KEY POINTS
• Evidence before this study: Most COVID-19 seroprevalence studies were carried out on the general population, usually showing low rates of antibodies. Our study is the first detailed seroprevalence evaluation of a highly vulnerable population in a large slum in South America.
• Contribution: This is the first population-based study that
presents seroprevalence of antibodies against SARSCoV-2 with probabilistic sampling on vulnerable populations in an Urban Slum of Buenos Aires City, Argentina. The high seroprevalence observed in the context of an intense epidemic in a vulnerable area might serve as a reference to other countries.
Population serological data are essential for understanding the prevalence of subclinical infections and the population’s herd immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Several COVID-19 seroprevalence studies were carried out on the general population showing low rates of antibodies2-5. However such evidence has been obtained from cities with different living conditions than the ones prevailing among slum dwellers of Latin American cities and can hardly be extrapolated to them6.
Buenos Aires City (CABA), the capital of Argentina, is a large urban conglomerate in a country of the Southern hemisphere. It has nearly three million inhabitants, of whom approximately 5.7% are a very vulnerable population living within 17 well-defined neighborhoods. In most cases, there are households with scarce potable water and sanitary conditions, poor ventilation, space constraints, and overcrowding, making physical distancing and selfquarantine impractical, thus facilitating the rapid spread of SARS-CoV2 infection7,8.
Barrio Mugica is one of the most overcrowded slums with more than 40 000 inhabitants, and almost 1500 people experiencing homelessness9. Its first case of SARSCoV-2 infection, linked to community transmission, was reported four days after the national mandatory quarantine was set on March 19th, 2020. Preventive measures were taught to community-based organizations that provided food assistance, temporary isolation centers for older adults located in churches were set up and an immediate plan for emergency and health care was established in the three medical centers allocated in Barrio Mugica. Despite these measures, this slum was the first one in Argentina to become affected by a high number of cases, with a sharp rise of infected people.
On May 5th, 2020, an active policy named Coronavirus Testing Strategy in Argentinian Territory (“DETeCTAr”) was set to dampen the spread by testing, diagnosing, and early treating of cases7. A crisis planning committee joined weekly to enforce the emergency plan actions related to health access, economic aid and food assistance. Social and health community workers were deployed in active surveillance on cases, and contact tracing. Local sampling for real-time polymerase chain reaction (RT-qPCR) testing was performed, and each positive person, according to clinical severity, was admitted to an out-of-hospital institution (repurposed hotels) or a hospital.
Until July 1st, the COVID-19 incidence rate at Barrio Mugica was 5.9% (2949 cases diagnosed by RT-qPCR) and the case fatality rate was 1.5% (44 deaths). In parallel with the mitigation measures, the basic reproductive number (R0) in Barrio Mugica decreased from 3.24 to 0.6 in six weeks.
To understand population immunity against SARSCoV2, on June, 10th, participatory research, the SeroCovid-POB study, started to detect SARS-CoV2-IgG presence and the housing conditions associated with infection. The final aim of the present study is to contribute to future decision making on control measures in similar neighbourhoods.
Materials and methods
A cross-sectional study for seroprevalence survey was carried out between June 10th and June 26th at Barrio Mugica.
Barrio Mugica, a slum with more than 40 000 inhabitants, and almost 1500 people experiencing homelessness is located in a strategic place, next to the main passenger transfer center of the City of Buenos Aires and a few meters from the most sought-after neighborhoods, named Retiro and Recoleta
It is a heterogeneous slum, with 10 different areas, each presenting particular cultural and social characteristics, they are: Bajo Autopista, Comunicaciones, Cristo Obrero, Ferrovi ario, Güemes, Inmigrantes, Playón Este, Playón Oeste, San Martín and YPF.
There are strong differences between Barrio Mugica’s living conditions and the ones shown in the rest of Buenos Aires City. In Barrio Mugica, around 60% of the population inhabits precarious houses, a quarter of them in cramped conditions. Three out of 10 do not have private toilets9.
Barrio Mugica sociodemographic data show that there is a predominance of the youngest age group, there is a high rate of households with young couples that have children, which represent a strong tendency to overcrowded house holds9. In other words, there are a high number of children and houses with children. Moreover, the number of migrants is higher in Barrio Mugica than in the rest of Buenos Aires City, mainly represented by people coming from neighboring countries such as Peru, Bolivia and, Paraguay9. Besides, Barrio Mugica has a high rate of unemployment, and when gender is considered, women present lower-income and suffer from higher rates of unemployment than men in the same community9. Figures 1A and 1B show Buenos Aires City and Barrio Mugica’s respective population pyramids. We included all residents above 14 years that consented to the study.
Prevalence positive SARS-CoV2 IgG was the main variable of this study. It was obtained from blood samples collected with a validated Serokit in a capillary tube from a finger prick take n at the doorstep of each person (serological test is explained below). Samples were processed and analyzed at the Hospital de Niños Dr. R. Gutierrez Virology laboratory.
The survey contained the following explanatory variables: age, biological sex; the presence of any related symptom during the past two months before this study was conducted, living, and sharing closed spaces with a confirmed case for COVID-19, number of households in the building and the sector of Barrio Mugica. Blood sample collection and epidemio logical data were collected and entered in a secure database.
The test COVIDAR IgG, an enzyme-linked immunosorbent assay [ELISA] developed and validated in Argentina (Laborato rio Lemos SRL, Buenos Aires, Argentina), was used to detect antibodies. Performance characteristics of the kit indicate a sensitivity of 75% after 7 days from symptoms onset and more than 90% after 21 days, using RT-PCR as the gold standard. The specificity was near 100% corroborated by studying 200 samples obtained before the pandemic (data in process of publication). The test detects antibodies against two viral an tigens, trimeric spike and the receptor-binding domain (RBD) of the spike protein. Viral glycoproteins were expressed in human cells. The test has obtained regulatory approval from Argentina’s national drug regulatory agency (ANMAT, National Administration for Drugs, Food and Medical Devices)10.
A sample size of 406 households was calculated for an estimated seroprevalence of 7% or higher with a precision of 3.5%, accounting for non-response and potential clustering of seropositivity by household (design effect 2).
A two-stage random sampling method was applied where the first level unit was a sector of Barrio Mugica; the second level unit was geographical areas determined by the De partment of Statistic and Census where thirty houses were selected at this level. People over 14 years old were tested at the front door of their houses. Figure 2 shows an example of a geographical area of one sector the neighbourhood with the 30 houses selected.
The SeroCovid-POB CABA sample dataset was expanded to that of the last census to estimate weighted prevalences. Specifically, we accounted for non-response; projecting the sample to the entire population, and finally calibrating age and sex groups11. A choropleth map was performed with QGIS software version 2.18.13.
In the descriptive analysis we used median and interquar tile range (IQR) for quantitative data and absolute (n) and relative frequencies (%) for categorical data.
As household members share exposure to SARS-CoV2, the outcome (prevalence of SARS-CoV2 IgG) clustering effect was included in a random-effects logistic regression model (multilevel model) as it includes the variation between clus ters explicitly in the likelihood and therefore takes account of intracluster correlation12-14.
Explanatory variables were fitted in the models according to a) individual level: age and sex; the presence of any related symptom two months before, b) household level: cohabiting with a confirmed case, number of households in the building, and c) the sectors of Barrio Mugica were grouped in six ordinal categories according to the level of vulnerability, being Bajo Autopista de more deprived sector. A household ID was set for people living together in a household (defined as those who shared income and food) because in some houses there is more than one household sharing a bathroom and kitchen. Odds Ratios (OR) and their confidence intervals 95% (95% CI) from the coefficients obtained in the statistical models were estimated. Free license R software version 4.0.2 was used.
The study was approved by the institutional review board of the Hospital de Niños Dr. R. Gutierrez. Oral in formed consent was obtained from every participant. The study protocol was registered in clinicaltrials.gov. Identifier: NCT04472078.
The National and local Ministries of Health provided medi cal supplies for the survey and for the virology laboratory to perform the ELISA test for SARS-COV2 antibodies detection.
The National Research Council (CONICET) provided the serokits test COVIDAR IgG.
None of the funding sources provided economical support for the data collection, statistical analysis, or were used to write the manuscript, or to submit it for publication.
The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Results
The study was carried out immediately after the number of confirmed COVID-19 cases flattened, between June 10th to June 26th. Figure 3 shows COVID-19 incident cases at Barrio Mugica and the period of the SeroCovid- POB study (June 10th to June 26th).
A total of 460 houses were visited, having a response rate of 73%. A total of 398 houses were included, in which 577 households (families) lived. Out of them, 873 people accepted to be tested at their house’s doorstep. The median age was 38 years (IQR 28-49) and 499 (57.2%) were women. Seventy-two people (16.8%) reported being symptomatic and 489 houses shared bathrooms and kitchens (55.3%). Table 1 shows the descriptive characteristics of the sample according to Barrio Mugica’s sector The weighted SARS-CoV2 IgG seroprevalence was 53.4% (95% CI 52.8%-54.1%). Prevalence among males was 51.5% (95%CI 50.6-52.4) and for women 55.3% (95% CI 54.4-56.2). Sex and age-group specific prevalence is shown in Figure 4.
The SARS-CoV2 IgG seroprevalence according to Barrio Mugica’s every sector is shown in Figure 5.
We have found strong evidence of within-household clustering effect (rho = 0.52; 95% CI 0.36-0.67; LRT 43.8 p-value < 0.001). We did not find an association between being symptomatic and a positive result in the serological assay (OR 1.01; 95% CI 0.54-1.87).
An association between being IgG positive and living with a RT-qPCR confirmed COVID-19 case was found (OR 2.13; 95% IC 1.17-3.85). Living in the Bajo Autopista sector of the neighborhood had the highest risk of infection (OR 30.39 95% CI 5.50-168.0). Other variable associa tions are shown in Table 2.
Discussion
We found an unexpectedly high seroprevalence (53%) and strong evidence of a within household clustering ef fect in an extremely deprived population in Buenos Aires, Argentina.
Although a small geographical area was covered in this community-level seroprevalence survey, selecting participants in a probabilistic way, allows extrapolation of results to similar low-income urban communities.
Our study is the first detailed seroprevalence evaluation in a highly vulnerable population in a large slum in Buenos Aires. Most COVID-19 seroprevalence studies to date were carried out on the general population, showing usu ally low rates of antibodies, ranging from 0.9% to 21%2-5.
The high seroprevalence found is consistent with the recent evidence that COVID-19 has disproportionately affected marginalized populations; the UK and US are reporting higher in-hospital mortality rates for black people and minority ethnic groups15,16.
The COVID-19 incidence rate at Barrio Mugica, ac cording to RT-qPCR of suspected cases, was 5.9%. Strikingly, we found that in these communities, for each patient diagnosed by RT-qPCR there were nine IgG-positive individuals, suggesting a strikingly high rate of asymptomatic infection. This relationship has also shown in other studies, it was 1 to 11 in Geneve3 and 1 to 10 in New York17.
Reporting bias could be present in the IgG rate for symptomatic cases, minimal symptoms might not have been noticed since the survey asked for symptoms during the two previous months when only people having fever were considered to be COVID-19 cases. Even though case definition has changed as new evidence, such as lack of taste and smell, was discovered about the course of the infection around the world, the high degree of cases under ascertainment suggests that clinical criteria and epidemiological nexus should be considered.
The precise percentage of the population required to be immune against SARS-CoV-2 for herd immunity to occur is currently undefined; however, assuming projec tions, if the SARS-CoV-2 basic reproductive number (R0) shifted from 2 to 3.5, the threshold would shift from 40% to 75%18,19. In our series, the R0 reached that threshold and the prevalence found was in agreement with such assumptions.
A caveat must be kept in mind: sex was not associated with higher prevalence, but male subjects between 14 and 19 years showed the highest prevalence of IgG compared with the other groups. This could be attributed to lower risk perception and lower compliance with the quarantine measures among young people.
Due to the high virus transmission found in our study, we would have expected a higher lethality rate among this population. However, in Barrio Mugica 1.5% of people are older than 65 years vs. 17% in the rest of Buenos Aires City, with a higher working-age population (37% vs. 30%). As a working-class neighborhood, it has a high immigration rate that tends to avoid elders, who stay living in their places of origin9. In our study, we also found a low proportion of elderly people (4.5%), this finding makes a difference with the rest of Buenos Aires City and also with many cities in developed countries, and could contribute to explain why, in spite of high virus transmission, the le thality rate was not as high as reported in other countries.
Social distancing recommendations intended to reduce SARS-CoV-2 transmission have a low impact in these settings. Our study showed a high cluster correlation, the variance within the households was smaller compared with that between households, showing a household-specific effect: an individual in one household is more likely to be SARS-CoV2 positive than an individual in another house hold (between correlation)20. In this regard, those who had a family member diagnosed with RT-qPCR had two-fold chance of becoming infected by the virus. Recently evi dence shows that household contacts, tested for SARS-CoV-2 by RT-PCR in a clinical follow-up, were at higher risk of infection (odds ratio 6.27 (95% CI 1.49-26.33) than other close contacts, and those having a household member who had received a diagnosis of COVID-19 were 15 times more likely to have had positive IgG test results for SARS CoV-2 than were those who did not21,22.
We also found sector differences: those living in worse conditions (Bajo Autopista) had a higher rate of infection. This could be associated with a severe shortage of water supply in April 2020, which put the whole community in distressing alert.
IgG antibody response against different SARS-CoV-2 antigens becomes detectable in immunocompetent patients after at least eight days with over 90% of indi viduals seropositive after day 14 of infection. In theory, seropositive individuals are expected to be at lower risk for re-infection compared to seronegative persons. However, neither the level nor the duration of protective immunity against COVID-19 is currently known22, therefore we will consider this study as a baseline cohort for a serial sero prevalence study that could provide a better understanding of transmission patterns and may help to determine if it’s possible to reach the herd immunity state