Serological and cellular non-responders in a long-term cross-sectional
cohort of SARS-CoV-2-specific PCR-positive individuals
Abstract
During the first pandemic wave, the dark figure of SARS-CoV-2 exposure
was estimated to be high, however, an accelerated loss of antibodies was
reported after about 6 months post infection. This study was performed
to unveil the group of serological non-responders (NR) in PCR+
individuals 6-9 months after the first pandemic SARS-CoV-2 wave in
spring 2020 and to evaluate their specific cellular immune response
towards spike-molecule compared to PCR- and not PCR-tested (NT)
household contact persons. SARS-CoV-2-specific antibodies were
quantified using a commercial ELISA kit. The synergistic binding
strength was assessed as relative avidity index (RAI) using
ammonium-thiocyanate as chaotropic agent. The specific IFNγ-production
in response to spike-protein was determined in spot-forming-units (SFU)
by ELISPOT-assay. In PCR- 50.0%, in PCR+ 35.3% and in NT 20.7% had
undetectable IgG-anti-SARS-CoV-2 and were considered non-responders
(NR). All seropositive responders from the PCR-, 45.5% of PCR+ and
43.0% of NT developed high avidity (RAI>60%). In
serological responders, cellular responses were detected in 75.0% PCR-,
75.8% PCR+ and 66.7% NT. In serological NR, positive SFU were found in
75.0% PCR-, 22.2% PCR+ and 17.4% NT. Significantly higher
stimulation-indices were seen in PCR+ responders compared to PCR+
serological NR. Our findings showed that also PCR- and household contact
persons who were not tested (NT) developed SARS-CoV-2-specific humoral
and cellular immune responses. The relatively large proportion of
serological non-responders but also the proportion of cellular
non-responders within the group of IgG-positive individuals after PCR+
infection underlines the need for COVID-19 vaccinations in the
reconvalescent group.