SÃO PAULO – Study released this Monday, 21, on the platform medRxiv points out that when the city of Manaus (AM) experienced the peak of the covid-19 in mid-May, approximately 46% of the local population had already contracted SARS-CoV-2. A month later, the percentage of infected people would have reached 65% and, in the following two months, it would have stabilized at around 66%.
In the authors’ assessment, this “exceptionally high” infection rate suggests that herd immunity may have contributed significantly to determining the final size of the epidemic in the capital of Amazonas.
“Apparently, exposure to the virus itself led to a drop in the number of new cases and deaths in Manaus. However, our results indicate a much higher seroprevalence than that estimated in previous studies, says Ester Sabino, professor at the Faculty of Medicine of University of Sao Paulo (FM-USP) and research coordinator – conducted with support from São Paulo State Research Support Foundation (FAPESP).
The conclusions presented in the article – still without peer review – are based on a combination of mathematical modeling e serological analyzes made on blood samples donated to the Hematology and Hemotherapy Foundation of Amazonas (Hemoam) between February and August.
“We selected samples from a thousand donors each month and analyzed the presence of antibodies against SARS-CoV-2. Then, we made a series of corrections in the results through mathematical modeling ”, says the first author of the study, Lewis Buss, to the FAPESP Agency, master’s student at the Institute of Tropical Medicine and the Department of Preventive Medicine at FM-USP.
This type of analysis is subject to a series of biases that need to be compensated, explains Buss. One is the fact that blood donors they are, in general, younger and healthier (asymptomatic) than the average population. In addition, in the specific case of Manaus, there is also a greater male representation.
Another point considered by the researchers was the sensitivity of the serological test used, estimated at 85% for asymptomatic individuals or those with mild disease (the false negative rate, therefore, can reach 15%). The key adjustment, however, was what sought to correct the natural decline in seroprevalence against SARS-CoV-2 – something that has been observed in serological surveys conducted in several countries.
“Something that was evident in our study – and that is also being shown by other groups – is that antibodies against SARS-CoV-2 decay quickly, a few months after infection. This is clearly occurring in Manaus, which shows the importance of taking serious measures to understand the evolution of the disease ”, says Buss.
The gross seroprevalence found in the survey, that is, without any type of correction, varied from 0.7% in March, to 5.5% in April, 39.9% in May, 46.3% in June, 36.5 % in July and 27.5% in August. With the adjustments of the mathematical model, however, the estimated numbers were respectively: 0.7%, 5%, 45.9%, 64.8%, 66.1% and, again, 66.1%.
Sample analysis in São Paulo
A similar strategy was adopted for the municipality of São Paulo, where the researchers analyzed samples of donated blood in the Pro-Blood Foundation between February and August. In this case too, 1,000 samples were selected per month and, in addition, a geographic quota criterion was adopted to give representativeness to residents of all regions of the city.
Gross seroprevalence found in the capital of São Paulo varied from 0.9% in March to 3% in April, 5.3% in May, 11.9% in June, 9.6% in July and 12.1% in August. After adjusting the model, the figures were respectively: 0.8%, 3.1%, 6.9%, 16.1%, 17.2% and 22.4%.
“The two cities have very different epidemiological curves and it is very difficult to explain why based only on serological data”, says Buss. “Perhaps the new information is that seroprevalence was already high in Manaus when deaths started to fall, which suggests the contribution of collective immunity. In São Paulo, on the other hand, seroprevalence is much lower and the curve is flatter. It is likely, therefore, that other factors have influenced the drop in the number of new cases in the capital of São Paulo ”, he evaluates.
Ester points out that after reaching the peak of deaths, between May and June, the capital of São Paulo entered a kind of plateau. “Contrary to what was observed in Manaus, here the fall is occurring slowly and the data for August are similar to those for the beginning of April. But today we see many more people wearing masks and, although commerce has reopened, mobility is still restricted and schools remain closed, as well as cinemas and theaters. It is possible that these factors have prevented the growth of the disease here ”, he says. “It is worth mentioning that if the curve were similar to that of Manaus São Paulo, it would have had a mortality rate three times higher”, warns the researcher.
Currently, the group coordinated by Ester is conducting serological analyzes with donor samples from Rio de Janeiro (RJ), Salvador (BA), Recife (PE), Fortaleza (CE), Curitiba (PR), Belo Horizonte (MG) and Campo Grande (MS). The results will be released soon.
“Working with data from blood banks allows us to measure the seroprevalence of a given disease more quickly and cheaply than studies that go from door to door collecting samples,” he says.
However, the researcher points out, the strategy has its limitations, the main one being the difference in profile between blood donors and the general population of the city, which requires care to make the sample representative.
“When we started research in São Paulo, with the help of FAPESP, one of the first things we did was to study the geography of blood donors in order to better stratify the samples. With resources from the Todos Pela Saúde initiative (Itaú Unibanco) and serology kits donated by the pharmaceutical company Abbott, we were able to expand the analysis to other capitals ”, he says.
“When comparing Manaus and São Paulo, we see very different epidemiological curves, despite the fact that public policies to contain the spread of the disease were adopted in the near future and the social isolation index is not radically different in the two places. The next step is to analyze the curves of other cities and then create models that allow us to understand which factors weighed more in each case ”, says Ester.
The research has been conducted under the scope of the Brazil-United Kingdom Center for Discovery, Diagnosis, Genomics and Epidemiology of Arbovirus (CADDE), funded by FAPESP, Medical Research Council and Newton Fund (the last two in the United Kingdom).