Even as the coronavirus disease 20-19 (COVID-19) pandemic continues to spread, much remains unclear regarding its immunological and clinical features, as well as its pathogenesis. Among these questions, one which has attracted a great deal of controversy is the observed rapid waning of antibodies within a few months of recovery from active infection.
A preprint appearing on the medRxiv* server reports a correlation between the loss of smell and taste and an observed persistence or rise in antibody levels at five months after infection.
Duration of antibody response in SARS-CoV-2 infection
Earlier reports have established that SARS-CoV-2 infection can elicit specific antibodies, which last for six months or more in symptomatic patients. However, the issue is more confused in asymptomatic infection, which seems to be accompanied by a rapid waning of antibody titers.
Along with the induction of antibodies, the host establishes a memory B cell response, which increases at six months. On the other hand, not much is known about the features that can predict such a response.
In this context, an earlier study showed that SARS-CoV-2 serology could track the virus's spread within healthcare facilities, in areas with different incidence and prevalence rates.
Follow-up at five months
The same researchers followed up their previous data after five months, aiming to establish, firstly, whether the antibody response was still observable, and secondly, whether its trend could be predicted by or correlated with any clinical features. They used machine learning algorithms to sift through more than 90 variables, looking for clear correlations.
The researchers found that females had a more sustained antibody response than males. Healthcare personnel who were not in the medical field, that is, healthcare partner operators, had higher antibody rates.
Individuals in the Bergamo hospitals had higher antibodies than others, and this area was harder hit by COVID-19 when the pandemic first emerged.
Rise in antibody levels in seropositives
People with immunoglobulin G (IgG) antibodies at 12 AU/mL or higher (the cut-off for a positive result) in the earlier study showed an increase at this time point, five months later. While the increase was small in those with asymptomatic infection, or those with mild infection, it was noticeably robust in symptomatic infections.
Those who had IgG titers above 3.8 AU/mL, but below 12 AU/mL, and were considered to have intermediate serological levels, showed a marked decline in IgG levels.
Antibody levels rise in symptomatic patients
In the second analysis, the investigators included only those patients whose IgG rates fell below the tenth percentile or above the 90th percentile, so as to exclude bias. The previous findings held good.
Males still showed lower antibody levels compared to females, but the difference lost statistical significance. Bergamo hospital patients still showed higher antibody levels while the relatively spared Humanitas Rozzano showed a fall in antibodies.
In asymptomatic patients, the antibody levels fell, but remained steady in those with mild infection, increasing only in symptomatic individuals. Most asymptomatic individuals and symptomatic patients fell below the tenth and above the 90th percentile of antibody levels, respectively.
Reduction in antibody levels at this time point was associated with initial intermediate IgG levels, perhaps due to noise in the testing. A history of tumors was also associated with reduced antibody levels. The odds that antibody levels would be raised 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 rise in antibodies
Interestingly, symptoms such as fever, cough, myalgia, tachycardia, weakness and the 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 the 90th 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.
The researchers also found that over half of the individuals with chest pain shared the symptom of anosmia or dysgeusia. However, only a fifth of individuals with anosmia or dysgeusia had chest pain as well.
This pair of observations suggested that IgG increase in symptomatic patients is correlated mainly with anosmia and dysgeusia. Patients with these symptoms have 2.75 times higher odds of increased antibody levels after five months, compared to 2.3 times higher odds for chest pain.
What are the implications?
The five-month re-analysis of the level of antibodies to SARS-CoV-2, compared to the baseline, shows a stable response in symptomatic and asymptomatic individuals. Females and healthcare workers in the non-medical field had higher levels. Those with intermediate IgG levels showed a decrease, but the reason requires further study.
At the two extreme levels of increase or decrease in antibody levels, the researchers found that asymptomatic infected individuals had higher rates of declining antibodies, while antibody levels continued to rise in symptomatic infection. The use of an extreme rise or fall in the antibody level thus distinguished symptomatic from asymptomatic infection.
The study also demonstrated that anosmia/dysgeusia and chest pain may associate with a rise in antibodies against SARS-CoV-2. Both these symptoms are persistent in COVID-19 patients, perhaps because they are the result of viral infection of the olfactory epithelial cells (the olfactory sensory neurons, support cells and immune cells), via the host cell receptors for the virus, the angiotensin-converting enzyme 2 (ACE2) and the serine protease, TMPRSS2.
The persistence of the virus in the olfactory epithelium, with resulting local inflammation and abnormalities of the structure and function of the olfactory bulb, could be responsible for the sustained loss of taste and smell observed in some patients even after they test negative by RT-PCR for the virus.
The presence of the virus, with antigen release, may continue to stimulate the immune system, thus sustaining and enhancing the antibody response.
“This study opens new perspectives on the immunity to SARS-CoV-2 and warrants further investigation on the role of anosmia/dysgeusia on antibody response,” the researchers conclude.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.