COVID-19 News: Imperial College London Study Finds That Nasal Mucosal Defenses Wanes 9 Months After SARS-CoV-2 Infection!
: A new study led by researchers from Imperial College London-UK has found that UK SARS-CoV-2-specific nasal immunoglobin A or IgA wanes 9 months after hospitalization or infections with COVID-19 and is not induced by subsequent COVID-19 shots or boosters!
The short-lived first-line immune defenses against COVID-19 may help explain frequent reinfections.
The study team also comprised of researchers from MRC-University of Glasgow Centre for Virus Research-UK, University of Sheffield-UK, University of Liverpool-UK, University of Edinburgh-UK, University of Leicester-UK, University of Oxford-UK, London School of Hygiene & Tropical Medicine-UK, University of Manchester-UK and University of Dundee-UK.
Already, in our recent COVID-19 News
coverage, we covered a study by Russian researchers that worryingly showed that SARS-CoV-2 damages mucosal immunity!
To date, most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defenses that prevent viral replication and onward transmission.
The research team studied nasal and plasma antibody responses one year after hospitalization for COVID-19, including a period when SARS-CoV-2 shots was introduced.
Plasma and nasosorption samples were prospectively collected from 446 adults hospitalized for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia.
IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralization data.
The study findings showed that strong and consistent nasal anti-NP and anti-S IgA responses were present, which remained elevated for nine months (p < 0.0001).
The nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralizing titers that were raised against all variants compared to controls (p < 0.0001).
It was noted that of 323 with complete data, 307 were jabbed between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titers for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls.
Interestingly, samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by COVID-19 shots.
The study findings showed a decline in nasal IgA responses 9 months after infection and minimal impact of subsequent COVID-19 shots and boosters may explain the lack of lo
ng-lasting nasal defense against reinfection and the limited effects of COVID-19 shots on transmission.
The study findings highlight the need to urgently develop COVID-19 shots that enhance nasal immunity.
The study findings were published in the peer reviewed journal: eBioMedicine (Lancet)
This is the first study to date to discover that antibodies produced in the nose decline nine months after COVID-19 infection, while antibodies found in the blood last at least a year.
The antibodies in the nasal fluid (known as immunoglobulin A, or IgA) typically provide first-line defense against COVID-19 by blocking SARS-CoV-2 virus when it first enters the respiratory tract. These antibodies are very effective at preventing the virus from entering cells and causing infection.
The study team worryingly discovered that the nasal antibodies were only present in those recently infected and were particularly short-lived against the omicron variant, compared to earlier variants.
This study finding may explain why individuals who have recovered from COVID are at risk of reinfection, and especially with omicron and its subvariants.
The research finding also showed that COVID-19 shots and boosters are very effective in creating and boosting antibodies in the blood, which prevent severe disease, but had very little effect on nasal IgA levels.
Dr Felicity Liew, from the National Heart and Lung Institute at Imperial College London, the first author of the study, commented, "Before our research, it was unclear how long these important nasal antibodies lasted. Our study found durable immune responses after infection and shots, 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."
The study team noted that further studies that directly study these nasal antibodies and reinfections are warranted to confirm their results.
The study involved almost 450 individuals who had been hospitalized with COVID-19 between February 2020 and March 2021, before the emergence of omicron variant and prior to COVID-19 jabs rollout.
The research also found that whilst current COVID-19 shots are effective at boosting blood antibody which can prevent serious illness and death, they do not significantly boost nasal IgA antibodies.
The study team calls for the next generation of COVID-19 shots to include nasal spray or inhaled shots that target these antibodies more effectively. They say that COVID-19 shots capable of boosting these antibodies could potentially reduce infections more effectively and prevent transmission.
Professor Dr Peter Openshaw, from the National Heart and Lung Institute at Imperial College London, co-senior author of the study, said, "Our study findings 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 individuals 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."
"Our current vaccines are designed to reduce severe disease and death and are dramatically effective in this aim. It's now essential to also develop nasal spray vaccines that can provide better protection against infection. 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," he further added.
The research analyzed the antibodies of the study participants to understand how long nasal antibodies lasted, compared with antibodies found in the blood. They also studied the effect of subsequent COVID-19 vaccines on antibodies in the nose and blood.
Nasal and blood samples were taken when people were hospitalized and at six months and one year after. Since most people were vaccinated during the study, many samples were also taken before and after vaccination.
The study team measured how well the antibodies neutralized the original SARS-CoV-2 virus, and the delta and omicron variants to see how long the antibodies were effective for after infection or vaccination.
The research included 446 individuals admitted to hospital in the early phase of the COVID-19 pandemic, including 141 who provided samples at the start of the study and six and 12 months later.
For study participants who only had one sample taken during the 12-month period of study, the study team used modeling to estimate how the average antibody responses changed over time.
It was noted that of those who confirmed whether they had been vaccinated (323 people), 95% (307 people) 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 defense nasal antibodies (IgA) was small and temporary.
The study team found that the participants' sex, disease severity and age did not impact how long their nasal immunity lasted, but caution that their study was only in individuals with severe disease that required hospitalization.
The study team also found that blood antibody from participants continued to bind the original SARS-CoV-2 virus, and the delta and omicron variants a year after infection, but found that booster vaccines are needed to maintain this immunity.
Dr Lance Turtle, Senior Clinical Lecturer at the University of Liverpool and Consultant in Infectious Diseases at Liverpool University Hospitals, co-senior author of the study, said, "Our research findings suggest that this first-line defense immunity is separate from other immune responses, and although it is increased by vaccination and infection, it only lasts for about nine 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 study team noted that their study did not screen participants for reinfection, but that this was unlikely to have occurred since the study took place during periods of national restrictions and lockdowns when COVID-19 incidence was low and people were not mixing. In a preliminary analysis, they found only two cases of reinfection in their study, suggesting that the overall trends seen are accurate.
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