Stability of hybrid versus vaccine immunity against BA.5 infection over 8 months
2023; Elsevier BV; Volume: 23; Issue: 2 Linguagem: Inglês
10.1016/s1473-3099(22)00833-7
ISSN1474-4457
AutoresJoão Malato, Ruy M. Ribeiro, Eugénia Fernandes, Pedro Pinto Leite, Pedro Casaca, Carlos Antunes, Válter R. Fonseca, Manuel C. Gomes, Luís Graça,
Tópico(s)COVID-19 Clinical Research Studies
ResumoThe coverage of SARS-CoV-2 vaccination in large parts of the world, together with the high number of breakthrough infections, especially following the emergence of Omicron subvariants, makes hybrid immunity (resulting from vaccine and infection) common. Hybrid immunity, particularly after BA.1 or BA.2 infection, confers substantial protection against the BA.5 infection.1Malato J Ribeiro RM Leite PP et al.Risk of BA.5 Infection among persons exposed to previous SARS-CoV-2 Variants.N Engl J Med. 2022; 387: 953-954Crossref PubMed Scopus (50) Google Scholar, 2Altarawneh HN Chemaitelly H Ayoub HH et al.Protective effect of previous SARS-CoV-2 infection against omicron BA.4 and BA.5 subvariants.N Engl J Med. 2022; 387: 1620-1622Crossref PubMed Scopus (53) Google Scholar, 3Hansen CH Friis NU Bager P et al.Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark.Lancet Infect Dis. 2022; (published online Oct 18.)https://doi.org/10.1016/S1473-3099(22)00595-3Summary Full Text Full Text PDF Scopus (43) Google Scholar However, although the waning of protection afforded by natural infection in non-vaccinated individuals or by vaccination has been well documented,4Chemaitelly H Tang P Hasan MR et al.Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar.N Engl J Med. 2021; 385: e83Crossref PubMed Scopus (505) Google Scholar, 5Goldberg Y Mandel M Bar-On YM et al.Protection and waning of natural and hybrid immunity to SARS-CoV-2.N Engl J Med. 2022; 386: 2201-2212Crossref PubMed Scopus (184) Google Scholar the stability of hybrid immunity, specifically against the BA.5 subvariant, now dominant in many countries, has not been thoroughly addressed. We used the Portuguese COVID-19 registry (SINAVE), which includes all notified cases of infection in the country on the basis of an official positive test and irrespective of clinical presentation, to investigate the risk of reinfection with BA.5 in a highly vaccinated population previously infected with BA.1 or BA.2 subvariants. We included the population aged 12 years or older, for whom the vaccination coverage was greater than 98% at the end of 2021 (appendix pp 4–5). The registry is very comprehensive due to legal requirements for compensation payment during mandatory isolation. We include infection data from the start of the pandemic until Sept 14, 2022. We identified the periods of dominance (over 90% of the isolates) of BA.1 and BA.2 (Jan 1–Apr 17, 2022) and BA.5 infections (June 1–Sept 14, 2022) using the national SARS-CoV-2 genetic surveillance data and divided those periods into 15 day intervals (figure 1A). We then calculated the relative risk (RR) of BA.5 infection in each interval for individuals that had the first infection during each BA.1 and BA.2 dominance subinterval, compared with individuals also vaccinated but without any previous documented infection. Reinfection was defined as two positive tests in the same individual, at least 90 days apart. We found that the RR increased from around 0·06 to around 0·35 between 3 months and 8 months post BA.1 or BA.2 infection (figure 1B, appendix p 12). Indeed, the RR initially increases rapidly, then more slowly, stabilising at around 0·37. The present authors previously assessed the effect of unreported infections in the calculation of RR.1Malato J Ribeiro RM Leite PP et al.Risk of BA.5 Infection among persons exposed to previous SARS-CoV-2 Variants.N Engl J Med. 2022; 387: 953-954Crossref PubMed Scopus (50) Google Scholar Here, we mitigate this effect by calculating the RR for the same interval of BA.5 infection for individuals infected by BA.1 or BA.2 in distinct periods, thus with a constant frequency of unreported infections. In any case, our findings are consistent throughout the entire dataset (appendix p 12). Our registry-based dataset includes data on essentially the whole population, but only includes data on positive tests. This feature precludes using a test-negative study design, which has been successfully used in other studies of RR.2Altarawneh HN Chemaitelly H Ayoub HH et al.Protective effect of previous SARS-CoV-2 infection against omicron BA.4 and BA.5 subvariants.N Engl J Med. 2022; 387: 1620-1622Crossref PubMed Scopus (53) Google Scholar, 6Ayoub HH Tomy M Chemaitelly H et al.Estimating protection afforded by prior infection in preventing reinfection: applying the test-negative study design.Epidemiology. 2022; (published online Jan 3.) (preprint).https://doi.org/10.1101/2022.01.02.22268622Google Scholar However, previous reports indicate that the estimates of protection efficacy using the national registry are well aligned with studies that used a test-negative design, albeit in a different population.1Malato J Ribeiro RM Leite PP et al.Risk of BA.5 Infection among persons exposed to previous SARS-CoV-2 Variants.N Engl J Med. 2022; 387: 953-954Crossref PubMed Scopus (50) Google Scholar, 2Altarawneh HN Chemaitelly H Ayoub HH et al.Protective effect of previous SARS-CoV-2 infection against omicron BA.4 and BA.5 subvariants.N Engl J Med. 2022; 387: 1620-1622Crossref PubMed Scopus (53) Google Scholar Studies since 2021 have made clear the potential for immune imprinting, with one study7Chemaitelly H Tang P Coyle P et al.Protection against reinfection with SARS-CoV-2 omicron BA.2.75* sublineage.Epidemiology. 2022; (published online Oct 30.) (preprint).https://doi.org/10.1101/2022.10.29.22281606Google Scholar suggesting that protection against infection waned after the booster (relative to primary series). In our study, essentially the whole population is vaccinated with the booster dose, and therefore we cannot distinguish effects of booster versus primary series. However, our results of increased protection with hybrid immunity versus vaccine immunity, agrees with the overall conclusion of that study that “imprinting effects are unlikely to negate the overall public health value of booster vaccinations”.7Chemaitelly H Tang P Coyle P et al.Protection against reinfection with SARS-CoV-2 omicron BA.2.75* sublineage.Epidemiology. 2022; (published online Oct 30.) (preprint).https://doi.org/10.1101/2022.10.29.22281606Google Scholar This study shows that hybrid immunity following infection with Omicron BA.1 or BA.2 when compared with vaccine-only immunity leads to substantially increased protection against BA.5 reinfection for up to 8 months. JM reports funding by Fundação para a Ciência e a Tecnologia, Portugal (grant numbers SFRH/BD/149758/2019 and UIDB/00006/2020). RMR reports funding by Fundação para a Ciência e a Tecnologia, Portugal (grant number PTDC/MAT-APL/31602/2017), and National Institutes of Health, USA (grant numbers R01-AI116868 and 5TU54ACTHL143541). CA reports funding by the Fundação para a Ciência e a Tecnologia, Portugal (PIDDAC; grant number UIDB/50019/2020). LG reports funding by Fundação para a Ciência e a Tecnologia, Portugal (grant number 081_596653860) and Fundacion la Caixa, Spain (grant number HR22–00741). All other authors declare no competing interests. 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