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Public health systems reported low mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in East Asia, in low-income countries, and for children during the first year of the SARS-CoV-2 pandemic. These reports led commentators to suggest that cross-reactive immunity from prior exposure to other pathogens reduced fatality risk. Resolution of initial infection waves also contributed to speculation that herd immunity prevented further waves prior to vaccination. Serology instead implied that immunity was too limited to achieve herd immunity and that there was little impact from cross-reactive protection. Paediatric deaths exceeded those from influenza, with higher age-specific fatality risk in lower-income nations and similar fatality risk in East Asia compared with demographically similar regions. Neither pre-outbreak exposure to related pathogens nor immunity induced by initial infection waves are necessarily a reliable response to future pathogen outbreaks. Preparedness for future pathogen outbreaks should instead focus on strategies such as voluntary behavioural changes, nonpharmaceutical interventions, and vaccination.
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The martial art of jiu jitsu capitalizes on the strength of a sparring partner by redirecting their momentum. Jiu jitsu persuasion similarly redirects the concerns motivating an objection in a manner that undermines the objection. This method of persuasion effectively addresses criticisms that motivate vaccine hesitancy, including moral criticisms. Critics argue that human papillomavirus vaccination causes young women to become more promiscuous. Evidence undermines this objection, but such evidence fails to persuade many objectors because of countervailing moral concerns regarding promiscuity. Healthcare professionals, therefore, need to consider supplementing evidence with moral arguments against the objection, using a framework that appeals to the core values motivating vaccine objections. A jiu jitsu model of persuasion is one such framework. By employing a jiu jitsu model healthcare professionals can facilitate collaborative, normative discussion that persuades more objectors and fulfills healthcare professionals' obligations with respect to patient care vis-à-vis vaccination.
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Princípios Morais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Comunicação Persuasiva , Vacinação , Humanos , Vacinas contra Papillomavirus/administração & dosagem , Feminino , Infecções por Papillomavirus/prevenção & controle , Vacinação/psicologia , Vacinação/ética , Hesitação Vacinal/psicologia , Papillomavirus HumanoRESUMO
BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Sensibilidade e Especificidade , Teste para COVID-19 , Testes Sorológicos/métodos , Anticorpos AntiviraisRESUMO
INTRODUCTION: The infection fatality rate (IFR) of COVID-19 has been carefully measured and analysed in high-income countries, whereas there has been no systematic analysis of age-specific seroprevalence or IFR for developing countries. METHODS: We systematically reviewed the literature to identify all COVID-19 serology studies in developing countries that were conducted using representative samples collected by February 2021. For each of the antibody assays used in these serology studies, we identified data on assay characteristics, including the extent of seroreversion over time. We analysed the serology data using a Bayesian model that incorporates conventional sampling uncertainty as well as uncertainties about assay sensitivity and specificity. We then calculated IFRs using individual case reports or aggregated public health updates, including age-specific estimates whenever feasible. RESULTS: In most locations in developing countries, seroprevalence among older adults was similar to that of younger age cohorts, underscoring the limited capacity that these nations have to protect older age groups.Age-specific IFRs were roughly 2 times higher than in high-income countries. The median value of the population IFR was about 0.5%, similar to that of high-income countries, because disparities in healthcare access were roughly offset by differences in population age structure. CONCLUSION: The burden of COVID-19 is far higher in developing countries than in high-income countries, reflecting a combination of elevated transmission to middle-aged and older adults as well as limited access to adequate healthcare. These results underscore the critical need to ensure medical equity to populations in developing countries through provision of vaccine doses and effective medications.
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COVID-19 , Países em Desenvolvimento , Idoso , Teorema de Bayes , COVID-19/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Política Pública , Estudos SoroepidemiológicosRESUMO
Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
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COVID-19/mortalidade , Pandemias/estatística & dados numéricos , Política Pública , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/virologia , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Mortalidade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
INTRODUCTION: Uropathogenic Escherichia coli (UPEC), the causative agent of over 85% of urinary tract infections (UTIs), elaborate a number of siderophores to chelate iron from the host. On the other hand, the host immune imperative is to limit the availability of iron to the bacteria. Little is known regarding the mechanisms underlying this host-iron-UPEC interaction. Our objective was to determine whether macrophages, in response to UPEC infection, retain extracellular siderophore-bound and free iron, thus limiting the ability of UPEC to access iron. METHODS: Quantitative PCR, immunoblotting analysis, and gene expression analysis of wild type and IL-6-deficient macrophages was performed. RESULTS: We found that (1) macrophages upon UPEC infection increased expression of lipocalin 2, a siderophore-binding molecule, of Dmt1, a molecule that facilitates macrophage uptake of free iron, and of the intracellular iron cargo molecule ferritin, and decreased expression of the iron exporter ferroportin; (2) bladder macrophages regulate expression of genes involved in iron retention upon UPEC infection; (3) IL-6, a cytokine known to play an important role in regulating host iron homeostasis as well as host defense to UPEC, regulates this process, in part by promoting production of lipocalin 2; and finally, (4) inhibition of IL-6 signaling genetically and by neutralizing antibodies against the IL-6 receptor, promoted intra-macrophagic UPEC growth in the presence of excess iron. CONCLUSIONS: Together, our study suggests that macrophages retain siderophore-bound and free iron in response to UPEC and IL-6 signaling is necessary for macrophages to limit the growth of UPEC in the presence of excess iron. IL-6 signaling and iron regulation is one mechanism by which macrophages may mediate UPEC clearance.
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Infecções por Escherichia coli/imunologia , Interleucina-6/fisiologia , Ferro/fisiologia , Macrófagos/imunologia , Escherichia coli Uropatogênica/patogenicidade , Animais , Proteínas de Escherichia coli , Camundongos , Camundongos Endogâmicos C57BL , Sideróforos , Transdução de Sinais , Infecções UrináriasRESUMO
Xenophagy is an autophagic phenomenon that specifically involves pathogens and other non-host entities. Although the understanding of the relationship between autophagosomes and invading organisms has grown significantly in the past decade, the exact steps to confirm xenophagy has been not been thoroughly defined. Here we describe a methodical approach to confirming autophagy, its interaction with bacterial invasion, as well as the specific type of autophagic formation (i.e. autophagosome, autolysosome, phagolysosome). Further, we argue that xenophagy is not limited to pathogen interaction with autophagosome, but also non-microbial entities such as iron.
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Autofagia/genética , Infecções/genética , Biologia Molecular/métodos , Brucella/genética , Brucella/patogenicidade , Interações Hospedeiro-Patógeno/genética , Humanos , Infecções/microbiologia , Lisossomos/metabolismo , Fagossomos/genética , Fagossomos/microbiologia , Fagossomos/patologiaRESUMO
Antigen-immunoglobulin fusion protein expressing B cells have been shown as excellent tolerogenic antigen-presenting cells in multiple disease models. Using efficient protein transduction by fusion with a HIV TAT protein transduction domain, we herein tested the TAT-fusion protein transduced B cells for their effects in antigen-specific tolerance induction in two animal models, experimental autoimmune encephalomyelitis (EAE) and type 1 diabetes. We demonstrated that transfer of TAT-MOG35-55 (myelin oligodendrocyte glycoprotein)-Ig 'transduced B cells' 10 days after EAE induction significantly protected mice from disease. Similarly, the onset of disease was delayed when NOD mice received insulin specific TAT-B9-23-B cells. Surprisingly, no protection against EAE was observed in a prophylactic protocol when transduced B cells were given before disease induction. Moreover, TAT-ovalbumin transduced cells were tolerogenic in primed but not naïve mice. Our results suggest that TAT-fusion protein transduced B cells were tolerogenic in antigen primed recipients, a condition clinically relevant to autoimmune diseases.