A snapshot of a representative Brazilian state of illegal mining in indigenous areas during the era of malaria elimination.

Malaria is a public health problem and the cases diagnosed in the capital of Roraima, Brazil, show potential to characterize the burden of the disease in the state. This study aimed to describe the epidemiological, clinical, and laboratory aspects of malaria cases diagnosed in Boa Vista. For this purpose, a descriptive, cross-sectional study was conducted in two health units in the city, with individuals diagnosed and who agreed to respond the questionnaire. Of the total of 206 participants, characterized as men, mixed-race, and young, 96% (198) reported participating in illegal mining activity. Among the group of miners, 66% (131) came from other states of Brazil or other countries. The mines were mainly located in the Yanomami territory in Roraima. Plasmodium vivax infection occurred in 74% (153) of participants. In the miner's group, hospitalizations for severe malaria, previous malaria attacks, and delays in treatment after the onset of symptoms were reported. Although 73% (145) of miners reported knowing how malaria was transmitted, only 54% (107) used mosquito nets or repellents. The use of Artecom and chloroquine by miners is not for the complete treatment but only to relieve symptoms for returning to gold mines, highlighting the importance of molecular surveillance to antimalarial resistance. Indigenous peoples are considered vulnerable to malaria and miners promotes the increase of malaria in Roraima Indigenous Lands. Therefore, access to diagnosis and treatment in Indigenous areas invaded by miners is imperative to confront this disease that ravages Indigenous communities and threatens public health on a large scale to achieve the goal of eliminating malaria in the state.

Molecular Surveillance of Artemisinin-Resistant Plasmodium falciparum Parasites in Mining Areas of the Roraima Indigenous Territory in Brazil.

Multidrug- and artemisinin-resistant (ART-R) Plasmodium falciparum (Pf) parasites represent a challenge for malaria elimination worldwide. Molecular monitoring in the Kelch domain region (pfk13) gene allows tracking mutations in parasite resistance to artemisinin. The increase in illegal miners in the Roraima Yanomami indigenous land (YIL) could favor ART-R parasites. Thus, this study aimed to investigate ART-R in patients from illegal gold mining areas in the YIL of Roraima, Brazil. A questionnaire was conducted, and blood was collected from 48 patients diagnosed with P. falciparum or mixed malaria (Pf + P. vivax). The DNA was extracted and the pfk13 gene was amplified by PCR. The amplicons were subjected to DNA-Sanger-sequencing and the entire amplified fragment was analyzed. Among the patients, 96% (46) were from illegal mining areas of the YIL. All parasite samples carried the wild-type genotypes/ART-sensitive phenotypes. These data reinforce the continued use of artemisinin-based combination therapies (ACTs) in Roraima, as well as the maintenance of systematic monitoring for early detection of parasite populations resistant to ART, mainly in regions with an intense flow of individuals from mining areas, such as the YIL. This is especially true when the achievement of falciparum malaria elimination in Brazil is planned and expected by 2030.

Molecular Epidemiology of Mayaro Virus among Febrile Patients, Roraima State, Brazil, 2018-2021.

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

A snapshot of a representative Brazilian state of illegal mining in indigenous areas during the era of malaria elimination / Um retrato de um estado brasileiro representativo do garimpo ilegal em áreas indígenas durante a campanha de erradicação da malária / Un retrato de un estado brasileño representativo de la minería ilegal en zonas indígenas durante la campaña de erradicación de la malaria

Abstract: Malaria is a public health problem and the cases diagnosed in the capital of Roraima, Brazil, show potential to characterize the burden of the disease in the state. This study aimed to describe the epidemiological, clinical, and laboratory aspects of malaria cases diagnosed in Boa Vista. For this purpose, a descriptive, cross-sectional study was conducted in two health units in the city, with individuals diagnosed and who agreed to respond the questionnaire. Of the total of 206 participants, characterized as men, mixed-race, and young, 96% (198) reported participating in illegal mining activity. Among the group of miners, 66% (131) came from other states of Brazil or other countries. The mines were mainly located in the Yanomami territory in Roraima. Plasmodium vivax infection occurred in 74% (153) of participants. In the miner's group, hospitalizations for severe malaria, previous malaria attacks, and delays in treatment after the onset of symptoms were reported. Although 73% (145) of miners reported knowing how malaria was transmitted, only 54% (107) used mosquito nets or repellents. The use of Artecom and chloroquine by miners is not for the complete treatment but only to relieve symptoms for returning to gold mines, highlighting the importance of molecular surveillance to antimalarial resistance. Indigenous peoples are considered vulnerable to malaria and miners promotes the increase of malaria in Roraima Indigenous Lands. Therefore, access to diagnosis and treatment in Indigenous areas invaded by miners is imperative to confront this disease that ravages Indigenous communities and threatens public health on a large scale to achieve the goal of eliminating malaria in the state.

Resumo: A malária é um problema de saúde pública e os casos diagnosticados na capital de Roraima, Brasil, têm potencial para caracterizar a carga da doença em todo o estado. O objetivo deste estudo foi descrever os aspectos epidemiológicos, clínicos e laboratoriais dos casos de malária diagnosticados em Boa Vista. Para tanto, foi realizado um estudo descritivo e transversal em duas unidades de saúde do município, com indivíduos diagnosticados com malária e que concordaram em responder ao questionário. De 206 participantes, caracterizados como homens, pardos e jovens, 96% (198) relataram atividade de garimpo ilegal. Entre garimpeiros, 66% (131) vieram de outros estados do Brasil ou de outros países. As minas estavam localizadas principalmente no território Yanomami, em Roraima. A infecção por Plasmodium vivax ocorreu em 74% (153) dos participantes. Entre garimpeiros, houve relatos de internações por malária grave, ataques prévios de malária e atrasos no tratamento após o início dos sintomas. Embora 73% (145) dos garimpeiros tenham relatado saber como a malária era transmitida, apenas 54% (107) usavam mosquiteiros ou repelentes. O uso de Artecom e cloroquina pelos garimpeiros não se destina ao tratamento completo, mas apenas ao alívio dos sintomas, permitindo o retorno às minas de ouro. Isso ressalta a importância da vigilância molecular para detectar a resistência antimalárica. Os indígenas são considerados uma população vulnerável à malária, e os garimpeiros promovem o aumento da malária nas Terras Indígenas de Roraima. Portanto, o acesso ao diagnóstico e tratamento em áreas indígenas invadidas por garimpeiros é imperativo para o enfrentamento dessa doença que assola as comunidades indígenas e ameaça a saúde pública em larga escala na meta de erradicar a malária no estado.

Resumen: La malaria es un problema de salud pública y los casos diagnosticados en la capital de Roraima, Brasil, tienen el potencial de caracterizar la carga de la enfermedad en todo el estado. El objetivo de este estudio fue describir los aspectos epidemiológicos, clínicos y de laboratorio de los casos de malaria diagnosticados en Boa Vista. Para ello, se realizó un estudio descriptivo y transversal en dos unidades de salud del municipio, con personas diagnosticadas con malaria y que aceptaron responder el cuestionario. De 206 participantes, caracterizados como hombres, pardos y jóvenes, el 96% (198) reportó actividad minera ilegal. Entre los mineros, el 66% (131) procedían de otros estados de Brasil o de otros países. Las minas estaban ubicadas principalmente en el territorio Yanomami, en Roraima. La infección por Plasmodium vivax se produjo en el 74% (153) de los participantes. Entre los mineros, hubo relatos de hospitalizaciones por malaria grave, ataques previos de malaria y retrasos en el tratamiento tras de la aparición de los síntomas. Aunque el 73% (145) de los mineros informó saber cómo se transmitía la malaria, solo el 54% (107) usaba mosquiteros o repelentes. El uso de Artecom y cloroquina por parte de los mineros no está destinado a un tratamiento completo, sino al alivio de los síntomas para permitir el regreso a las minas de oro. Esto resalta la importancia de la vigilancia molecular para detectar la resistencia a los antipalúdicos. Los indígenas son considerados una población vulnerable a la malaria, y los mineros promueven el aumento de la malaria en las Tierras Indígenas de Roraima. Por lo tanto, el acceso al diagnóstico y tratamiento en zonas indígenas invadidas por mineros es imperativo para combatir esta enfermedad que asola a las comunidades indígenas y amenaza la salud pública a gran escala en el objetivo de erradicar la malaria en el estado.

SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

Antigen-Specific Antibody Signature Is Associated with COVID-19 Outcome.

Numerous studies have focused on inflammation-related markers to understand COVID-19. In this study, we performed a comparative analysis of spike (S) and nucleocapsid (N) protein-specific IgA, total IgG and IgG subclass response in COVID-19 patients and compared this to their disease outcome. We observed that the SARS-CoV-2 infection elicits a robust IgA and IgG response against the N-terminal (N1) and C-terminal (N3) region of the N protein, whereas we failed to detect IgA antibodies and observed a weak IgG response against the disordered linker region (N2) in COVID-19 patients. N and S protein-specific IgG1, IgG2 and IgG3 response was significantly elevated in hospitalized patients with severe disease compared to outpatients with non-severe disease. IgA and total IgG antibody reactivity gradually increased after the first week of symptoms. Magnitude of RBD-ACE2 blocking antibodies identified in a competitive assay and neutralizing antibodies detected by PRNT assay correlated with disease severity. Generally, the IgA and total IgG response between the discharged and deceased COVID-19 patients was similar. However, significant differences in the ratio of IgG subclass antibodies were observed between discharged and deceased patients, especially towards the disordered linker region of the N protein. Overall, SARS-CoV-2 infection is linked to an elevated blood antibody response in severe patients compared to non-severe patients. Monitoring of antigen-specific serological response could be an important tool to accompany disease progression and improve outcomes.

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study.

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Heterogeneity of humoral response patterns in mildly symptomatic, non-hospitalized COVID-19 patients: A one-year longitudinal study.

The duration and protectiveness of antibodies against SARS-CoV-2 in infected subjects are still uncertain; nonetheless, anti-S-specific antibodies can contribute to protective immunity against new infections. It has been described that the level of antibodies produced in COVID-19 is related to the severity of symptoms, and the majority of the humoral response studies have been conducted in hospitalized patients who have been, then, followed over time. However, about 80% of SARS-CoV-2 infections in unvaccinated people are mild to asymptomatic, and this percentage reaches more than 95% in vaccinated individuals. Therefore, understanding the long-term dynamics of the antibody responses in this predominant part of the COVID-19-affected population is essential. In this study, we followed a cohort of individuals with mild COVID-19 who did not require hospitalization. We collected blood samples at sequential times after the SARS-CoV-2-positive qRT-PCR result. From 65 recruited patients, 50 had detectable antibodies at screening. Anti-SARS-CoV-2 IgM levels peaked around two weeks post-COVID-19 diagnostics, becoming undetectable after 65 days. IgG levels reached a peak in approximately one month and remained detectable for more than one year. In contrast to the levels of anti-SARS-CoV-2, antibody neutralization potency indexes persisted over time. In this study, humoral responses in mild COVID-19 patients persisted for more than one year. This is an important long-term follow-up study that includes responses from COVID-19 patients before and after vaccination, a scenery that has become increasingly difficult to evaluate due to the growing vaccination of the world human population.

Antibody cross-reactivity and evidence of susceptibility to emerging Flaviviruses in the dengue-endemic Brazilian Amazon.

OBJECTIVES: Several Flaviviruses can co-circulate. Pre-existing immunity to one virus can modulate the response to a heterologous virus; however, the serological cross-reaction between these emerging viruses in dengue virus (DENV)-endemic regions are poorly understood. METHODS: A cross-sectional study was performed among the residents of Manaus city in the state of Amazonas, Brazil. The serological response was assessed by hemagglutination inhibition assay (HIA), enzyme-linked immunosorbent assay, and neutralization assay. RESULTS: A total of 74.52% of the participants were immunoglobulin G-positive (310/416), as estimated by lateral flow tests. Overall, 93.7% of the participants were seropositive (419/447) for at least one DENV serotype, and the DENV seropositivity ranged between 84.8% and 91.0%, as determined by HIA. About 93% had antiyellow fever virus 17D-reactive antibodies, whereas 80.5% reacted to wild-type yellow fever virus. Zika virus (ZIKV) had the lowest seropositivity percentage (52.6%) compared with other Flaviviruses. Individuals who were DENV-positive with high antibody titers by HIA or envelope protein domain III enzyme-linked immunosorbent assay reacted strongly with ZIKV, whereas individuals with low anti-DENV antibody titers reacted poorly toward ZIKV. Live virus neutralization assay with ZIKV confirmed that dengue serogroup and ZIKV-spondweni serogroup are far apart; hence, individuals who are DENV-positive do not cross-neutralize ZIKV efficiently. CONCLUSION: Taken together, we observed a high prevalence of DENV in the Manaus-Amazon region and a varying degree of cross-reactivity against emerging and endemic Flaviviruses. Epidemiological and exposure conditions in Manaus make its population susceptible to emerging and endemic arboviruses.

SARS-CoV-2 infected children form early immune memory responses dominated by nucleocapsid-specific CD8+ T cells and antibodies.

This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.

Gold miners augment malaria transmission in indigenous territories of Roraima state, Brazil.

BACKGROUND: Endemic malaria is present in all 15 municipalities of Roraima state, Brazilian Amazonia. Knowledge of epidemiological data of specific populations can guide health policies to formulate effective strategies for integrated control of health-disease care. This study aims to ascertain when, where and who fell ill with malaria in Roraima state from 2010 to 2020. METHODS: This descriptive study was based on statistical secondary surveillance data through the analysis of relationships underlying numbers of cases, hospitalizations and deaths using the Malaria Epidemiological Surveillance Information System, Mortality Information System and Hospitalization Information System. RESULTS: From 2010 to 2020, there were 138,504 autochthonous cases, 26,158 Venezuelan imported cases, 3765 hospitalizations, and 77 deaths from malaria reported in Roraima. Annual parasitic incidence and the number of hospitalizations showed impressive changes over the period, but without significantly correlating with number of deaths. The proportion of Plasmodium falciparum infections had significant shifts throughout this study. Malaria prevalence in indigenous and mining areas has been increasing since 2014. CONCLUSION: The presence of miners in indigenous areas is a reality that has been contributing to the increase of malaria cases in Roraima. The need to implement health policies that also meet this contingent is reinforced.

UV 254 nm is more efficient than UV 222 nm in inactivating SARS-CoV-2 present in human saliva.

Ultraviolet (UV) light can inactivate SARS-CoV-2. However, the practicality of UV light is limited by the carcinogenic potential of mercury vapor-based UV lamps. Recent advances in the development of krypton chlorine (KrCl) excimer lamps hold promise, as these emit a shorter peak wavelength (222 nm), which is highly absorbed by the skin's stratum corneum and can filter out higher wavelengths. In this sense, UV 222 nm irradiation for the inactivation of virus particles in the air and surfaces is a potentially safer option as a germicidal technology. However, these same physical properties make it harder to reach microbes present in complex solutions, such as saliva, a critical source of SARS-CoV-2 transmission. We provide the first evaluation for using a commercial filtered KrCl excimer light source to inactivate SARS-CoV-2 in saliva spread on a surface. A conventional germicidal lamp (UV 254 nm) was also evaluated under the same condition. Using plaque-forming units (PFU) and Median Tissue Culture Infectious Dose (TCID50) per milliliter we found that 99.99% viral clearance (LD99.99) was obtained with 106.3 mJ/cm2 of UV 222 nm for virus in DMEM and 2417 mJ/cm2 for virus in saliva. Additionally, our results showed that the UV 254 nm had a greater capacity to inactivate the virus in both vehicles. Effective (after discounting light absorption) LD99.99 of UV 222 nm on the virus in saliva was ∼30 times higher than the value obtained with virus in saline solution (PBS), we speculated that saliva might be protecting the virus from surface irradiation in ways other than just by intensity attenuation of UV 222 nm. Due to differences between UV 222/254 nm capacities to interact and be absorbed by molecules in complex solutions, a higher dose of 222 nm will be necessary to reduce viral load in surfaces with contaminated saliva.

Identification and characterization of the anti-SARS-CoV-2 activity of cationic amphiphilic steroidal compounds.

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biology. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiology is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis.

Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report.

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients.

Previous Infection with SARS-CoV-2 Correlates with Increased Protective Humoral Responses after a Single Dose of an Inactivated COVID-19 Vaccine.

Previous studies have indicated that antibody responses can be robustly induced after the vaccination in individuals previously infected by SARS-CoV-2. To evaluate anti-SARS-CoV-2 humoral responses in vaccinated individuals with or without a previous history of COVID-19, we compared levels of anti-SARS-CoV-2 antibodies in the sera from 21 vaccinees, including COVID-19-recovered or -naïve individuals in different times, before and after immunization with an inactivated COVID-19 vaccine. Anti-SARS-CoV-2-specific antibodies elicited after COVID-19 and/or immunization with an inactivated vaccine were measured by ELISA and Plaque Reduction Neutralizing assays. Antibody kinetics were consistently different between the two vaccine doses for naïve individuals, contrasting with the SARS-CoV-2-recovered subjects in which we observed no additional increase in antibody levels following the second dose. Sera from SARS-CoV2-naïve individuals had no detectable neutralizing activity against lineage B.1 SARS-CoV-2 or Gamma variant five months after the second vaccine dose. Contrarily, SARS-CoV-2-recovered subjects retained considerable neutralizing activity against both viruses. We conclude that a single inactivated SARS-CoV-2 vaccine dose may be sufficient to induce protective antibody responses in individuals with previous history of SARS-CoV-2 infection.

Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection.

The COVID-19 (Coronavirus Disease 2019), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affects mainly individuals with pre-existing comorbidities. Here our aim was to correlate the mTOR (mammalian/mechanistic Target of Rapamycin) and autophagy pathways with the disease severity. Through western blotting and RNA analysis, we found increased mTOR signaling and suppression of genes related to autophagy, lysosome, and vesicle fusion in Vero E6 cells infected with SARS-CoV-2 as well as in transcriptomic data mining of bronchoalveolar epithelial cells from severe COVID-19 patients. Immunofluorescence co-localization assays also indicated that SARS-CoV-2 colocalizes within autophagosomes but not with a lysosomal marker. Our findings indicate that SARS-CoV-2 can benefit from compromised autophagic flux and inhibited exocytosis in individuals with chronic hyperactivation of mTOR signaling.

Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines.

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8-3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.

Ultraviolet germicidal irradiation is effective against SARS-CoV-2 in contaminated makeup powder and lipstick.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is mainly transmitted by airborne droplets generated by infected individuals. Since this and many other pathogens are able to remain viable on inert surfaces for extended periods of time, contaminated surfaces play an important role in SARS-CoV-2 fomite transmission. Cosmetic products are destined to be applied on infection-sensitive sites, such as the lips and eyelids. Therefore, special biosafety precautions should be incorporated into the routine procedures of beauty parlors and shops. Indeed, innovative cosmetics companies are currently searching for disinfection protocols that ensure the customers' safety in makeup testing. Here, we propose an ultraviolet germicidal irradiation (UVGI) strategy that can be used to reduce the odds of COVID-19 fomite transmission by makeup testers. It is well-known that UVGI effectively inactivates pathogens on flat surfaces and clear fluids. However, ultraviolet-C (UVC) radiation at 254 nm penetrates poorly in turbid and porous materials, such as makeup and lipstick formulations. Thus, we investigated the virucidal effect of UVGI against SARS-CoV-2 deposited on such substrates and compared their performance to that of flat polystyrene surfaces, used as controls. Concentrated infectious SARS-CoV-2 inoculum (106 PFU/mL) deposited on lipstick and makeup powder was completely inactivated (>5log10 reduction) following UVC exposures at 1,260 mJ/cm2, while flat plastic surfaces required 10 times less exposure (126 mJ/cm2) to reach the same microbicidal performance. We conclude that UVGI comprises an effective disinfection strategy to promote biosafety for cosmetics testers. However, appropriate UVC dosimetry must be implemented to overcome inefficiencies caused by the optical properties of turbid materials in lipsticks and makeup powders.

Identification of SARS-CoV-2 on the ocular surface in a cohort of COVID-19 patients from Brazil.

In this cross-sectional study, we investigate the presence of Severe Acute Respiratory Syndrome Coronavirus 2 Ribonucleic Acid (SARS-CoV-2 RNA) in the tears of hospitalized COVID-19 patients. After laboratory confirmation of SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR) analysis, tear samples from both eyes of each patient were collected using conjunctival swab for RT-PCR. Detailed demographic profile, systemic and ocular symptoms, comorbidities, clinical, ancillary, and ocular manifestations were evaluated. Of the 83 patients enrolled in the study, 7 (8.43%) had SARS-CoV-2 RNA detected in the tear samples. Neutrophils' count, C-reactive protein, and D-dimer were higher in patients with SARS-CoV-2 detected in tears than in patients without virus in ocular surface samples. One patient with SARS-CoV-2 in tears showed mild ocular eyelid edema, hyperemia, and chemosis. No relevant ocular manifestations were detected in the other patients. Although the levels of viral RNA on ocular surface samples were low for most patients (5/7), with positivity only for gene N and CT higher than 30, two patients were positive for all viral targets tested (N, E, and RpRd), with viral load near 1 × 105 ePFU/mL, indicating that the ocular transmission of SARS-CoV-2 is a possibility that needs to be considered, especially in the hospital environment. Further studies need to be conducted to demonstrate whether infective viral particles could be isolated from tears.