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      COVID-19 and dengue fever: A dangerous combination for the health system in Brazil

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          Abstract

          To the Editor, The outbreak of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The number of COVID-19 cases has been on a rapid rise in Brazil, with the first records of death [1]. Simultaneously, the country is facing the outbreak of dengue fever, a known tropical disease. According to the Ministry of Health, the number of probable dengue cases increased by almost 19%, from 79,131 between December 29 and February 01 in 2019 to 94,149 in the same period in 2020. In 2019, about 2.3 million dengue cases were registered nationwide. Even in south regions of the country where the outbreak of dengue fever had never occurred, the number of dengue cases has been increasing at an alarming rate, with several deaths being recorded [2]. The number of dengue cases is often observed to increase at the beginning of the year due to the rainy season and high temperatures and peak between March and April. Meanwhile, the peak of the COVID-19 outbreak in Brazil is forecast to occur between late April and early May, when respiratory diseases are most commonly found. This temporal coincidence implies that the two outbreaks may happen at the same time. This would cause great damage to population and therefore require intensive attention from both the private health system and the public Unified Health System (SUS). Dengue fever and COVID-19 are difficult to distinguish because they share clinical and laboratory features [3]. Some authors described cases who were wrongly diagnosed as dengue but later confirmed to be COVID-19 [4]. Besides, co-infections with arboviruses and SARS-CoV-2 have not been well studied. In the midst of this complex epidemiological scenario, the fragile healthcare system in Brazil is facing the risk of collapse and multiple socio-economic issues [5]. For example, Constitutional Amendment 95 established the public spending limits, and in 2019, the health budget reduced by R$ 9 billion. There may not be enough intensive care units to accommodate even 25% of hospitalized patients with COVID-19. The lack of specific diagnostic tests, especially the real-time RT-PCR, would also make it challenging to perform early detection of virus importation and prevent onward transmission [5]. Another concern lies in the costs of hospitalization due to dengue fever. The Brazilian government paid R$ 31 million for the hospitalization of approximately 100,000 dengue cases during the outbreak in 2010. With over 150 million Brazilians depending exclusively on the SUS, this situation can become absolutely critical. COVID-19 alone has a great potential to overwhelm the health system. If it was accompanied by dengue fever, this burden would be even greater. Brazil is making every effort to keep the number of COVID-19 cases from rising. However, a proportion of patients have been not diagnosed due to the insufficiency of specific tests. According to recent studies, many infected cases were not documented, thereby accelerating the spread of SARS-CoV-2 [6]. Therefore, to contain the epidemic, large investments in research are required to gain an insight into the epidemiology, transmission, and incubation period of COVID-19, and develop tests, vaccines, and medicines. In response to COVID-19, the Brazilian Government has declared a state of emergency, allowing cities to take extraordinary measures. For example, based on the Annual Budget Law, more than R$ 5 billion will be dedicated to combating the outbreak of COVID-19. Intensified surveillance, resources, and viral identification assays should be urgently prioritized to detect COVID-19 cases and to limit transmission. A combination of these measures may help to increase reporting of these cases, thus slowing down the spread of the COVID-19 outbreak(see Fig. 1 ). Fig. 1 Hypothetical scenario of dengue and COVID-19 emergence. The number of dengue cases is inclined to increase at the start of the year due to the hot, humid weather, and hit a peak between March and April. The outbreak of COVID-19 in Brazil is predicted to peak sometime in the most favourable season for respiratory diseases between late April and early May. As the two outbreaks have a high likelihood of coinciding in terms of time, the burden of diseases may boost, requiring the Unified Health System (SUS) to put their greatest efforts into the double-fight against the outbreaks. *The number of dengue cases is not proportional to that of COVID-19 cases; this is only an extrapolation to visualize each peak. Fig. 1 Ethics approval and consent to participate The ethical approval or individual consent was not applicable. Availability of data and materials All data and materials used in this work were publicly available. Consent for publication Not applicable. Funding FAPESP 2017/10297-1. Disclaimer The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Authors' contributions All authors conceived the study, discussed the results, drafted the first manuscript, critically read and revised the manuscript, and gave final approval for publication. Declaration of competing interest The authors declared no competing interests.

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          Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

          Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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            Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2)

            Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.
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              COVID-19 in Latin America: The implications of the first confirmed case in Brazil

              Over the past weeks the spread of the Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1], has been steady in Asia and other regions in the world. Latin America was an exception until February 25, 2020, when the Brazilian Ministry of Health, confirmed the first case. This first case was a Brazilian man, 61 years-old, who traveled from February 9 to 20, 2020, to Lombardy, northern Italy, where a significant outbreak is ongoing. He arrived home on February 21, 2020, and was attended at the Hospital Albert Einstein in São Paulo, Brazil. At this institution, an initial real-time RT-PCR was positive for SARS-CoV-2 and then confirmed by the National Reference Laboratory at the Instituto Adolfo Lutz using the real-time RT-PCR protocol developed by the Institute of Virology at Charité in Berlin, Germany [2]. The established protocol also included now, as part of the Sao Paulo State Health Secretary, metagenomics and immunohistochemistry with PCR, as part of the response plan to COVID-19 outbreak in the city [3]. The patient presented with fever, dry cough, sore throat, and coryza. So far, as of February 27, the patient is well, with mild signs. He received standard precautionary care, and in the meantime, he is isolated at home [4]. Local health authorities are carrying out the identification and tracing of contacts at home, at the hospital, and on the flight. For now, other cases are under investigation in São Paulo, and other cities in Latin America. In addition to the São Paulo State Health Secretary, the Brazilian Society for Infectious Diseases have developed technical recommendations [4]. This is the first case of COVID-19 in the South American region with a population of over 640 million people [5] who have also experienced significant outbreaks of infections which were declared Public Health Emergencies of International Concern (PHIC), by the World Health Organization (WHO). So it was with Zika in 2016. The Zika outbreak also began in Brazil [6]. In the current scenario, the spread of COVID-19 to other neighboring countries is expected and is probably inevitable in the light of the arrival of suspected cases from Italy, China, and other significantly affected countries. São Paulo is the most populated city in South America, with more than 23 million people and high flight connectivity in the region (Fig. 1 ). Its main airport, the São Paulo-Guarulhos International Airport, is the largest in Brazil, with non-stop passenger flights scheduled to 103 destinations in 30 countries, and 52 domestic flights, connecting not only with major cities in Latin America but also with direct flights to North America, Europe, Africa and the Middle East (Dubai). There are also buses that offer a service to and from the metropolitan centers of Paraguay, Argentina, Uruguay and Bolivia. Brazil also connects with the countries of Chile, Argentina and Bolivia through some rail connections. The main seaport of Brazil is in Rio de Janeiro, where many international cruises also arrive. Thus, over the course of the next few days, a significant expansion in the region would be possible. Fig. 1 Flight connections from São Paulo's main international airport, Brazil. Source: flightconnections.com. Fig. 1 The healthcare systems in this region are already fragile [7]. Moreover, fragmentation and segmentation are ongoing challenges for most of these vulnerable systems. Multiple social and economic issues are ongoing and will impact the situation, including the massive exodus from Venezuela to many countries in the region. This human migration is associated with other infectious diseases, such as malaria or measles [8]. The burden that will be imposed on the region, if and when COVID-19 spreads, would be an additional challenge for the healthcare systems and economies in the region, as we faced with Zika and even the Chikungunya outbreaks [9]. For example, there is concern about the availability of intensive care units, that are necessary for at least 20–25% of patients hospitalized with COVID-19—also, the availability of specific diagnostic tests, particularly the real-time RT-PCR is a crucial challenge for early detection of COVID-19 importation and prevention of onward transmission. Even maybe in some countries, cases have been not diagnosed due to lack of availability of specific tests. Are Latin American healthcare systems sufficiently prepared? Probably not, but in general, this is the same in other regions of the world, such as in many parts of Asia and Africa [10]. Although most countries in Latin America are trying to step up their preparedness to detect and cope with COVID-19 outbreaks, it will be essential to intensify inter-continental and intra-continental, communication and health workforce training. In the Latin American region, there is a large heterogeneity of political and social development, economic growth, and political capacities. For example, in the Caribbean subregion, countries such as Haiti have a low Human Development Index. In such areas, and Venezuela where a humanitarian crisis had occurred since 2019 spreading measles, diphtheria, and vector-borne diseases, such as malaria, over the region [[11], [12], [13]], the impact of a COVID-19 outbreak will be more devastating than in the more developed economies, such as Brazil or Mexico. Most of the countries in the region are remembering the lessons learned during SARS (2003) and pandemic influenza (2009). Protocols already developed during those crises, including laboratory and patient management, may prove useful in this new situation. Good communication strategies for preventive measures in the population, and in neighboring countries in addition to Brazil, will be essential and this response should be aligned with the recommendations of the WHO. In Latin America, the Pan-American Health Organization (PAHO/WHO) recent epidemiological alert for measles shows that from January 1, 2019 to January 24, 2020, 20,430 confirmed cases of measles were reported, including 19 deaths, in 14 countries: Argentina, Bahamas, Brazil, Chile, Colombia, Costa Rica, Cuba, Curaçao, Mexico, Peru, Uruguay and Venezuela. Brazil contributed 88% of the total confirmed cases in the Americas [14]. In the first 4 weeks of 2020, a staggering 125,514 cases of measles were notified. The dengue incidence rate is 12.86 cases/100,000 inhabitants in the region for the ongoing year, including 27 deaths, 12,891 cases confirmed by laboratory and 498 cases classified as severe dengue (0.4%). Countries like Bolivia, Honduras, Mexico and Paraguay have reported an increase of double or triple the number of cases of dengue compared to the same period from the previous year [15]. In this complex epidemiological scenario, we are about to witness a syndemic [16] of measles, dengue, and COVID-19, among others, unfold. The World Health Organization (WHO) has published guidelines encouraging the provision of information to health professionals and the general public. Resources, intensified surveillance, and capacity building should be urgently prioritized in countries with a moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission, as has already occurred in Brazil. [For the moment of proofs correction of this Editorial –Mar. 1, 2020–, 2 cases have been confirmed in Brazil, but also new 5 confirmed cases were also reported in Mexico (2° country that reported cases), 6 in Ecuador (3°) and 1 in Dominican Republic (4°), summarizing 14 cases in Latin America]. Credit author statement AJRM conceived the idea of the Editorial and wrote the first draft. The rest of the authors reviewed and improved the second draft. All authors approved the final version. Author contributions Conceptualization: AJRM. Writing—original draft preparation: AJRM. Writing—review, and editing: All the authors. Funding source None. Ethical approval Approval was not required. Declaration of competing interest 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.
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                Author and article information

                Contributors
                Journal
                Travel Med Infect Dis
                Travel Med Infect Dis
                Travel Medicine and Infectious Disease
                Elsevier Ltd.
                1477-8939
                1873-0442
                9 April 2020
                9 April 2020
                : 101659
                Affiliations
                [1]Department of Epidemiology, School of Public Health, Universidade de São Paulo, 01246-904, Sao Paulo, Brazil
                [2]Secretary of Health, Municipality of Santa Barbara d'Oeste, Santa Bárbara d´Oeste, 13450-021, Sao Paulo, Brazil
                [3]Department of Epidemiology, School of Public Health, Universidade de São Paulo, 01246-904, Sao Paulo, Brazil
                Author notes
                []Corresponding author. camilalorenz@ 123456usp.br
                Article
                S1477-8939(20)30127-7 101659
                10.1016/j.tmaid.2020.101659
                7144614
                32278756
                b4203a99-200a-4941-9e18-33706cde49b7
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 28 March 2020
                : 30 March 2020
                : 31 March 2020
                Categories
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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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