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New Study Suggests Reasons for COVID Reinfection

First-line defences against COVID-19 are short-lived and might explain repeat re-infections, researchers have suggested.

A study by Imperial College London and the University of Liverpool found that antibodies produced in the nose declined 9 months after infection with SARS-CoV-2, while antibodies in the blood lasted at least a year.

Call For Nasal Spray Vaccines

The study, published in eBioMedicine, found that vaccination was very effective in creating and boosting antibodies in the blood, protecting against severe disease and death. However, current COVID vaccines had very little effect on nasal IgA levels, prompting the researchers to recommend that the next generation of vaccines should include intra-nasal or inhaled versions, which could potentially reduce infections and prevent transmission more effectively.

Antibodies in the nasal fluid, known as immunoglobulin A, or IgA, provide a barrier against COVID-19 by blocking the SARS-CoV-2 virus when it first enters the respiratory tract. The researchers found that the nasal antibodies were only present in people who'd been recently infected and didn't last long, especially against the Omicron variant, compared with earlier variants. The findings could explain why people who've already had COVID remain susceptible to re-infection, especially from Omicron and its subvariants.

Vaccination Boosts Blood Antibodies Better

Prior to the research, it was unclear how long these nasal antibodies lasted. The study's first author, Dr Felicity Liew, from the National Heart and Lung Institute at Imperial College London, said: "Our study found durable immune responses after infection and vaccination, but these key nasal antibodies were shorter-lived than those in the blood. While blood antibodies help to protect against disease, nasal antibodies can prevent infection altogether. This might be an important factor behind repeat infections with the SARS-CoV-2 virus and its new variants."

Better Control of New Variants

Co-senior author of the study, Prof Peter Openshaw, from the National Heart and Lung Institute at Imperial College London, said: "Our results highlight a need for nasal spray vaccines that can boost these local antibodies in the nose and lungs. Such vaccines might be able to prevent people from getting infected with the SARS-CoV-2 virus and reduce transmission of the virus between people. This could help us to better control the pandemic and stop new variants emerging."

He continued: "It's brilliant that current vaccines mean fewer people are becoming seriously ill, but it would be even better if we could prevent them from getting infected and transmitting the virus." 

Effect of Subsequent COVID-19 Vaccines

The study involved 446 adults who had been hospitalised with COVID-19 between February 2020 and March 2021.

Samples were taken when patients were hospitalised and at 6 months and 1 year after. Since most people were vaccinated during the study, samples were also taken before and after vaccination.  

The researchers measured how well the antibodies neutralised the original SARS-CoV-2 virus, and the Delta and Omicron variants, to see how long the antibodies remained effective after infection or vaccination.  

Of those with confirmed COVID vaccination (323 people), 95% received their first vaccination during the study follow-up period. This led to increases in all nasal and blood antibodies, but the change in the first-line defence nasal antibodies (IgA) was small and temporary. The researchers found that the participants' sex, disease severity and age did not impact how long their nasal immunity lasted, but cautioned that their study was only in people with severe disease that required hospitalisation.  

Importance of Booster Vaccines

They also found that blood antibodies from participants continued to bind the original SARS-CoV-2 virus, and the Delta and Omicron variants, a year after infection, but booster vaccines were needed to maintain this immunity.  

Co-senior author of the study, Dr Lance Turtle, senior clinical lecturer at the University of Liverpool and consultant in infectious diseases at Liverpool University Hospitals, said: "Our study suggests that this first-line defence immunity is separate from other immune responses, and although it is increased by vaccination and infection, it only lasts for about 9 months. Nonetheless, booster vaccines can increase it slightly and otherwise have a significant impact on other areas of immunity, protecting against severe disease and death very effectively, so remain very important." 

The researchers noted that studies to specifically examine the nasal antibodies and reinfections were needed to confirm their results. 

The study was supported by the ISARIC4C, UKCIC and PHOSP-COVID consortia. It was jointly funded by the National Institute for Health and Care Research, UK Research and Innovation, and the Medical Research Council.  

No competing conflicts of interest were declared.