RESUMO
IntroductionSARS-CoV-2 infections have very different clinical manifestations and anti-SARS-CoV-2 immunisation may also trigger very different levels and length of protection. While (re)infection after previous COVID-19 illness or following vaccination are known, their impact and the optimal timing of any booster vaccination is currently debated. International evidence about potential underlying immune response differences remains limited and is currently not available in Hungary. MethodsWe prospectively investigated the magnitude of immune responses to infection or immunisation, their over-time changes and the occurrence of new infections through anti-SARS-CoV-2 IgG levels and the association with selected individual and clinical parameters in two voluntary cohorts of healthcare workers at a public teaching hospital in a real-world longitudinal cohort study in Hungary. In the first cohort, the anti-nucleocapsid IgG levels of 42 health care workers (female: 100%) with SARS-CoV-2 infection were followed-up over 8 months between June 2020 and February 2021. Beyond the change in immune response, associations with age, selected existing chronic conditions, blood type and severity of symptoms were investigated. In the immunised cohort, anti-spike-RBD protein IgG levels of 49 health care workers (female: 73%) with no prior COVID-19 infection were monitored up to 4 months following initial immunisation with BNT162b2 vaccine between December 2020 and April 2021. Statistical analyses included median analysis, linear regression, ANCOVA, Kruskal-Wallis test and Skillings-Mack test for block designs as relevant. ResultsWithin the infected cohort, the median time of anti-SARS-CoV-2 IgG level reduction below the positive test cut-off was 6 months. First month IgG levels were on average the highest among those in illness severity category 4, but the difference to less severe categories was not statistically significant. Higher age was associated with higher IgG levels. Within the immunised cohort, the anti-SARS-CoV-2 spike-RBD protein IgG levels increased 25-fold between the first and second immunisations, significantly decreased to 33% of the peak level after 90 days, and had an overall negative tendency with older age and male sex. IgG monitoring revealed 17% (7/42) and 14% (7/49) new infections in the infected and the immunised cohorts, respectively, all symptomless. DiscussionOur study is the first to investigate the level, change and associations of anti-SARS-CoV-2 IgG immune response in infected or immunised healthcare workers in Hungary. It provides further evidence about the significantly declining IgG protection through initial infection beyond 6 months. While immunisation with mRNA vaccination shows a similar pattern of reduction in protection, IgG levels remained within the positive range at 4 months. The observed rate of 15% new, asymptomatic infections and their potential broader impacts call for further investigations. Overall, our findings are confirmative of the effectiveness of vaccination to prevent illness, recent considerations for booster vaccination beyond 6 months, and indicate the potential benefit of anti-SARS-CoV-2 IgG monitoring for optimisation.
RESUMO
Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019 the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of the 21th of April, 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.
