The Omicron BA.4 and BA.5 subvariants emerged in early 2022 and rapidly became the dominant strains of COVID-19 worldwide, including in Europe and the United States1 2. These variants are notable for their increased transmissibility and ability to evade immunity from prior infections and vaccinations, contributing to new waves of infections and hospitalizations3 1. Despite their rapid spread, the clinical severity of BA.4 and BA.5 infections remains similar to or slightly less than earlier Omicron subvariants4 5.
BA.4 and BA.5 Variant Differences
BA.4 and BA.5 were first detected in South Africa in early 2022 and quickly replaced earlier Omicron subvariants due to mutations that enhanced their transmissibility and immune escape capabilities2 1. Both subvariants share identical spike proteins with key mutations such as L452R and F486V, which increase their infectivity and ability to evade antibodies generated by previous infections or vaccinations6 7. These mutations enable the virus to bind more effectively to human cells, facilitating infection6 8.
Epidemiologically, BA.5 has been more dominant, accounting for the majority of COVID-19 cases in the United States by October 2022, while BA.4 caused a smaller but significant proportion of infections9 10. The enhanced immune evasion of these subvariants means that antibodies from prior Omicron infections or vaccines are less effective, although vaccines still provide strong protection against severe illness, hospitalization, and death11 310.
Public health authorities have recommended updated bivalent booster vaccines targeting BA.4 and BA.5 to improve immunity and reduce the impact of these variants9 10. Despite their increased transmissibility, BA.4 and BA.5 have not been associated with increased clinical severity compared to earlier Omicron variants4 5.
- BA.4 and BA.5 share identical spike protein mutations, including L452R and F486V, enhancing infectivity and immune escape6 7.
- BA.5 became the dominant variant in the US by late 2022, causing about 65% of cases; BA.4 accounted for approximately 17% 910.
- Mutations allow these subvariants to partially evade antibodies from vaccines and prior infections, reducing neutralization11 8.
- Updated bivalent boosters targeting BA.4/5 are recommended to improve protection9 .
- Despite immune evasion, vaccines remain effective at preventing severe disease and death3 10.
💡 Did You Know?
The Omicron subvariants BA.4 and BA.5 are behind an increase in COVID-19 infections and hospitalizations. They're the most transmissible and immune-evasive strains of the COVID-19 virus to date. 3
Common BA.4 and BA.5 Symptoms
The symptom profile of BA.4 and BA.5 infections is dominated by upper respiratory tract symptoms, resembling a common cold more than earlier COVID-19 variants12 13. The most frequently reported symptoms include cough, sore throat, nasal congestion or runny nose, fatigue, and headache12 14. Fever and muscle aches are also common, especially with BA.5 infections, which may cause more systemic symptoms than earlier Omicron subvariants BA.1 and BA.215 16.
Loss of smell (anosmia) and taste (ageusia), hallmark symptoms of earlier COVID-19 variants, are less common with BA.4 and BA.517 10. Gastrointestinal symptoms such as diarrhea can occur but are less frequent12 . Symptom severity and presentation can vary widely depending on vaccination status, prior infection, and individual host factors13 .
- Persistent cough, sore throat, and nasal congestion are common symptoms of BA.4 and BA.5 infections12 14.
- Fatigue and headache frequently accompany respiratory symptoms12 14.
- Fever, chills, muscle aches, and body pain are more prevalent in BA.5 compared to earlier Omicron variants15 16.
- Loss of smell and taste are significantly less frequent in BA.4/5 infections17 10.
- Gastrointestinal symptoms like diarrhea are possible but less common12 .
BA.4 and BA.5 subvariants cause symptoms similar to a cold, including runny nose, sore throat, headache, and fatigue. Fever occurs in less than one-third of cases, and loss of smell or taste is rare compared to earlier variants. 1018
Symptom Severity Comparison
Population-level studies from South Africa and Scotland have shown that BA.4 and BA.5 infections do not cause more severe disease than earlier Omicron variants5 4. Hospitalization rates increased during BA.5 waves primarily due to higher case numbers, not because of increased virulence5 . Mortality and intensive care unit (ICU) admission rates remained stable during BA.4/5 predominance, indicating no rise in fatality5 .
Most BA.4 and BA.5 infections cause mild to moderate illness manageable at home, with severe respiratory symptoms requiring medical attention9 . Vaccination and prior immunity continue to play critical roles in reducing disease severity and preventing progression to severe outcomes5 . Ongoing studies are needed to fully understand the clinical impact of these subvariants5 13.
| Outcome Measure | BA.4/BA.5 vs Earlier Omicron | Notes |
|---|---|---|
| Hospitalization Rate | Similar or slightly lower5 4 | Increase due to case volume, not severity5 |
| ICU Admission Rate | No significant increase5 | Stable compared to prior waves5 |
| Mortality Rate | Stable5 | No rise in deaths during BA.4/5 waves5 |
| Symptom Severity | Mild to moderate9 13 | Most cases managed at home12 |
- BA.4 and BA.5 infections show similar or slightly reduced severity compared to earlier Omicron variants4 5.
- Increased hospital admissions reflect higher case numbers, not increased virulence5 .
- Mortality and ICU admission rates remained stable during BA.4/5 predominance5 .
- Mild symptoms can be managed at home; severe respiratory distress requires medical care9 .
- Vaccination and early treatment are key to preventing severe disease5 .
“The virus is moving in a direction of escaping our vaccines more and more, but it has not found a way to escape the vaccines to a really significant degree.”
— David Montefiori, Duke University Medical Center10
Key Takeaways
- BA.4 and BA.5 are highly transmissible Omicron subvariants with mutations that enhance infectivity and immune escape, leading to widespread global dominance in 20222 13.
- These variants primarily cause upper respiratory symptoms such as cough, sore throat, nasal congestion, fatigue, and headache, with less frequent loss of smell and taste compared to earlier variants12 1710.
- Fever and systemic symptoms like muscle aches are more common with BA.5 than with earlier Omicron subvariants15 16.
- Clinical severity of BA.4 and BA.5 infections is comparable to or slightly lower than previous Omicron variants, with stable hospitalization, ICU admission, and mortality rates5 4.
- Vaccination, including updated bivalent boosters targeting BA.4/5, remains essential to prevent severe illness, hospitalization, and death9 3.
