Discussion
In this study, we evaluated the detection of SARS-CoV-2 antibodies (IgM/A or IgG) with 14 different serological assays. As expected, we found that sensitivity was higher if the test was performed starting from day 8 after symptom onset, as compared to earlier time points. With the exception of one assay (Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin), all tests resulted in a sensitivity for IgG higher than 87% starting from day 8 after symptom onset. Specificity ranged from 79%-100%.
Recently, the first studies evaluating several commercial serology assays have been published. Geurts van Kessel et al [17]. studied three rapid tests, four ELISAs and a high throughput chemiluminescent assay. Sensitivity ranging from 81–100% was calculated by using a total of 187 sera from 107 RT-PCR confirmed COVID-19 patients. Specificity was determined using 147 serum and plasma samples from individuals exposed to human coronaviruses and other respiratory viruses with values ranging from 85–100%. Similar to our findings, the performance of the Liaison SARS-CoV-2 S1/S2 IgG (DiaSorin) was worst with a sensitivity of 81% (compared to 59% in our results) and specificity of 90% (compared with 100% in our results). The group of Haselmann et al [16]. evaluated the performance of two IgG ELISA assays and one IgG electrochemiluminescence immunoassay (ECLIA) based on 51 serum samples from 26 COVID-19 patients and another 51 serum samples from control patients. They report a sensitivity of 92–100% and specificity of 84–96%. The Austrian Red Cross Blood Service [15] evaluated 100 SARS-CoV-2 convalescent plasma donors and SARS-CoV-2 antibodies were characterized using three different IgG-ELISAs (EUROIMMUN IgG and NCP-IgG ELISA, Wantai ELISA), two CLIA (Elecsys, LIAISON) and two lateral flow tests (MEDsan IgM/IgG-Rapid-Test, Wantai Rapid Test). The Wantai ELISA and the Elecsys provided the highest sensitivities in this sample (98 and 95 % respectively). Serrano et al [18]. compared the performance of 3 lateral flow immunoassays (IgM/IgG combined) to 2 ELISAs (IgA and IgG) in serum samples from 109 RT-PCR confirmed patients in different weeks after symptom onset. The IgA ELISA was most sensitive the first week after symptom onset (71%). The sensitivity improved to 97% for IgA ELISA in the second week. In the third week IgA ELISA, IgG ELISA and 2 out 3 IgG lateral flow tests had a sensitivity of > 96%. The lateral flow immunoassays showed variable performances. Pieri et al. also found that IgA detected by the ELISA assay might be a more reliable and stable early serological marker than IgM. Instead, IgG, as expected, showed stable level after 10 days from symptoms onset [21]. These findings are in accordance with our study results.
Serological tests could be useful in some clinical settings. In our database, we found an added diagnostic value of serological assays in 2% of the COVID-19 suspect patients. Although the detection of SARS-CoV-2 antibodies does not provide information on the presence of the viral RNA, it confirms recent or past infection. This is especially relevant in clinical cases where high clinical suspicion for COVID-19 which cannot be confirmed with SARS-CoV-2 PCR.
The availability of these serological tests might avoid the need for more invasive sampling methods like BAL in the pursuit of diagnostic confirmation of COVID-19, especially. Furthermore, serology can aid in infection prevention management. Nuccetelli et al. suggest screening flowcharts for asymptomatic workers that is based on serological assays, workers that have already overcome the disease are subjected to molecular screening methods [22]. Next the development of antigen detection assays are underway, which have the potential to rapidly detect active SARS-CoV-2 infection. As the pandemic evolves, more and more insights will be gained in the value of serology as well as antigen detection [23].
The main limitation of the current study is the limited number of samples included. Nevertheless, this study has evaluated the performance of 14 different serological assays and therefore could provide useful information in this stage of the pandemic.
In conclusion, our findings show that sensitivity was variable but increased in a later stage of infection (at least 8 days after symptom onset). Interpretation of the combination of IgM or IgA and IgG resulted in the highest sensitivity. Our data suggest that virus-specific antibody detection for SARS-CoV-2 can complement molecular testing for diagnosis of COVID-19, especially for patients presenting in the 2nd week or later after symptom onset. Larger datasets should be used to confirm current findings.