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Even as the coronavirus disease 20-19 (COVID-19) pandemic continues to spread, much remains to be done regarding its immunological and clinical characteristics, as well as its pathogenesis. Among these issues, one that has generated much controversy is the rapid decline in antibodies observed within months of recovery from active infection.
A preprint appearing on the medRxiv * The server reports a correlation between the loss of smell and taste and an observed persistence or increase in antibody levels five months after infection.
Duration of antibody response in SARS-CoV-2 infection
Previous reports have established that infection with SARS-CoV-2 can trigger specific antibodies, which last six months or more in symptomatic patients. However, the problem is more confused in asymptomatic infection, which appears to be accompanied by a rapid decrease in antibody titers.
Along with the induction of antibodies, the host establishes a memory B-cell response, which increases at six months. In contrast, little is known about the characteristics that can predict such a response.
In this context, an earlier study showed that SARS-CoV-2 serology could follow the spread of the virus within health facilities, in areas with different incidence and prevalence rates.
Five-month follow-up
The same researchers followed their previous data after five months, with the aim of establishing, on the one hand, whether the antibody response was still observable, and on the other hand, whether its trend could be predicted by or correlated with clinical features. They used machine learning algorithms to sift through more than 90 variables, looking for clear correlations.
The researchers found that women had a more sustained antibody response than men. Health personnel who were not in the medical field, that is to say the partner health operators, had higher levels of antibodies.
People in Bergamo hospitals had higher antibodies than others, and this region was hit hardest by COVID-19 when the pandemic first emerged.
Increased antibody levels in people with HIV
People with immunoglobulin G (IgG) antibodies of 12 AU / mL or more (cutoff for a positive result) in the previous study showed an increase at that time, five months later. While the increase was small in people with asymptomatic infection or in those with mild infection, it was significantly robust in symptomatic infections.
Those who had IgG titers greater than 3.8 AU / ml, but less than 12 AU / ml, and who were considered to have intermediate serological levels, showed a marked decrease in IgG levels.
Antibody levels increase in symptomatic patients
In the second analysis, the investigators included only patients with IgG levels below the tenth percentile or above the 90e percentile, so as to exclude bias. The previous results were good.
Males still had lower antibody levels than females, but the difference was losing statistical significance. Patients at the Bergamo hospital still had higher antibody levels while the relatively spared Humanitas Rozzano showed a drop in antibodies.
In asymptomatic patients, antibody levels fell, but remained stable in those with mild infection, increasing only in symptomatic individuals. Most asymptomatic individuals and symptomatic patients fell below the tenth and above the 90e percentile of antibody levels, respectively.
The reduction in antibody levels at this time was associated with the initial intermediate IgG levels, possibly due to noise in the tests. A history of tumors was also associated with reduced antibody levels. The odds of antibody levels being increased after five months were only 0.2 times that of controls, in the group with intermediate IgG levels or with a history of tumors.
Anosmia / dysgeusia correlated with increased antibodies
Interestingly, symptoms like fever, cough, myalgia, tachycardia, weakness, and loss of taste or smell were found to be associated with higher antibody levels at five months.
These symptoms all showed a strong association with individuals above 90e percentile of antibody levels, indicating that these correlate with a high or sustained antibody response. Adjusting for multiple variables, they observed that anosmia and dysgeusia, as well as chest pain, had the strongest association with increased antibody levels over time.
Researchers also found that more than half of people with chest pain shared the symptom of anosmia or dysgeusia. However, only a fifth of people with anosmia or dysgeusia also suffered from chest pain.
This pair of observations suggests that the increase in IgG in symptomatic patients is mainly correlated with anosmia and dysgeusia. Patients with these symptoms have a 2.75 times higher likelihood of increased antibody levels after five months, compared to 2.3 times higher for chest pain.
What are the implications?
The five-month re-analysis of anti-SARS-CoV-2 antibody level from baseline shows a stable response in symptomatic and asymptomatic individuals. Women and non-medical health workers had higher levels. Those with intermediate IgG levels showed a decrease, but the reason requires further study.
At both extreme levels of increasing or decreasing antibody levels, researchers found that asymptomatic infected people had higher levels of declining antibodies, while antibody levels continued to rise in the infection. symptomatic. The use of an extreme rise or fall in antibody levels thus distinguishes symptomatic infection from asymptomatic infection.
The study also showed that anosmia / dysgeusia and chest pain may be associated with increased antibodies against SARS-CoV-2. Both of these symptoms persist in COVID-19 patients, possibly because they are the result of viral infection of the olfactory epithelial cells (the olfactory sensory neurons, support cells, and immune cells), via receptors for host cells of the virus, angiotensin-converting enzyme 2 (ACE2) and serine protease, TMPRSS2.
The persistence of the virus in the olfactory epithelium, with resulting local inflammation and abnormalities in the structure and function of the olfactory bulb, could be responsible for the prolonged loss of taste and smell observed in some patients even after their test. RT-PCR negative for the virus.
The presence of the virus, along with the release of antigen, can continue to stimulate the immune system, thus maintaining and strengthening the antibody response.
“This study opens up new perspectives on immunity to SARS-CoV-2 and warrants further investigation into the role of anosmia / dysgeusia on the antibody response,” the researchers conclude.
*Important Notice
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.
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