Uninfected Individuals Research Articles

American COVID: An Econometric Analysis of Variants

BACKGROUND: Immunity to a disease arises from previous infection as well as vaccinations against it. However, it is important to know which cause has the most prophylactic benefit. Medical research so far has been unable to provide a definitive answer to this question. METHODS: This paper uses time series econometric techniques to analyze American COVID 19 data from February 2020 to the end of October 2022. Distributed lag models are employed to uncover the unobservable effects that occur when uninfected individuals come in contact with other individuals whose COVID status is unknown. The purpose of the study is to compare the immunological benefits of vaccinations with those that arise from a previous infection. RESULTS: The main results obtained here is that this relation depends on the variant being considered: earlier variants produced similar benefits whereas the benefits from being previously infected by the Delta and Omicron varieties provided considerably less protection against further infection. CONCLUSIONS: The benefits from infection by earlier variants are small for the current variant. This casts doubt on the idea that herd immunity might be possible. The best form of protection is vaccination.

Cognition, function, and mood post-COVID-19: Comparative analysis using the health and retirement study.

Millions of Americans endure post-COVID conditions (PCC), yet research often lacks pre-illness measurements, relying primarily on follow-up assessments for analysis. The study aims to examine the prevalence of PCC, including cognitive impairment, functional limitation, and depressive symptoms, along with relevant risk factors, while controlling for individuals' pre-illness status measured in 2018. A cross-sectional retrospective study utilized the 2018 and 2020 Health and Retirement Study surveys. Sample included individuals with COVID-19 (n = 409; average age 64) and individuals without COVID-19 (n = 8689; average age 59). COVID-19 positive: Individuals with positive tests, physician diagnoses, emergency room visits, or hospitalizations for COVID-19 between 2019-2020. Cognition was assessed using immediate and delayed word-recall tests, serial seven subtractions, and backward counting. Functional status was measured using limitations in activities of daily living (ADLs) and instrumental ADLs. Depressive symptoms were measured using the modified Center for Epidemiology Studies Depression scale. Participants' perception of experiencing PCC was collected. Logistic regression and propensity score matching were employed for these analyses. Among 409 COVID-19-positive respondents (14% hospitalized), 24% exhibited new impairments after COVID-19 infection. Noteworthy increases in functional limitation (OR [95% CI]: 2.18 [0.95, 0.97], p < 0.001) and a marginal rise in cognitive impairment (1.79 [0.99, 3.32], p = 0.053) following COVID-19 infection were observed in comparison to their pre-COVID-19 baseline. Compared to 8689 non-COVID-19 cases, the 409 COVID-19 positives showed increased functional decline (1.78 [1.26, 2.51], p = 0.001) and depressive symptoms (1.41 [1.04, 1.91], p = 0.03). Factors associated with PCC included pre-existing impairments, lower education, female gender, prior hospitalization, higher comorbidity, lower wealth, and mild COVID-19. A notable number of respondents, especially older individuals with fewer pre-existing health conditions, experienced PCC without awareness. Compared to an individual's pre-illness baseline and uninfected individuals, being positive for COVID-19 raised the risk of functional limitation, depressive symptoms, and cognitive impairment. Additionally, addressing PCC through both subjective and objective approaches is essential to alleviate individual and societal burdens.

Eight-fold increased COVID-19 mortality in autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations: an observational study

BackgroundMUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1.MethodsTo determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths.ResultsSurveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60–3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22–69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9–29.5), kidney transplant 5.5 (1.6–9.1), body mass index (kg/m2) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1).ConclusionsIndividuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

A systematic review and meta-analysis of blood level of MCP-1/CCL-2 in severe and uncomplicated malaria

Monocyte chemoattractant protein-1 (MCP-1) or C-C Motif Chemokine Ligand 2 (CCL-2) is a key chemokine implicated in the inflammatory response to malaria. The objective of the study was to synthesize the evidence on variations in MCP-1/CCL-2 levels in relation to Plasmodium spp. infections and the severity of malaria. The protocol for this systematic review and meta-analysis was registered at PROSPERO (CRD42024565867). To identify relevant studies, a comprehensive search strategy was conducted using major databases, including PubMed, Scopus, Embase, Medline, Journals@Ovid, and Nursing & Allied Health Premium. The Joanna Briggs Institute (JBI) critical appraisal checklists were used to determine the risk of bias in selected studies. The pooled standardized mean difference (SMD, Hedge’s g) and their 95% confidence interval (CI) were estimated using the random-effects model. Thirty-three studies, with a total of 6,804 participants enrolled, were included in the systematic review. Most studies (60.6%) were published between 2010 and 2019; the majority (57.6%) were conducted in Africa. The predominant Plasmodium species studied was P. falciparum (66.7%). The meta-analysis revealed no significant difference in MCP-1/CCL-2 levels between Plasmodium-infected and uninfected individuals (P: 0.16, SMD: 0.99, 95% CI: -0.39–2.37, I2: 97.2%, number of participants: 2140). Subgroup analysis found an increase in MCP-1/CCL-2 levels in children with Plasmodium infections, with no heterogeneity observed (I2: 0%). Subgroup analysis found no difference in MCP-1/CCL-2 levels between P. falciparum-infected participants and uninfected participants, as well as between P. falciparum or non-P. falciparum-infected participants and uninfected participants. The meta-analysis revealed significantly higher MCP-1/CCL-2 levels in participants with severe Plasmodium infections compared to those with non-severe malaria (P: 0.04, SMD: 1.51, 95% CI: 0.06–2.95, I2: 98.5%, number of participants: 1371). The systematic review and meta-analysis suggest no statistically significant difference in MCP-1/CCL-2 levels in participants with Plasmodium infections overall. However, there was a significant increase in MCP-1/CCL-2 levels in patients with severe malaria. These findings suggest that MCP-1/CCL-2 may have potential as a prognostic biomarker for severe malaria. Future research should focus on large-scale, well-designed studies to validate the role of MCP-1/CCL-2 in malaria and further explore its prognostic potential.

Upregulation of interferon gamma gene expression among asymptomatic malaria adults in Bayelsa State, Nigeria

Despite concerted efforts, malaria remains a global public health problem. Treatment for asymptomatic malaria will reduce the health care burden of malaria. However evidence-based data for the presence of systemic pathology in asymptomatic malaria, which might inform treatment remains limited. The present study investigated the current prevalence of asymptomatic malaria in Bayelsa State, Nigeria and differences in interferon gamma (IFNγ) mRNA expression between asymptomatic malaria individuals (AMIs) and uninfected individuals (UIs), in relation to ABO blood groups and hemoglobin genotype (Hb) variants. A cross-sectional design was employed to randomly select 146 non-febrile participants from Sagbama LGA, Bayelsa State. Plasmodium falciparum infection was determined using high-resolution melting analysis and participants were grouped into UIs and AMIs. Hb, blood groups, and IFNγ mRNA expression were determined using electrophoresis, agglutination, and real-time PCR method respectively. Logistic regression and t-test were used to determine significant differences between groups at p < 0.05. The current prevalence of asymptomatic malaria in Bayelsa State was found to be 89.73 %. Age and sex were associated with asymptomatic malaria (p < 0.05). Plasmodium falciparum DNA melt curves for AMIs aligned at 83.89 ± 0.34 °C, while the amplification cycle thresholds were below 30 cycles. Compared with UIs, the gene expression of IFNγ mRNA was significantly (p < 0.001) higher among AMIs. Also, among AMIs those with A, B, and AB blood groups expressed significantly higher levels of IFNγ mRNA compared with blood groups O AMIs. Furthermore, AMIs with HbAA expressed significantly higher levels of IFNγ mRNA compared with HbAS AMIs. The novelty of the present study is the demonstration of the existence of systemic pathology in asymptomatic malaria and the demonstration that the intensity of systemic pathology is dependent on blood types and haemoglobin genotype variants. Findings of the present study have implications for policy creation towards asymptomatic malaria treatment.

Understanding Fatigue, Insomnia, and COVID-19 PTSS Among Mainland Chinese During Initial Post-Zero-COVID Infection Wave: A Multi-Group Analysis.

In early 2023, China experienced its first widespread COVID-19 outbreak after a policy shift. This study examines the relationship between fatigue and COVID-19-related post-traumatic stress symptoms (PTSS) in infected and uninfected individuals, exploring the potential mediating role of insomnia symptoms. An online survey of 5953 Chinese participants was conducted from 10 to 16 January 2023. Participants reported their COVID-19 infection status, fatigue, insomnia symptoms, and PTSS. Multi-group structural equation modeling (SEM) was used to test whether the mediation paths differed between infected and uninfected groups. The prevalence of fatigue, insomnia symptoms, and COVID-19 PTSS were 30.0%, 36.4%, and 5.8%. The SEM based on the bootstrapping showed that after controlling for demographics, chronic fatigue positively associated with COVID-19 PTSS in a significant way, with insomnia symptoms playing a mediating role. The multi-group analyses further revealed a partial mediation effect of insomnia symptoms on the relationship between fatigue and COVID-19 PTSS in the uninfected group (UG). However, for the infected group (IG), insomnia symptoms fully mediated the relationship between fatigue and COVID-19 PTSS. Infected individuals were more subject to the aforementioned mechanism than uninfected individuals. Addressing chronic fatigue, insomnia, and developing targeted interventions are crucial for supporting mental health across different infection statuses.

Metabolic reprogramming tips vaccinia virus infection outcomes by stabilizing interferon-γ induced IRF1.

Interferon (IFN) induced activities are critical, early determinants of immune responses and infection outcomes. A key facet of IFN responses is the upregulation of hundreds of mRNAs termed interferon-stimulated genes (ISGs) that activate intrinsic and cell-mediated defenses. While primary interferon signaling is well-delineated, other layers of regulation are less explored but implied by aberrant ISG expression signatures in many diseases in the absence of infection. Consistently, our examination of tonic ISG levels across uninfected human tissues and individuals revealed three ISG subclasses. As tissue identity and many comorbidities with increased virus susceptibility are characterized by differences in metabolism, we characterized ISG responses in cells grown in media known to favor either aerobic glycolysis (glucose) or oxidative phosphorylation (galactose supplementation). While these conditions over time had a varying impact on the expression of ISG RNAs, the differences were typically greater between treatments than between glucose/galactose. Interestingly, extended interferon-priming led to divergent expression of two ISG proteins: upregulation of IRF1 in IFN-γ/glucose and increased IFITM3 in galactose by IFN-α and IFN-γ. In agreement with a hardwired response, glucose/galactose regulation of interferon-γ induced IRF1 is conserved in unrelated mouse and cat cell types. In galactose conditions, proteasome inhibition restored interferon-γ induced IRF1 levels to that of glucose/interferon-γ. Glucose/interferon-γ decreased replication of the model poxvirus vaccinia at low MOI and high MOIs. Vaccinia replication was restored by IRF1 KO. In contrast, but consistent with differential regulation of IRF1 protein by glucose/galactose, WT and IRF1 KO cells in galactose media supported similar levels of vaccinia replication regardless of IFN-γ priming. Also associated with glucose/galactose is a seemingly second block at a very late stage in viral replication which results in reductions in herpes- and poxvirus titers but not viral protein expression. Collectively, these data illustrate a novel layer of regulation for the key ISG protein, IRF1, mediated by glucose/galactose and imply unappreciated subprograms embedded in the interferon response. In principle, such cellular circuitry could rapidly adapt immune responses by sensing changing metabolite levels consumed during viral replication and cell proliferation.

Post-infection symptoms up to 24 months after COVID-19: a matched cohort study in Berlin, Germany

Abstract Background Long-term health consequences after mild COVID-19 are not well described. Our aim was to estimate their prevalence and describe the time course of signs and symptoms for a period of up to 24 months after confirmed SARS-CoV-2 infection. Methods We conducted a cohort study matched for age, sex, and test week among individuals who had attended the public COVID-19 test center at Charité - Universitätsmedizin Berlin, Germany. In early 2022, 576 former COVID-19 patients (&amp;gt;95% non-hospitalised) and 302 uninfected individuals responded to a questionnaire on retrospective monthly symptoms since the test date up to 24 months after. Results Symptoms compatible with long COVID were present in 42.9% (247/576) of former COVID-19 patients, compared with 21.2% (64/302) in the uninfected group. In former patients, unadjusted odds ratios (OR) were highest for disturbed taste/smell (OR 9.1 [95% CI: 4.0 - 21.1]), memory difficulties (OR 5.1 [95% CI: 2.9 - 8.9]) and shortness of breath at rest (OR 4.5 [95% CI: 1.9 - 10.6]). Whilst in most former COVID-19 patients, symptoms occurred in one coherent period and resolved after a median of 6.5 months, taste/smell disturbance and neurological/cognitive symptoms showed longer times until recovery and 28.7% (31/108) still reported long COVID-compatible symptoms 18 months after initial COVID-19. Factors associated with long COVID-compatible symptoms included hospitalisation (OR 4.2 [95% CI: 1.7 - 10.8], symptomatic COVID-19 infection (OR 3.4 [95% CI: 1.9 - 6.3], low household income (OR 1.8 [95% CI: 1.2 - 2.7], and female sex (OR 1.7 [95% CI: 1.2 - 2.4]). Conclusions Post-infection symptoms in mild COVID-19 mostly persist for about half a year, but sometimes longer. Among uninfected individuals who never experienced COVID-19, 21.2% also reported long COVID-compatible symptoms. The current long COVID definition might require revision to prevent misclassification and over-reporting, and to improve diagnosis and prevalence estimates. Key messages • A more precise definition of long COVID is needed to prevent over-reporting of symptoms compatible with long COVID, and to improve diagnosis, prevalence estimates and research harmonisation. • Post-infection symptoms after mild COVID-19 are common, mostly persist for about half a year but sometimes longer for more than 20 months.

Non-classical monocyte levels correlate negatively with HIV-associated cerebral small vessel disease and cognitive performance.

Despite antiretroviral treatment (cART), aging people living with HIV (PWH) are more susceptible to neurocognitive impairment (NCI) probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, transmigration of inflammatory CD16+ monocytes through the altered blood brain barrier (BBB) may exacerbate cerebral small vessel disease (CSVD), a known cause of vascular cognitive impairment. PWH on cART (n=108) and age, sex, and Reynold's cardiovascular risk score-matched uninfected individuals (PWoH, n=111) were enrolled. This is a longitudinal observational study but only cross-sectional data from entry visit are reported. Neuropsychological testing and brain magnetic resonance imaging (MRI) were performed. CSVD was diagnosed by Fazekas score ≥1. Flow cytometric analyses of fresh whole blood were conducted to evaluate circulating levels of monocyte subsets (classical, intermediate, and non-classical) and markers of monocyte activation (CCR2, CD40, PSGL-1, TNFR2 and tissue factor). ELISAs were used to measure sCD14, ICAM, and Osteoprotegerin. Two-way analysis of variance (ANOVA), and linear regression models were performed to study the effects of HIV status, CSVD status, and their interaction to outcome variables such as cognitive score. Two-sample t-tests and correlation analyses were performed between and within PWoH with CSVD and PWH with CSVD participants. PWH with CSVD (n=81) had significantly lower total cognitive scores, higher levels of NCMs and soluble CD14 and intracellular adhesion molecule 1 (ICAM-1) as compared to PWoH with CSVD group (n=68). sCD14 and ICAM1 were positively correlated with each other indicating that monocyte and endothelial activation are associated with each other. Cognition was negatively correlated with NCMs, especially in the PWH with CSVD group. Among other blood biomarkers measured, osteoprotegerin levels showed mild negative correlation with cognitive performance in individuals with CSVD irrespective of HIV status. Elevated levels of NCMs may contribute to neuroinflammation, CSVD and subsequent cognitive impairment. This finding is of particular relevance in aging PWH as both HIV and aging are associated with increased levels of NCMs. NCMs may serve as a potential biomarker to address these comorbidities. Further longitudinal studies are needed to evaluate whether changes in NCM levels are associated with changes in CSVD burden and cognitive impairment.

Inter-laboratory harmonization of microsphere immunoassays for SARS-CoV-2 antibody detection in dried blood spots and oral fluids.

Dried blood spots (DBS) and oral fluids (OF) are easily attainable biospecimen types that have enabled population scale antibody monitoring for SARS-CoV-2 exposure and vaccination. However, the degree to which the two different biospecimen types can be used interchangeably remains unclear. To begin to address this question, we generated contrived DBS (cDBS) and OF (cOF) from serum panels from SARS-CoV-2 infected, vaccinated, and uninfected individuals. The contrived samples were evaluated using SARS-CoV-2 multiplexed microsphere immunoassays (MIAs) at two different institutions. Intra-laboratory tests revealed near perfect agreement between cDBS and cOF for N and S antigens, as evidenced by κ = 0.97-1 and 98%-100% agreement. Inter-laboratory comparisons were equally robust for both N (κ = 0.94-0.96; 97.5%-98 % agreement) and S (κ = 0.98 -1.0; 99.0%-100%). Furthermore, assays were transferred between labs, including methods and reagents, and a subset of cDBS and cOF samples (n = 52) were tested. Qualitative concordance remained high (κ = 0.94-1.0; 97.5%-100% agreement), confirming that integrity of the assays is retained upon transfer. In summary, our results provide evidence that DBS and OF can be used interchangeably across laboratories and institutions for the qualitative assessment of SARS-CoV-2 antibody determinations.

Ex-vivo evaluation of Plasmodium falciparum-induced cytokine expression in chronic hepatitis B virus-infected and uninfected individuals

Background Chronic Hepatitis B virus (CHB) infection remains a significant public health problem. Exhaustion of T cells usually contribute to the progression of HBV infection to the chronic state, which can impact the induction of immune responses to other pathogens like Plasmodium falciparum. This, in turn, may affect the effectiveness of malaria vaccines when deployed. This case-control longitudinal study sought to determine how early this T cell exhaustion state establishes, since most of the available data relates to CHB cases that have persisted for much longer times. Methods This longitudinal case-control study compared the expression of 13 cytokines between cases and controls at four time points over one year. These cytokines were induced using whole blood ex-vivo stimulation with three Plasmodium falciparum (3D7 strain) antigens. Results Hepatitis B virus-negative and CHB individuals had comparable levels of TNF-α, IL-1β, IL-6 and IL-10. Interleukin 6 which is important for the elimination of HBV was produced in very high amounts by the two groups. There was no significant difference between the groups in their ability to produce pro-inflammatory cytokines in response to malaria antigens. Conclusion Cytokine responses to the vaccine candidates from both groups were similar, indicating no impairment to the effective immune responses to malaria vaccines and probably parasites in this category of early CHB infected individuals.

Metabolic reprogramming tips vaccinia virus infection outcomes by stabilizing interferon-γ induced IRF1.

Interferon (IFN) induced activities are critical, early determinants of immune responses and infection outcomes. A key facet of IFN responses is the upregulation of hundreds of mRNAs termed interferon-stimulated genes (ISGs) that activate intrinsic and cell-mediated defenses. While primary interferon signaling is well-delineated, other layers of regulation are less explored but implied by aberrant ISG expression signatures in many diseases in the absence of infection. Consistently, our examination of tonic ISG levels across uninfected human tissues and individuals revealed three ISG subclasses. As tissue identity and many comorbidities with increased virus susceptibility are characterized by differences in metabolism, we characterized ISG responses in cells grown in media known to favor either aerobic glycolysis (glucose) or oxidative phosphorylation (galactose supplementation). While these conditions over time had a varying impact on the expression of ISG RNAs, the differences were typically greater between treatments than between glucose/galactose. Interestingly, extended interferon-priming led to divergent expression of two ISG proteins: upregulation of IRF1 in IFN-γ/glucose and increased IFITM3 in galactose by IFN-α and IFN-γ. In agreement with a hardwired response, glucose/galactose regulation of interferon-γ induced IRF1 is conserved in unrelated mouse and cat cell types. In galactose conditions, proteasome inhibition restored interferon-γ induced IRF1 levels to that of glucose/interferon-γ. Glucose/interferon-γ decreased replication of the model poxvirus vaccinia at low MOI and high MOIs. Vaccinia replication was restored by IRF1 KO. In contrast, but consistent with differential regulation of IRF1 protein by glucose/galactose, WT and IRF1 KO cells in galactose media supported similar levels of vaccinia replication regardless of IFN-γ priming. Also associated with glucose/galactose is a seemingly second block at a very late stage in viral replication which results in reductions in herpes- and poxvirus titers but not viral protein expression. Collectively, these data illustrate a novel layer of regulation for the key ISG protein, IRF1, mediated by glucose/galactose and imply unappreciated subprograms embedded in the interferon response. In principle, such cellular circuitry could rapidly adapt immune responses by sensing changing metabolite levels consumed during viral replication and cell proliferation.

Dynamics and backward bifurcations of SEI tuberculosis models in homogeneous and heterogeneous populations

The main difference between tuberculosis (TB) and other infectious diseases is that the transmission of the bacterium should be considered not only as the development of a primary infection, but also as exogenous reinfection or endogenous reactivation. Moreover, individuals in the population may have heterogeneous contact rates, which can be described by complex networks. To this end, we present two differential equation-based TB models in homogeneous and heterogeneous populations. The first model assumes that the number of contacts per unit time is constant for the whole population, whereas the second model considers the heterogeneous number of contacts per unit time for each individual. We derive the basic reproduction number of each model using the next-generation matrix method, and analyze the dynamical properties of each model in detail. We find that the two models undergo backward bifurcations and have the same threshold condition for backward bifurcation. From this threshold condition, we see that the reduced rate of exogenous reinfection of individuals plays an important role in causing the backward bifurcation. Interestingly, the second model allows the threshold condition for backward bifurcation to be independent of network parameters. Thus, unlike other infectious disease models on complex networks, in controlling the spread of tuberculosis among populations with different numbers of contacts, we only need to focus on disease parameters during treatment. Finally, numerical simulations more intuitively demonstrate the impact of parameter changes on the prevalence of tuberculosis and reveal the model's richer and more interesting dynamical properties, such as bistability. Sensitivity analysis indicates that the basic reproduction number is highly correlated with both the relapse rate of latent individuals progressing to active infection and the probability of healthy individuals becoming infected after contact with the pathogen. Therefore, enhancing the detection and treatment of latent cases and reducing contact between infected and uninfected individuals are the most crucial public health interventions.

The Effect of Malaria on Responses to Unrelated Vaccines in Animals and Humans: A Systematic Review and Meta-Analysis.

Vaccine efficacy varies globally, often showing reduced immune responses in low- and middle-income countries, possibly due to the immunomodulatory effects of parasitic infections like malaria. This systematic review evaluates the impact of malaria on immune responses to unrelated vaccines in humans and animals. We systematically searched five databases-MEDLINE, Web of Science, Global Health, Scopus and Embase-up to 5th December 2023. Eligible studies compared immune responses to WHO-approved vaccines between malaria-infected and uninfected groups, or between antimalarial-treated and untreated groups. Meta-analysis was performed using random-effects models with standardised mean differences (SMDs) as summary statistics. The study is registered with PROSPERO (CRD42022298053). Twenty-four articles (17human, 7 animal) met the inclusion criteria, with 13 human articles contributing data for the meta-analysis. Significant heterogeneity was observed. Vaccine responses were higher in malaria uninfected individuals (SMD 0.34, 95% CI 0.07 to 0.60, I2 = 87.15%) with weaker differences between antimalarial-treated and untreated groups (SMD 0.07, 95% CI -0.01 to 0.16, I2 = 85.01%). The overall SMD for malaria uninfected/treated vs. infected/untreated was 0.15, 95% CI 0.05-0.26, I2 = 90.91. Narrative analysis suggested malaria's adverse impact on vaccine responses in animals. Malaria infection may impair vaccines responses; with preventive treatment of malaria partially reversing these effects, highlighting the need for targeted public health interventions.

Monitoring humoral responses against three SARS-CoV-2 vaccines in a university population from Chihuahua, Mexico.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has spread worldwide since 2019. Survey of the antibodies against SARS-CoV-2 is one of the most important measures of immunity since it can give an idea on the effectiveness of administered vaccines and the serologic status of individuals. We determined the concentrations of blood IgM and IgG against three SARS-CoV-2 proteins in vaccinated teachers and students among a university population from Chihuahua, Mexico. Humoral response surveillance against the 3C-like proteinase (3CLpro), nuclear protein (NP), and receptor binding domain (RBD) of SARS-CoV-2 was carried out. A total of 239 samples were analyzed: 67 from teachers who were vaccinated with CanSino and 172 from students (27.9% were vaccinated with AstraZeneca, 32.6% with Sinovac, 24.4% with Pfizer-BioNTech, 15.1% with other vaccines). Significant differences in the levels of IgG were observed between serum from individuals prior to vaccination (preimmunization serum) and from those that were vaccinated with CanSino. However, samples from asymptomatic individuals did not show differences between the preimmunization and post-immunization serum. The three vaccinated groups (AstraZeneca, Pfizer and Sinovac) did not show significant differences in anti-RBD IgG antibody titers compared to the positive control group, except for a Pfizer non-COVID-19 subgroup where the level of antibodies in the Pfizer group was 1.7 times higher. Neither vaccine group showed significant differences between those individuals who previously had COVID-19 and uninfected individuals. These results provide a picture of the situation at the time when in-person classes resumed.

High chytrid prevalence and infection intensities in tadpoles of Mixophyes fleayi

Context The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has caused catastrophic biodiversity loss globally, but species and life stages within species respond differently to the pathogen. Although tadpoles are often reported to be less vulnerable to disease, they can constitute important infection reservoirs in ecosystems. Aims We aimed to describe Bd infection patterns of a long-lived tadpole in a species where post-metamorphic animals appear to exhibit limited mortality as a result of chytridiomycosis. We further investigated how oral dekeratinisation can be used as an indicator of infection. Methods We conducted surveys of tadpoles of Mixophyes fleayi (Fleay’s barred frog) over 2 years, at two rainforest streams on the east coast of Australia, to assess patterns in Bd infection prevalence and intensity. We developed an integrated hierarchical model propagating pathogen-detection errors and incorporating how Bd infections affect oral dekeratinisation. Key results We found that Bd infection prevalence was strongly associated with lower temperatures and a larger body size, consistent with Bd optimal thermal range and a cumulative risk of exposure for tadpoles. The individual probability of a tadpole being infected with Bd was estimated to be 0.58 [95% HPDI: 0.432, 0.713], the odds of which were approximately eight times greater than for adults at the same sites. Tadpoles infected with Bd were 113 [29, 293] times more likely to have oral dekeratinisation than were uninfected tadpoles, where uninfected individuals were estimated to have a 0.05 [95% HPDI: 0.011, 0.11] probability of having mouthpart loss. Conclusions Our results showed that M. fleayi tadpoles are more likely to be infected with Bd than are adults, suggesting that tadpoles could contribute to Bd maintenance in streams. We further showed that sites can be rapidly assessed for Bd by visually checking for oral dekeratinisation. Implications Long-lived tadpoles, in general, may contribute to Bd maintenance in ecosystems. We suggest continued exploration of Bd immunocompetence across amphibian life stages to further understand the vastly different infection patterns.

High abundance of butyrate-producing bacteria in the naso-oropharynx of SARS-CoV-2-infected persons in an African population: implications for low disease severity

BackgroundThe association of the oral microbiome with SARS-CoV-2 infections and disease progression has been documented in European, Asian, and American populations but not in Africa.MethodsWe conducted a study in Ghana to evaluate and compare the naso-oropharyngeal microbiome in SARS-CoV-2-infected and uninfected persons before (pre-vaccine) and after vaccine availability (post-vaccine) in the country. 16S rRNA V3-V4 variable region was sequenced and analysed from DNA extracted from naso-oropharyngeal swabs.ResultsConsidering only the infection status, infected and uninfected groups had no difference in their within-group diversity and was evident in the study population pre- and post-vaccine availability. The introduction of vaccines reduced the diversity of the naso-oropharyngeal microbiome particularly among SARS-CoV-2 positive persons and, vaccinated individuals (both infected and uninfected) had higher microbial diversity compared to their unvaccinated counterparts. SARS-CoV-2-positive and -negative individuals were largely compositionally similar varying by 4–7% but considering vaccination*infection statuses, the genetic distance increased to 12% (P = 0.003) and was mainly influenced by vaccination. Common among the pre- and post-vaccine samples, Atopobium and Finegoldia were abundant in infected and uninfected individuals, respectively. Bacteria belonging to major butyrate-producing phyla, Bacillota (particularly class Clostridia) and Bacteroidota showed increased abundance more strikingly in infected individuals before vaccines were available. They reduced significantly after vaccines were introduced into the country with Fusobacterium and Lachnoanaerobaculum being the only common bacteria between pre-vaccine infected persons and vaccinated individuals, suggesting that natural infection and vaccination correlate with high abundance of short-chain fatty acids.ConclusionOur results show, in an African cohort, the abundance of bacteria taxa known for their protective pathophysiological processes, especially during infection, suggesting that this population is protected against severe COVID-19. The immune-related roles of the members of Bacillota and Bacteroidota that were found associated with infection and vaccination require further studies, and how these may be linked to ethnicity, diet and age. We also recommend expansion of microbiome–disease association studies across Africa to identify possible bacterial-mediated therapeutics for emerging infections.

Haemosporidian Infection Is Associated with the Oxidative Status in a Neotropical Bird

Haemosporidians are common blood parasites in wild bird populations, yet their effects on oxidative status remain understudied. Here, we measured the levels of thiobarbituric acid-reactive substances (TBARS) as an indicator of reactive oxygen species (ROS), total antioxidant capacity (TAC) as an indicator of non-enzymatic molecular antioxidants, and TBARS/TAC ratio as an indicator of oxidative status. We also used parasite genus-specific primers and PCR techniques to detect haemosporidians in 117 adults of Rufous-collared Sparrow (Zonotrichia capensis) from four locations in south–central Chile. Mixed-effect models were employed to compare oxidative indicators between infected and uninfected birds. Infected birds showed significantly higher TBARS levels, but no significant differences in TAC, leading to a higher TBARS/TAC ratio, especially in reproductive individuals. This suggests increased oxidative damage in infected birds, irrespective of sex or body condition. A positive relationship between TBARS and TAC was observed in both groups, but the antioxidant response was weaker in infected birds, indicating differential oxidative stress responses based on infection status. Body condition did not differ significantly between infected and uninfected individuals. These results demonstrate that haemosporidian infections impose oxidative costs on birds, potentially compounding the oxidative costs associated with reproduction.

NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control.

Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells. Functional analyses indicated that ECs had limited production of functional molecules upon NK stimulation and consequently reduced natural cytotoxicity against non-HIV target cells. Importantly, ECs showed an exceptional ability to kill primary HIV-infected cells by the antibody-dependent cell cytotoxicity adaptive mechanism, which was achieved by a specific memory-like NK population expressing CD16, NKG2A, NKG2C, CD57, and CXCR3. In-depth single-cell RNA-seq unveiled a unique transcriptional signature in these NK cells linked to increased cell metabolism, migration, chemotaxis, effector functions, cytokine secretion, and antiviral response. Our findings underscore a pivotal role of NK cells in the immune control of HIV and identify specific NK cells as emerging targets for immunotherapies.

Long-Term Immunity against SARS-CoV-2 Wild-Type and Omicron XBB.1.5 in Indonesian Residents after Vaccination and Infection.

In the post-pandemic era, evaluating long-term immunity against COVID-19 has become increasingly critical, particularly in light of continuous SARS-CoV-2 mutations. This study aimed to assess the long-term humoral immune response in sera collected in Makassar. We measured anti-RBD IgG levels and neutralization capacity (NC) against both the Wild-Type (WT) Wuhan-Hu and Omicron XBB.1.5 variants across groups of COVID-19-vaccinated individuals with no booster (NB), single booster (SB), and double booster (DB). The mean durations since the last vaccination were 25.11 months, 19.24 months, and 16.9 months for the NB, SB, and DB group, respectively. Additionally, we evaluated the effect of breakthrough infection (BTI) history, with a mean duration since the last confirmed infection of 21.72 months. Our findings indicate fair long-term WT antibody (Ab) titers, with the DB group showing a significantly higher level than the other groups. Similarly, the DB group demonstrated the highest anti-Omicron XBB.1.5 Ab titer, yet it was insignificantly different from the other groups. Although the level of anti-WT Ab titers was moderate, we observed near-complete (96-97%) long-term neutralization against the WT pseudo-virus for all groups. There was a slight decrease in NC against Omicron XBB.1.5 compared to the WT among all groups, as DB group, SB group, and NB group showed 80.71 ± 3.9%, 74.29 ± 6.7%, and 67.2 ± 6.3% neutralization activity, respectively. A breakdown analysis based on infection and vaccine status showed that booster doses increase the NC against XBB.1.5, particularly in individuals without BTI. Individuals with BTI demonstrate a better NC compared to their counterpart uninfected individuals with the same number of booster doses. Our findings suggest that long-term immunity against SARS-CoV-2 persists and is effective against the mutant variant. Booster doses enhance the NC, especially among uninfected individuals.