BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Anti-viral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown.ObjectiveWe aimed to evaluate SARS-CoV-2 immunity in children with asthma based on infection or vaccination history and in comparison with respiratory syncytial virus (RSV) or allergen (e.g., cockroach, dust mite) specific immunity.MethodsFifty-three children from an urban asthma study were evaluated for medical history, lung function, and viral or allergen-specific immunity using antibody or T-cell assays.ResultsPolyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization following SARS-CoV-2 infection or vaccination. T-helper (Th)-1 responses to SARS-CoV-2 and RSV correlated with antigen-respective IgG. Cockroach-specific T-cell activation, as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent healthcare utilization. Reduced lung function (FEV1 ≤ 80%) was independently associated with (SARS-CoV-2) viral peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses.ConclusionMechanisms underpinning atopic and non-atopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infections in these children.

SARS CoV-2 in children or special populations post-infection has not been well studied. Asthma is a heterogenous disease marked by chronic airway inflammation; triggers include cockroaches (CRA), and other inhaled irritants. Asthma also has links to viral infections like respiratory syncytial virus (RSV). Additionally, some with moderate to severe asthma are more likely to be hospitalized with COVID. T cells play key roles in asthma and control of viruses such; however, there is limited information connecting T cell responses in people with asthma to viral infections. We aimed to evaluate T cells and antibodies in an asthma confirmed cohort. Thirty-five children aged 5–17 years were included. We measured SARS CoV-2 spike (S) and Nucleoprotein (N) plasma antibody responses or effector functions and CD4, CD8 T cells specific to CRA or peptide pools made from RSV, S and N antigen using an activation induced markers (AIM) assay. Surprisingly, in this population many CD4 and CD8 T-cell AIM responses to S, N, CRA, and RSV were significantly associated, particularly for CD8 T-cells (Spearmans r = 0.57–0.76) and the restimulation antigens CRA and RSV. N-specific CD4 AIM was the only immune measure to correlate to a recent asthma attack within a month of the blood collection visit, though anti-N antibodies, CD4 AIM to CRA, RSV or CD8 AIM to CRA, RSV, or N antigens also correlated with asthmatic outcomes (e.g., ER visits, night waking from symptoms, etc.) whereas allergen specific IgE or anti-S IgG did not. Taken together these results indicate an immunological association between viral infection and asthma, broadly allowing for the conjecture that viral infections, in particular RSV and SARS-CoV-2 could act together as possible triggers of asthma.

Pregnant women and neonates are at risk for adverse SARS CoV-2 infection outcomes, but few studies have evaluated this population for adaptive immunity. Here, we utilized samples collected from pregnant women 18 years or older reporting two or more respiratory symptoms. Information about trimester of COVID positive test or history of vaccination was also collected. Maternal blood (MB) samples were collected at prenatal clinic visits, or at delivery together with the fetal cord blood (CB)(n=70 dyads). Groups were selected based on trimester of infection, vaccination only, or no history of vaccination or infection (n=9–24) and compared with banked samples from a non-pregnant, age-matched woman from the same time period (n=7–12). Data shows IgG transfer to baby irrespective of trimester of infection (n=9–24 per group). Highest levels of antibodies were observed with vaccinated, uninfected women. Functional antibodies are transferred from mother to fetus following infection and vaccination. CD4 and CD8 T-cell activation and cytokine secretion were detected in maternal PBMCs, with highly variable expression between subjects. In at least one dyad with a PCR-confirmed infection during second trimester, both maternal and cord blood samples had low level expression of anti-S, N, RBD antibodies at delivery and the cord blood mononuclear cells showed CD4 T cell activation (CD134+) and cytokine secretion (IL-2, IL-6, TNFalpha) to spike antigens. These results indicate the unusual immunity to SARS CoV-2 infection during pregnancy and suggest at least one case of a neonate with anti-viral cellular immunity. Ongoing analyses and surveillance for perinatal outcomes may reveal how these immune responses impact infant respiratory outcomes.

Background Schistosomiasis is known to induce inflammatory immune responses. C-reactive protein (CRP), resistin and P-selectin are serological inflammatory markers that rise during the acute stages of infection. Here, we propose such inflammatory biomarkers have a potential for use in urogenital schistosomiasis diagnostic screening for exposure and infection in preschool-aged children. Methods As part of a larger study on urogenital schistosomiasis, 299 preschool children aged 1–5 years were included in this cross-sectional study. Parasitological diagnosis was conducted using urine filtration for Schistosoma haemtobium infection, and Kato Katz for S. mansoni infection. Serum levels of P-selectin, resistin, CRP, and antibodies against S. haematobium cercarial antigen preparation (CAP) and soluble worm antigen preparation (SWAP) were measured by ELISA. Results Of the 299 participants, 14% were egg positive for S. haematobium . Serology showed 46 and 9% of the participants to have been exposed to S. haematobium cercarial antigens and adult worm antigens, respectively. Levels of P-selectin were significantly higher in participants infected with S. haematobium (egg-positive) than in uninfected participants ( p = 0.001). Levels of P-selectin were also higher in those exposed to cercarial antigen than in unexposed participants ( p = 0.019). There was a positive correlation between P-selectin and infection intensity ( r = 0.172; p = 0.002), as well as with IgM responses to CAP and SWAP ( r = 0.183; p = 0.001); ( r = 0.333; p < 0.0001) respectively. CRP significantly correlated with IgM responses to CAP ( r = 0.133; p = 0.029) while resistin correlated with IgM responses to CAP and SWAP ( r = 0.127; p = 0.016); ( r = 0.197; p = 0.0004). CRP levels were higher in those exposed to cercarial and adult worm antigens than unexposed participants ( p = 0.035); ( p = 0.002) respectively, while resistin was higher in participants exposed to cercarial antigen than unexposed participants ( p = 0.024). Conclusion In this preschool population, P-selectin is significantly associated with urogenital schistosome infection and intensity; hence a potential biomarker for infection diagnosis and disease monitoring. The inflammatory biomarkers (P-selectin, Resistin and CRP) were significantly higher in participants exposed to cercarial antigens than unexposed individuals indicating an underlying inflammatory environment.

Praziquantel (PZQ) is an anthelminthic human and veterinary drug used to treat trematode and cestode worms. Changes in immune responses have been demonstrated in humans following curative PZQ treatment of schistosome infections. These changes have been attributed to the removal of immunosupressive worms and immune responses to parasite antigens exposed from dying worms. To date, there has been no study investigating the potential direct effect of PZQ on the host immune cells. Herein, we analyzed the effect of PZQ on human CD4+ T cells classically costimulated by CD3/CD28 or costimulated by the complement regulator CD46 to induce Type 1 regulatory T cells (Tr1). Our results show that PZQ enhanced T‐cell proliferation, increased secretion of IL‐17 and IL‐10 but had no effect on secretion of GM‐CSF or IFNγ. Moreover, PZQ increased the coexpression of CD49b and LAG‐3, a hallmark of Tr1 cells, suggesting increased Tr1 differentiation. Indeed, supernatants from PZQ‐treated cells were able to decrease bystander T‐cell activation, and this was partly reduced when blocking IL‐10. Hence, our study demonstrates that PZQ directly modulates human T‐cell activation and promotes Tr1 differentiation, suggesting that PZQ may have immunomodulatory functions in parasite‐unrelated human inflammatory diseases.

Background Recent research has shown that in schistosome-endemic areas preschool-aged children (PSAC), that is, ≤5 years, are at risk of infection. However, there exists a knowledge gap on the dynamics of infection and morbidity in this age group. In this study, we determined the incidence and dynamics of the first urogenital schistosome infections, morbidity and treatment in PSAC. Methods Children (6 months to 5 years) were recruited and followed up for 12 months. Baseline demographics, anthropometric and parasitology data were collected from 1502 children. Urinary morbidity was assessed by haematuria and growth-related morbidity was assessed using standard WHO anthropometric indices. Children negative for Schistosoma haematobium infection were followed up quarterly to determine infection and morbidity incidence. Results At baseline, the prevalence of S haematobium infection and microhaematuria was 8.5% and 8.6%, respectively. Based on different anthropometric indices, 2.2%–8.2% of children were malnourished, 10.1% underweight and 18.0% stunted. The fraction of morbidity attributable to schistosome infection was 92% for microhaematuria, 38% for stunting and malnutrition at 9%–34%, depending on indices used. S haematobium -positive children were at greater odds of presenting with microhaematuria (adjusted OR (AOR)=25.6; 95% CI 14.5 to 45.1) and stunting (AOR=1.7; 95% CI 1.1 to 2.7). Annual incidence of S haematobium infection and microhaematuria was 17.4% and 20.4%, respectively. Microhaematuria occurred within 3 months of first infection and resolved in a significant number of children, 12 weeks post-praziquantel treatment, from 42.3% to 10.3%; P<0.001. Conclusion We demonstrated for the first time the incidence of schistosome infection in PSAC, along with microhaematuria, which appears within 3 months of first infection and resolves after praziquantel treatment. A proportion of stunting and malnutrition is attributable to S haematobium infection. The study adds scientific evidence to the calls for inclusion of PSAC in schistosome control programmes.