In Denmark, Omicron cases reveal ineffective immunity after COVID-19

In a recent study published in medRxiv* Preprint server Researchers investigated re-infection with SARS-CoV-2 in Denmark.

The evolution of SARS-CoV-2 has given rise to several variants of concern (VOC) with increased transmissibility and immune evasiveness such as Omicron, resulting in increased incidence of SARS-CoV-2 infections and difficulties in mitigating COVID-19 globally. Studies have investigated the frequencies of SARS-CoV-2 reinfection but have been limited to RT-PCR data, as no SARS-CoV-2 Pango strains have been identified. In addition, genetic sequencing report is usually categorized as either primary infection or reinfection, but next generation sequencing (NGS) data for both primary infection and reinfection is rarely reported for an individual.

Stady: Increase in omicron SARS-CoV-2 infections reveals ineffective immunity after COVID-19 in Denmark and conveys need for continuation of next-generation sequencing. Image Credit: Noiel / Shutterstock

about studying

In this study, researchers describe SARS-CoV-2 re-infections by variant based on the integration of RT-PCR and next-genome sequencing (NGS) analysis of sequences obtained from Danish individuals infected with SARS-CoV-2 and GISAID (Initiative Global Avian Influenza Data Exchange) database.

NGS data and clinical metadata of primary SARS-CoV-2 infection and infection from the same individual residing in Denmark were analyzed. In total, 21,708 entries from re-infections were available between March 1, 2020 and August 28, 2022, with data on sample collection dates on primary SARS-CoV-2 infections and re-infections.

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

The team excluded 70 cases (less than one percent of the total cases) (n = 70) with identical pango strains for primary infection and re-infection because such entries could be representative of unresolved SARS-CoV-2 infection rather than re-infection. In addition, Beta, Gamma, and ‘others’ VOC data (without globally accepted Pango nomenclature) were excluded due to low sequencing levels.

Re-infections were classified by variable and variable. The GISAID database was accessed for two files: one set of files containing current metadata for more than 12 million SARS-CoV-2 sequences and a second set containing filtered metadata files for only the Danish population with two SARS-CoV-associated infections -2 documented.


Primary infection and re-infection with omicron (ie, omicron-omicron infection) have been reported within a short period (even within three weeks, on average of 22 weeks) of non-omicron-omicron infection. Re-infection of an omicron within ten weeks of initial omicron infection was largely reported due to BA.1 followed by BA.2.

The frequency of re-infection was significantly higher with Omicron (25%, N = 1875) after initial infections with any of the VOCs. No cases of alpha VOC-induced re-infection were reported, while delta VOC caused re-infection in 2.3% (n = 169) of cases. Pre-Omicron estimates of natural immunity to infection were above 90%, which fell to less than 10% at three to four months.

Among individuals with primary delta-induced infections, recurrent infections due to the delta variant were less than 1% (n = 18) but for omicron re-infections it was 41% (n = 3060 cases). Moreover, re-infections with the same VOCs but different subvariables were only 0.3% (n = 24), except for Omicron (4.6%, n = 340). 93% of infected individuals as of March 2020 had omicron re-infection, indicating that initial infection of SARS-CoV-2 with Wuhan-Hu-1, Alpha VOC or Delta VOC was not able to confer adequate immune protection against re-infection. , especially for Omicron re-infection.

Omicron re-infection was reported among 62% (n = 211), 20%, (n = 68), and 30% (n = 102) of cases in which Omicron BA.1, BA caused. .2 and BA.5, respectively, individuals with primary BA.2 infection showed a high frequency of infection (38%, n = 129) using the Omicron BA.5 variant (26%, n = 89). The results indicated that although the SARS-CoV-2 spike(S) protein of the three Omicron sub variants is similar, the differences in the Omicron sub variants were sufficient to prevent Omicron BA.1/2 infection-induced nAbs (neutralizing antibodies) from Association with Omicron BA.5 S.


The results of the study showed that most of the re-infection with SARS-CoV-2 occurred due to Omicron. Re-infection of omicron occurred among those with primary omicron infection within a short period, less than three weeks. The results indicated that primary infection with non-omicron VOCs was insufficient in providing immune protection to prevent re-infection with omicron.

Furthermore, the findings highlight the transmissibility and immune evasion of Omicron and the need for updated SARS-CoV-2 vaccines, continued surveillance of SARS-CoV-2, and evolutionary assessments of SARS-CoV-2 to guide policy-making for improving public health. all over the world. In addition, the analysis underscores the need to analyze NGS data at the individual level to provide accurate estimates of the risk of re-infection with SARS-CoV-2.

*Important note

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