Seroprevalence and immune response to SARS-CoV-2 in Paris

By Dr. Ramya Dwivedi, Ph.D.Oct 30 2020

A large working population in Paris was tested to understand the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection. This population, not particularly exposed to SARS-CoV-2 infection, represented active workers, as opposed to other epidemiological model studies that may underestimate infection's true prevalence.

François Anna et al. published this study in a recent medRxiv* preprint paper, where they present the results of assessing the serological response in the selected population. They tested for specific IgG response against the SARS CoV-2 Nucleoprotein and Spike protein and performed a pseudo-neutralization assay in sera of urban dwellers in Paris.

Study: High seroprevalence but short-lived immune response to SARS-CoV-2 infection in Paris. Image Credit: Kateryna Kon / Shutterstock

Since January 2020, this virus has spread rapidly in France, leading to a saturation of hospitals' ICUs due to the severe coronavirus disease 2019 (CODIV-19). Because of the high transmission rate, the extent of exposure to SARS-CoV-2 in the French population is poorly documented. Also, compared to the RT-qPCR (which was primarily used to detect infection), the serological study is an efficient way to monitor virus propagation.

However, employing the serological assay for large cohorts is a significant challenge, and results may not be accurate. Thus, the authors in this study developed a robust and highly sensitive method for a broad dynamic range of the measurement. These methods exceed the performance of currently marketed serological assays.

They developed two original bioluminescence-based serological assays allowing a high throughput assessment of the specific antibody responses to the Spike (S) and Nucleoprotein (N) proteins of SARS-CoV-2. They also tested the antibodies' ability to neutralize the virus fusion with a permissive human cell line.

The authors monitored individual serology against SARS-CoV-2 in a large cohort of 1847 workers in March-April 2020 - the pandemic peak in Paris and followed it up for six months.

The participants (from Institut Curie - a hospital and research center specialized in oncology) have been marginally in contact with COVID-19 patients and are domiciled in the Paris conurbation. These participants are representative of healthy, active adults from an urban area.

The study found a high prevalence of immunization but relatively short-lived responses.

Other studies across the world show variable levels of observations in seroprevalence. Among seropositive individuals, 20% of them were observed to be asymptomatic in this study. In similar study reports, the percentage of asymptomatic individuals ranged from 40% - 80%.

Based on their results, the authors further emphasized the predictive value and specificity of the anosmia (or loss of smell) / ageusia (or loss of taste) symptoms. Anosmia and ageusia were observed in 52% of the IgG-positive individuals and only 3% of the negative ones. In contrast, 30% of the anosmia-ageusia cases were seronegative, suggesting that infection's true prevalence may reach 16.6%.

The authors discuss in detail the serological complexity of long-lasting immunity based on their results: the slow drop of anti-S IgG titer did not correlate with the major decrease of pseudo-neutralization activity observed (53%). The occurrence of other Ig isotypes, such as IgM or IgA, may explain the neutralization activity - in this case, in which the pseudo-neutralization assay is exclusively associated with anti-S response.

The prevalence of immunization was 11.6% (CI:10.2-13.2), considering positivity in at least one assay. Interestingly, 5% of RT-qPCR positive individuals did not show the presence of systemic IgGs. Also, among those individuals who had the antibodies, 21% were asymptomatic.

In the second sampling stage, sera obtained 4-8 weeks, anti-N and anti-S IgG titers, and pseudo-neutralization activity declined enormously with time.

Since there appears to be a gradual loss of the virus-specific IgG titer, the authors point out that their observed seroprevalence (11.6-16.6%) results may still underestimate the number of individuals who have been infected by the SARS-CoV-2. Therefore an accurate retrospective assessment is difficult to achieve - because of the fast decrease of the antibody titer. This study spotlights the fact that SARS-CoV-2 has a high prevalence in a high-density population; along with a short-lived immune response, chances of reinfection and virus persistence is too high.