A Review on COVID-19 Diagnosis Tests Approved for Use in Brazil and the Impact on Pandemic Control

Abstract With the COVID-19 pandemic, many diagnostic tests (molecular or immunological) were rapidly standardised, given the urgency of the situation, many are still in the process of being validated. The main objective of this study was to review the aspects of the diagnostic kits approved in Brazil and their application in the different federative units to gather epidemiological information. In order to achieve these objectives, a survey was carried out on the data available at the regulatory agency (ANVISA) and in the literature. The main countries that have registered products in Brazil are China (51.4%), Brazil (16.6%), South Korea (9.2%), USA (8.8%) and Germany (3.6%). The methodologies of these products are based on the detection of nucleic-acid (15.8%), antigen (13%) and antibody (71.2%). In the immunological tests, it was verified that the sensitivity ranged from 55 to 100% and the specificity from 80 to 100%. The percentage of cases in the samples tested in Brazil is elevated in almost all federative units since eight states showed 40% of positive cases in tested samples, while 18 states displayed between 20 and 40%. In conclusion, this review showed that Brazil is dependent on external technology to respond to pandemics, epidemics and endemics disease and needs to improve its biotechnological scheme to solve further diseases outbreaks.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines.

Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines / SARS-CoV-2: coronavirus previos, respuesta inmune y desarrollo de vacunas

Abstract Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Resumen Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.

Pharmacological therapies for patients with human coronavirus infections: a rapid systematic review. / Terapia medicamentosa para infecções por coronavírus em humanos: revisão sistemática rápida.

This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.

Effectiveness of the use of non-woven face mask to prevent coronavirus infections in the general population: a rapid systematic review. / Eficácia da máscara facial (TNT) na população para a prevenção de infecções por coronavírus: revisão sistemática.

OBJECTIVES: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. METHODS: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. RESULTS: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. CONCLUSION: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.

The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century.

At the beginning of the 21st century, a new deadly infectious disease known as severe acute respiratory syndrome (SARS) was recognized as a global public health threat. Subsequently, ten years after the initial SARS cases occurred in 2002, new cases of another atypical respiratory disease caused worldwide concern. This disease became known as Middle East respiratory syndrome (MERS) and was even more lethal than SARS. Currently, history has repeated itself with the emergence of a new Chinese epidemic at the end of 2019. For this respiratory disease, called COVID-19, a novel coronavirus (SARS-CoV-2) was identified as the etiologic agent. In sum, SARS, MERS and COVID-19 are caused by recently discovered coronaviruses that cause flu-like illnesses, but with a clinical outcome that tends to be more severe. As a result of the current importance of coronaviruses in global public health, we conducted a review to summarize and update, above all, the epidemiological historical aspects of the three major diseases in humans caused by coronaviral infection.

Revisión rápida: monitoreo de la presencia e infectividad del virus SARS-CoV-2 y otros coronavirus en aguas residuales.

Objetivo. Describir la evidencia sobre la presencia e infectividad de SARS-CoV-2 y otros coronavirus en aguas residuales y su potencial uso como herramienta de vigilancia epidemiológica. Material y métodos. Búsqueda de publicaciones en PubMed y medRxiv desde enero 2003 hasta el 8 de junio de 2020 de acuerdo con la guía de revisiones rápidas de Cochrane. Resultados. Se incluyeron 29 publicaciones. El ARN de SARS-CoV-2 no infectivo se encontró en agua residual hospitalaria, agua residual cruda, tratada y lodos de plantas de tratamiento. Los niveles cuantitativos de ARN viral en agua residual presentan relación con el número de casos de Covid-19. SARS-CoV-1 y otros coronavirus permanecieron infectivos en agua residual cruda hasta por dos días. Conclusiones. Hasta esta revisión no existe evidencia sobre la presencia de virus infectivos de SARS-CoV-2 en agua residual cruda o tratada. La cuantificación de ARN de SARS-CoV-2 en agua residual es útil para la vigilancia epidemiológica.

Terapia medicamentosa para infecções por coronavírus em humanos: revisão sistemática rápida / Pharmacological therapies for patients with human coronavirus infections: a rapid systematic review

Resumo O objetivo deste trabalho foi avaliar efeitos de tratamentos medicamentosos para infecções por coronavírus. Revisão sistemática rápida com buscas nas bases MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov e International Clinical Trials Registry Platform. Foram incluídos 36 estudos avaliando alternativas medicamentosas contra SARS, SARS-CoV-2 e MERS. A maioria dos estudos incluídos foi conduzida na China com delineamento observacional para tratamento da COVID-19. Os tratamentos mais estudados foram antimaláricos e antivirais. Nos antimaláricos, a metanálise de dois estudos com 180 participantes não identificou benefício da hidroxicloroquina em relação à negativação da carga viral via reação em cadeia de polimerase em tempo real e o uso de antivirais comparado ao cuidado padrão foi similar em relação aos desfechos. As evidências científicas disponíveis são preliminares e de baixa qualidade metodológica, o que sugere cautela na interpretação dos dados. Pesquisas que avaliem a eficácia comparativa em ensaios clínicos randomizados, controlados, com tempo de acompanhamento adequado e com os métodos devidamente divulgados e sujeitos à revisão científica por pares são necessárias. Recomenda-se atualização periódica da presente revisão.

Abstract This work aimed to evaluate the effects of drug therapies for coronavirus infections. Rapid systematic review with search in the MEDLINE, EMBASE, Cochrane, BVS, Global Index Medicus, Medrix, bioRxiv, Clinicaltrials.gov and International Clinical Trials Registry Platform databases. Thirty-six studies evaluating alternative drugs against SARS, SARS-CoV-2 and MERS were included. Most of the included studies were conducted in China with an observational design for the treatment of COVID-19. The most studied treatments were with antimalarials and antivirals. In antimalarial, the meta-analysis of two studies with 180 participants did not identify the benefit of hydroxychloroquine concerning the negative viral load via real-time polymerase chain reaction, and the use of antivirals compared to standard care was similar regarding outcomes. The available scientific evidence is preliminary and of low methodological quality, which suggests caution when interpreting its results. Research that evaluates comparative efficacy in randomized, controlled clinical trials, with adequate follow-up time and with the methods properly disclosed and subject to scientific peer review is required. A periodic update of this review is recommended.

Eficácia da máscara facial (TNT) na população para a prevenção de infecções por coronavírus: revisão sistemática / Effectiveness of the use of non-woven face mask to prevent coronavirus infections in the general population: a rapid systematic review

Resumo O objetivo deste artigo é avaliar a eficácia das máscaras faciais padrão tecido não tecido (TNT) para a prevenção de doenças respiratórias (MERS CoV, SARS-CoV e SARS-CoV-2) na população. Foi realizada busca nas bases de dados Medline, Embase, Cinahl, The Cochrane Library, Trip. Também busca complementar no Google Acadêmico, Rayyan e medRxiv. Não foram aplicados filtros relacionados a data, idioma ou status de publicação. Títulos e resumos foram rastreados e, posteriormente, textos completos foram avaliados. Foram incluídos três estudos: um ensaio clínico randomizado tipo cluster e duas revisões sistemáticas. O ensaio clínico indica benefício potencial de máscaras médicas para controle da fonte de infecção, para a doença respiratória clínica. Em uma das revisões sistemáticas, não foi possível estabelecer relação conclusiva entre uso da máscara e proteção contra infecção respiratória. Por fim, outra revisão sistemática demonstrou que máscaras são eficazes na prevenção da propagação de vírus respiratórios. As evidências apontam para benefício potencial das máscaras faciais padrão TNT. Para o cenário atual de pandemia por COVID 19, recomenda-se educação sobre uso adequado de máscaras, associado a medidas individuais de proteção.

Abstract Objectives: to evaluate the effectiveness of non-woven face masks for the prevention of respiratory infections (MERS CoV, SARS-CoV, and SARS-CoV-2) in the population. Methods: search in Medline, Embase, Cinahl, The Cochrane Library, Trip databases. Google Scholar, Rayyan and medRxiv were also consulted for complementary results. No filters related to date, language or publication status were applied. Titles and abstracts were screened, and later, full texts were evaluated. Results: three studies were included: a randomized cluster clinical trial and two systematic reviews. The clinical trial indicates a potential benefit of medical masks to control the source of clinical respiratory disease infection. In one of the systematic reviews, it was not possible to establish a conclusive relationship between the use of the mask and protection against respiratory infection. Finally, another systematic review indicated that masks are effective in preventing the spread of respiratory viruses. Conclusion: Evidence points to the potential benefit of standard non-woven face masks. For the current pandemic scenario of COVID-19, education on the appropriate use of masks associated with individual protection measures is recommended.

[Severe acute respiratory syndrome. The public health laboratory in a global emergency]. / Síndrome respiratorio agudo grave. El laboratorio de salud pública frente a una emergencia global.

By the end of year 2002 there was an outbreak of atypical pneumonia in Southeast Asia which soon spread to other continents. This new severe acute respiratory syndrome (SARS) was produced by a novel coronavirus. Due to the severity of the situation and risk of introduction of this pathology in our country, the need to arrange specific laboratory diagnostic tests arose. Classic techniques, such as the electron microscopy and molecular biology test such as retrotranscription followed by the polymerase chain reaction (RT-PCR) were implemented. The araldit included cells infected with bovine coronavirus which allowed the viral particles to be visualized easily but it took more time in comparison with the negative staining of free particles from viral cultures. RT-PCR was able to detect RNA of isolated viruses from cases in Hong Kong and Germany.

Síndrome respiratorio agudo grave. El laboratorio de salud pública frente a una emergencia global / Severe acute respiratory syndrome: the public health laboratory in a global emergency

By the end of year 2002 there was an outbreak of atypical pneumonia in Southeast Asia which soon spread to other continents. This new severe acute respiratory syndrome (SARS) was produced by a novel coronavirus. Due to the severity of the situation and risk of introduction of this pathology in our country, the need to arrange specific laboratory diagnostic tests arose. Classic techniques, such as the electron microscopy and molecular biology test such as retrotranscription followed by the polymerase chain reaction (RT-PCR) were implemented. The araldit included cells infected with bovine coronavirus which allowed the viral particles to be visualized easily but it took more time in comparison with the negative staining of free particles from viral cultures. RT-PCR was able to detect RNA of isolated viruses from cases in Hong Kong and Germany.

A fines del año 2002 se inicia un brote de neumonía atípica en el Sudeste asiático el cual se extiende posteriormente a otros continentes. El nuevo síndrome respiratorio agudo grave (SARS) era producido por un coronavirus novedoso. Debido a la gravedad de la situación y al riesgo de introducción de esta patología en Argentina, se implementaron técnicas de diagnóstico clásicas como la microscopía electrónica, y moleculares como una reacción de retrotranscripción seguida de una reacción en cadena de la polimerasa (RT-PCR). La inclusiónen araldita de células infectadas con un coronavirus bovino permitió visualizar más fácilmente las partículas virales, pero requirió más tiempo en comparación con la coloración negativa de partículas libres de cultivos virales.La RT-PCR implementada fue capaz de detectar ARN de cepas de casos de Hong Kong y de Alemania.

Síndrome respiratorio agudo grave. El laboratorio de salud pública frente a una emergencia global / Severe acute respiratory syndrome: the public health laboratory in a global emergency

By the end of year 2002 there was an outbreak of atypical pneumonia in Southeast Asia which soon spread to other continents. This new severe acute respiratory syndrome (SARS) was produced by a novel coronavirus. Due to the severity of the situation and risk of introduction of this pathology in our country, the need to arrange specific laboratory diagnostic tests arose. Classic techniques, such as the electron microscopy and molecular biology test such as retrotranscription followed by the polymerase chain reaction (RT-PCR) were implemented. The araldit included cells infected with bovine coronavirus which allowed the viral particles to be visualized easily but it took more time in comparison with the negative staining of free particles from viral cultures. RT-PCR was able to detect RNA of isolated viruses from cases in Hong Kong and Germany. (AU)

A fines del año 2002 se inicia un brote de neumonía atípica en el Sudeste asiático el cual se extiende posteriormente a otros continentes. El nuevo síndrome respiratorio agudo grave (SARS) era producido por un coronavirus novedoso. Debido a la gravedad de la situación y al riesgo de introducción de esta patología en Argentina, se implementaron técnicas de diagnóstico clásicas como la microscopía electrónica, y moleculares como una reacción de retrotranscripción seguida de una reacción en cadena de la polimerasa (RT-PCR). La inclusiónen araldita de células infectadas con un coronavirus bovino permitió visualizar más fácilmente las partículas virales, pero requirió más tiempo en comparación con la coloración negativa de partículas libres de cultivos virales.La RT-PCR implementada fue capaz de detectar ARN de cepas de casos de Hong Kong y de Alemania. (AU)

The threat of severe acute respiratory syndrome (SARS).

Severe acute respiratory syndrome (SARS) is a recently recognized infectious disease associated with severe morbidity and mortality. It presents with non-specific signs and symptoms and because no definitive laboratory test is readily available, it poses a great risk to healthcare workers as well as difficulty in quarantine. The global response has been coordinated and enthusiastic in trying to understand and control this disease. Severe acute respiratory syndrome poses a threat to the Caribbean because of easy and convenient travel and the vibrant tourist industry.

The threat of severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is a recently recognized infectious disease associated with severe morbidity and mortality. It presents with non-specific signs and symptoms and because no definitive laboratory test is readily available, it poses a great risk to healthcare workers as well as difficulty in quarantine. The global response has been coordinated and enthusiastic in trying to understand and control this disease. Severe acute respiratory syndrome poses a threat to the Caribbean because of easy and convenient travel and the vibrant tourist industry