The rise of the variants

Contemporary PEDS JournalJanuary/February 2023

More contagious but less severe, XBB takes over as dominant Omicron strain of COVID-19

Since the onset of the COVID-19 pandemic, numerous versions of the SARS-CoV-2 virus have emerged. Each variant has had its own unique characteristics, but the Omicron family of variants has proved to be particularly infectious, as well as resistant to the protection of vaccines or prior infections.

COVID-19 cases were on the decline throughout much of 2022, but the Omicron variant also emerged as the primary circulator. BA variants came first, but in the last quarter of the year the XBB variant took over, causing nearly half of all active COVID-19 cases in the United States as of December 31, 2022.1

Variants by the numbers

According to year-end data from the Centers of Disease Control and Prevention (CDC), the proportions of variants—all from the Omicron family—circulating at the close of 2022 included the following1:

XBB.1.5: 40.5%

  • BQ1.1: 26.9%
  • BQ.1: 18.3%
  • BA.5: 3.7%
  • BN.1: 2.4%
  • BF.7: 2.1%

Less than 1% of cases were caused by Omicron variants BA and BF. Additionally, no significant number of cases reported were caused by Delta or other previous variants by the end of 2022 in the United States, according to the CDC.1

The growth seen in the COVID-19 cases caused by the Omicron XBB variant was similar to that seen overseas earlier in the year. In comparison to the December 31 total of 40.5% of cases, the CDC revealed that the XBB variant made up just 4.2% of cases the previous week (ending December 24, 2022). The first cases of XBB were tracked by CDC around the beginning of October, according to agency reports.1

Are the new variants spreading more easily?

The Omicron family has been on the watch list of infectious disease experts for some time, but as the new year began, XBB seemed to receive the most attention.

There are not a lot of data on how this strain behaves clinically compared with others just yet, but reports from countries that saw this variant surge before it spiked in the United States show that XBB has a slight edge over previous Omicron relatives in a few areas.

A report from the government of New South Wales in Australia compared several of the most recent Omicron variants, including BA.5, BA.2.75, BA.4.6, and XBB. The data showed that most of these variants are descended from the same group of mutations, such as S:R346X, but most had differences in spike mutations. These changes in spike mutations contributed to a number of changes, especially in terms of site binding and transmissibility.2

The XBB variant—a recombinant of BA.2.10.1 and BA.2.75.2—had a weekly growth rate of 56.94% in that study compared with the 38.6% weekly growth rate of the BA.5 variant and the 24.18% rate of the BA.2.75 variant. The variants were not compared in terms of the risk of hospitalization or death because of a lack of data, the report revealed; however, it was noted that BA.5 resulted in similar risks for hospitalization and death to earlier Omicron variants.2

Do vaccines or prior infections offer protection?

Australian researchers also compared how the variants performed against vaccines and prior COVID-19 infections, and found that the XBB variant was more resistant to protection from either antibodies or vaccines than previous Omicron strains—even the B.5 variant. However, the report did note a better response against XBB in people who were vaccinated with a BA.5-adapted bivalent booster instead of just an original monovalent booster. People who received the BA-5 booster and also had a previous COVID-19 infection had even better protection, the study revealed.2

Finally, the report detailed the response of different variants against typical COVID-19 treatments, noting that XBB was the least responsive to treatment with imdevimab/casirivimab (REGEN‑COV; Regeneron) or tixagevimab/cilgavimab (Evusheld; AstraZeneca). As with other strains, there was a similar response to treatments such as remdesivir (Veklury; Gilead Sciences), molnupiravir (Lagevrio; Merck), and nirmatrelvir (Paxlovid; Pfizer).2

Are new variants really that different?

Other reports have also drawn comparisons between the now-dominant Omicron variants and previous lines such as Delta. One review of cases from 50 countries found that the Omicron family of variants had an incidence of about 62 cases per 100,000 people, whereas the Delta family of variants averaged around 17 per 100,000. Case fatality rates were lower during the Delta-dominated period than the Omicron period, however.3

Similar patterns were found in almost every country studied, seemingly confirming suspicions that Omicron is more easily transmissible but less fatal than previous SARS-CoV-2 variants. The report included the caveat, however, that vaccination rates also increased from the period of Delta-dominated infections until Omicron took over.3

Although the US increase in the Omicron XBB variant is still relatively new, it has been significant, rising from about 4% of cases in a week to more than 40%,1 dwarfing the Australian study’s estimates of a weekly growth rate of around 57%.2

It is still too early to estimate the exact impact of the Omicron XBB variant, but some experts believe they have zeroed in on the source of its potency. The mechanism for higher transmissibility in this variant is still a mystery, but increased angiotensin-converting enzyme 2 binding in this latest variant explains its superior growth and resistance to antibodies.4 Changes to the spike protein—the major target for vaccines—and monoclonal antibodies in the XBB variant make it more immune evasive than previous Omicron variants, data from another study suggested.5

Omicron, XBB, and children

Most of the data on the impact of the Omicron strains that have taken over US COVID-19 infections focuses on adult patients, but some reports have estimated the impact on the pediatric population specifically.

A report from the American Academy of Pediatrics put the tally of total COVID-19 infections in children at around 18% since the pandemic started, with pediatric cases making up nearly 12% of the cases being reported in the last week of December 2022. For perspective, the academy adds that children under 18 years make up 22% of the general population and that current reports of infections in children are likely undercounted.7

Researchers from the United Kingdom revealed in a September 2022 commentary in the New England Journal of Medicine that vaccine efficacy about 4 weeks after immunization with the Omicron-modified booster in children 5 to 11 years of age was about 63.2%. That protection increased to 69.6% in children who were vaccinated with the booster and had also been previously infected with a version of the SARS-CoV-2 virus.

But the team found that these protections did not last. By 16 weeks, efficacy rates dropped to about 16% in infection-naïve children and 22% in children who had already had COVID-19, according to the findings.6

The authors also pointed out that Omicron infection was more than 90% protective against reinfection with another Omicron-type virus even 2 month later. By 4 months, however, this protection dropped to about 80% in vaccinated children and 63% among unvaccinated children.6

Hospitalization rates among children infected with an Omicron strain of the virus were low in general among both vaccinated and unvaccinated children (less than 0.5%), the authors added. Further, hospitalizations were most common in children with other high-risk comorbidities.6

Mobeen H. Rathore, MBBS, FAAP, professor and associate chair of the Department of Pediatrics at the University of Florida College of Medicine – Jacksonville, and hospital epidemiologist and chief of pediatric infectious diseases and immunology at Wolfson Children’s Hospital, noted that he is seeing results similar to those being reported in the literature.

Few children becoming sick with current variants of the SARS-CoV-2 virus are requiring hospitalization in his community, he said, and most can be treated in the outpatient setting. “They seem to be sick for a longer time, but they are certainly not getting as sick as we saw with the Delta variant, or even Omicron early on.”

Rathmore, who also serves as chair of the Infection Prevention and Control Committee at Baptist Health System, said symptoms in children who develop COVID-19 infections do not seem to be much different overall from those of previous strains, although his patients have had significant coughs. Treatment-wise, Rathmore noted, management is similar to any other viral illness. In fact, he said, influenza has taken over both COVID-19 and respiratory syncytial virus (RSV) cases in his community. He added that especially after the holidays, COVID-19 may not be the only thing children are infected with at a time.

“We are seeing more influenza than the other 2 [RSV and COVID-19] put together,” Rathmore said. “I’m not sure this lingering sickness is just COVID[-19], but [it] may be also some other viruses circulating in the community.”


  1. Variant proportions. Centers for Disease Control and Prevention. Accessed December 31, 2022.
  2. Living evidence: SARS-CoV-2 variants. Agency for Clinical Innovation. Accessed December 28, 2022.
  3. Wang C, Liu B, Zhang S, et al. Differences in incidence and fatality of COVID-19 by SARS-CoV-2 Omicron variant versus Delta variant in relation to vaccine coverage: a world-wide review. J Med Virol. 2023;95(1):e28118. doi:10.1002/jmv.28118
  4. Yue C, Song W, Wang L, et al. Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion. bioRxiv. Preprint posted online January 3, 2023. doi:10.1101/2023.01.03.522427
  5. Imai M, Ito M, Kiso M, et al. Efficacy of antiviral agents against Omicron subvariants BQ.1.1 and XBB. N Engl J Med. 2023;388(1):89-91. doi:10.1056/NEJMc2214302
  6. Ladhani SN, Amirthalingam G, Khalil A. More on Omicron infections in children. N Engl J Med. 2022;387(10):1911. doi:10.1056/NEJMc2212691
  7. Children and COVID-19: state-level data report. American Academy of Pediatrics. Updated December 29, 2022. Accessed December 30, 2022.
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