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Risk of BA.5 Infection among Persons Exposed to Previous SARS-CoV-2 Variants

by Ozva Admin

To the editor:

In recent months, omicron (B.1.1.529) became the dominant variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing some degree of immune evasion.1 The initial omicron subvariants, BA.1 and BA.2, are being progressively displaced by BA.5 in many countries, possibly due to increased transmissibility and partial evasion of immunity induced by BA.1 and BA.2.23 The protection provided by BA.1 against infection by the BA.5 subvariant is critical because adapted vaccines in clinical trials are based on BA.1.

Portugal was one of the first countries affected by a BA.5 dominance. We used the national registry of coronavirus disease 2019 (Covid-19) (SINAVE) to estimate the risk of BA.5 infection among people with documented infection with past variants, including BA.1 and BA.2. The registry includes all cases reported in the country, regardless of clinical presentation.

Protective effect of prior SARS-CoV-2 infection on infection with the Omicron BA.5 subvariant.

As shown in Panel A, we identified the periods (in different colors) in which a variant was represented in more than 90% of the isolates (data from the national severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] monitoring of genetic diversity4). Gray periods represent times when more than one variant was in circulation. Given the relatively slow transition between the dominance of the omicron BA.1 subvariant and the dominance of the omicron BA.2 subvariant, we grouped BA.1 and BA.2 in the analysis. We did not include anyone infected in the 90 days prior to dominance of the omicron BA.5 subvariant. Panel B shows the efficacy of protection against infection during the BA.5 dominance period (from June 1, 2022) among people with an infection at the dominance periods of different variants, as depicted in Panel A. , compared to people without any documented infection. Until the 1st of June. People with two infections before June 1 were not included in the study. The 𝙸 bars represent 95% confidence intervals.

The national genetic surveillance of SARS-CoV-2 identified periods in which different variants represented more than 90% of isolates.4 We identified all the people who had a first infection in periods of dominance of each variant, to calculate their risk of infection during the period of dominance BA.5 (Figure 1A). We combined BA.1 and BA.2 due to the slow transition between the two subvariants in the population. Finally, we calculated the risk of BA.5 infection for the population that had no documented infection prior to BA.5 dominance (June 1, 2022).

We found that prior SARS-CoV-2 infection had a protective effect against BA.5 infection (Figure 1B and Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org), and this protection was greatest for previous infections with BA.1 or BA.2. These data should be considered in the context of outbreak infections in a highly vaccinated population, given that in Portugal more than 98% of the study population completed primary vaccination before 2022.

The study design cannot eliminate all confounding factors (see Discussion section in the Supplementary Appendix). Furthermore, a limitation is the putative effect of lowering immunity in a population with hybrid immunity (prior infection and vaccination). We found that BA.1 or BA.2 infection in vaccinated individuals provided greater protection against BA.5 than infection with pre-omicron variants, in line with a recent report with a negative test design.5 However, BA.1 or BA.2 infections occurred closer to the period of BA.5 dominance than infections with earlier variants. There is a perception that protection from prior BA.1 or BA.2 infection is very low, given the high number of BA.5 infections among people with prior BA.1 or BA.2 infection. Our data indicate that this perception is likely a consequence of the larger group of people with BA.1 or BA.2 infection than with infection with other subvariants, and is not supported by the data.

Overall, we found that breakthrough infections with the BA.5 subvariant were less likely among people with a history of SARS-CoV-2 infection in a highly vaccinated population, especially for prior BA.1 or BA.2 infections, than among people with a history of SARS-CoV-2 infection. uninfected people. .

João Malato, M.Sc.
Institute of Molecular Medicine João Lobo Antunes, Lisbon, Portugal

Ruy M. Ribeiro, D. Phil.
Los Alamos National Laboratory, Los Alamos, NM

Dr. Pedro P. Leite
Dr. Pedro Casaca
Eugenia Fernandes, Ph.D.
General Directorate of Health, Lisbon, Portugal

Carlos Antunes, Ph.D.
University of Lisbon, Lisbon, Portugal

Valter R. Fonseca, MD, Ph.D.
General Directorate of Health, Lisbon, Portugal

Manuel C. Gomes, Ph.D.
University of Lisbon, Lisbon, Portugal

Luis Graca, MD, D.Phil.
Institute of Molecular Medicine João Lobo Antunes, Lisbon, Portugal
[email protected]

Supported by the European Union horizon 2020 research and innovation program (ERA project number, 952377–iSTARS) and by Foundation for Science and Technology through 081_596653860 and PTDC/MAT-APL/31602/2017 and through National Institutes of Health grant R01-AI116868.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on August 31, 2022 on NEJM.org.

Drs. Gomes and Graca contributed equally to this letter.

  1. 1. what Q, pharaoh j, jp evans, et al. Neutralization of SARS-CoV-2 subvariants omicron BA.4/5 and BA.2.12.1. N English J Med 2022;386:25262528.

  2. two. yu j, Collier AY, Rowe M, et al. Neutralization of SARS-CoV-2 omicron BA.1 and BA.2 variants. N English J Med 2022;386:15791580.

  3. 3. cao and, Yisimayi A, Jian F., et al. BA.2.12.1, BA.4, and BA.5 escape antibodies raised by omicron infection. Nature 2022;608:593602.

  4. Four. National Institute of Health Doutor Ricardo Jorge. Genetic diversity of the new coronavirus SARS-CoV-2 (COVID-19) in Portugal. (In Portuguese) 2022 (https://insaflu.insa.pt/covid19).

  5. 5. Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Protection of natural SARS-CoV-2 infection against reinfection with omicron BA.4 or BA.5 subvariants. July 12, 2022 (https://www.medrxiv.org/content/10.1101/2022.07.11.22277448v1). prepress

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