key: cord-0791390-z5dy8kxf
authors: Simbana-Rivera, K.; Gomez-Barreno, L.; Guerrero, J.; Simbana-Guaycha, F.; Fernandez, R.; Lopez-Cortes, A.; Lister, A.; Ortiz-Prado, E.
title: Interim Analysis of Pandemic Coronavirus Disease 2019 (COVID-19) and the SARS-CoV-2 virus in Latin America and the Caribbean: Morbidity, Mortality and Molecular Testing Trends in the Region
date: 2020-04-29
journal: nan
DOI: 10.1101/2020.04.25.20079863
sha: 7d9fcbf04bb480628206a83ff8f0a707a0dc6f62
doc_id: 791390
cord_uid: z5dy8kxf

Background: The relentless advance of the SARS-CoV-2 virus pandemic has resulted in a significant burden on countries, regardless of their socio-economic conditions. The virus has infected more than 2.5 million people worldwide, causing to date more than 150,000 deaths in over 210 countries. Objective: The aim of this study was to describe the trends in cases, tests and deaths related to novel coronavirus disease (COVID-19) in Latin American and Caribbean (LAC) countries. Methodology: Data were retrieved from the WHO-Coronavirus Disease (COVID-2019) situation reports and the Center for Systems Science and Engineering (CSSE) databases from Johns Hopkins University. Descriptive statistics including death rates, cumulative mortality and incidence rates, as well as testing rates per population at risk were performed. A comparison analysis among countries with [≥]50 confirmed cases was performed from February 26th, 2020 to April 8th, 2020. Results: Brazil had the greatest number of cases and deaths in the region. Panama experienced a rapid increase in the number of confirmed cases with Trinidad and Tobago, Bolivia and Honduras having the highest case fatality rates. Panama and Chile conducted more tests per million inhabitants and more tests per day per million inhabitants, followed by Uruguay and El Salvador. Dominican Republic, Bolivia, Ecuador and Brazil had the highest positive test rates. Conclusions: The COVID-19 disease pandemic caused by the SARS-CoV-2 virus has progressed rapidly in LAC countries. Some countries have been affected more severely than others, with some adopting similar disease control methods to help slow down the spread of the virus. With limited testing and other resources, social distancing is needed to help alleviate the strain on already stretched health systems.

The aim of this study was to describe the trends of COVID-19 in each Latin American and the Caribbean (LAC) countries through the calculation of different rates that reflect the reality of each one. These were then compared with the rates seen in China and Italy recorded up until April, 8 th 2020.

A descriptive observational study using secondary international reports was carried out for all Latin American and Caribbean countries from February 26 th , 2020 to April 8th, 2020 that showed more than 50 confirmed cases by April 8 th . Furthermore, China for being the first country to report cases, and Italy for being the European country with highest mortality reported, were added to the analysis from January 21 st , 2020 to April 8 th , 2020 as comparison models.

Secondary data was retrieved from the three main publicly available databases that are publishing information about COVID-19. We use the daily reports from WHO-Coronavirus Disease (COVID-19) situation reports [13] , the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University [14] and the on-line data repository https://ourworldindata.org/coronavirus-source-data [15] .

Sequences and amino acid replacement of SARS-CoV-2 virus information were retrieved from the Global Initiative on Sharing All Influenza Data (GISAID) (https://www.gisaid.org/), an initiative that promotes the international sharing of SARS-CoV-2 virus sequences to better understand how the novel coronavirus evolves, spreads and how it causes pathology [16, 17] as well as the CoV-GLUE Project (http://cov-glue.cvr.gla.ac.uk/#/home). The CoV-GLUE Project is a database of amino acid replacements that have been observed in sequences sampled from the pandemic strain [18] . Lastly, Supplementary Table 1 details the knowledge of all contributions and laboratories of this study according to GISAID requirement.

All confirmed COVID-19 countries with more than fifty cases reported in the region up to April 8 th were included in the analysis.

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To reduce the risk of observer bias, data collection was performed using the triangulation technique with three researchers of our team. Using this technique described by Carvalho and White [19] , it aided in the reduction of bias as any errors in data collection could be highlighted through comparison between analysts.

The number of confirmed cases and deaths attributed to COVID-19 were transformed into crude and cumulative numbers to obtain cumulative confirmed cases (CCC) and cumulative confirmed deaths (CCD) per country.

The morbidity and mortality incidence, case-fatality rate, positive-test rate and test performed were calculated according to the entire population per country.

The rate of cumulative incidence of confirmed cases (CICC) and deaths (CICD) per million inhabitants was calculated to reflect the impact of the coronavirus for each country using the population projection for 2020, according to the World Population Prospects 2019 [20] .

The case fatality rate (CFR%) and positive test rate (PTR%) with a confidence interval of 95% for crude rates were computed for each country by April 8 th as follow: For an approach related to the test performed in each country. The influence of population size was reduced by the calculation of tests per million inhabitants (TMI) and to control time distribution daily tests per million inhabitants (DTMI) with the formulas:

?AB = ) >./10/,.5 7.979 >0@+C67403 01 .62ℎ 20+37/D : × 1,000,000 F?AB = (>./10/,.5 7.979 ÷ 20+37/D @0@+C67403 ÷ 56D9 9432. 14/97 /.@0/7) × 1,000,000

Additionally, to control the time distribution of cases per population and time since the first report, the DCMI was calculated:

F!AB = (!0314/,.5 269.9 ÷ 20+37/D @0@+C67403 ÷ 56D9 9432. 14/97 /.@0/7) × 1,000,000

Finally, results were grouped as confirmed case-related data (CCC, CICC, DCMI), deathrelated data (CCD, CICD, CFR%) and test-related data (TMI, DTMI and PTR%).

In the first 40 days since the first LAC countries' report, the number of cases in the region reached 44,233 with more than 1,770 deaths. The total number of cases reported in the region until early-April 2020 represents 1% of the total number of confirmed cases worldwide. (Figure 1 ).

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Countries with higher population density had fewer rates including Brazil (6.2 per million), Mexico (2.1 per million) and Argentina (3.9 per million) inhabitants on the first 40 days after its first official case was reported in relationship with less populate countries.

On April 8 th , Italy reached 34 confirmed cases per million inhabitants (DCMI) daily, 68 days after its first official report. This number is still lower for Latin-American countries, such as Panama, that with only 29 days after the initial case had already reached 17.9 daily confirmed cases per million people, followed by Chile with 8 (36 th day), Ecuador 6.6 (38 th day), the Dominican Republic 5.1 (38 th day) and Uruguay 4.9 (25 th day) ( Table 1) .

The number of deaths reached an exponential growth, especially in Italy, reaching 1,809 CCD after 45 days since its first report. In comparison, cases reported by April 8 th . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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In Italy, the cumulative incidence of confirmed deaths per million inhabitants reached 10 death per million people after 40 days after the first official report (March 11 th ). Only five days later, this number duplicated. In contrast, China showed a plateau since the 34 th day (February 25 th ) after the first case was reported, reaching less than 2.3 deaths per million inhabitants.

In Latin America, countries such as Panama and Ecuador reached 10 deaths per million inhabitants as fast as the 26 th (April 5 th ) and the 35 th day (April 5 th ) after the first case was reported, respectively. The Dominican Republic reached 9 cumulative incidence death rate per million inhabitants on the 38 th day (April 8 th ) after the first case report.

Other countries had a slower start, reaching a lower CICD rate after the 34th day of the initial report as Chile (2. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted April 29, 2020. . https://doi.org/10.1101/2020.04. 25.20079863 doi: medRxiv preprint **https://ourworldindata.org/coronavirus-source-data; ***CFR calculated from Johns Hopkins University data base. + Days calculated until 08-04-2020

In terms of testing, by April 8 th , Italy reported a total of 807,125 performed tests. In addition, when it was corrected by population level, it demonstrated 13,349 tests performed per million inhabitants (TMI). In Latin America, the country with the highest number of tests performed was Chile with 60,391, followed by Brazil with 54,824 (Table 1) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The ratio between the number of tests and number of tests which resulted positive was analysed for Italy and Latin-American countries on April 8 th . Italy reported a ratio of 17.27% of confirmed cases from the total tests performed (PTR%). In Latin America, some countries with highly effective testing strategies such as Chile and Uruguay have reported a positive test ratio of 9.18% and 7.38%, respectively (Table 1) . On the other hand, countries with lower testing capabilities have reported higher positive testing rates. For instance, Dominican Republic reported the highest positive rate ,up to April the 8 th , with at least 46.4% of the total number of tests being positive, followed by Bolivia (35.5%), Ecuador (30.9%) and Brazil (29.5%) ( Table   1) . 

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The Pan-American Health Organization and United Nations announced that Latin American and Caribbean countries had a slight time advantage on preparation for the coronavirus pandemic arrival [21, 22] due to the delay in seeing cases arising compared to other locations.

LAC countries have some of the highest urbanization rates in the world, often with unequal access to public services in urban settings and high mortality rates for transmittable diseases [23, 24] . In some countries, out-of-pocket expenditure for healthcare services places a substantial restriction on access, debilitating viral control efforts [25, 26] . Furthermore, the region has experienced a wave of political and economic changes during the previous years and with the arrival of COVID-19, increased pressure is placed on already overstretched healthcare services. This combination of inequality, lack of governability, and debilitated services have already resulted in tragic scenarios during the COVID-19 pandemic in some LAC countries.

Our analysis depicts Panama as the most affected country in the region when a population correction is applied, not only due to the increase in positive cases (CCC, CICC) but also due to the number of official deaths reported (CCD, CICD). Panama in comparison with Italy, one of the most heavily affected countries in the world showed a dramatic increase in the number of cases, an exponential growth that was reached 18 days earlier than Italy. We speculate that as Panama has high aerial and maritime international traffic, these factors that might have played an important role importing asymptomatic cases earlier than its first report [27, 28] .

Other countries have case-related data (CCC, CICC, DCMI) increasing at a faster rate than Italy. Chile, for instance, one of the richest countries in the region had a marked increase in the number of confirmed cases during the third week of the local out-brake. This situation could be explained due to the Chilean effective testing strategies [29, 30] . For instance, Chile performed 88 molecular test per million people every day with one of the lowest positive test ratios in the region (9.18%). Chile is also one of the countries with the lowest COVID-19 related deaths in the region (CCID, CCD and CFR) [31] . Uruguay had initially increased in a similar trend like Panama or Ecuador, nevertheless, as the days passed and more test arrived, this country showed cumulative rates similar to those seen in Chile [32] .

Another fact about other LAC countries compared with Chile is that not enough tests are being performed, thus a sub-registration of COVID-19 is evident. Countries such as the Dominican . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020. . https://doi.org/10.1101/2020.04. 25.20079863 doi: medRxiv preprint Republic, Bolivia and Ecuador have limited testing capabilities [33] , a fact that is supported by the low number of TMI, DTMI and the high PTR% in relationship with the number of tests performed.

Estimation of the real number of cases of the novel coronavirus (SARS-CoV2) infections is critical for understanding the frequency of presentation of COVID-19 and the overall pandemic potential of this infection [34] . A recent report from China suggested that at least 86% of all infections were not identified, while the transmission rate of undocumented cases was estimated to be at least 55% of the total of reported infections [34] .

In the region, Ecuador has been highlighted due to its COVID-19 pandemic management and the rapid geographic spread of the novel coronavirus [35] . This equatorial country received worldwide attention due to the excessive number of undocumented deaths upon the arrival of the SARS-CoV-2 virus within the region [35] . According to the official figures published by the National Emergency Management Committee Ecuador reported in April 16 th , at least 10,939 deaths were officially recorded during the first 45 days of the arrival of the virus in Ecuador (March to April 15 th ), a number 202% higher than the 3,622 deaths recorded during the first two months of 2020 [35] . These number is largely dependent on the number of cases reported in the province of Guayas, the province with the highest impact of the arrival of COVID-19 in the country. Although the government has not officially stated that the excessive numbers of deaths are due to COVID-19, a significant number of these deaths are likely COVID-19 related, especially when other violent causes of deaths (traffic accidents and homicides) have been reduced due to the partial cuff implemented in the country during the first week of March [36] [37] [38] .

Brazil, the most populated country in the region, had the highest number of cases reported in the region, nevertheless, when the population-size was corrected a reduction in CICC, CICD, TMI, DTMI and DCMI values were observed. Brazil has been struggling with a lack of strong political leadership to minimize the effects of COVID-19 within the communities which undoubtedly has contributed to the high daily confirmed cases per million inhabitants.

Concerning the positive test rate percentage within the region, the 10% threshold suggested by the World Health Organization is an indicator that helps us determine the diagnosis efforts performed for each country seems to be too high to accomplish for several countries. For instance, Dominican Republic reported the highest positive rate in April the 8 th with at least . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted April 29, 2020. . 46.4% of the total number of tests being positive, followed by Bolivia (35.5%), Ecuador (30.9%) and Brazil (29.5%). When we compare these figures with other countries, we can observe that Ecuador, one of the most affected in the region has almost 120% more positive cases per every test performed than Italy, 1,500% more than South Korea and almost 7,000% more than Vietnam [30] .

It is important to empathize that the figures reported rely on national government statistics, nevertheless, is critical to understand that testing capabilities are widely reduced in some countries in the region. Without adequate mechanisms of efficiently testing as much population as possible, contact tracing strategies, and effective isolation of suspected cases becomes a real challenge [29] .

The analysis of these trends is an interim insight into the current situation in the region. The best action that countries can take is implementing social distancing measures and reducing travel, so individuals are less likely to come into contact with each other, therefore reducing the rate of transmission and alleviating pressure on health systems.

During the performance of this study, a disparity of the reports obtained from the different freely accessible published databases was evidenced regarding the reporting dates of the first case, confirmed cases and registered deaths values. For this reason, to maintain uniformity of the data, Johns Hopkins University database was used for graphs and tables.

Regarding the rates used, it's evident that CFR% and PTR% are highly variable during the pandemic, therefore they don't reflect correctly the impact of deaths and tests carried out in a country. Furthermore, the recovered case data was not used because, until the end of the study, any country reported more than a thousand cases, and it is suggested that these variables and the adjusting for outcome delay in CFR estimates should be analysed in subsequent studies.

It is important to understand that there is lack of reliable diagnostic tests (RT-PCR) data in the region. On top of that, some countries do not report the results of private providers, thus the analysis is often performed with the available data.

Another critical limitation is the lack of information for most of the countries when distinguishing between tests that were collected versus those which were processed.

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The copyright holder for this preprint this version posted April 29, 2020. . https://doi.org/10.1101/2020.04. 25.20079863 doi: medRxiv preprint Understanding the role of good testing strategies is important for the correct understanding of the health crisis at the individual and collective level. The lack of installed capabilities in some countries can produce a false sensation of fewer cases, while there are more cases out there, cases that cannot be identified [34] .

This study only used confirmed cases of COVID-19, and undoubtedly there will be a large proportion of individuals who have died without testing conducted or are in remote communities which may go unreported.

The experience and trends from Italy showed that the COVID-19 pandemic is progressing rapidly in LAC Countries. Thus, hospitals should prepare themselves for an increase in the number of patients with COVID-19 requiring healthcare, and in particular intensive care units where patients may require ventilation. Most LAC counties have implemented different public health measures to decrease the pressure on healthcare since the third week of March to mitigate the impact of the pandemic, such as travel restriction and social distancing. Finally, there is a wide variety of scenarios established between LAC countries, however, in this study, there was a lack of testing for a number of countries. This is an issue which needs addressing, and requires strong political will and resource to be able to provide the best care for patients and their families.

KSR, LGB, EOP conceived the idea of the Editorial. The rest of the authors reviewed and improved the first and second draft. All authors approved the final version.

KSR, LGB and EOP were responsible for the original conceptualization of the project and they are fully responsible for every aspect of the current manuscript. They were fully involved in data acquisition and analysis.

JG and FSG were responsible for part of the data acquisition and they also contributed with the drafting of the manuscript.

RFN was fully responsible for generating the figures and part of the statistical analysis.

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The copyright holder for this preprint this version posted April 29, 2020. . https://doi.org/10.1101/2020.04. 25.20079863 doi: medRxiv preprint ALC was responsible for the genomic analysis within the region and the conceptualization and creation of figure eight.

AL critically reviewed and edited the manuscript, as well as offered important insights that strengthened the manuscript significantly.

We thank Universidad de las Americas for its economic support funding the publication of this document through the approved project entitled "Clinical, genetic and epidemiological characterization of COVID-19 and SARS-CoV-2 in Ecuador".

According to the local guidelines and good clinical practice, all secondary publicly available anonymized data does not require IRB approval.

None of the authors has any conflict of interest to declare. All authors report no potential conflicts. All authors have submitted the Form for Disclosure of Potential.

All the data is publicly available through the servers that were described within the methodology section.

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According to GISAID requirement, we included a supplementary Table acknowledging to all contributions and laboratories that are part of such an institution [16, 17]