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The Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. In 2020 between the 17th and 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 h after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatalities associated with COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.6%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy countrywise could have contributed to a better control of the COVID-19 spread in Brazil. Quarantine decree by the local administration, comprehensive molecular testing coupled to scientific analysis of COVID-19 spreading, prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil.

Increasing attention has been directed to cytotoxic CD4+ T cells (CD4CTLs) in different pathologies, both in humans and mice. The impact of CD4CTLs in immunity and the mechanisms controlling their generation, however, remain poorly understood. Here, we show that CD4CTLs abundantly differentiate during mouse infection with the intracellular parasite Trypanosoma cruzi. CD4CTLs display parallel kinetics to Th1 cells in the spleen, mediate specific cytotoxicity against cells presenting pathogen-derived antigens and express immunoregulatory and/or exhaustion markers. We demonstrate that CD4CTL absolute numbers and activity are severely reduced in both Myd88-/- and Il18ra-/- mice. Of note, the infection of mixed-bone marrow chimeras revealed that WT but not Myd88-/- cells transcribe the CD4CTL gene signature and that Il18ra-/- and Myd88-/- CD4+ T cells phenocopy each other. Moreover, adoptive transfer of WT CD4+GzB+ T cells to infected Il18ra-/- mice extended their survival. Importantly, cells expressing the CD4CTL phenotype predominate among CD4+ T cells infiltrating the infected mouse cardiac tissue and are increased in the blood of Chagas patients, in which the frequency of CD4CTLs correlates with the severity of cardiomyopathy. Our findings describe CD4CTLs as a major player in immunity to a relevant human pathogen and disclose T-cell intrinsic IL-18R/MyD88 signaling as a key pathway controlling the magnitude of the CD4CTL response.

Background Brazilian strategy to overcome the spread of COVID-19 has been particularly criticized due to the lack of a national coordinating effort and an appropriate testing program. Here, a successful approach to control the spread of COVID-19 transmission is described by the engagement of public (university and governance) and private sectors (hospitals and oil companies) in Macaé, state of Rio de Janeiro, Brazil, a city known as the National Oil Capital. Methods Until the 38th epidemiological week, over two percent of the 206,728 citizens were subjected to symptom analysis and massive RT-qPCR testing by the Federal University of Rio de Janeiro, with positive individuals being notified up to 48 hours after swab collection. Geocodification and spatial cluster analysis were used to limit COVID-19 spreading in Macaé. Findings: Within the first semester after the outbreak of COVID-19 in Brazil, Macaé recorded 1.8% of fatality associated to COVID-19 up to the 38th epidemiological week, which was at least five times lower than the state capital (10.92%). Overall, considering the successful experience of this joint effort of private and public engagement in Macaé, our data suggest that the development of a similar strategy country wise would have saved over 50,000 lives. Interpretation: Quarantine decree by the local government, molecular massive testing coupled to scientific analysis of COVID-19 spreading prevented the catastrophic consequences of the pandemic as seen in other populous cities within the state of Rio de Janeiro and elsewhere in Brazil.

Cytotoxic CD4+ T cells (CD4CTLs) have been described in humans and mice, but the mechanism leading to their differentiation is not fully understood and remains a fundamental question. Here, we investigate the generation of CD4CTLs during infection with Trypanosoma cruzi, an important human pathogen. We demonstrate the critical role of T-cell intrinsic IL-18R/MyD88 signaling for the development of CD4CTLs in infected mixed-BM chimeras: WT but not Myd88-/- CD4+ T cells display the CD4CTL gene signature and IL-18R deficiency phenocopied the absence of MyD88. Moreover, IL-12p40, but not IFN-γ, is required for CD4CTL differentiation. Functionally, degranulating CD4CTLs are massively present in the spleen and myocardium of infected mice, exhibit FasL-dependent antigen-specific cytotoxicity against macrophages in vitro, eliminate target cells in vivo and express important immunoregulatory molecules. The present work discloses a mechanistic framework required for the induction of a robust CD4CTL response to infection with an intracellular parasite.

The saponins of Chiococca alba are triterpene bidesmosides that contain glycidic moieties attached to the C-3 and C-28 carbon of their aglycone. We describe that their adjuvant potential increases in direct relationship to the length and hydrophilicity of the C-28 attached sugar chain which contains: arabinose–rhamnose in the CA2, arabinose–rhamnose–xylose in the CA3X; arabinose–rhamnose–apiose in the CA3 and arabinose–rhamnose–apiose–apiose in the CA4 saponin. The hydrophile/lipophile balance calculated for CA2 was 12.7, for CA3 and CA3X was 15.8 and for CA4 19.9. All saponins were formulated with the FML antigen for mice prophylaxis against visceral leishmaniasis. The immune response was studied using an ELISA-antibody assay and monitoring of the intradermal response (IDR) to Leishmania antigens, the cytokine expression in supernatants and the intracellular staining of in vitro cultured splenocytes. After challenge, significant increases of IgG and IgG2a antibodies were noted only in the CA4 vaccinated mice that showed extended IDR, higher IFN-γ production by CD8+ and TNF-α production by CD4+ T cells, higher TNF-α secretion and the highest reduction of the parasite load (78%). The increases in IDR, CD4–TNF-α, CD8–IFN-γ and CD8–TNF-α by the CA4 vaccine were strong correlates of protection and were significantly correlated to the decrease of parasite load ( p = −0.007). Protection generated by the CA4 vaccine was mainly mediated by a CD4+ T cell and a TNF-α driven response with a lower contribution of CD8+ T cells, as confirmed by an in vivo depletion with monoclonal antibodies and by vaccination assays in TNF-α-receptor knock-out mice. Our results confirm that the superiority of the CA4 saponin is related to the higher hydrophilicity of its longer carbohydrate chain. C. alba saponins were non-toxic and only the xylose-containing saponin CA3X was hemolytic (HD 50 = 87 μg/ml). The increase in sugar units of the saponins is positively correlated to the increase of IDR and to the decrease of parasite load.