key: cord-0765131-xhi3xd4x
authors: Mattar, Salim; Alvis-Guzman, Nelson; Garay, Evelin; Rivero, Ricardo; García, Alejandra; Botero, Yesica; Miranda, Jorge; Galeano, Ketty; de La Hoz, Fernando; Martínez, Caty; Arrieta, Germán; Faccini-Martínez, Álvaro A; Guzmán, Camilo; Kerguelen, Hugo; Moscote, Maria; Contreras, Hector; Contreras, Veronica
title: SARS-CoV-2 seroprevalence among adults in a tropical city of the Caribbean area, Colombia: are we much closer to herd immunity than developed countries?
date: 2020-11-12
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofaa550
sha: 63eb6229e9ce4136807a12a97c41c7d1ef2c5fdd
doc_id: 765131
cord_uid: xhi3xd4x

A serological survey was carried out in Monteria (500,000 population), a mid-size city in Colombia. An overall prevalence of 55.3% (CI95% 52.5%-57.8%) was found among a sample of 1.368 people randomly selected from the population. Test positivity was related to economic characteristics with the highest prevalence found in the most impoverished areas, representing 83.8% of the city’s population. We found a prevalence that might be associated with some important level of population immunity.

M a n u s c r i p t 3 Colombia (50,3 million inhabitants) identified its first case of COVID-19 (SARS-CoV-2 infection) on March 2nd, and by October 14st has reported 930,159 cases (incidence 1,753,9 per 100.000 people) and 28,306 deaths (mortality 53,39 per 100.000 people), with variations for incidence and mortality by department and region [1] . Monteria is a medium-size city (~500,000 people) in the Caribbean region, with a high proportion of the population living in poverty (~80%). Local SARS-CoV-2 circulation was detected first on March 15th, and by October 14th, it has reported 25,208 cases and 1585 deaths (incidence rate 1,377,6 per 100.000 people and mortality 1,525,8 per 100.000 people) ( Figure 1 ).

Seroprevalence studies are essential because they allow a more reliable estimation of the population infected after COVID-19 epidemics and estimate the likelihood of a second peak of transmission [2] . Colombia, according to the website https://serotracker.com/Data, has no reported seroprevalence studies of SARS-CoV-2.

This study aimed to estimate the prevalence of SARS-CoV-2 past infections in Monteria. A population-based serological study was carried out over a random sample (n=1,368) of the population selected from all city areas. The neighborhood population size weighted the sample. The steps to select the sample were as follows i. Blocks of houses were randomly selected from every neighborhood (10 neighborhoods Once the blood samples were obtained, the tubes were sent to the University of Cordoba laboratory, where they were centrifuged. The ELISA test was carried out by microbiologists who are experts in this type of test.

Sera were analyzed using INgezim® COVID 19 DR test (Ingenasa, Eurofins Madrid, Spain), a dual recognition ELISA detecting semi-quantitatively total SARS-CoV-2 virus N-protein-specific antibodies (IgG, IgM, and IgA). The assay was previously validated by both the manufacturer and us [3] , with a 90 -93% sensitivity and specificity of 91 -99% (Table 1) . From 1,368 people (male n=577, n= female 791), we found an overall prevalence of 55.3% (CI 95% 52.5 -57.8), with the most massive prevalence among people between 20 to 60 years old (53.9% CI95% 49.4 58.3%). Prevalence varied by neighborhood, from 11.5% to 75% (Table 2) . Three neighborhoods had prevalence above the average (75%, 70.9%, and 57.1%), and all of them were placed in disadvantaged areas of the city. People living in rural areas had a prevalence under the city average (46.8%, CI95% 38.6 -68.5) ( Table 2 ). There were no differences by sex; male had 57.2% of seroprevalence (CI 95% 53.1-61.3%), and female had 54.4% of seroprevalence (CI 95% 50.8-58.0%).

The present work is the first serological study reported from Colombia, where SARS-CoV-2 has been circulating for more than seven months. It yields a similar proportion of infection than the study conducted by Del Brutto et al. [4] in Atahualpa (Ecuador), a small rural population, where they found a prevalence of 44%. Remarkably, these Latin American results are higher than those reported from European cities [5, 6] and China [7] , where positivity to serological tests ranged from 0.9% to 13%, suggesting a lower attack rate in the population.

A c c e p t e d M a n u s c r i p t 5 Monteria's high prevalence suggests that there are many people entirely or partially immune to SARS-CoV-2, resulting in some level of population protection against the second wave of infection.

During the first wave, Monteria detected 12,226 cases and 709 deaths, and the local hospital near could collapse. However, if 55% of the population is already non-susceptible, the second wave may not occur since the level of population immunity to reach protection against COVID-19 outbreaks is around 65% [2] .

Low adherence to quarantine recommendation is one of the main reasons behind this unexpected high prevalence. It is not surprising if the socioeconomic conditions of Monteria's population are reviewed. Employment in the informal sector is as high as 60% in the whole city but maybe 83.8% in some areas, which forces people to remain on the streets struggling to gain enough to pay for the everyday food and shelter.

This study may help to clarify the true magnitude of COVID-19 mortality in Monteria. Currently, the city has reported 709 deaths, which amount to a case fatality rate (CFR) of 5.7%, two times the national average CFR. However, if our results are valid, the true CFR would be 0.26% because ~275,000 people would have been infected in Monteria during the first peak of transmission.

The study also has some limitations. First, the recombinant antigen N was used for laboratory testing, which has excellent sensitivity; however, recombinant antigens are not usually specific (3).

Although we indeed have a large circulation of SARS-CoV-2, other coronaviruses that could have cross-reactions with the N antigen cannot be ruled out (3). Besides, cross-reactions with arboviruses and SARS-CoV-2 were recently reported [3, 8, 9] , and Monteria is an endemic region for dengue, Zika, and Chikungunya. Therefore, false positives could also be possible. Also, the ELISA used by us detects A c c e p t e d M a n u s c r i p t 6 total gamma globulins (IgM, IgG, IgA), and it is believed that IgA produces false positives [10] .

Second, no information about antecedents of COVID-19 nor contact confirmed cases was collected from participants, which precluded us from analyzing the performance of the test by the presence or absence of clinical symptoms.

The main strength of this study is that it shows, for the first time, the prevalence of SARS-CoV-2 in a small capital city of Colombia using a randomly selected sample. It allows us to extrapolate the sample results to the city's whole population and contribute epidemiological elements for decisionmaking by municipal public health authorities. Vaccination strategies are already being discussed in Colombia, but a high prevalence of natural infection, such as observed in the present study, may preclude vaccines as a population strategy because it may not be cost-effective. However, the possibility of reinfection suggests that people that have been infected once cannot be considered to be immune. Although so far, long-established reinfections seem to be very scarce cases, and additional verification and longer supplement time are essential to apprehend the length of immunity, transmissibility, and the probability and consequences of reinfection [11] . Assumed presently, clinical management, infection prevention/control, and contact tracing concerns are not expected to diverge for a second infection related to people infected for the first time [11] .

We do not know if immunity provided by the natural infection is long-lasting. However, we will soon find out because, from September 1, the national government opened trade, national and international road and air transportation, and restaurants. If the number of cases in Monteria maintains its current decreasing trend, it could be a sign that the city has reached some vital level of protection by natural infection even if it is below 65%, proposed as the cut-off point for herd immunity (2) . If we assume that approximately 50% of the population reached natural immunity in the city of Monteria, we could be moderately optimistic, and we are likely to have less occupancy in ICU beds, and the possible reinfections could be clinically milder.

A c c e p t e d M a n u s c r i p t 7

The study was supported by Ministerio de Ciencia Tecnología e Innovación, Colombia (MINCIENCIAS). Research project: "Fortalecimiento de capacidades instaladas de ciencia y tecnología de la Universidad de Córdoba para atender problemáticas asociadas con agentes biológicos de alto riesgo para la salud humana en el departamento de Córdoba", Acta 76, May 5th, 2020. To Alcaldia de Monteria for their support on collecting the blood samples. 1 Serum samples were collected before two weeks in 32 patients, and after passed two weeks in 31 patients, since to date of SARS-CoV-2 RT-qPCR-positive collected swab sample. 2 Serum samples of symptomatic patients were collected at the first two weeks of symptoms in 1 patient, and after two weeks symptoms in 5 patients. 3 Serum samples were collected the same day of dengue-tests (RT-qPCR, NS1 antigen, ELISA IgM) positive samples. 4 Serum samples were collected the same day of Zika-RT-qPCR positive samples. 5 Serum samples were collected the same day of Chikungunya-ELISA IgG positive samples. 6 Serum samples were collected the same day of spotted fever group rickettsiae-IFA IgG positive samples. A c c e p t e d M a n u s c r i p t 12 

Alvis-Guzmán N. Is Colombia an example of successful containment of the COVID-19 2020 pandemic? A critical analysis of the epidemiological data

SARS-CoV-2 seroprevalence in COVID-19 hotspots

Serological crossreactivity using a SARS-CoV-2 ELISA test in acute Zika virus infection, Colombia

SARS-CoV-2 in rural Latin America. A population-based study in coastal Ecuador

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

Spread of SARS-CoV-2 in the Icelandic population

Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China

Potential antigenic cross-reactivity between SARS-CoV-2 and Dengue viruses

Low risk of serological cross-reactivity between dengue and COVID-19

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19

European Centre for Disease Prevention and Control. Reinfection with SARS-CoV: considerations for public health response: ECDC; 2020

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