In Denmark, Omicron reinfections reveal ineffective post-COVID-19 immunity

In a recent study posted to the medRxiv* preprint server researchers examined variant cases of SARS-CoV-2 reinfection in Denmark.

The evolution of SARS-CoV-2 has led to the emergence of multiple variants of care (VOC) with increased transmissibility and immune evasion, such as Omicron, which has led to an increase in SARS-CoV-2 reinfections and difficulties in mitigation. COVID-19 worldwide. Studies have examined the frequencies of SARS-CoV-2 reinfection, but have been limited to reverse transcriptase polymer chain reaction (RT-PCR) analysis data, in which SARS-CoV-2 Pango lines are not specified. In addition, a genomic sequencing report is usually categorized as initial infection or reinfection, but next-generation sequencing data (NGS) for initial infection and reinfection are rarely reported together for an individual.

Study: Increasing Cases of SARS-CoV-2 Omicron Reinfection Reveals Ineffective Post-COVID-19 Immunity in Denmark and Indicates the Need for Continued Next Generation Sequencing. Image credit: Noiel/Shutterstock

About the study

In the present study, researchers characterized SARS-CoV-2 reinfections by variant based on the integration of RT-PCR analysis and next-genome sequencing (NGS) analysis of sequences obtained from Danish SARS-CoV-2 positive individuals and the GISAID (Global Bird Flu Data Sharing Initiative) database.

NGS data and clinical metadata of primary SARS-CoV-2 infections and reinfections from the same individual living in Denmark were analysed. A total of 21,708 reinfection records were available between March 1, 2020 and August 28, 2022, with data from sample collection data on primary SARS-CoV-2 infections and reinfections.

The team documented clinical SARS-CoV-2 metadata as the times of initial and subsequent SARS-CoV-2 infections to measure the duration between initial and subsequent SARS-CoV-2 infections. In addition, RT-PCR analysis results and NGS analysis results were available for primary infections and reinfections, respectively.

The team excluded 70 cases (

Reinfection cases were stratified by variant and subvariant. The GISAID database was opened to two files: one set of files containing current metadata for >12 million SARS-CoV-2 sequences and the second set containing filtered metadata files from only residents of Denmark with two associated SARS-CoV-2 infections documented .


Primary infection and reinfection with Omicron (ie, Omicron-Omicron infections) occurred within a shorter period of time (even within three weeks, averaging 22 weeks) than non-Omicron-Omicron infections. Omicron reinfections within ten weeks of the first Omicron infection were largely reported due to BA.1 followed by BA.2.

The frequency of reinfection was significantly higher with Omicron (25%, N=1875) after primary infections with a VOC. No cases of reinfection by Alpha VOC were reported, while Delta VOC caused reinfections in 2.3% (n=169) of cases. Pre-Omicron estimates of natural infection-induced immunity were over 90%, falling to less than 10% in three to four months.

Among subjects with Delta-induced primary infections, re-infections due to Delta variant were <1% (n=18) but for Omicron re-infections 41% (n=3060 cases). Furthermore, reinfections with the same VOC but with different subvariants were only 0.3% (n=24), except for Omicron (4.6%, n=340). 93% of individuals reinfected as of March 2020 had Omicron reinfections, indicating that initial SARS-CoV-2 infection with Wuhan-Hu-1 strain, Alpha VOC or Delta VOC variant was not adequate could provide immune protection against reinfections, especially for Omicron reinfections.

Omicron reinfections were reported in 62% (n=211), 20%, (n=68), and 30% (n=102) of primary SARS-CoV-2 infections caused by Omicron BA.1, BA .2 and BA.5, respectively. Subjects with primary BA.2 infections showed high re-infection rates (38%, n=129) with the Omicron BA.5 subvariant (26%, n=89). The findings indicated that while the SARS-CoV-2 spike (S) protein of the three Omicron subvariants is similar, the differences in the Omicron subvariants were sufficient to prevent Omicron BA.1/2 infection-induced nAbs. (neutralizing antibodies) would bind. with Omicron BA.5 S.


The study results showed that most cases of SARS-CoV-2 reinfection occurred by Omicron. Reinfection with Omicron among those with primary Omicron infection occurred within a short period of time, less than three weeks. The findings indicated that primary infections with non-Omicron VOCs were insufficient to provide immune protection to prevent reinfection with Omicron.

Further, the findings highlight Omicron’s transmissibility and immune evasion and the need for updated SARS-CoV-2 vaccines, continued SARS-CoV-2 surveillance, and SARS-CoV-2 evolutionary assessments to guide policy making for better public health around the world. . In addition, the analysis underscores the need to analyze NGS data on an individual level to provide accurate estimates of SARS-CoV-2 reinfection risks.

*Important announcement

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.

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