Article published in a journal eLife reports a study in which researchers concluded that the proportion of a population previously infected with SARS-CoV-2 (infection-induced seroprevalence) can be estimated using donated blood samples. The findings offer a kind of “portrait” of the first year of the COVID-19 epidemic in Brazil. According to the authors, their new methodology can also be used to monitor and estimate collective immunity to other infectious diseases.
The usual method of estimating seroprevalence in Brazil is based on random samples of the population. The authors note that this method is expensive and difficult to perform regularly in real time. Serosurveillance is important for understanding the characteristics of epidemics and for formulating public policy, for example by identifying where prevention and treatment are effective.
The lead authors are affiliated with the Brazil-UK Center for Arbovirus Discovery, Diagnosis, Genomics & Epidemiology (CADDE). They tested 97,950 blood samples for antibodies against immunoglobulin G (IgG). The samples were taken in the eight most populous capital cities of Brazil: Belo Horizonte, Curitiba, Fortaleza, Manaus, Recife, Rio de Janeiro, Salvador and São Paulo. The study took place from March 2020 to March 2021.
The results showed that the COVID-19 epidemic spreads unevenly and affects the population of these cities at different times. Seroprevalence was generally highest in men and younger people.
Initially, some lines of investigation assumed that they were all infected at the same time, but we have shown that this is not the case. Regarding the portrait of the epidemic, we concluded that it was extremely heterogeneous in Brazil, with different levels of infection between groups and significant differences in mortality rates. We didn’t expect this result.”
Carlos Augusto Prete Junior, first author of the article
Prete Junior is a researcher at the School of Engineering of the University of São Paulo (POLI-USP). The study was part of his doctoral research. His thesis advisers are Vitor Heloiz Nascimento, professor at POLI-USP, and Ester Sabino, professor at the University Medical School (FM-USP) and principal investigator at CADDE. Nascimento and Sabino are final authors of the paper.
The study was supported by FAPESP through CADDE and a scholarship awarded to Prete Junior. It also received funding from the Instituto Todos pela Saúde (“Everything for Health”, an initiative led by Itaú, Brazil’s largest private sector bank). The other authors are scientists from Imperial College London and Oxford University in the United Kingdom.
In another recent article published in Vaccines, the group analyzed donated blood samples to show that their method could be used to predict the arrival of the SARS-CoV-2 delta variant (first detected in India in 2020 and originally named B.1.617.2) in Brazil. They performed anti-spike protein microparticle assays to measure levels of IgG antibodies that bind to the viral S (spike) protein and prevent it from infecting cells. They found correlations between the protection provided by the vaccine, the number of cases, and the mortality due to the delta variant (read more at: agencia.fapesp.br/39629).
Methodology
The COVID-19 epidemic in Brazil was one of the most severe in the world, with 35.4 million cases and 690,000 deaths recorded by the beginning of December 2022. However, these figures do not reveal significant differences between regions and population subgroups, nor the proportion previously infected with the novel coronavirus. Estimating this proportion is important for predicting the impact of future waves caused by new virus variants.
In the study, as well as estimating the attack rate or seroprevalence of the disease over time for eight cities using donated blood samples, stratified by gender and age, the researchers also estimated the age-specific infection death rate (IFR) and infection hospitalization rate for each city .
The researchers had 1,000 samples tested per city per month. In order to be representative, the samples were selected so that the location of the donors’ dwellings corresponded to the spatial distribution of the population in the affected areas.
According to the law, blood donations in Brazil are stored for six months, so the researchers were able to select and test frozen samples between February (before the start of the pandemic in Brazil) and July 2020. After this period, the samples were collected and tested in real time.
IgG antibodies against SARS-CoV-2 nucleocapsid (N) were detected by chemiluminescence microparticle immunoassay, as this was the only automated kit commercially available in Brazil when the study began (July 2020). However, this type of test may suffer a loss of sensitivity over time due to declining antibody levels, and the declining proportion of individuals testing positive may increasingly lead to an underestimation of the true number of attacks as the epidemic progresses.
To correct for this loss of antibody detectability due to weakening of the immune system or declining antibody concentrations over time (seroreversion), the researchers developed a Bayesian model using data from repeat blood donors (people who donate blood several times a year) and a cohort of non-hospitalized symptomatic convalescent plasma donors who have tested positive for SARS-CoV-2 by PCR within 60 days of symptom onset.
“The inclusion of repeat donors was important because some studies done early in the pandemic corrected for seroreversion using only plasma donors. We showed that repeat donors were more representative of the population in each city,” said Prete Junior.
He noted that this model was not presented in a paper by the same group published in Science in December 2020 with information from the Manaus blood bank, as the data available at that time was insufficient. In this study, led by Sabino, they estimated that 76% of the urban population had immunity to the virus, but this was before the arrival of other variants such as gamma, later considered more aggressive and deadly (read more at: agecia.fapesp.br/35011).
“Shortly after the publication of the article, there was a second wave of COVID-19 in Brazil. At the time, many people thought that reinfection would not occur. We have now confirmed that blood donation samples can be used to estimate seroprevalence in For the purpose of monitoring other diseases, provided that certain adjustments are made, such as correction for seroreversion and estimation of attack rates for each age-sex group using spatially representative samples,” said Prete Junior.
The results showed that attack rates in December 2020, before the gamma variant became prevalent, ranged from 19.3% in Curitiba to 75% in Manaus. Seroprevalence was consistently lower in women and donors older than 55 years.
Cities with higher levels of seroprevalence also had higher mortality rates (deaths per 1,000 population). Between March 1, 2020 and March 31, 2021, the age-standardized death rate ranged from 1.7 in Belo Horizonte to 5.3 in Manaus, where the death rate was double that of Fortaleza, the city with the second highest death rate among those analyzed.
The infection case fatality rate (IFR) also varied between cities, ranging from 0.24% in Manaus to 0.54% in Curitiba, and the age-specific IFR increased consistently with age.
The researchers estimated the IFR using total deaths from severe acute respiratory infection (SARI), including PCR- and clinically confirmed SARS-CoV-2 infection, as well as SARI deaths without a final diagnosis, and excluded SARI deaths confirmed to be were caused by other diseases. This approach corrected the effect of underreporting, especially in 2020 when testing was not widely available.
Manaus
The gamma variant (P.1) was detected in November 2020 and its prevalence increased rapidly, reaching 87% on 4 January 2021 with a high proportion of reinfections, and for this reason the IFR and attack rate were estimated separately. for the second wave in Manaus, when gamma was dominant.
The study showed that the proportion of the Manaus population infected in the second wave was 37.5% compared to 75% in the first wave. The number of hospitalizations with infection in the city increased during the second wave, indicating the increased severity of the disease caused by gamma compared to previous variants.
The increased penetration of COVID-19 and the inability of the Manaus health system to cope with the influx of cases resulted in gamma-related IFRs reaching levels at least 2.91 times higher than in the first wave.
Source:
São Paulo Research Foundation (FAPESP)
Link to journal:
Prete Jr, CA, et al. (2022) Dynamics of SARS-CoV-2 antibodies in blood donors and the epidemiology of COVID-19 in eight Brazilian state capitals: A serial cross-sectional study. eLife. doi.org/10.7554/eLife.78233.