Resumo em Inglês:

Abstract The emergence of the new corona virus (SARS-CoV-2) and the resulting COVID-19 pandemic requires fast development of novel prevention and therapeutic strategies. These rely on understanding the biology of the virus and its interaction with the host, and on agnostic phenotypic screening for compounds that prevent viral infection. In vitro screenings of compounds are usually performed in human or animal-derived tumor or immortalized cell lines due to their ease of culturing. However, these platforms may not represent the tissues affected by the disease in vivo, and therefore better models are needed to validate and expedite drug development, especially in face of the COVID-19 pandemic. In this scenario, human induced pluripotent stem cells (hiPSCs) are a powerful research tool due to their ability to generate normal differentiated cell types relevant for the disease. Here we discuss the different ways hiPSCs can contribute to COVID-19 related research, including modeling the disease in vitro and serving as a platform for drug screening.

Resumo em Inglês:

Abstract Host shifts, when a cross-species transmission of a pathogen can lead to successful infections, are the main cause of emerging infectious diseases, such as COVID-19. A complex challenge faced by the scientific community is to address the factors that determine whether the cross-species transmissions will result in spillover or sustained onwards infections. Here we review recent literature and present a perspective on current approaches we are using to understand the mechanisms underlying host shifts. We highlight the usefulness of the interactions between Drosophila species and viruses as an ideal study model. Additionally, we discuss how cross-infection experiments — when pathogens from a natural reservoir are intentionally injected in novel host species— can test the effect cross-species transmissions may have on the fitness of virus and host, and how the host phylogeny may influence this response. We also discuss experiments evaluating how cooccurrence with other viruses or the presence of the endosymbiont bacteria Wolbachia may affect the performance of new viruses in a novel host. Finally, we discuss the need of surveys of virus diversity in natural populations using next-generation sequencing technologies. In the long term, these approaches can contribute to a better understanding of the basic biology of host shifts.

Resumo em Inglês:

Abstract SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), as well as SARS-CoV from 2003 along with MERS-CoV from 2012, is a member of the Betacoronavirus genus of the Nidovirales order and is currently the cause of the pandemic called COVID-19 (or Coronavirus disease 2019). COVID-19, which is characterized by cough, fever, fatigue, and severe cases of pneumonia, has affected more than 23 million people worldwide until August 25th, 2020. Here, we present a review of the cellular mechanisms associated with human coronavirus replication, including the unique molecular events related to the replication transcription complex (RTC) of coronaviruses. We also present information regarding the interactions between each viral protein and cellular proteins associated to known host-pathogen implications for the coronavirus biology. Finally, a specific topic addresses the current attempts for pharmacological interventions against COVID-19, highlighting the possible effects of each drug on the molecular events of viral replication. This review intends to aid future studies for a better understanding of the SARS-CoV-2 replication cycle and the development of pharmacological approaches targeting COVID-19.

Resumo em Inglês:

Abstract The current SARS-CoV-2 pandemic gave rise to a spirit of methodological anarchy in some fronts of biomedical research, embraced by some under the excuses of urgency and time restraints. This movement, however, comes at the same time when social sciences begin to recognize the value and soundness of the clinical research rationale - the need for randomization, of fair comparisons between intervention groups, the humility of acknowledging ignorance and accepting uncertainty, these last two imperatives usually subsumed under the principle of “equipoise”.

Resumo em Inglês:

Abstract The ongoing COVID-19 pandemic has caught the attention of the global community and rekindled the debate about our ability to prevent and manage outbreaks, epidemics, and pandemics. Many alternatives are suggested to address these urgent issues. Some of them are quite interesting, but with little practical application in the short or medium term. To realistically control infectious diseases, human, animal, and environmental factors need to be considered together, based on the One Health perspective. In this article, we highlight the most effective initiatives for the control and prevention of infectious diseases: vaccination; environmental sanitation; vector control; social programs that encourage a reduction in the population growth; control of urbanization; safe sex stimulation; testing; treatment of sexually and vertically transmitted infections; promotion of personal hygiene practices; food safety and proper nutrition; reduction of the human contact with wildlife and livestock; reduction of social inequalities; infectious disease surveillance; and biodiversity preservation. Subsequently, this article highlights the impacts of human genetics on susceptibility to infections and disease progression, using the SARS-CoV-2 infection as a study model. Finally, actions focused on mitigation of outbreaks and epidemics and the importance of conservation of ecosystems and translational ecology as public health strategies are also discussed.

Resumo em Inglês:

Abstract The estimation of evolutionary parameters provides essential information for designing public health policies. In short time intervals, however, nucleotide substitutions are ineffective to record all complexities of virus population dynamics. In this sense, the current SARS-CoV-2 pandemic poses a challenge for evolutionary analysis. We used computer simulation to evolve populations in scenarios of varying temporal intervals to evaluate the impact of the age of an epidemic on estimates of time and geography. Before estimating virus timescales, the shape of tree topologies can be used as a proxy to assess the effectiveness of the virus phylogeny in providing accurate estimates of evolutionary parameters. In short timescales, estimates have larger uncertainty. We compared the predictions from simulations with empirical data. The tree shape of SARS-CoV-2 was closer to shorter timescales scenarios, which yielded parametric estimates with larger uncertainty, suggesting that estimates from these datasets should be evaluated cautiously. To increase the accuracy of the estimates of virus transmission times between populations, the uncertainties associated with the age estimates of both the crown and stem nodes should be communicated. We place the age of the common ancestor of the current SARS-CoV-2 pandemic in late September 2019, corroborating an earlier emergence of the virus.

Resumo em Inglês:

Abstract COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. Here we present a brief review on the known order of events from infection to severe system-wide disturbance due to COVID-19 and summarize potential candidate genes and pathways. Finally, we propose a strategy of subject’s ascertainment based on phenotypic extremes to take part in genomic studies and elucidate intrinsic risk factors involved in COVID-19 severe outcomes.

Resumo em Inglês:

Abstract December 2019 marked the beginning of the current Coronavirus disease pandemic (COVID-19). Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) was identified as the causative agent of a viral pneumonia outbreak in Wuhan, Hubei Province, China. The alarming spread levels and clinical severity elevated the status of COVID-19 to the global pandemic by the World Health Organization. In 6 months, more than 25 million cases of infected people and more than 890,000 deaths by COVID-19 had been reported worldwide. The main goal of this review is to shed light upon the current COVID-19 epidemic situation in Brazil with a health approach highlighting some unique environmental, animal and epidemiological aspects.

Resumo em Inglês:

Abstract SARS-CoV-2 virus was first identified in the beginning of 2020 and has spread all over the world, causing the Coronavirus Disease 2019 (COVID-19) pandemic. The virus is a member of the Coronavirus family, which includes viruses that cause common cold, Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). MERS and SARS are known by causing adverse events in pregnancy. Considering that SARS-CoV-2 is a new infection agent, little is known about the risk of its infection to human embryo/fetal development. However, SARS and MERS were associated with negative outcomes, such as miscarriage, preterm birth, intrauterine growth restriction and perinatal death. Here, we raise concerns and possibilities related the harmful potential of SARS-CoV-2 and COVID-19 to pregnancy, discussing symptoms, immunological changes during pregnancy, SARS-CoV-2 mutation rate (and the risks related to it). Finally, we point out recommendations to be performed by the scientific community and health care workers in order to identify and to manage potential risks to pregnant women and their babies.

Resumo em Inglês:

Abstract Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)- associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different levels and functional efficiency of their encoded proteins, modulating susceptibility and severity to diseases. Our review highlights the possible role of MASPs in SARS-COV-2 binding and activation of the lectin pathway and blood coagulation cascades, as well as their associations with comorbidities of COVID-19. MASP-1 and/or MASP-2 present an increased expression in patients with COVID-19 risk factors: diabetes, arterial hypertension and cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and cerebrovascular disease. Based also on the positive results of COVID-19 patients with anti-MASP-2 antibody, we propose the use of MASPs as a possible biomarker of the progression of COVID-19 and the investigation of new treatment strategies taking into consideration the dual role of MASPs, including MASP inhibitors as promising therapeutic targets against COVID-19.

Resumo em Inglês:

Abstract In this article, we explore elements that highlight the interdependent nature of demands for knowledge production and decision-making related to the appearance of emerging diseases. To this end, we refer to scientific production and current contextual evidence to verify situations mainly related to the Brazilian Amazon, which suffers systematic disturbances and is characterized as a possible source of pathogenic microorganisms. With the acceleration of the Anthropocene's environmental changes, socio-ecological instabilities and the possibility of the emergence of infectious diseases merge into a background of a ´twin insurgency´. Furthermore, there is a tendency to impose economic hegemony in the current Brazilian context, corroborating discourses and pressures to a scientific simplification and denial. With this, we assert that developmental sectoral actions and monoculture of knowledge characterize an agenda of omission, that is, a process of decision making that indirectly reinforces ecological degradation and carelessness in the face of the possibility of the emergence and spreading of new diseases, such as COVID-19. Tackling the socio-ecological complexity inherent in the risk of the emergence of infectious diseases requires robust co-construction of scientific knowledge, eco-social approaches, and corresponding governance and sophisticated decision-making arrangements.

Resumo em Inglês:

Abstract The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for the development of vaccines. The most advanced strategies have focused on modifications of technologies that were already under development for other viruses, such as SARS, MERS, and even Influenza. Classic and new technologies, such as inactivated and attenuated viruses (non-replicative and replicative), DNA and mRNA vaccines, and nanoparticles containing SARS-CoV-2 antigens, are some of the strategies currently investigated. Although there is a very high expectation for the effectiveness of the most advanced vaccine candidates, there are still no established correlates of protection. Previous experience in vaccine development for other pathogens shows that differences in vaccine formulation can result in diverse immune responses and consequently, different protective properties. Therefore the importance of continuing investigations on a broad range of strategies. Expertise in vaccine development in Brazil was refocused to the new coronavirus. Impressive collaboration between institutions will support further developments until we have available a safe, effective, and economically viable vaccine. Established competence and collaborations will allow preparedness for future challenges and can also be used to address local issues as neglected infectious diseases.

Resumo em Inglês:

Abstract The transmission of pathogens from wild animals to humans is called “zoonotic spillover”. Most human infectious diseases (60-75%) are derived from pathogens that originally circulated in non-human animal species. This demonstrates that spillover has a fundamental role in the emergence of new human infectious diseases. Understanding the factors that facilitate the transmission of pathogens from wild animals to humans is essential to establish strategies focused on the reduction of the frequency of spillover events. In this context, this article describes the basic aspects of zoonotic spillover and the main factors involved in spillover events, considering the role of the inter-species interactions, phylogenetic distance between host species, environmental drivers, and specific characteristics of the pathogens, animals, and humans. As an example, the factors involved in the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic are discussed, indicating what can be learned from this public health emergency, and what can be applied to the Brazilian scenario. Finally, this article discusses actions to prevent or reduce the frequency of zoonotic spillover events.

Resumo em Inglês:

Abstract For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population genetics and of sequencing data in the design of genetic association studies in different human populations: the high linkage disequilibrium (LD) between rs2070788 and rs383510 is Asian-specific. Leveraging on a combination of genotyping and sequencing data for Native Americans (neglected in genetic studies), we show that while their frequencies of the Asian tag-SNP rs2070788 is, surprisingly, the highest worldwide, it is not in LD with the eQTL rs383510, that therefore, should be directly genotyped in genetic association studies of SARS in populations with Native American ancestry.

Resumo em Inglês:

Abstract Meeting the challenges brought by the COVID-19 pandemic requires an interdisciplinary approach. In this context, integrating knowledge of immune function with an understanding of how genetic variation influences the nature of immunity is a key challenge. Immunogenetics can help explain the heterogeneity of susceptibility and protection to the viral infection and disease progression. Here, we review the knowledge developed so far, discussing fundamental genes for triggering the innate and adaptive immune responses associated with a viral infection, especially with the SARS-CoV-2 mechanisms. We emphasize the role of the HLA and KIR genes, discussing what has been uncovered about their role in COVID-19 and addressing methodological challenges of studying these genes. Finally, we comment on questions that arise when studying admixed populations, highlighting the case of Brazil. We argue that the interplay between immunology and an understanding of genetic associations can provide an important contribution to our knowledge of COVID-19.

Resumo em Inglês:

Abstract Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China’s Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients’ overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.