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[...]immunity against infection might have already begun to wane by December, 2020, because of a general decrease in immune protection against SARS-CoV-2 after a first exposure. [...]SARS-CoV-2 lineages might evade immunity generated in response to previous infection.15 Three recently detected SARS-CoV-2 lineages (B.1.1.7, B.1.351, and P.1), are unusually divergent and each possesses a unique constellation of mutations of potential biological importance.16–18 Of these, two are circulating in Brazil (B.1.1.7 and P.1) and one (P.1) was detected in Manaus on Jan 12, 2021.16 One case of SARS-CoV-2 reinfection has been associated with the P.1 lineage in Manaus19 that accrued ten unique spike protein mutations, including E484K and N501K.16 Moreover, the newly classified P.2 lineage (sublineage of B.1.128 that independently accrued the spike E484K mutation) has now been detected in several locations in Brazil, including Manaus.20 P.2 variants with the E484K mutation have been detected in two people who have been reinfected with SARS-CoV-2 in Brazil,21,22 and there is in-vitro evidence that the presence of the E484K mutation reduces neutralisation by polyclonal antibodies in convalescent sera.15 Fourth, SARS-CoV-2 lineages circulating in the second wave might have higher inherent transmissibility than pre-existing lineages circulating in Manaus. The protocols and findings of such studies should be coordinated and rapidly shared wherever such variants emerge and spread. Since rapid data sharing is the basis for the development and implementation of actionable disease control measures during public health emergencies, we are openly sharing in real-time monthly curated serosurvey data from blood donors through the Brazil–UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) Centre GitHub website and will continue to share genetic sequence data and results from Manaus through openly accessible data platforms such as GISAID and Virological.

BackgroundHepatitis C virus (HCV) infection, clearance, and reinfection are best studied in injection drug users (IDUs), who have the highest incidence of HCV and are likely to represent most infections MethodsA prospective cohort of HCV-negative young IDUs was followed up from January 2000 to September 2007, to identify acute and incident HCV and prospectively study infection outcomes ResultsAmong 1,191 young IDUs screened, 731 (61.4%) were HCV negative, and 520 (71.1%) of the 731 were enrolled into follow-up. Cumulative HCV incidence was 26.7/100 person-years of observation (95% confidence interval [CI], 21.5–31.6). Of 135 acute/incident HCV infections, 95 (70.4%) were followed; 20 (21.1%) of the 95 infections cleared. Women had a significantly higher incidence of viral clearance than did men (age-adjusted hazard ratio, 2.91 [95% CI, 1.68–5.03]) and also showed a faster rate of early HCV viremia decline (P<.01). The estimated reinfection rate was 24.6/100 person-years of observation (95% CI, 11.7–51.6). Among 7 individuals, multiple episodes of HCV reinfection and reclearance were observed ConclusionsIn this large sample of young IDUs, females show demonstrative differences in their rates of viral clearance and kinetics of early viral decline. Recurring reinfection and reclearance suggest possible protection against persistent infection. These results should inform HCV clinical care and vaccine development

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells.

The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates near complete discrimination of these two groups, with improved performance from use of antigen combinations that include both spike protein and nucleoprotein. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes. COVID-19 diagnosis is commonly performed by PCR testing, however, serologic methods are more accurate and versatile for monitoring disease burden and epidemiology. Here the authors report a protein microarray with antigens from SARS-CoV-2, SARS-CoV, MERS-CoV as well as common human respiratory viruses.

The effectiveness of anti-parasite treatment with benznidazole in the chronic Chagas disease (ChD) remains uncertain. We evaluated, using data from the NIH-sponsored SaMi-Trop prospective cohort study, if previous treatment with benznidazole is associated with lower mortality, less advanced cardiac disease and lower parasitemia in patients with chronic ChD. The study enrolled 1,959 ChD patients and abnormal electrocardiogram (ECG) from in 21 remote towns in Brazil. A total of 1,813 patients were evaluated at baseline and after two years of follow-up. Those who received at least one course of benznidazole were classified as treated group (TrG = 493) and those who were never treated as control group (CG = 1,320). The primary outcome was death after two-year follow-up; the secondary outcomes were presence at the baseline of major ChD-associated ECG abnormalities, NT-ProBNP levels suggestive of heart failure, and PCR positivity. Mortality after two years was 6.3%; it was lower in the TrG (2.8%) than the CG (7.6%); adjusted OR: 0.37 (95%CI: 0.21;0.63). The ECG abnormalities typical for ChD and high age-adjusted NT-ProBNP levels suggestive of heart failure were lower in the TrG than the CG, OR: 0.35 [CI: 0.23;0.53]. The TrG had significantly lower rates of PCR positivity, OR: 0.35 [CI: 0.27;0.45]. Patients previously treated with benznidazole had significantly reduced parasitemia, a lower prevalence of markers of severe cardiomyopathy, and lower mortality after two years of follow-up. If used in the early phases, benznidazole treatment may improve clinical and parasitological outcomes in patients with chronic ChD. ClinicalTrials.gov, Trial registration: NCT02646943.

Acute human immunodeficiency virus (HIV) infection (AHI) can be defined as the time from HIV acquisition until seroconversion. Incident HIV infection is less well defined but comprises the time from the acquisition of HIV (acute infection) through seroconversion (early or primary HIV infection) and the following months until infection has been well established, as characterized by a stable HIV viral load (viral load set point) and evolution of antibodies with increased concentration and affinity for HIV antigens. During AHI, a viral latent pool reservoir develops, the immune system suffers irreparable damage, and the infected (often unsuspecting) host may be most contagious. It has proved very difficult to find individuals with AHI either in longitudinal cohorts of subjects at high risk for acquiring the virus or through cross-sectional screening, and the opportunity for diagnosis is generally missed during this phase. We review the technical strategies for identifying individuals with acute or incident HIV infection. We conclude that further technical advances are essential to allow more widespread detection of patients with AHI and to affect HIV treatment outcomes and transmission prevention.

This work aims at reviewing the most impactful results obtained on the development of Cu-based photocathodes. The need of a sustainable exploitation of renewable energy sources and the parallel request of reducing pollutant emissions in airborne streams and in waters call for new technologies based on the use of efficient, abundant, low-toxicity and low-cost materials. Photoelectrochemical devices that adopts abundant element-based photoelectrodes might respond to these requests being an enabling technology for the direct use of sunlight to the production of energy fuels form water electrolysis (H2) and CO2 reduction (to alcohols, light hydrocarbons), as well as for the degradation of pollutants. This review analyses the physical chemical properties of Cu2O (and CuO) and the possible strategies to tune them (doping, lattice strain). Combining Cu with other elements in multinary oxides or in composite photoelectrodes is also discussed in detail. Finally, a short overview on the possible applications of these materials is presented.

Most longitudinal studies of COVID-19 incidence have used unlinked samples. The city of Manaus, Brazil, has a blood donation program which allows sample linkage, and was struck by two large COVID-19 epidemic waves between mid-2020 and early 2021. We estimated the changing force of infection, i.e. incidence in susceptible individuals. Seroconversion was inferred by a mixture model for serial values from the Abbott Architect SARS-CoV-2 nucleocapsid (N) IgG assay. We estimated the number of suspected COVID-19 hospitalizations arising from each infection over calendar time. Whole blood donations between April 2020 and March 2021 were included from 6734 people, 2747 with two or more donations. The inferred criterion for seroconversion, and thus an incident infection, was a 6.07 fold increase in N IgG reactivity. The overall force of infection was 1.19 per person year (95% confidence interval 1.14-1.24) during the two main waves. The estimated number of suspected hospitalizations per infection, was approximately 4.1 times higher in the second wave than in the first. Serial values from this assay can be used to infer seroconversion over time, and in Manaus show a higher number of suspected COVID-19 hospitalizations per infection in the second wave relative to the first.

IL28B and hepatitis C Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, leading in many cases to chronic liver disease. Here the authors show that an SNP recently identified to associate with response to HCV drug treatment also associates with viral clearance. This study identifies the strongest and most significant genetic effect associated with natural clearance of HCV, implicating a primary role for IL28B in this process. There are approximately 170 million people infected with hepatitis C virus (HCV) worldwide. About 30% of individuals with persistent HCV infection develop chronic liver disease, with various epidemiological, viral and host factors having been implicated in the differences in HCV clearance or persistence. Here, a single nucleotide polymorphism recently shown to be strongly associated with a difference in response to HCV drug treatment is also shown to be associated with viral clearance. Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide 1 . Most (70–80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma 2 . Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance 3 , 4 . Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-λ3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment 5 . To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus ( n = 388) or had persistent infection ( n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.