1. Introduction
By the end of the year, 2019, Chinese local health authorities reported the occurrence of a cluster of pneumonia cases in Wuhan in the Hubei Province [1]. Shortly after, a novel beta coronavirus—which is now designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [2]—was discovered in the bronchoalveolar lavage fluid of a patient with pneumonia [1,3]. This enveloped virus has a single-stranded positive sense ribonucleic acid (RNA) genome of approximately 30 kilobases. Several surface proteins, known as the spike (S), envelope (E), and membrane (M) proteins, are embedded in a lipid bilayer. These proteins mediate the viral entry (S; S1 unit: binding to host receptor angiotensin-converting enzyme 2 via its receptor binding domain (RBD) and S2 unit: membrane fusion) and are also responsible for viral fusion (M), morphogenesis (E), assembly (E and M), and budding (M). The RNA is associated with the nucleocapsid (N) protein. The latter plays a role in the viral replication and transcription cycle [4,5,6,7].
SARS-CoV-2 emerged globally. As of 24 September 2020, the World Health Organization reported 31,664,104 SARS-CoV-2 infections and 972,221 deaths worldwide. So far, 278,070 cases and 10,982 deaths have been registered for Germany (Robert Koch-Institute, data of 24 September 2020).
The diagnosis of acute coronavirus-induced disease 2019 (COVID-19) requires the demonstration of SARS-CoV-2 RNA in respiratory samples by real-time reverse transcription polymerase-chain reaction (real-time RT-PCR). The specificity of the SARS-CoV-2 real-time RT-PCR has been reported up to 100% [8], while sensitivity under clinical conditions seems to be lower and was roughly estimated with 70% [9].
More recently, the measurement of the immune response against SARS-CoV-2 came into the focus of clinical diagnostics, particularly by the detection of virus-specific antibodies. The use of SARS-CoV-2 antibody tests could clarify the etiology of the disease in patients who present late, after two weeks from the onset of symptoms. These tests can also demonstrate the viral spread in the community and may even identify individuals who are potentially protected from reinfection by neutralizing antibodies [8].
It is believed that the majority of antibodies are raised against the abundant N protein, while antibodies directed against the S protein are considered more specific and correlate with the neutralizing capacity [7,8]. Earlier works on the antibody response in SARS (2002/2003) patients showed a significantly higher sensitivity of tests based on the N protein as the antigen [10,11]. The diagnostic value of SARS-CoV-2 antibody tests, however, may be limited due to their potential cross-reactivity with other human coronaviruses. So far, the duration of the acquired immunity after a SARS-CoV-2 infection is unclear. However, based on experience with reinfections from other human coronaviruses, it remains yet open if the immunity is long-lasting [12]. Several studies reported a rapid decay of SARS-CoV-2 immunoglobulin G (IgG) in asymptomatic individuals [13] and mild COVID-19 cases [14] but, more surprisingly, also in hospitalized patients presenting with the full clinical spectrum of COVID-19 [5,15]. Very recently, differences in the kinetics of N- or S-specific IgG came into the focus of research [16]. While a decline in the IgG directed against the N protein was evident, the response to the S protein or its RBD was found to be more stable [16,17] and was associated with the presence of virus-neutralizing antibodies [17]. To the best of our knowledge, clinically validated assays for the specific detection of IgG directed against the SARS-CoV-2 surface proteins E and M are not yet available. However, it would make sense to investigate such antibody responses as well, since they can also correlate with virus-neutralizing capacities [4].
In the following, we present data on the diagnostic performance of eight commercially available SARS-CoV-2 IgG or total SARS-CoV-2 antibody tests. Variations in their diagnostic sensitivity and specificity were observed. In terms of their performance, two IgG assays using the N or S proteins of SARS-CoV-2 were selected for an analysis of follow-up sera to obtain data on the kinetics of IgG. The development of IgG avidities and the kinetics of SARS-CoV-2-neutralizing antibodies were also examined over time.