Seroprevalence and correlates of SARS-CoV-2 neutralizing antibodies: Results from a population-based study in Bonn, Germany

Abstract

Background
Accurate estimates of SARS-CoV-2 seroprevalence are crucial for the implementation of effective public health measures, but are currently largely lacking in regions with low infection rates. This is further complicated by inadequate test performance of many widely used serological assays. We therefore aimed to assess SARS-CoV-2 seroprevalence in a region with low COVID-19 burden, especially focusing on neutralizing antibodies that presumably constitute a major component of acquired immunity.

Methods
We invited all individuals who were enrolled in the Rhineland Study, an ongoing community-based prospective cohort study in people aged 30 years and above in the city of Bonn, Germany (N=5427). Between April 24th and June 30th, 2020, 4771 (88%) of these individuals participated in the serosurvey. Anti-SARS-CoV-2 IgG levels were measured using an ELISA assay, and all positive or borderline results were subsequently examined through both a recombinant immunofluorescent assay and a plaque reduction neutralisation test (PRNT).

Findings
Seroprevalence was 0.97% (95% CI: 0.72-1.30) by ELISA and 0.36% (95% CI: 0.21-0.61) by PRNT, and did not vary with either age or sex. All PRNT+ individuals reported having experienced at least one symptom (odds ratio (OR) of PRNT+ for each additional symptom: 1.12 (95% CI: 1.04-1.21)). Apart from living in a household with a SARS-CoV-2 confirmed or suspected person, a recent history of reduced taste or smell, fever, chills/hot flashes, pain while breathing, pain in arms/legs, as well as muscle pain and weakness were significantly associated with the presence of neutralizing antibodies in those with mild to moderate infection (ORs 3.44 to 9.97, all p<0.018).

Interpretation
Our findings indicate a relatively low SARS-CoV-2 seroprevalence in Bonn, Germany (until June 30th, 2020), with neutralizing antibodies detectable in only one third of those with a positive immunoassay result, implying that almost the entire population in this region remains susceptible to SARS-CoV-2 infection.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The Rhineland Study is predominantly funded through the German Center for Neurodegenerative Diseases (DZNE) by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia. The National Consultant Laboratory for Coronaviruses is funded by the Federal Ministry of Health (BMG). No additional funding was received for this seroprevalence study.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Approval to undertake the Rhineland Study was obtained from the ethics committee of the University of Bonn, Medical Faculty. The Rhineland Study is carried out in accordance with the recommendations of the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) standards (ICH-GCP) after obtainment of written informed consent from all participants in accordance with the Declaration of Helsinki. No separate ethical approval for this serosurvey was required given its embedding in the Rhineland Study, the ethical mandate of which already covered follow-up measurements, including collection of serial bio-samples.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

The Rhineland Study’s dataset is not publicly available because of data protection regulations. Access to data can be provided to scientists in accordance with the Rhineland Study’s Data Use and Access Policy. Requests for further information or to access the Rhineland Study’s dataset should be directed to RS-DUAC@dzne.de.

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