New method can help predict cases of Covid-19 variants

Researchers at the Joint Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) have developed a faster and cheaper method to analyze population serological data that can contribute to the assessment and prediction of the epidemiological behavior of Covid -19.

The scientists demonstrated that the methodology was able to predict the transmission of the delta variant (detected in India in 2020 and originally called B.1.617.2) in Brazil. Now they are looking to validate the method as a way to carry out surveillance in the population for new variants of Sars-CoV-2 and even for other types of disease, thus helping to speed up the response.

The group used samples from blood banks installed in seven capital cities —São Paulo, Rio de Janeiro, Manaus, Recife, Fortaleza, Curitiba and Belo Horizonte— to measure the amount of immunoglobulin G-type (IgG) antibodies in the population by performing microparticle assays. of anti-S, that is, to detect antibodies capable of binding to the spike protein of the coronavirus. With this, he was able to relate vaccine protection to cases of the delta variant and to the level of mortality.

At the beginning of the pandemic, seroprevalence studies were important to estimate the proportion of infected people. But they ended up losing relevance as almost 100% of the Brazilian population and other countries started to have antibodies against Sars-CoV-2, either through vaccination or infection. Hence the importance of seeking new ways of analyzing the behavior of the disease, with the possibility of predicting the number of cases by region for the formulation of public policies.

“In this study, instead of calculating the percentage of the population with antibodies, which was almost 100%, we analyzed the amount of antibodies in the blood and we were able to associate their level with the morbidity caused by the delta variant. share this type of data”, explains to Agência Fapesp the first author of the article, Lewis Buss, a researcher at Imperial College London (United Kingdom) who was a postgraduate student at the Institute of Tropical Medicine of the Faculty of Medicine of the University of São Paulo (FM-USP).

The results of the study, published in the scientific journal Vaccines, demonstrated that, during the growth phase of delta variant cases in Brazil, the low incidence of severe acute respiratory syndrome (SARS) records was strongly correlated with antibody levels measured in blood donors.

The risk of infection by the variant was shown to be lower in people who had already been infected with Sars-CoV-2 or vaccinated – hybrid immunity (vaccine plus previous infection) led to higher protection.

“The vaccine is very important to increase immunity. The infection alone does not solve it. We saw in the study that the amount of antibodies increases very quickly right after the first dose of the vaccine in cities that had a greater epidemic in the first wave of Covid-19, such as Manaus and Fortaleza, while the second dose had a greater effect in capitals with late epidemics, such as Curitiba and Rio de Janeiro.

As the population was already more protected, this helps to explain why the delta variant did not enter Brazil as effectively as it had in other countries”, explains professor Ester Sabino, from FM-USP, one of the authors of the study and responsible for CADDE in Brazil.

Sabino was in charge of the first sequencing of Sars-CoV-2 in the country, in March 2020, and of the first cases of the gamma variant, which appeared in Manaus about a year later (read more at: agencia.fapesp.br/32637/ and agencia.fapesp.br/35290/).

For her trajectory, the professor was honored, naming the Ester Sabino Award for Women Scientists, granted this year for the first time by the government of the State of São Paulo (read more at: agencia.fapesp.br/37931/).

In addition to supporting CADDE, Fapesp supported research through a scholarship for doctoral student Carlos Augusto Prete Júnior, from the Polytechnic School of USP. The work was also supported by Instituto Todos pela Saúde.

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The study showed that, driven by vaccination, which began in Brazil in January 2021, the average amount of antibodies grew 16 times during the period analyzed – between March and November of that year. Among residents in the age group eligible for blood donation (15 to 69 years), coverage with the first dose reached more than 75% in all cities by the end of the survey period. Coverage with the second dose was also high.

“We were looking for a marker that could facilitate and be used routinely to infer how well the vaccine was protecting the population. In epidemics, we have to use simple tools that can give quick answers. do”, adds Sabino.

Previous work has shown that neutralizing antibody levels are highly predictive of protection against symptomatic SARS-CoV-2 infection. However, to detect these antibodies, which effectively prevent the virus from entering human cells, complex and expensive tests are required. Not all anti-S are necessarily neutralizing, but in this study the researchers found that high levels of anti-Spike may predict a lower incidence of severe cases caused by a new variant introduced into an HIV-positive population. They used semiquantitative tests, which provide an estimate of the amount of a patient’s antibodies produced against SARS-CoV-2 infection.

From there, the group conducted different types of analyzes with samples collected in 2021, when the gamma, delta and omicron variants were successively replacing one another. We assessed the extent to which vaccination and previous infection contributed to the population’s anti-S IgG levels and the degree to which these variables predicted the incidence of severe delta-caused Covid-19 cases.

Tests were performed on 850 samples per month. From the second week of each month, samples were selected among all donations or within the neighborhoods of the capitals surveyed to obtain representativeness. Chemiluminescent microparticle immunoassays that detect IgG antibodies against the Spike protein of Sars-CoV-2 were applied. Data for administered vaccine doses were taken from OpenDataSUS.

To arrive at the Covid-19 numbers, three sources were consulted — records of severe acute respiratory syndrome and deaths from SIVEP-Gripe; total number of confirmed cases of Covid-19 by the Ministry of Health and the time series of the positivity of the Sars-CoV-2 test in a pharmacy chain in the city of São Paulo.

Metadata of all virus genomes deposited on the Gisaid platform between March 2020 and the same month of 2022 in the seven states were also used.

Context

The analyzed capitals recorded different moments of the epidemic. The cumulative attack rate (inferred through seroprevalence) in December 2020, before the second wave caused by the gamma variant and still without vaccination campaigns in Brazil, ranged from 20.3%, in Curitiba (PR), to 76, 3% in Manaus (AM).

While all cities had a large gamma-dominated peak in cases and deaths, the following period, with the delta variant, was not marked by the same characteristics, when the incidence of cases and deaths was low in Manaus, Fortaleza (CE) and Recife. (PE) and fell in Belo Horizonte (MG) and São Paulo.

Regarding the onomicron, there was a variable peak in the number of cases, with growth in all cities, but in relation to deaths, the variation was 3.7% in the period. The exception was Fortaleza, where there was an increase in records of severe acute respiratory syndrome attributable to the variant.

Therefore, the study pointed out that antibodies acquired through infection and/or vaccination were high enough in Brazil to avoid a significant impact on public health by the entry of new variants at that time.

Job data is open and accessible on the GitHub platform.

The article Predicting Sars-CoV-2 Variant Spread in a Completely Seropositive Population Using SemiQuantitative Antibody Measurements in Blood Donors can be read here.