Dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the Czech unvaccinated population: nationwide prospective seroconversion (PROSECO) study

BackgroundAlthough the Czech Republic weathered the first wave of the COVID-19 epidemic with relatively low incidence, the second wave of the global pandemic saw it rank among countries bearing the greatest COVID-19 burden, both in Europe and on a worldwide scale. The aim of the nationwide prospective seroconversion (PROSECO) study was to investigate the dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the Czech population.MethodsAll clients of the second largest health insurance company in the Czech Republic were sent a written invitation to participate in this longitudinal study. The study includes the first 30,054 persons who provided a blood sample between October 2020 and March 2021. Seroprevalence was compared between calendar periods of blood sample collection, RT-PCR test results, sociodemographic factors, and other characteristics.FindingsThe data show a dramatic increase in seropositivity over time, from 28% in October/November 2020 to 43% in December 2020/January 2021 to 51% in February/March 2021. These trends were consistent with government data on cumulative viral antigenic prevalence in the population captured by PCR testing – although the seroprevalence rates established in this study were considerably higher than those listed in government data. Data pooled across the entire study period exhibited minor differences in seropositivity between sexes, age groups and body mass index categories; results were similar between test providing laboratories. Seropositivity was substantially higher among symptomatic vs. asymptomatic persons (76% vs. 34%). At least one third of all seropositive participants were asymptomatic, and 28% participants who developed antibodies against SARS-CoV-2 never underwent PCR testing.InterpretationAntibody response provides a better marker of past SARS-CoV-2 infection than PCR testing data. Our data on seroconversion confirm the rapidly increasing prevalence in the Czech population during the dramatically rising pandemic wave prior to the beginning of massive vaccination. The planned second and third assessment of the study participants (April 2021 – September 2021, October 2021 – March 2022) will provide valuable evidence on the seroprevalence changes following vaccination and persistence of antibodies resulting from natural infection and vaccination.Research in contextEvidence before this studySimilarly to most European countries, the first COVID-19 epidemic wave in the Czech Republic produced a relatively low incidence (86.9 confirmed cases per 100,000 persons over three months). At the peaks of the second wave, however, over 100 confirmed cases per 100,000 persons were diagnosed daily and the Czech Republic ranked among the countries with the greatest burden of COVID-19 in Europe and in the world. Only a few nationwide population-based studies have been published covering the second wave of the epidemic in Europe, and none of them from the Central and Eastern European region.Added value of this studyThe PROSECO study will provide key data from the heavily affected Central European region and contribute to the epidemiological and serological characteristics of the SARS-CoV-2 infection. All 30,054 study participants were recruited between October 2020 and March 2021, thus covering all three epidemic peaks (November 2020, January and March 2021) of the second COVID-19 epidemic wave. This allows us to follow the dynamics of seroconversion of anti-SARS-CoV-2 IgG antibodies in the immunologically naive and unvaccinated population during the COVID-19 pandemic. The study participants will be re-assessed in the second (April 2021 – September 2021) and third (October 2021 – March 2022) PROSECO phases to further study the post-infection/post-vaccination dynamics of seroconversion in/after a period of massive vaccination.Implications of all the available evidenceData from the first phase of the PROSECO study indicate that the percentage of the population that has been exposed to the SARS-CoV-2 may be substantially higher than estimates based on official data on cumulative viral positivity incidence as at least one third of seropositive participants were asymptomatic, and 28% of participants who developed antibodies against SARS-CoV-2 never underwent PCR testing. Regional seroprevalence data provide key information to inform, in combination with other surveillance data, public health policies and will be instrumental for the successful management of the subsequent phases of the global pandemic.The number of seropositive participants who never underwent RT-PCR testing demonstrates the importance of serological population-based studies describing the spread and exposure to the virus in the population over time.