BA.4 and BA.5 now account for the majority of Covid cases in the U.S.¹  Several concerning features of BA.4 and BA.5 when compared to earlier strains of SARS-CoV-2 include:^2-6

1. High reproductive rate or R0 ie, the average number of new infections generated by an infectious person in a totally naïve population. BA.4/5 has an estimated R0 of 18.6, according to a one report.  For comparison, the R0 for the original Wuhan variant was estimated at 3.3, for Delta  5.1, early Omicron  9.5, BA.1 13.3, mumps 12, and measles 18.  So, it’s not surprising that we are currently experiencing higher rates of SARS-CoV-2 transmission in the population than just a few weeks ago.³
2. Suboptimal existing immunity following prior infections due to Omicron variants BA.1 and BA.2, or prior vaccinations (including 3 doses of Pfizer vaccine).^2,4
3. More efficient spread than BA.2 when studied in human lung cells invitro. ²
4. More pathogenic than BA.2 in hamsters. ²
5. Reduced activity of SARS-CoV-2 therapeutic monoclonal antibodies.⁴
6. Antigenically distant from other SARS-CoV-2 variants, with 50 mutations, including more than 30 on the spike protein, the viral protein targeted by Covid vaccines to induce immunity.^5,6

Despite these potentially ominous traits, currently there is no evidence that  BA.4 or BA.5 is inherently more likely to cause severe disease than that caused by other Omicron subvariants.   The sheer number of infected persons in the population due to high transmission rates, however, will likely translate into higher hospitalization and deaths which has already happened in many areas.

High transmission rates also mean that we should not abandon the usual public health measures (eg, social distancing, masking indoors in public spaces) and vaccination with boosters for eligible persons with the aim of reducing hospitalization and death, if not infections.  

Bonus Pearl: Did you know that BA.4 and BA.5 became dominant in South Africa in April, 2022, despite 98% of the population reportedly having some antibodies from vaccination or previous infection or both?  

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References

1. Leatherby L. What the BA.5 subvariant could mean for the United States. NY Times, July 7, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
2. Kimura I, Ymasoba D, Tamura T, et al. Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. bioRxiv, preprint doi: https://doi.org/10.1101/2022.05.26.493539 , posted May 26, 2022. Accessed July, 13, 2022.
3. Esterman D. The Conversation. Australia is heading for its third Omicron wave. Here’s what to expect from BA.4 and BA.5. July 4, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
4. Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, et al. Antibody escape of SARS-COV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum.
5. Katella K. Omicron and BA.5: A guide to what we know. YaleMedicine, July 6, 2022. https://www.yalemedicine.org/news/5-things-to-know-omicron
6. Topol E. The BA.5 story. The takeover by this Omicron sub-variant is not pretty. Ground Truths. June 27, 2022. https://erictopol.substack.com/p/the-ba5-story

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!