Previous Omicron BA.1 infection does not protect against BA.2 variant

A new study by researchers from Statens Serum Institut-Denmark along with scientists from the University of Copenhagen-Denmark, University of Denmark and Deakin University-Australia have found that previous Omicron BA.1 infection does not protect against BA.2 variant.

The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2022.02.19.22271112v1

The present study confirms the occurrence of Omicron BA.2 reinfection shortly after a previous BA.1 infection. This is to our knowledge the first study that reports aggregated Omicron BA.2 reinfection cases and document a time interval as short as 20 days after initial infection.

Among the 1,848,466 million infected individuals in the study period, we identified 1,739 cases that fulfilled the criteria of two positive samples with more than 20 and less than 60 days apart. From a randomly selected group of 263 paired samples that were successfully analyzed by WGS, we found 187 (71%) cases of reinfections and 47 (18%) of these were Omicron BA.1-BA.2 reinfections.

The reinfection rate appears to be low given the high number of positive SARS-CoV-2 tests during the study period but still highlights the need for continuous assessment of length of vaccine-induced and/or natural immunity. Given the short time period between infections it could be reasonable to re-evaluate the definition by ECDC that requires two positive samples with more than 60 days apart in order to consider reinfection.

Omicron BA.2 reinfections after either Delta or BA.1 initial infections, were mainly observed among young individuals below the age of 30 and the majority of these cases were not vaccinated, further emphasizing the enhanced immunity obtained by the combination of vaccination and infection compared to infection induced immunity only. For the Omicron BA.1 infection to BA.2 reinfection among cases aged 15 or above, only 13% (3/24) had completed the primary vaccination program contrary to the overall vaccination rate in Denmark of >80%.

Reinfections were characterized by overall mild symptoms comparable to the initial infection and did lead to neither hospitalization nor death. It is, however, striking that mainly children and adolescents become reinfected, since children to a higher degree than adults develop a sustained cross-reactive immunity¹⁶.

This may be explained by the very high incidences among children in the chosen study period, whereas adults and elderly had lower incidences. A change in indication for testing was noted between the first and second infection, and this may reflect a general change in why individuals are tested over time. With more widespread infections and restrictions lifted, the urge to test due to exposure to a person testing positive may have been reduced in general, leading to an increase in the proportion of individuals tested because of symptoms.

To evaluate if cases of Omicron BA.2 reinfections are caused by a specific subset of BA.2 variants circulating with intrinsically different properties than BA.2 in general, we compared the paired samples with randomly sampled Danish BA.1 and BA.2 genomes. Here we found no sign of clustering among BA.2 or BA.1 variants involved in reinfection compared with the randomly selected BA.1 and BA.2 sequences.

The differences in age group and vaccination status between the paired reinfection data and the randomly sampled data did not give rise to any clustering either. This indicates that the capability of Omicron BA.2 to cause reinfections in recently infected Omicron BA.1 cases with low or no vaccination protection may be an intrinsic BA.2 property. For the Omicron BA.1-BA.1 cases, we found the genomes to be near identical (0-1 SNP) in most cases, thus indicating a residual infection.

We observed significantly reduced overall viral load in secondary BA.2 infection samples compared to initial infection together with a lower ratio of subgenomic to genomic RNA. Taken together, this may indicate a more superficial and transient secondary infection that could be explained by T cell-mediated immunity obtained during the first infection¹⁷.

We have previously speculated that infections in the early stage may be associated with the pattern that we see here for the Omicron BA.2 study population¹⁸, and it is possible that the BA.2 infection in these individuals, happening within a short window after an initial BA.1 infection, may somehow differ, perhaps by being more superficial or transient than the BA.2 infections observed in the randomly selected samples used for comparison.

In conclusion, we provide evidence that Omicron BA.2 reinfections are rare but can occur relatively shortly after a BA.1 infection, causing mostly mild disease in unvaccinated young individuals. The reinfections were identified among SARS-CoV-2 cases testing positive for more than one time in a country with a high PCR test capacity and extensive community transmission.