Brazil's COVID-19 Epicenter in Manaus: How Much of the Population Has Already Been Exposed and Are Vulnerable to SARS-CoV-2?

Is Brazil's COVID-19 epicenter really approaching herd immunity? A recent study estimated that in October 2020 three-quarters of the population of Manaus (the capital of the largest state in the Brazilian Amazon) had contact with SARS-CoV-2. We show that 46% of the Manaus population having had contact with SARS-CoV-2 at that time is a more plausible estimate, and that Amazonia is still far from herd immunity. The second wave of COVID-19 is now evident in Manaus.

How Brazil's President turned the country into a global epicenter of COVID-19.

In this manuscript, we point out that the federal government headed by President Bolsonaro has pursued a political agenda that contributed to the spread of COVID-19, transforming the country into a major repository for SARS-CoV-2 and its variants, thus representing a risk for worldwide containment efforts. Furthermore his actions are also weakening democratic institutions, which could counter his political agenda, effectively facilitating the spread of COVID-19. Thus, the perpetuation of the COVID-19 pandemic in Brazil is due to human behaviour factors, especially high-level public decision makers.

The cutaneous secretion of the casque-headed tree frog Corythomantis greeningi: Biochemical characterization and some biological effects.

Corythomantis greeningi is a tree-frog endemic of the Brazilian semi-arid (Caatinga), mainly characterized by the flat, mineralized and spiny head, which is associated with phragmotic habits. It is already known that the skin secretion of this amphibian from both head and body is quite toxic and is used as an efficient chemical defence against predators. However, the biochemical characteristics and pharmacological effects of this secretion are still very little studied.

Cross neutralization of coral snake venoms by commercial Australian snake antivenoms.

Context: Although rare, coral snake envenomation is a serious health threat in Brazil, because of the highly neurotoxic venom and the scarcely available antivenom. The major bottleneck for antivenom production is the low availability of venom. Furthermore, the available serum is not effective against all coral snake species found in Brazil.

Biochemical and biopharmaceutical properties of PEGylated uricase.

PEGylation is a successful strategy for improving the biochemical and biopharmaceutical properties of proteins and peptides through the covalent attachment of polyethylene glycol chains. In this work, purified recombinant uricase from Candida sp. (UC-r) was modified by PEGylation with metoxypolyethilenoglycol-p-nitrophenyl-carbonate (mPEG-pNP) and metoxypolyethyleneglycol-4,6-dichloro-s-triazine (mPEG-CN).

First production of fluorescent anti-ribonucleoproteins conjugate for diagnostic of rabies in Brazil.

The laboratory tests recommended by the World Health Organization for detection of rabies virus and evaluation of specific antibodies are performed with fluorescent antibodies against the virus, the ribonucleoproteins (RNPs), or by monoclonal antibodies. In this study, we purified the rabies virus RNPs for the production of a conjugate presenting sensibility and specificity compatible with commercial reagents. The method employed for the purification of RNPs was ultracentrifugation in cesium chloride gradient, the obtained product being used for immunizing rabbits, from which the hyperimmune sera were collected.

Haematopoietic effects induced in mice by the snake venom toxin jararhagin.

Venom toxins have been tested as anti-thrombotic, and anti-metastatic drugs in experimental models. The jararhagin toxin, from Bothrops jararaca snake venom, acts upon several biological processes, as inflammation, pain, platelet aggregation, etc. In this article, the systemic effects of intra-peritoneal injections of different jararhagin doses were determined in mice.

Antibody responsiveness during immunization and challenge of genetically modified antibody responder mice with murine hepatitis virus 3.

The aim of this study was to evaluate some immunological patterns involved in natural and acquired resistance against MHV3 using the original model of genetically modified lines of mice selected for high (HIII) and low (LIII) antibody responsiveness. As previously shown, a lower pre-existing anti-MHV antibody level was found in susceptible HIII mice as compared to resistant LIII mice. Mortality rates of the F1 (H x L) hybrids and F2 and backcross segregants reflected co-dominance of both characters and the survivors had higher preexisting anti-MHV antibody titers.

Down-regulation of Bgp1(a) viral receptor by interferon-gamma is related to the antiviral state and resistance to mouse hepatitis virus 3 infection.

Together with the evidence that the reduced virus growth and the antiviral state induced by interferon (IFN)-gamma, occurring only in macrophages from resistant animals, correlated with the decrease of MHV3 binding to macrophage membrane proteins, we show here the expression of cellular and viral genes in resistant (A/J) and susceptible (BALB/c) mouse macrophages after IFN-gamma activation/infection. The expression of interferon response gene 47 and interferon regulatory factor 1 genes takes place after IFN-gamma activation in both macrophages, indicating their activation. The expression of the biliary glycoprotein 1(a) (Bgp1(a), the main virus receptor) decreased only in IFN-gamma-activated A/J mouse macrophages, in contrast to the expression of the Bgp2 (alternative receptor), which was not influenced by IFN-gamma activation.

Effect of bacillus of Calmette-Guérin, avridine and Propionibacterium acnes as immunomodulators on rabies in mice.

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment.

Effect of the bacillus of Calmette-Guérin, Propionibacter acnes and avridine as immunomodulators in antirabies vaccination of mice using the Fuenzalida-Palacios mouse brain vaccine.

Using the laboratory mice, Fuenzalida-Palacios mouse brain human rabies vaccine was administered in groups of animals previously inoculated with rabies virus and then submitted to treatments with the immunomodulators onco-BCG, avridine and Propionibacterium acnes. Humoral and cellular immune responses were evaluated through the macrophage inhibition factor (MIF), intra-pad inoculation (IPI) and serum neutralization (SN) tests and by the detection of gamma-interferon (IFN-gamma). The IPI test was not effective in detecting the response of delayed-type hypersensitivity, contrary to MIF, which showed the immune cellular response.

Failure of protection induced by a Brazilian vaccine against Brazilian wild rabies viruses.

This report shows that the SMB vaccine currently used in Brazil for human immunisation provides different degrees of protection in mice, depending on the rabies virus strain used as challenge. Using the NIH and Habel potency tests to evaluate the protective activity of rabies vaccine, we observed that vaccinated mice showed a higher resistance to a challenge with a fixed rabies virus (CVS-Challenge Virus Strain). The vaccine potency using the Habel or NIH tests was respectively > 6.

Effect of vaccination and the immunomodulators "bacillus of Calmette-Guérin, avridine and Propionibacterium acnes" on rabies in mice.

Responses of vaccination and treatment to immunomodulators against rabies in mice were evaluated through macrophage inhibition factor (MIF), intra-pad inoculation (IPI) and serum neutralization (SN) tests and by the detection of gamma-interferon (IFN-gamma). Onco-BCG, Avridine and Propionibacterium acnes were administered to groups of mice. Higher survival rates were found in animals treated with P.

Polygenic control of antibody production and correlation with vaccine induced resistance to rabies virus in high and low antibody responder mice.

The amplification of "high" (H) and "low" (L) multispecific antibody responses achieved respectively by H and L lines of selection GP represents a valuable tool in the genetic study of host-infection interactions. These lines were obtained by bidirectional selective breeding for high (HGP) or low (LGP) antibody production to natural complex antigens. HGP and LGP parental lines and reciprocal F1 hybrids, as well as their F2 segregants and backcrosses were submitted to immunization and challenge with rabies virus CVS strain.

Specific T-cell response correlates with resistance of genetic heterogeneous mouse populations to mouse hepatitis virus 3 infection.

In a recently published study [Vassão RC, Mello IGC, Pereira CA (1994) Arch Virol 137: 277-288] we have shown that the genetically selected high antibody responder mice (HIII) are susceptible and the low antibody responder counterparts (LIII) are resistant to death induced by experimental infection with mouse hepatitis virus 3 (MHV3). This report shows that the MHV3 titers in the peritoneal exudate (PE) of HIII mice, 3 days after infection, were more than 2 log greater than in the resistant LIII mice, the interferon gamma (IFN gamma) titers in the PE of both mouse populations being not significantly different. The treatment with monoclonal antibodies (mAb) against CD4+ or CD8+ T cells induced susceptibility among LIII mice.

Interferon-gamma levels during the course of Trypanosoma cruzi infection of Calomys callosus (Rodentia-Cricetidae) and Swiss mice.

Serum levels of interferon-gamma (IFN-gamma) were evaluated in Calomys callosus and Swiss mice during the course of infection by four strains of Trypanosoma cruzi. All strains stimulated the production of this interleukine; however, the timing of its onset and permanence varied among strains and between the two animal models. When chronically infected animals with no detectable serum IFN-gamma were challenged with the homologous strain, they produced quantities comparable with those obtained during the acute phase of infection.

Antiviral activity of interferon gamma in vivo during mouse hepatitis virus infection.

A/J mice became resistant to experimental MHV3 infection after immunization with UV-inactivated MHV3 (0% mortality, 0/10). Depletion of interferon (IFN) gamma-producing CD4+ T lymphocytes with monoclonal antibodies to CD4+ led to susceptibility to virus infection (60% of mortality, 6/10). The resistance to MHV3 infection of CD4+ T lymphocyte-depleted-A/J mice was restored by treatment with 1000 U of IFN gamma on days -1, 0, 1, 2, 3 and 4 (10% of mortality, 1/10).

Gamma-IFN and macrophage respiratory burst in Calomys callosus challenged with Trypanosoma cruzi bloodstream and metacyclic forms.

Parasitemia levels of Calomys callosus inoculated with a high dose (HBT) of 4 x 10(3) Trypanosoma cruzi strain M226 bloodstream trypomastigotes (BT) exceeded those with the same inoculum of metacyclic trypomastigotes (MT) while a similar parasitemia was obtained with a low dose (LBT) of 5 x 10(2) of BT. Serum IFN-gamma levels during the acute phase of infection were higher in the LBT inoculated group when compared with the group inoculated with HBT, while the IFN-gamma levels in MT inoculated animals were close to uninfected controls. Spontaneous liberation of H2O2 of peritoneal macrophages explanted from animals on days 21 and 28 after infection was comparable to that of controls for HBT and LBT groups while that of the MT inoculated group was significantly higher.

Role of macrophages, interferon gamma and procoagulant activity in the resistance of genetic heterogeneous mouse populations to mouse hepatitis virus infection.

Genetic heterogeneous mouse populations selected for high (HIII) and low (LIII) antibody response were used to study some aspects of mouse hepatitis virus 3 (MHV3) infection, such as the resistance pattern, virus replication in the liver and peritoneal exudate or in cultured peritoneal macrophages, the interferon (IFN) synthesis in the serum and peritoneal exudate and the procoagulant activity (PCA) of the peritoneal exudate (PEC) and spleen cells (SC). The HIII mice, when compared to their LIII mice counterparts, were susceptible to MHV3 infection showing higher virus titres in the liver and peritoneal exudate, comparable IFN alpha/beta or IFN gamma titres in the peritoneal exudate or in the serum, and higher levels of PCA of PEC and SC. A higher virus titre was detected in the supernatants of HIII mouse macrophages infected with MHV3.