Uninfected Subjects Research Articles

Morbidity of SARS-CoV-2 in the evolution to endemicity and in comparison with influenza

BackgroundThere are three possible SARS-CoV-2 post-pandemic scenarios: (i) ongoing severity, (ii) influenza-like severity, and (iii) a transition to an endemic disease with lesser morbidity similar to that of other human coronaviruses.MethodsTo assess a possible evolution of the pandemic under the three scenarios, we use data from the US National Covid Cohort Collaborative, CDC COVID-NET, and CDC Fluview and from the WastewaterSCAN Dashboard. We include influenza disease and treatment response as benchmark. The US National Covid Cohort Collaborative allows the quantification of viral-specific morbidity using electronic health records from 424,165 SARS-CoV-2 cases, 53,846 influenza cases, and 199,971 uninfected control subjects from 2021–2022. Evolution of hospitalization rates is estimated from the correlation between national SARS-CoV-2 and influenza hospitalization data and viral gene copies in wastewater.ResultsOur findings reveal that medically attended SARS-CoV-2 infections exhibit similar morbidity to influenza [indicative of scenario (ii)], but SARS-CoV-2 hospitalization rates are one order of magnitude lower than influenza when considering virus concentration in wastewater [indicative of scenario (iii)]. Moreover, SARS-CoV-2 displays a more favorable response to antiviral therapy.ConclusionsOur analysis confirms a rapid decline in SARS-CoV-2 morbidity as it transitions to an endemic state.

Multiplex array analysis of circulating cytokines and chemokines in COVID-19 patients during the first wave of the SARS-CoV-2 pandemic in Milan, Italy

BackgroundThe systemic inflammatory syndrome called “cytokine storm” has been described in COVID-19 pathogenesis, contributing to disease severity. The analysis of cytokine and chemokine levels in the blood of 21 SARS-CoV-2 positive patients throughout the phases of the pandemic has been studied to understand immune response dysregulation and identify potential disease biomarkers for new treatments. The present work reports the cytokine and chemokine levels in sera from a small cohort of individuals primarily infected with SARS-CoV-2 during the first wave of the COVID-19 pandemic in Milan (Italy).ResultsAmong the 27 cytokines and chemokines investigated, a significant higher expression of Interleukin-9 (IL-9), IP-10 (CXCL10), MCP-1 (CCL2) and RANTES (CCL-5) in infected patients compared to uninfected subjects was observed. When the change in cytokine/chemokine levels was monitored over time, from the hospitalization day to discharge, only IL-6 and IP-10 showed a significant decrease. Consistent with these findings, a significant negative correlation was observed between IP-10 and anti-Spike IgG antibodies in infected individuals. In contrast, IL-17 was positively correlated with the production of IgG against SARS-CoV-2.ConclusionsThe cytokine storm and the modulation of cytokine levels by SARS-CoV-2 infection are hallmarks of COVID-19. The current global immunity profile largely stems from widespread vaccination campaigns and previous infection exposures. Consequently, the immunological features and dynamic cytokine profiles of non-vaccinated and primarily-infected subjects reported here provide novel insights into the inflammatory immune landscape in the context of SARS-CoV-2 infection, and offer valuable knowledge for addressing future viral infections and the development of novel treatments.

CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth

Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, Mycobacteria tuberculosis (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ). Consistently, Mtb antigen (Ag) HMBPP stimulation induced sustainable high-level CD137 expression in fresh and activated Vγ2Vδ2 T cells from uninfected subjects, but not TB patients. CD137+Vγ2Vδ2 T-cell subtype predominantly displayed central memory phenotype and mounted better proliferative responses than CD137−Vγ2Vδ2 T-cells. In response to HMBPP, CD137+Vγ2Vδ2 T-cell subtype rapidly differentiated into greater numbers of pleiotropic effector cells producing anti-Mtb cytokines compared to CD137−Vγ2Vδ2 T subtype, with the non-canonical NF-κB pathway involved. CD137 expression in Vγ2Vδ2 T cells appeared to signal anti-Mtb effector functions leading to intracellular Mtb growth inhibition in Mɸ, and active TB disrupted such CD137-driven anti-Mtb effector functions. CD137+Vγ2Vδ2 T-cells subtype exhibited an epigenetic-driven high-level expression of GM-CSF and de novo production of GM-CSF critical for Vγ2Vδ2 T-cell controlling of Mtb growth in Mϕ. Concurrently, exosomes produced by CD137+Vγ2Vδ2 T cells potently inhibited intracellular mycobacterial growth. Furthermore, adoptive transfer of human CD137+Vγ2Vδ2 T cells to Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, our data suggest that CD137 expression/signaling drives pleiotropic γδ T-cell effector functions that inhibit intracellular Mtb growth.

Differential Epigenetic Regulation in Uninfected and Tuberculosis-Human Immunodeficiency Virus Co-Infected Patients.

This study aimed to compare the degree of epigenetic modifications between a TB-HIV co-infected cohort and uninfected subjects. Formalin-fixed paraffin-embedded (FFPE) tissues were retrieved from 45 TB-HIV co-infected and 45 control individuals. Real-time PCR was applied to compare the level of expression of genes involved in epigenetic regulation. The protein multiplex assay was used to assess the degree of protein modification. DNA sequencing was used to determine the evolutionary relationships between the infecting HIV and Mtb strains. Our results indicated a significant increase in the expression of the five candidate genes in the patients with TB-HIV relative to the control cohort. A sharp increase in the degree of histone methylation, acetylation and phosphorylation was observed in TB-HIV co-infected patients. The phylogenetic analysis classified the strains into three distinct HIV clusters and five Mtb clusters. The disparities in the expression profiles of our candidate genes between the TB-HIV cohort and non-TB-HIV group highlights the important role played by various TB and HIV strains in regulating the host gene expression landscape.

Genomic surveillance and serological profile of SARS-CoV-2 variants circulating in Macaé and nearby cities, southeastern Brazil.

A characteristic of the COVID-19 pandemic has been the sequential emergence and global dissemination of SARS-CoV-2 variants, noted for their enhanced transmission efficiency. These variants with mutations in the Spike glycoprotein (S-glycoprotein), which interacts with ACE2 receptors in human cells is critical for infection, affects the transmissibility of the virus, which is a matter of great concern for public health. This research analyses the effects these variants on a cohort of vaccinated and naturally infected individuals from the cities of Macaé-RJ, Rio das Ostras-RJ, and Campos dos Goytacazes-RJ, Brazil, from March 2021 to March 2023. This investigation encompasses the Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2, B.1.671.3), and Omicron (BQ.1, BQ.1.1 sublines, and BF.7) variants, focusing on their genomic surveillance and implications for the disease's epidemiology. The experimental analysis included a control group (vaccinated and uninfected subjects), and an infected group (post-vaccinated subjects). Samples from nasopharyngeal swabs underwent viral detection via RT-qPCR for diagnosis confirmation. RNase H-dependent RT-qPCR (rhAmp-PCR) and third-generation sequencing were used to detect SARS-CoV-2 variants. Anti-S-glycoprotein immunoglobulins were also evaluated for vaccinated infected and noninfected volunteers. Symptoms from infected individuals were compiled in order to reveal patterns of clinical signs associated with viral infection. The study included 289 participants, with infections identified by Gamma (n = 44), Delta (n = 189), and Omicron (n = 56) variants. The prevalent symptoms among the naturally infected participants were cough, fever, sore throat, headache, and runny nose. For Omicron, cognitive symptoms such as memory loss and concentration issues were reported. Interestingly, the infected vaccinated group had higher anti-S-glycoprotein IgM production (n = 28, 0.2833 ± 0.09768 OD) compared to the uninfected vaccinated group (n = 14, 0.1035 ± 0.03625 OD). Conversely, anti-S-glycoprotein IgG production was higher in the control group (n = 12, 1.770 ± 0.1393 OD) than in the infected vaccinated group (n = 26, 1.391 ± 0.1563 OD). This comprehensive study enables monitoring of predominant variants and their correlation with clinical cases, providing valuable insights for public health. Our research group continues to survey circulating variants, contributing to the global understanding of the pandemic.

Global stability and optimal vaccination control of SVIR models

<abstract> <p>Vaccination is widely acknowledged as an affordable and cost-effective approach to guard against infectious diseases. It is important to take vaccination rate, vaccine effectiveness, and vaccine-induced immune decline into account in epidemic dynamical modeling. In this paper, an epidemic dynamical model of vaccination is developed. This model provides a framework of the infectious disease transmission dynamics model through qualitative and quantitative analysis. The result shows that the system may have multiple equilibria. We used the next-generation operator approach to calculate the maximum spectral radius, that is, basic reproduction number $ {R_{vac}} $. Next, by dividing the model into infected and uninfected subjects, we can prove that the disease-free equilibrium is globally asymptotically stable when $ {R_{vac}} < 1 $, provided certain assumptions are satisfied. When $ {R_{vac}} > 1 $, there exists a unique endemic equilibrium. Using geometric methods, we calculate the second compound matrix and demonstrate the Lozinskii measure $ \bar q \leqslant 0 $, which is equivalent to the unique endemic equilibrium, which is globally asymptotically stable. Then, using center manifold theory, we justify the existence of forward bifurcation. As the vaccination rate decreases, the likelihood of forward bifurcation increases. We also theoretically show the presence of Hopf bifurcation. Then, we performed sensitivity analysis and found that increasing the vaccine effectiveness rate can curb the propagation of disease effectively. To examine the influence of vaccination on disease control, we chose the vaccination rate as the optimal vaccination control parameter, using the Pontryagin maximum principle, and we found that increasing vaccination rates reduces the number of infected individuals. Finally, we ran a numerical simulation to finalize the theoretical results.</p> </abstract>

Characterizing the acute antibody response of monkeypox and MVA-BN vaccine following an Australian outbreak.

In response to the emergence of the monkeypox virus (MPXV) in Australia in May 2022, we developed and evaluated indirect immunofluorescence assays (IFA) for MPXV and Vaccinia virus (VACV) IgG and IgM antibodies using serum samples from patients with nucleic acid amplification test (NAAT)-confirmed mpox and uninfected unvaccinated controls. Additionally, 47 healthcare workers receiving two doses of the third-generation smallpox vaccine Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) undertook serial serum collection to describe the serological response to vaccination. MPXV antibodies were detected in 16/18 individuals with NAAT-confirmedmpox (sensitivity 0.89, specificity 1.00), and VACV antibodies were detected in 28/29 individuals who received two doses of MVA-BN vaccine (sensitivity 0.97, specificity 1.00). Detectable antibody in subjects historically vaccinated with early-generation vaccines against smallpox was found in 7/7 subjects, at a median of 48 years following vaccination. MPXVNAAT-positivepatients with serum samples collected within the first 14 days after rash onset had detectable IgG and IgM in 9/12 and 5/12 of patients, respectively, with maintenance of IgG and disappearance of IgM titersafter 60 days. Whilespecificity was high when testing unvaccinated and uninfected subjects, significant cross-reactivity between MPXV and VACV antibodies was observed.

Humoral response against spike protein and fifth and sixth COVID-19 mRNA vaccine in the uninfected and infected subjects: What should be for the seventh dose?

Humoral response against spike protein and fifth and sixth COVID-19 mRNA vaccine in the uninfected and infected subjects: What should be for the seventh dose?

Protection Conferred by COVID-19 Vaccination, Prior SARS-CoV-2 Infection, or Hybrid Immunity Against Omicron-Associated Severe Outcomes Among Community-Dwelling Adults.

We assessed protection from coronavirus disease 2019 (COVID-19) vaccines and/or prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection against Omicron-associated severe outcomes during successive sublineage-predominant periods. We used a test-negative design to estimate protection by vaccines and/or prior infection against hospitalization/death among community-dwelling, polymerase chain reaction (PCR)-tested adults aged ≥50 years in Ontario, Canada, between 2 January 2022 and 30 June 2023. Multivariable logistic regression was used to estimate the relative change in the odds of hospitalization/death with each vaccine dose (2-5) and/or prior PCR-confirmed SARS-CoV-2 infection (compared with unvaccinated, uninfected subjects) up to 15 months since the last vaccination or infection. We included 18 526 cases with Omicron-associated severe outcomes and 90 778 test-negative controls. Vaccine protection was high during BA.1/BA.2 predominance but was generally <50% during periods of BA.4/BA.5 and BQ/XBB predominance without boosters. A third/fourth dose transiently increased protection during BA.4/BA.5 predominance (third-dose, 6-month: 68%, 95% confidence interval [CI] 63%-72%; fourth-dose, 6-month: 80%, 95% CI 77%-83%) but was lower and waned quickly during BQ/XBB predominance (third-dose, 6-month: 59%, 95% CI 48%-67%; 12-month: 49%, 95% CI 41%-56%; fourth-dose, 6-month: 62%, 95% CI 56%-68%, 12-months: 51%, 95% CI 41%-56%). Hybrid immunity conferred nearly 90% protection throughout BA.1/BA.2 and BA.4/BA.5 predominance but was reduced during BQ/XBB predominance (third-dose, 6-month: 60%, 95% CI 36%-75%; fourth-dose, 6-month: 63%, 95% CI 42%-76%). Protection was restored with a fifth dose (bivalent; 6-month: 91%, 95% CI 79%-96%). Prior infection alone did not confer lasting protection. Protection from COVID-19 vaccines and/or prior SARS-CoV-2 infections against severe outcomes is reduced when immune-evasive variants/subvariants emerge and may also wane over time. Our findings support a variant-adapted booster vaccination strategy with periodic review.

True prevalence of long COVID in children: a narrative review.

Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children's emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders.

'Immunization during ART and ATI for HIV-1 vaccine discovery/development'.

Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that promote and guide the full maturation of broadly neutralizing antibody responses. The HIV-1 envelope glycoprotein (Env) does not efficiently engage the germline precursors of broadly neutralizing antibodies (bnAbs). However, Env-derived proteins specifically designed to precisely do that, have been recently developed. These 'germline-targeting' Env immunogens activate naïve B cells that express the germline precursors of bnAbs but by themselves cannot guide their maturation towards their broadly neutralizing forms. This requires sequential immunizations with heterologous sets of Envs. These 'booster' Envs are currently unknown. Combining germline-targeting Env immunization approaches during ART with ATI could lead to the identification of natural Envs that are responsible for the maturation of broadly neutralizing antibody responses during infection. Such Envs could then serve as booster immunogens to guide the maturation of glBCRs that have become activated by germline-targeting immunogens in uninfected subjects.

Altered T-cell receptor β repertoire in adults with SARS CoV-2 inactivated vaccine of BBIBP-CorV

ObjectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the prolonged and widespread epidemic of coronavirus disease 2019 (COVID-19). The inactivated BBIBP-CorV vaccine has shown safety, efficacy and immunogenicity against COVID-19 in in-vitro studies and clinical trials. However, the characteristics changes of the TCRβ repertoire in patients receiving BBIBP-CorV remain unclear. MethodsTCRβ repertoire difference were analyzed between 54 uninfected subjects who received a third dose of the enhanced BBIBP-CorV vaccine and the 16 healthy donors who did not receive the vaccine and 44 COVID-19 patients with different courses of disease (asymptomatic, symptomatic and convalescent). Furthermore, antibody response, anti-inflammatory and pro-inflammatory cytokines also were examined. ResultsWe found that the third dose inactivated coronavirus vaccine induced widespread changes including the increased TCRβ repertoire diversity, a much shorter CDR3 length and high usage of V-J genes segments. Meanwhile, the vaccine-responding clones were also predicted. The results of the antibody response showed that 90.7 % of the vaccinated individuals were positive for NAb seroconversion and 88.9 % for IgG antibody about 60 days after the third dose. The concentration of IL-2 increased significantly compared to baseline inoculation. ConclusionAltered TCRβ repertoire in adults with SARS CoV-2 inactivated vaccine of BBIBP-CorV clarified the specific immunity induced by inactivated vaccines. Our research provides insights into the adaptive immune response induced by the new inactivated SARS-CoV-2 vaccine and strengthens the development of immunotherapy.

Prevalence and characteristics of HTLV-associated uveitis in patients from Bahia, an endemic area for HTLV − 1 in Brazil

BackgroundHTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely.ObjectiveTo determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms.MethodsCross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated.ResultsA total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1+ and HTLV-1− patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79–34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group.ConclusionThe prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.

COVID-19 alters human microbiomes: a meta-analysis.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected a substantial portion of the world's population, and novel consequences of COVID-19 on the human body are continuously being uncovered. The human microbiome plays an essential role in host health and well-being, and multiple studies targeting specific populations have reported altered microbiomes in patients infected with SARS-CoV-2. Given the global scale and massive incidence of COVID on the global population, determining whether the effects of COVID-19 on the human microbiome are consistent and generalizable across populations is essential. We performed a synthesis of human microbiome responses to COVID-19. We collected 16S rRNA gene amplicon sequence data from 11 studies sampling the oral and nasopharyngeal or gut microbiome of COVID-19-infected and uninfected subjects. Our synthesis included 1,159 respiratory (oral and nasopharyngeal) microbiome samples and 267 gut microbiome samples from patients in 11 cities across four countries. Our reanalyses revealed communitywide alterations in the respiratory and gut microbiomes across human populations. We found significant overall reductions in the gut microbial diversity of COVID-19-infected patients, but not in the respiratory microbiome. Furthermore, we found more consistent community shifts in the gut microbiomes of infected patients than in the respiratory microbiomes, although the microbiomes in both sites exhibited higher host-to-host variation in infected patients. In respiratory microbiomes, COVID-19 infection resulted in an increase in the relative abundance of potentially pathogenic bacteria, including Mycoplasma. Our findings shed light on the impact of COVID-19 on the human-associated microbiome across populations, and highlight the need for further research into the relationship between long-term effects of COVID-19 and altered microbiota.

Characterization of extracellular vesicles in AIDS-associated non-Hodgkin lymphoma.

Abstract Even with the use of anti-retroviral therapy, HIV +subjects develop non-Hodgkin lymphoma (NHL) at a higher frequency than uninfected subjects. Extracellular vesicles (EVs) secreted by cells may contain immunomodulatory molecules; for example, tumor cells can secrete EVs containing bioactive PD-L1 that can inhibit anti-tumor responses. We have shown EVs bearing PD-L1, TNF-RII or IL-6Rα can be biomarkers of NHL risk. Here we aim to characterize EVs isolated from EBV +and EBV −lymphoma cell lines to define their involvement in lymphomagenesis and identify more EV-associated biomarkers for NHL risk (like immune checkpoint molecules CD80, CD86, CD28). EVs were isolated from AIDS-NHL and NHL cell lines using a total exosome isolation kit and analyzed by Western blot. A subset of these were also analyzed by proteomics using Metascape, Reactome, and R. EVs were also isolated from archived serum of HIV +individuals before NHL onset (n = 51) and matched HIV +controls (n = 53) from participants of the MACS/WIHS Combined Cohort study, with a total exosome isolation kit and characterized by Western blot. EV-specific markers were detected in EVs isolated from cell lines and serum. EVs isolated from EBV +cell lines largely expressed LMP1, an EBV CD40 homolog that induces EBV-driven B cell transformation. In EVs isolated from serum, levels of CD80, CD86, or CD28 were comparable between pre-NHL samples and matched controls, though control samples tended to have greater CD80 and CD86 expression. Our findings shed light on the EV marker expression profiles of AIDS-NHL and NHL cell lines and show LMP1 expression in EBV +cell lines. Additionally, this research provides initial insight into the complex composition of EVs and their role in lymphomagenesis. Supported by grants from NIH (R01CA228157, P30CA016042-S, R01CA228157S)

Serum Ferritin and Asymptomatic Malaria: A study in Calabar, Nigeria.

Introduction Ferritin is a blood cell protein that contains iron. The serum ferritin level is widely accepted as an accurate indicator of body iron store being the only factor that can give a semi-quantitative indication of the levels of Iron storage. Increased serum ferritin has been reported in asymptomatic malaria infection.This study was done to determine the serum ferritin levels in asymptomatic malaria individuals in Calabar, Cross River State, Nigeria. Ninety (90) apparently healthy subjects were recruited, both male and female within the age of 18 to 65 years. Materials and Method The serum ferritin level was assayed using ELISA quantitative method. The Hb and PCV were also assayed using the automated cellular counter Sysmex Kx-21N. Malaria parasite detection was through examination of peripheral blood smears using 2% Giemsa. Results The mean serum ferritin levels for the malaria infected subjects was (25.11±1.27ng/ml), and this was significantly higher than the uninfected subjects (16.81±4.66ng/ml) (P&lt;0.05). Mean serum ferritin level for infected males was (20.95±8.79ng/ml) which is slightly higher than uninfected males (16.01±3.53ng/ml) (P&gt;0.05). The results also show mean serum ferritin for infected females to be (30.57±3.42ng/ml) which is higher than the uninfected females (18.65±1.98ng/ml). This result likewise shows significantly low level of Hb(12.97±1.5g/dl) and PCV (0.38±2.18L/L) in apparently healthy malaria infected individuals while high level of Hb(15.20±1.73g/dl) and PCV (0.44±1.58L/L) were observed among the uninfected subjects. There was also significant difference seen in infected male and infected female subjects, likewise the aparasitaemic males and females had significant difference (P&lt;0.05). Conclusion This study has shown that asymptomatic malaria parasitaemia increases serum ferritin level, hence serum ferritin estimation without examination for malaria parasitaemia in malaria endemic area such as Calabar, Nigeria may not be reliable. The study also shows that asymptomatic malaria parasitaemia constitutes a significant disease burden and a challenge that should be of global health concern

KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among Chinese high-risk population.

Killer-cell immunoglobulin-like receptors 2DL4 (KIR2DL4) and the human leukocyte antigen class I-G (HLA-G) display vital parts in immune responses against hepatitis C virus(HCV) infection. We select four potentially functional single nucleotide polymorphisms(SNPs) of KIR/HLA to explore the associations between KIR2DL4/HLA-G genetic variants and HCV infection results.In the present case-control study, a total of 2225 HCV-infected high-risk subjects, including 1778 paid blood donors (PBD) and 447 drug users were consecutively recruited before treatment from 2011 to 2018. KIR2DL4-rs660773, KIR2DL4-rs660437, HLA-G-rs9380142, and HLA-G-rs1707 SNPs were sorted as genotypes in the subdivided groups, involving 1095 uninfected controls subjects, 432 spontaneous HCV clearance subjects and 698 HCV persistent infection subjects. After genotyping experiments using the TaqMan-MGBassay, modified logistic regression was used to calculate the correlation among the SNPs and HCV infection. The SNPs were functionally annotated using bioinformatics analysis.Following adjusting by age, sex, alanine aminotransferase, aspartate aminotransferase, IFNL3-rs12979860, IFNL3-rs8099917, and the infection route, the logistic regression analysisdiscovered that KIR2DL4-rs660773 and HLA-G-rs9380142 were correlated with vulnerability to HCV infection (all p < 0.05). In a locus-dosage way, compared with subjects carrying the rs9380142-AA or rs660773-AA genotypes, subjects with rs9380142-AG or rs660773-AG/GG (all p < 0.05) were more vulnerable to HCV infection; the overall impact of their risk genotypes (rs9380142-AGrs660773-AG/GG) was correlated with an elevated incidence of HCV infection (ptrend < 0.001). In the Haplotype analysis, patients with haplotype AG were more likely to contract HCV compared to those with the highest common AA haplotype (p = 0.002) were higher in susceptibility to infect HCV. The SNPinfo web server estimated that rs660773 is a transcription factor binding site, whereas rs9380142 is a potential microRNA-binding site.In two Chinese high-risk population (PBD and drug uesrs), KIR2DL4 rs660773-G and HLA-G rs9380142-G alleles polymorphisms are related to HCV susceptibility. KIR2DL4/HLA-G pathway genes might affect the innate immune responses by regulating KIR2DL4/HLA-G transcription and translation play a potential role in HCV infection.

Helicobacter pylori Infection Is Associated with Long-Term Cognitive Decline in Older Adults: A Two-Year Follow-Up Study.

Previous cross-sectional studies have identified a possible link between Helicobacter pylori (H. pylori) infection and dementia. However, the association of H. pylori infection with longitudinal cognitive decline has rarely been investigated. This cohort study aims to demonstrate the effects of H. pylori infection on longitudinal cognitive decline. This cohort study recruited 268 subjects with memory complaints. Among these subjects, 72 had a history of H. pylori infection, and the rest 196 subjects had no H. pylori infection. These subjects were followed up for 24 months and received cognitive assessment in fixed intervals of 12 months. At baseline, H. pylori infected, and uninfected participants had no difference in MMSE scores. At 2 years of follow-up, H. pylori infected participants had lower MMSE scores than uninfected participants. H. pylori infection was associated with an increased risk of longitudinal cognitive decline, as defined by a decrease of MMSE of 3 points or more during follow-up, adjusting for age, sex, education, APOEɛ4 genotype, hypertension, diabetes, hyperlipidemia, and smoking history (HR: 2.701; 95% CI: 1.392 to 5.242). H. pylori infection was associated with larger cognitive decline during follow-up, adjusting for the above covariates (standardized coefficient: 0.282, p < 0.001). Furthermore, H. pylori infected subjects had significantly higher speed of cognitive decline than uninfected subjects during follow-up, adjusting for the above covariates. H. pylori infection increases the risk of longitudinal cognitive decline in older subjects with memory complaints. This study is helpful for further understanding the association between infection and dementia.

Immune profiling of SARS-CoV-2 epitopes in asymptomatic and symptomatic pediatric and adult patients

BackgroundThe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unpredictable manifestations of coronavirus disease (COVID-19) and variable clinical course with some patients being asymptomatic whereas others experiencing severe respiratory distress, or even death. We aimed to evaluate the immunoglobulin G (IgG) response towards linear peptides on a peptide array containing sequences from SARS-CoV-2, Middle East respiratory syndrome-related coronavirus (MERS) and common-cold coronaviruses 229E, OC43, NL63 and HKU1 antigens, in order to identify immunological indicators of disease outcome in SARS-CoV-2 infected patients.MethodsWe included in the study 79 subjects, comprising 19 pediatric and 30 adult SARS-CoV-2 infected patients with increasing disease severity, from mild to critical illness, and 30 uninfected subjects who were vaccinated with one dose of SARS-CoV-2 spike mRNA BNT162b2 vaccine. Serum samples were analyzed by a peptide microarray containing 5828 overlapping 15-mer synthetic peptides corresponding to the full SARS-CoV-2 proteome and selected linear epitopes of spike (S), envelope (E) and membrane (M) glycoproteins as well as nucleoprotein (N) of MERS, SARS and coronaviruses 229E, OC43, NL63 and HKU1 (isolates 1, 2 and 5).ResultsAll patients exhibited high IgG reactivity against the central region and C-terminus peptides of both SARS-CoV-2 N and S proteins. Setting the threshold value for serum reactivity above 25,000 units, 100% and 81% of patients with severe disease, 36% and 29% of subjects with mild symptoms, and 8% and 17% of children younger than 8-years reacted against N and S proteins, respectively. Overall, the total number of peptides in the SARS-CoV-2 proteome targeted by serum samples was much higher in children compared to adults. Notably, we revealed a differential antibody response to SARS-CoV-2 peptides of M protein between adults, mainly reacting against the C-terminus epitopes, and children, who were highly responsive to the N-terminus of M protein. In addition, IgG signals against NS7B, NS8 and ORF10 peptides were found elevated mainly among adults with mild (63%) symptoms. Antibodies towards S and N proteins of other coronaviruses (MERS, 229E, OC43, NL63 and HKU1) were detected in all groups without a significant correlation with SARS-CoV-2 antibody levels.ConclusionsOverall, our results showed that antibodies elicited by specific linear epitopes of SARS-CoV-2 proteome are age dependent and related to COVID-19 clinical severity. Cross-reaction of antibodies to epitopes of other human coronaviruses was evident in all patients with distinct profiles between children and adult patients. Several SARS-CoV-2 peptides identified in this study are of particular interest for the development of vaccines and diagnostic tests to predict the clinical outcome of SARS-CoV-2 infection.

Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination.

The introduction of anti-SARS-CoV-2 vaccines in late 2020 substantially changed the pandemic picture, inducing effective protection in the population. However, individual variability was observed with different levels of cellular response and neutralizing antibodies. We report data on the impact of age, gender, and 16 single nucleotide polymorphisms (SNPs) of cytokine genes on the anti-SARS-CoV-2 IgG titers measured 31 and 105 days after administration of the second dose of BNT162b2 vaccine to 122 healthy subjects from the health care staff of the Palermo University Hospital, Italy. The higher titers at 31 days were measured in the younger subjects and in subjects bearing T-positive genotypes of IL-1R1 rs2234650 or the GG homozygous genotype of IL-6 rs1800795 SNP. T-positive genotypes are also significantly more common in subjects with higher titers at day 105. In addition, in this group of subjects, the frequency of the CT genotype of IL-4 rs2243250 is higher among those vaccinated with higher titers. Moreover, these SNPs and TNFA rs1800629 are differently distributed in a group of subjects that were found infected by SARS-CoV-2 at day 105 of evaluation. Finally, subjects that were found to be infected by SARS-CoV-2 at day 105 were significantly older than the uninfected subjects. Taken together, these data seem to suggest that age and polymorphisms of key cytokines, which regulate inflammation and humoral immune response, might influence the magnitude of the antibody response to vaccination with BNT162B2, prompting speculation about the possible benefit of a genetic background-based assessment of a personalized approach to the anti-COVID vaccination schedule.