antibodies rapidly decline early on 1, 3 Wolfgang Korte*, 2,3 Marija Buljan, 2,3 Matthias Rösslein, 2,3 Peter Wick, 1 Valentina Golubov, 1 Jana Jentsch, 1 Michael Reut, 3, 4 Karen Peier, 3 Brigitte Nohynek, 3 Aldo Fischer, 3 Raphael Stolz, 3 This cohort study included patients with a history of a positive SARS-CoV-2 PCR test. The study is registered in the COVID-19 database (https://swissethics.ch/covid-19/approved-projects) and approved by the regional ethics committee (ID2020-00941). Potential participants were identified in the public health database and voluntary participation was based on the informed consent and documented positive SARS-CoV-2 PCR. After inclusion in the study, antibody tests were performed every week in the first month and then after another four weeks in the second month. Quantitative (optical index, OI) antibody measurements were performed using commercially available 3,4 ELISA assays (anti-SP IgG and IgA, Euroimmun, Lübeck, Germany; anti-NC IgG, Epitope Diagnostics, San Diego, USA) according to the recommendations of the manufacturers. Data were evaluated and visualized with the 3 statistical software R using the implemented statistical tests and the packages "tidyverse" and "ggplot2".
Results of the antibody course in 159 participants (52·2% females, 47·8% males), effectively spanning the time frame of two to ten weeks after a positive SARS-CoV-2 PCR test, are provided. Upon the first blood sampling (corresponding to the median of 5 weeks after the PCR test (95% CI 5-6 weeks)), 4·6%, 4·6% and 6·5% of participants have not developed measurable anti-SP IgG, anti-SP IgA or anti-NC IgG, respectively. This may suggest a delayed or missing primary humoral response in a sizeable proportion of patients (at a time when any IgM response is believed to have worn off 2 ). We speculate this to be secondary to a suspected virus' ability to modify or suppress innate immune responses 5 .
After a significant increase, we find the antibody response to peak 4-5 weeks after positive PCR, followed by an early decline. The decline is statistically significant for anti-SP and anti-NC IgG at weeks 8-10 ( Figure 1) ; this is remarkable, as a continued IgG response for more than 34 weeks was seen with the SARS-CoV(-1) outbreak 6 .
Moreover, significantly higher antibody concentrations are seen in men for all antibodies ( Figure 2 ).
In addition, anti-SP IgA antibody concentrations showed a striking dichotomy in the distribution of their values among the patients (Figures 1c and 2c) . A subgroup of individuals with extremely high values had a significantly higher fraction of men than the rest of the cohort (77% of samples with OD > 20, p < 0·01). This observation might help to explain the higher mortality risk in men with COVID compared to women 7 , e.g. through an 4 increased inflammatory response 8 . We speculate that the overall course of anti-SP IgA (with no further decline despite IgG declining, Figure 1c ) as well as the sex specific differences with an early, pronounced peak in men and a subpopulation of men with significantly higher IgA titers than the remainder (figure 2c) may be the result of an ongoing infection, which needs further attention and clarification (previous work has shown that IgA has a protective role against influenza A 9 ). Whether this represents a spike-"antibody dependent infection enhancement" in COVID-19, as suggested for SARS-CoV(-1) 10 , remains to be elucidated. Figure 2c ). Samples from predominantly male (77% of samples with OI > 20, p < 0·01, Fisher's exact test) patients with very high, dichotomically separated IgA antibody values were seen (inset 2c, see also 1c). Dotted lines separate increased (reactive) from non-increased antibody concentrations.