viral load.  
  • In the second and third week of illness, the sensitivities of Ab, IgM and IgG increased to 100%, 96.7% and 93.3%, respectively.  


  • Asymptomatic patients were not included; therefore, these results are only generalizable to symptomatic patients. 
  • Most samples were collected 1 month post onset; therefore, the duration of antibodies cannot be estimated. 
  • The prevalence of COVID-19 in this community at the time was high, which may limit the generalizability of the test characteristics to other communities. 


Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19) (Guo, March 2020). 

Overall, in this cross-sectional cohort study of patients with COVID-19, in confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively.  

Study population: 

  • 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation) of hospitalized patients with COVID-19 in Wuhan, China. 

Primary endpoint: 

  • Time kinetics of various antibodies produced against the SARS-CoV-2.  

Key findings: 

  • The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days. 
  • IgG was detected 14 (IQR, 10–18) days after symptom onset. 
  • The positive rates were 85.4%(IgM), 92.7% (IgA), and 77.9% (IgG), respectively.  
  • In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively.  
  • 22% (18/82) of the patients who were confirmed to be positive by qPCR were found to be negative by the IgM antibody tests. 13 of these patients were enrolled within less than 7 days after symptom onset. 
  • The positive detection rate was significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). 


  • A cross-sectional sample of specimens was used to determine the kinetics of SARS-CoV-2 antibodies, and individuals may have differing kinetics for antibody development. 
  • The prevalence of COVID-19 in this community at the time of the study was high, which may limit the generalizability of the test characteristics to other communities. 
  • Whether patients were receiving potential immune modulating therapies, as were part of Chinese national guidelines at the time, is not stated; this may have affected antibody results. 


Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019 (Zhao, March 2020).

Overall, in this case series of patients with COVID-19, the seroconversion rate during the acute phase of infection increased rapidly during the first 2 weeks. 

Study population: 

  • 173 hospitalized patients with SARS-CoV-2 infection, confirmed by RT-PCR, in China; of whom 32 (18.5%) were critically ill. 

 Primary endpoint: 

  • Determine the impact of total antibody (Ab), IgM, and IgG levels in patients with COVID-19 using the Wantai SARS-CoV-2 Ab ELISA.  

Key findings: 

  • 535 plasma samples were collected from the 173 patients and tested for antibodies against SARS-CoV-2.  
  • The seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively, with median seroconversion times of 11, 12 and 14 days, respectively. 
  • In the early phase of illness (within 7-day since onset), RT-PCR had the highest sensitivity of 66.7%, whereas the antibody assays had a positive rate of 38.3%. 
  • The presence of antibodies increased to 100% (Ab), 94.3% (IgM) and 79.8% (IgG) 15 days after the onset of symptoms. 
  • Combining RT-PCR and antibody tests significantly improved the sensitivity of the diagnosis for COVID-19 (p<0.001), even in early phase of 1-week since onset (p=0.007).  
  • A higher titer of Ab was independently associated with a worse clinical classification (p=0.006).  


  • Most of the RT-PCR tests were from upper respiratory tract specimens, which are not as sensitive as using lower respiratory tract specimens. 
  • Samples were collected during the acute phase of infection. 
  • The prevalence of COVID-19 in this community at the time of the study was high, which may limit the generalizability of the test characteristics to other communities. 


Additional Literature

Longitudinal dynamics of the neutralizing antibody response to SARS-CoV-2 infection (Wang, Aug 2020). In this cohort study, the longitudinal dynamics of SARS-CoV-2-specific neutralizing antibodies in 30 patients with COVID-19 were assessed.  SARS-CoV-2-specific NAb titers were low for the first 7–10 d after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 d (IQR 24–59 d) after symptom onset. NAb titers in 93·3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34·8% (IQR 19·6–42·4%). NAb titers increased over time in parallel with the rise in IgG antibody levels, correlating well at week 3 (r = 0·41, p & 0·05).

SARS-CoV-2 Antibody Responses Correlate with Resolution of RNAemia But Are Short-Lived in Patients with Mild Illness (Röltgen, August 2020). In this cohort study, 625 serial plasma samples from 40 hospitalized COVID-19 patients and 170 SARS-CoV-2-infected outpatients and asymptomatic individuals was assessed. Severely ill patients developed significantly higher SARS-CoV-2-specific antibody responses than outpatients and asymptomatic individuals. Outpatient and asymptomatic individuals' serological responses to SARS-CoV-2 decreased within 2 months. 

Viral dynamics and immune correlates of COVID-19 disease severity (Young, August 2020). In this prospective observational cohort study of 100 patients with confirmed SARS-CoV-2 infection, seroconversion occurred at a median of 12.5 days (IQR 9-18) for IgM and 15.0 days (IQR 12-20) for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels.   

Kinetics of viral load and antibody response in relation to COVID-19 severity (Wang, July 2020). In this small cohort study of 12 patients with severe COVID-19 and 11 mild patients, mild patients showed significantly lower IgM response. IgG responses were detected in most patients in both severe and mild groups at 9 days post onset and remained high level throughout the study. High-levels of neutralizing antibodies were induced after about 10 days post onset in both severe and mild patients, and were higher in the severe group. 

High neutralizing antibody titer in intensive care unit patients with COVID-19 (Liu, July 2020).  In this cohort study investigators compared the neutralizing antibody responses of eight COVID-19 patients admitted to the intensive care unit with those of 42 patients not admitted to the ICU. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% CI 1468-36099]) vs (671 [95% CI, 368-1223]). The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). 

Antibody tests for identification of current and past infection with SARS-CoV-2 (Deeks, June 2020). A Cochrane Review examining the diagnostic accuracy of antibody tests in 57 publications determined combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. They also found there is insufficient data to estimate the sensitivity of serology 35 days or more post-symptom onset. 

Antibody Responses to SARS-CoV-2 at 8 Weeks Post infection in Asymptomatic Patients (Choe, June 2020).  In this small case series, the levels of SARS-CoV02 neutralizing antibodies were assessed in 8 asymptotic patients. Neutralizing antibody occurred in all 7 patients, and 5/7 (71%) had positive serologic testing.  

Antibody Detection and Dynamic Characteristics in Patients with COVID-19 (Xiang, April 2020). In this prospective cohort study of 85 hospitalized patients with confirmed COVID-19 and 24 patients with suspected COVID-19, sensitivity, specificity, PPV, and NPV, of IgM were 77.3%, 100%, 100%, 80.0%, respectively, and those of IgG were 83.3%, 95.0%, 94.8%, 83.8%. IgM and IgG seroconversion occurred as early as 4 days after symptom onset, but the majority of seroconversions occurred in the second week of illness. 

A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease (Huang, April 2020). In this systematic review of literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses, 5 areas of focus are reviewed: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence.




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