PMC:7650537 / 20232-24156
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7650537","sourcedb":"PMC","sourceid":"7650537","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7650537","text":"With respect to the previous positive SARS-CoV-2 PCR result considered as the reference of first choice, following a recent suggestion [19], assay sensitivities were found to be relatively high and varied from 80.8% to 96.2% (Table 1). This finding is in accordance to other studies [21,22,24,25,26] and to a meta-analysis [23]. Six (23.1%; five, 19.2%, if the positive retesting result of the initial serum from patient 4 is taken into account; for details, see below) of the 26 SARS-CoV-2-infected patients did not develop SARS-CoV-2-neutralizing antibodies, as demonstrated by a PRNT ≤1:10. Among them were two individuals who were only recognized as IgG-positive in the Abbott and Virion-Serion assays and were partially reactive in the ViraChip® and the IgG immunoblots (Figure 1). This confirms a previous report of a high sensitivity of the Abbott IgG test [27]. The absence of neutralizing antibodies in several COVID-19 patients was also reported by others [28] and may be associated with the mild course of the infection mainly observed in outpatient patients. However, since no clinical data were available to us, a severe underlying disease or a serious course of the SARS-CoV-2 infection cannot be ruled out in the individuals of our study collective. Recently, presence of neutralizing antibodies was found to be associated with protection against reinfection [29]. If the PRNT was chosen as another reference (Figure S1), sensitivities varied from 88.9% to 96.3% (Table 1), which is largely comparable to the results obtained with the first method. These sensitivities can be even higher, as retesting of the initial serum from patient 4 in the second part of our study revealed the presence of low-level neutralizing antibodies (1:10 vs. 1:20–1:40; Figure 5 and Figures S1 and S2). With respect to a sample from patient 1 taken six days after the PCR, two S-based assays failed to detect SARS-CoV-2 IgG, while all assays that used the N as an epitope were reactive (Figure 1). Thus, usage of the latter may lead to the detection of IgG/total antibodies at an earlier stage post-infection. Furthermore, a lack of reactivity in some assays using the S antigen does not necessarily mean that SARS-CoV-2-neutralizing antibodies are missing (Figure 1). Seroconversion was clearly demonstrated in three patients (Figure 1). The majority of SARS-CoV-2 IgG in sera from SARS-CoV-2-infected patients were verified by both versions of an immunoblot (Figure 1). The latter can be used to differentiate the antibody reactivities against individual SARS-CoV-2 antigens. The specificities of the SARS-CoV-2 IgG/total antibody tests are at comparatively high levels between 96.0% and 100.0%, as has also been reported by others [21,22,24,26]. Interestingly, one sample collected in the winter 2018/2019 was found to be reactive in the Mikrogen, Roche, and Viramed assays, as well as in the prototype immunoblot, but could not be confirmed by the PRNT. For all other 99 archived samples, a random pattern of rare, isolated reactivity was demonstrated, and none was confirmed as possessing SARS-CoV-2-neutralizing antibodies by PRNT (Figure 2 and Figure S1). Potential cross-reactivity with the HCoVs responsible for common colds may therefore not be a major problem. The analysis of the immunoblot results shows, however, that sera from SARS-CoV-2-infected patients may simultaneously react with the antigens from HCoVs 229E, HKU-1, NL63, OC43, and SARS-CoV-2 (Figure S3). Due to the currently estimated low prevalence of SARS-CoV-2 IgG in the overall German population, even high specificities of 96–98% would produce a relevant number of false positive results. Thus, such assays, which all show an accuracy over 93%, should be preferentially used for the testing of patients with a history of a probable infection. In the case of doubt, the implementation of the labor-intensive and time-consuming PRNT may be 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