SARS-CoV-2 Reinfection in a Healthcare Worker Despite the Presence of Detectable Neutralizing Antibodies

Abstract

So far, only a few reports about reinfections with SARS-CoV-2 have been published, and they often lack detailed immunological and virological data. We report about a SARS-CoV-2 reinfection with a genetically distinct SARS-CoV-2 variant in an immunocompetent female healthcare worker that has led to a mild disease course. No obvious viral escape mutations were observed in the second virus variant. The infectious virus was shed from the patient during the second infection episode despite the presence of neutralizing antibodies in her blood. Our data indicate that a moderate immune response after the first infection, but not a viral escape, did allow for reinfection and live virus shedding.

Keywords: COVID-19; SARS-CoV-2; healthcare worker; immunity; neutralizing antibodies; reinfection.

Figure 1

Time course with quantitative detection of SARS CoV-2 RNA [log copies/mL] (blue) and quantitative anti SARS CoV-2 S1/S2 antibody levels [log AU/mL] (red). RNA level was 1 × 10⁶ copies/mL and 2 × 10⁷ copies/mL at first infection and reinfection respectively. Anti-SARS-CoV-2 spike (S1/S2) IgG was 40 IU/mL after first infection and a > 4-fold booster during reinfection was observed (97 AU/mL on 29 December 2020, and >400 AU/mL on 13 January 2021).

Figure 2

(a) Successful isolation of SARS-CoV-2 from swab sample (HH-24.II) reflected by > log4-fold in-crease of viral RNA in the supernatant of Vero cells at 72 h post infection (hpi) detected by qRT-PCR. Quantification of the virus stock produced of the rescued virus in cell culture revealed a TCID50 of 1.57 × 10⁷; (b) Virus neutralization assay was performed with serial dilutions of patient sera of one time point before (14 October 2020) and three time points after the reinfection (29 December 2020, 13 January 2021, 28 January 2021) and both the isolated virus of the patient (HH-24.II, red bars) and the HH-1 isolate (gray bars). Neutralizing antibody titers (IC50) were detected at all time points. No significant differences in the neutralizing capacity of the two linages were observed. Between 29 December 2020 and 13 January 2021 a > 4-fold titer increase was observed which reflects a significant increase.

Figure 3

(a) Variant nucleotide positions of the sequences HH-24.I and HH-24.II with respect to the reference sequence NC_045512.2 are given in dark grey, whereas light grey boxes indicate reference bases. Uncovered positions by amplicon seq are depicted as white boxes. The color bars on top represents feature assignment (ORF, open reading frame; AA, amino acid changes); (b) nextstrain phylogenetic visualization of HH-24.I and HH-24.II in the context of 100 random samples present in Europe from onset of the pandemic until February 2021. Clades are indicated by different colors.