Pre-existing humoral immunity and CD4+ T cell response correlate with cross-reactivity against SARS-CoV-2 Omicron subvariants after heterologous prime-boost vaccination.

BACKGROUND: Information regarding the heterologous prime-boost COVID vaccination has been fully elucidated. The study aimed to evaluate both humoral, cellular immunity and cross-reactivity against variants after heterologous vaccination. METHODS: We recruited healthcare workers previously primed with Oxford/AstraZeneca ChAdOx1-S vaccines and boosted with Moderna mRNA-1273 vaccine boost to evaluate the immunological response. Assay used: anti-spike RBD antibody, surrogate virus neutralizing antibody and interferon-γ release assay. RESULTS: All participants exhibited higher humoral and cellular immune response after the booster regardless of prior antibody level, but those with higher antibody level demonstrated stronger booster response, especially against omicron BA.1 and BA.2 variants. The pre-booster IFN-γ release by CD4+ T cells correlates with post-booster neutralizing antibody against BA.1 and BA.2 variant after adjustment with age and gender. CONCLUSIONS: A heterologous mRNA boost is highly immunogenic. The pre-existing neutralizing antibody level and CD4+ T cells response correlates with post-booster neutralization reactivity against the Omicron variant.

The cellular immunophenotype expression of influenza A virus and influenza B virus infection in children.

BACKGROUND: The innate immune response is the primary defense against influenza virus infection. METHODS: This is a prospective study carried out in children <18 years of age who were diagnosed with influenza A or influenza B infection. Demographic and clinical data, laboratory findings and cell immunophenotypes on first presentation were compared. RESULTS: With respect to immunophenotype, influenza A infection resulted in a higher fraction of CD14+ and CD4+IL-17A+cells compared to children infected with influenza B. By contrast, influenza B infection resulted in a comparatively higher percentage of double-negative CD4-CD8- lymphocyte subsets. Influenza A infection was associated with comparatively higher percentages of CD4+CD25highFoxp3+ and CD4+CD25lowFoxp3+ cells. By contrast, the percentage of CD8+CD25high and CD8+CD25low cells was similar among patients with influenza A infection and influenza B infection. CONCLUSIONS: An improved understanding of the fraction of regulatory T cells with influenza virus infections may provide further understandings on immune responses.

The potential role of pneumococcal conjugate vaccine in reducing acute respiratory inflammation in community-acquired pneumococcal pneumonia.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) reduces both invasive pneumococcal disease (IPD) and other pneumococcal infections worldwide. We investigated the impact of stepwise implementation of childhood PCV programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in Taiwan. METHODS: In total, 983 children diagnosed with community-acquired pneumococcal pneumonia were enrolled between January 2010 and December 2015. RESULTS: Proportions of pneumococcal vaccinations increased each year in age-stratified groups with PCV7 (32.2%) as the majority, followed by PCV13 (12.2%). The proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in 2-5 year group. Serotype 19A is the leading serotype either in vaccinated (6.4%) or unvaccinated patients (5.2%). In particular, vaccinated patients had significantly higher lowest WBC, lower neutrophils, lower lymphocytes and lower CRP values than non-vaccinated patients (p < 0.05). After stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < 0.05). CONCLUSION: Systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in 2-5 year group. Serotype 19A was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients.

Comparative study of clinical and epidemiological characteristics of major pediatric adenovirus epidemics in southern Taiwan.

BACKGROUND: Human adenoviruses (HAdV) are important pathogens of pediatric respiratory tract infections in Taiwan. There were two major HAdV epidemics in southern Taiwan in 2011 and 2014, respectively. METHODS: The demographic, clinical characteristics, and risk factors for hospitalization of pediatric patients with HAdV infection in the two outbreaks were retrospectively compared. The epidemic was defined as > 7% HAdV detection rate for six consecutive weeks. HAdV infection was defined as positive HAdV isolates from respiratory tract specimens. HAdV genotype was determined by PCR-based hexon gene sequencing. RESULTS: A total of 1145 pediatric patients were identified (635 cases in 2011; 510 cases in 2014). HAdV genotype 3 and 7 contributed to both epidemics, although the proportion of HAdV3 decreased significantly (64.7% in 2011 to 25.5% in 2014, p < 0.001) and was replaced by other genotypes (type 1, 4, and 6) in the 2014 epidemic. Among the hospitalized patients, there were more patients hospitalized with bronchopneumonia/or pneumonia in the 2011 epidemic (10.6% vs 5.1%, p < 0.001), while more patients hospitalized with acute pharyngitis/pharyngoconjunctival fever (63.9% vs. 38.6%, p < 0.001) in the 2014 epidemic. In both epidemics, hospitalized patients had higher WBC and C-reactive protein (CRP) levels than non-hospitalized patients. Using multivariate regression analysis, underlying disease and elevated CRP levels were independent risk factors for hospitalization in both epidemics. CONCLUSION: There were significant differences in clinical, viral characteristics and risk factors of hospitalization between the 2011 and 2014 epidemics. Understanding changes in the epidemiological and clinical characteristics of HAdV epidemics is important from a public health perspective.

Clinical features of community acquired adenovirus pneumonia during the 2011 community outbreak in Southern Taiwan: role of host immune response.

BACKGROUND: Human adenovirus 7 (HAdV-7) was responsible for a significant number of fatalities during the 2011 community outbreak in Taiwan. The mechanisms underlying the pathogenesis of severe adenovirus infections in non-immunocompromised individuals remain unclear. Adenovirus pneumonia was associated with pleural effusion in a number of patients from the 2011 outbreak suggesting that similar to bacterial pneumonia, patients diagnosed with adenovirus pneumonia who have pleural effusion are more severely and systemically infected, and may have a more protracted disease course. We hypothesized that the host immunological response determines the severity of adenoviral infection. METHODS: This retrospective case series study included patients diagnosed with severe lower respiratory tract infections at the National Cheng Kung University Hospital in southern Taiwan between December 2010 and October 2011. The main inclusion criteria were 1) presence of multifocal patchy infiltrates, lobar consolidation or reticular interstitial opacities in chest X-rays, and 2) presence of adenovirus isolated from respiratory specimens. All patients had adenovirus isolated from respiratory specimens, and were negative for other viruses. Pleural effusion was confirmed in all patients using chest echography. Clinical features and laboratory data were compared in patients with (n = 12) and without (n = 15) parapneumonic effusion. RESULTS: Presence of parapneumonic effusion was significantly associated with a longer febrile duration, more complicated clinical management, and a greater risk of extrapulmonary involvement, notably hepatitis. Patients without pleural effusion had significantly higher numbers of WBCs, platelets, and absolute segment cell counts (ASCs) compared to patients with pleural effusion (all p < 0.05). Patients without pleural effusion had significantly higher counts of CD4+, CD8+, and CD20+ T cells (all p < 0.05) compared to patients with pleural effusion. CONCLUSION: Our data indicated that presence of parapneumonic effusion in adenoviral pneumonia was associated with longer febrile duration, more complicated clinical management, a greater risk of hepatitis, and suppression of host cellular immunity. Further prospective, large-scale studies are needed to validate our results.

COVID-19 Vaccination in Pregnancy: Pilot Study of Plasma MicroRNAs Associated with Inflammatory Cytokines after COVID-19 mRNA Vaccination.

BACKGROUND: The impact of mRNA COVID-19 vaccines on the immunological profiles of pregnant women remains a crucial area of study. This research aims to explore the specific immunological changes triggered by these vaccines in this demographic. METHODS: In a focused investigation, we examined the effects of mRNA COVID-19 vaccination on microRNA expression in pregnant women. Key microRNAs, including miR-451a, miR-23a-3p, and miR-21-5p, were analyzed for expression changes post-vaccination. Additionally, we assessed variations in S1RBD IgG levels and specific cytokines to gauge the broader immunological response. RESULTS: Post-vaccination, significant expression shifts in the targeted microRNAs were observed. Alongside these changes, we noted alterations in S1RBD IgG and various cytokines, indicating an adapted inflammatory response. Notably, these immunological markers displayed no direct correlation with S1RBD IgG concentrations, suggesting a complex interaction between the vaccine and the immune system in pregnant women. CONCLUSIONS: Our pilot study provides valuable insights into the nuanced effects of the mRNA COVID-19 vaccine on immune dynamics in pregnant women, particularly emphasizing the role of microRNAs. The findings illuminate the intricate interplay between vaccines, microRNAs, and immune responses, enhancing our understanding of these relationships in the context of pregnancy. This research contributes significantly to the growing body of knowledge regarding mRNA COVID-19 vaccines and their specific impact on maternal immunology, offering a foundation for further studies in this vital area.

Pilot Study on Evaluating the Impact of Tetanus, Diphtheria, and Pertussis (Tdap), Influenza, and COVID-19 Vaccinations on Antibody Responses in Pregnant Women.

This study assessed IgG levels to influenza/pertussis and neutralizing antibody (Nab) responses of COVID-19 vaccines in blood of pregnant women following immunization with pertussis (Tdap), influenza, and COVID-19 vaccines. We prospectively collected 71 participants categorized by the following vaccine combinations: 3TI, 4TI, 3T, and 4T groups (three and four doses of COVID-19 vaccines plus Tdap/influenza or Tdap vaccines alone). Our findings have indicated that the 3TI group exhibited elevated IgG levels for influenza B compared to the 3T group (12.90 vs. 7.75 U, p = 0.001); this pattern was not observed for influenza A. Pertussis IgG levels remained uniform across all groups. The 4TI group demonstrated a greater Nab inhibition rate from COVID-19 vaccines compared to both the 3TI and 3T groups (61.34% vs. 22.5% and 15.16%, respectively, p = 0.001). We observed no correlation between Nab inhibition rate and IgG levels for Tdap/influenza, with the exception of a moderate correlation with influenza B in the 3TI group. The efficacy of Tdap vaccine in pregnant women remained consistent, regardless of the administration of COVID-19 or influenza vaccines. Interestingly, without the influenza vaccine, both three and four doses of the COVID-19 vaccine still offered protection against influenza A, but not B. Hence, co-administering COVID-19, influenza, and Tdap vaccines during prenatal care maintains immunogenicity and is highly advised to safeguard pregnant women fully.

TRAIL and IP-10 dynamics in pregnant women post COVID-19 vaccination: associations with neutralizing antibody potency.

Introduction: The aim of this study is to investigate changes in TNF-related apoptosis-inducing ligand (TRAIL) and gamma interferon-induced protein 10 (IP-10) after COVID-19 vaccination in pregnant women and to explore their association with neutralizing antibody (Nab) inhibition. Methods: The study evaluated 93 pregnant women who had previously received two (n=21), three (n=55) or four (n=17) doses of COVID-19 vaccine. Also we evaluated maternal blood samples that were collected during childbirth. The levels of TRAIL, IP-10 and Nab inhibition were measured using enzyme-linked immunosorbent assays (ELISA). Results and discussion: Our study revealed four-dose group resulted in lower TRAIL levels when compared to the two-dose and three-dose groups (4.78 vs. 16.07 vs. 21.61 pg/ml, p = 0.014). The two-dose group had reduced IP-10 levels than the three-dose cohort (111.49 vs. 147.89 pg/ml, p=0.013), with no significant variation compared to the four-dose group. In addition, the four-dose group showed stronger Nab inhibition against specific strains (BA.2 and BA.5) than the three-dose group. A positive correlation was observed between TRAIL and IP-10 in the two-dose group, while this relationship was not found in other dose groups or between TRAIL/IP-10 and Nab inhibition. As the doses of the COVID-19 vaccine increase, the levels of TRAIL and IP-10 generally increase, only by the fourth dose, the group previously vaccinated with AZD1222 showed lower TRAIL but higher IP-10. Despite these changes, more doses of the vaccine consistently reinforced Nab inhibition, apparently without any relation to TRAIL and IP-10 levels. The variation may indicate the induction of immunological memory in vaccinated mothers, which justifies further research in the future.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. METHODS: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. RESULTS: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. CONCLUSION: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Childhood invasive pneumococcal disease caused by non-7-valent pneumococcal vaccine (PCV7) serotypes under partial immunization in Taiwan.

BACKGROUND/PURPOSE: Emerging non-7-valent pneumococcal conjugate vaccine (PCV7) serotypes have replaced PCV7 serotypes in childhood invasive pneumococcal disease (IPD). This study was designed to describe the IPD caused by non-PCV7 serotypes under partial PCV7 immunization in Taiwan. METHODS: All children <18 years of age diagnosed with IPD at National Cheng Kung University Hospital from 1998 to 2010 were enrolled. Clinical and laboratory information was collected. Pneumococcal isolates were tested for antimicrobial susceptibility and interpreted using Clinical Laboratory Standard Institute guidelines (2008). Serotypes were determined using the capsular swelling method. RESULTS: One hundred and five patients with IPD were identified, including 75 PCV7 and 30 non-PCV7 isolates. Pneumonia (63.3%) was the leading clinical manifestation of non-PCV7 IPDs and 78.9% of pneumonia cases were associated with necrotizing pneumonia or empyema. Children with non-PCV7 IPDs had longer febrile days, required longer intensive care unit stays, and had a higher C-reactive protein level than those with PCV7 IPDs (p < 0.05). Serotype 3 is the most common non-PCV7 serotype (46.7%) and possesses the highest potential for pulmonary complications (p < 0.05, odds ratio: 0.114; 95% confidence interval, 0.013 - 0.973). CONCLUSION: The changing epidemiology of IPDs following the introduction of PCV7 has been noted. Expanded serotype coverage of the vaccine is warranted.

Impact of the COVID-19 vaccine booster strategy on vaccine protection: a pilot study of a military hospital in Taiwan.

Purpose: The global fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread vaccination efforts, yet the optimal dosing schedule for SARS-CoV-2 vaccines remains a subject of ongoing research. This study aims to investigate the effectiveness of administering two booster doses as the third and fourth doses at different intervals to enhance vaccine protection. Materials and Methods: This study was conducted at a military regional hospital operated by the Ministry of National Defense in Taiwan. A cohort of vaccinated individuals was selected, and their vaccine potency was assessed at various time intervals following their initial vaccine administration. The study participants received booster doses as the third and fourth doses, with differing time intervals between them. The study monitored neutralizing antibody titers and other relevant parameters to assess vaccine efficacy. Results: Our findings revealed that the potency of the SARS-CoV-2 vaccine exhibited a significant decline 80 days after the initial vaccine administration. However, a longer interval of 175 days between booster injections resulted in significantly higher neutralizing antibody titers. The individuals who received the extended interval boosters exhibited a more robust immune response, suggesting that a vaccine schedule with a 175-day interval between injections may provide superior protection against SARS-CoV-2. Conclusion: This study underscores the importance of optimizing vaccine booster dosing schedules to maximize protection against SARS-CoV-2. The results indicate that a longer interval of 175 days between the third and fourth doses of the vaccine can significantly enhance the neutralizing antibody response, potentially offering improved protection against the virus. These findings have important implications for vaccine distribution and administration strategies in the ongoing battle against the SARS-CoV-2 pandemic. Further research and large-scale trials are needed to confirm and extend these findings for broader public health implications.

Case report: Distinct neurologic manifestation and cytokine profile of a child with COVID-19-associated acute fulminant encephalitis.

The neurologic manifestations of coronavirus disease 2019 (COVID-19) may range from mild symptoms such as headache or confusion to profound encephalopathy with variable outcomes and sequelae. Here, we reported a case of fatal COVID-19-associated encephalitis with acute fulminant cerebral edema, presenting first with visual hallucination and then a rapid progression into comatose status in a few hours. Serial brain computed tomography depicted cerebral edematous changes from bilateral ventral temporal lobe to the whole brain leading to brain herniation. Multiple cytokines in serum and cerebrospinal fluid (CSF) were increased, with a more prominent rise in the CSF. Therefore, we postulated a hypothesis regarding the mechanism of this fulminant encephalitis that the SARS-CoV-2 virus attacked ventral temporal lobes initially, triggered a severe cytokine storm, and then led to subsequent disruption of the blood-brain barrier, diffuse brain edema, and brain herniation. The trend of cytokine profiles over time may aid in diagnosing and evaluating the severity and prognosis of COVID-19-associated encephalitis.

Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia-a pilot study.

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming. Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65-97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission. Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results (p < 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate (p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696). Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems.

COVID-19 Bivalent Booster in Pregnancy: Maternal and Neonatal Antibody Response to Omicron BA.5, BQ.1, BF.7 and XBB.1.5 SARS-CoV-2.

Our study was to investigate the effects of bivalent COVID-19 booster vaccination during pregnancy on neutralizing antibody (Nab) levels in maternal blood (MB), transplacental transmission in umbilical cord blood (CB), and efficacy against Omicron SARS-CoV-2 subvariants including BA.5, BF.7, BQ.1, and XBB.1.5. We collected MB and CB from 11 pregnant participants during baby delivery and detected Nab inhibition by enzyme-linked immunosorbent assays (ELISA). Nab inhibition was 89-94% in MB and 82-89% in CB for Omicron subvariants. Those receiving AZD1222 vaccines in previous monovalent vaccination demonstrated poorer maternal Nab inhibition of BA.5, BQ.1, and XBB.1.5 than others. Poorer maternal Nab inhibition of BA.5, BF.7, and BQ.1 was found in those receiving two-dose AZD1222 vaccinations than with either one or no AZD1222 vaccination. MB from those with infants weighing < 3100 g demonstrated better Nab inhibition of BF.7 than those > 3100 g (97.99 vs. 95.20%, p = 0.048), and there were also similar trends for Nab inhibition of BA.5 and BQ.1. No significant differences were seen in CB samples. Although diminished maternal Nab inhibition was seen in those with previous monovalent AZD1222 vaccination and heavier newborns, neonatal Nab inhibition was still strong after bivalent COVID-19 booster vaccination.

Corrigendum: Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia-a pilot study.

[This corrects the article DOI: 10.3389/fphar.2023.1166923.].

COVID-19 Vaccination in Pregnancy: Pilot Study for Maternal and Neonatal MicroRNA Profiles.

This pilot study explores alterations in miRNA profiles among pregnant women and their neonates upon receiving different doses of COVID-19 vaccines. Blood samples, including maternal blood (MB) and neonatal cord blood (CB), collected from five pregnant women were scrutinized using the miRNA PanelChip Analysis System, identifying nine distinct miRNAs, including miR-451a and miR-1972, which exhibited significant downregulation with two vaccine doses in both MB and CB. When compared with women vaccinated with four doses, miR-486-5p, miR-451a, and miR-1972 in the two-dose group also showed notable downregulation. Evaluating recipients of three and four doses, miR-423-5p and miR-1972 expression were significantly reduced in both MB and CB. Further comparative analysis highlighted a decline in miR-223-3p expression with increasing vaccine doses, while miR15a-5p, miR-16-5p, and miR-423-5p showed an upward trend. Notably, miR-451a, miR-1972, and miR-423-5p levels varied across doses and were associated with pathways such as "PI3K-Akt", "neurotrophin signaling", and "cortisol synthesis", suggesting the profound influence of vaccination on diverse molecular mechanisms. Our research has uncovered that escalating vaccine dosages impact miRNA profiles, which may be associated with the immunological response mechanisms in both the mother and fetus, thus indicating a substantial impact of vaccination on various molecular processes.

Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women.

Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.

Age and prior vaccination determine the antibody level in children with primary SARS-CoV-2 Omicron infection.

BACKGROUND: Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection relies on immunity generated after primary infection. However, humoral immunity following primary infection with the Omicron variant is not well understood. METHODS: We prospectively recruited children <19 years with virologically-confirmed SARS-CoV-2 infection at National Cheng Kung University Hospital from February 2022 to September 2022 during the first wave of Omicron BA.2 outbreak in Taiwan. Serum samples were collected one month after acute infection to measure anti-spike protein receptor binding domain antibody levels and surrogate virus neutralizing antibody (NAb) levels against wild type disease and variants. RESULTS: Of the 164 patients enrolled, most were under 5 years (65.2%) with a diagnosis of upper respiratory tract infection. Children under 6 months with maternal coronavirus disease 2019 (COVID-19) vaccination had higher levels of both anti-SARS-CoV-2 spike antibody (119.0 vs 27.4 U/ml, p < 0.05) and anti-wild type NAb (56.9% vs 27.6% inhibition, p = 0.001) than those without. Children aged 5-12 years with prior vaccination had higher anti-spike antibody, anti-wild type, and anti-Omicron BA.2 NAb levels than those without (all p < 0.05). In previously naïve children without maternal or self-vaccination, those 6 months to 2 years had the highest antibody levels. Multivariable linear regression analysis showed age was the only independent factor associated with antibody level. CONCLUSIONS: In our study, children aged 6 months to 2 years have the highest antibody responses to SARS-CoV-2 Omicron variant infection. Age and prior vaccination are the main factors influencing the immunogenicity of SARS-CoV-2 infection.

Trajectory of Humoral Responses to Two Doses of ChAdOx1 nCoV-19 Vaccination in Patients Receiving Maintenance Hemodialysis.

The ChAdOx1 nCoV-19 (AZD1222) vaccine is one of the most commonly delivered SARS-CoV-2 vaccines worldwide; however, few clinical studies have investigated its immunogenicity in dialysis patients. We prospectively enrolled 123 patients on maintenance hemodialysis at a medical center in Taiwan. All patients were infection-naive, had received two doses of the AZD1222 vaccine, and were monitored for 7 months. The primary outcomes were anti-SARS-CoV-2 receptor-binding domain (RBD) antibody concentrations before and after each dose and 5 months after the second dose and neutralization capacity against ancestral SARS-CoV-2, delta, and omicron variants. The anti-SARS-CoV-2 RBD antibody titers significantly increased with time following vaccination, with a peak at 1 month after the second dose (median titer, 498.8 U/mL; interquartile range, 162.5 to 1,050 U/mL), and a 4.7-fold decrease at 5 months. At 1 month after the second dose, 84.6, 83.7, and 1.6% of the participants had neutralizing antibodies against the ancestral virus, delta variant, and omicron variant, respectively, measured by a commercial surrogate neutralization assay. The geometric mean 50% pseudovirus neutralization titers for the ancestral virus, delta variant, and omicron variant were 639.1, 264.2, and 24.7, respectively. The anti-RBD antibody titers correlated well with neutralization capacity against the ancestral virus and delta variant. Transferrin saturation and C-reactive protein were associated with neutralization against the ancestral virus and delta variant. Although two doses of the AZD1222 vaccine initially elicited high anti-RBD antibody titers and neutralization against the ancestral virus and delta variant in hemodialysis patients, neutralizing antibodies against omicron variant were rarely detected, and the anti-RBD and neutralization antibodies waned over time. Additional/booster vaccinations are warranted in this population. IMPORTANCE Patients with kidney failure have worse immune response following vaccination compared to general population, but few clinical studies have investigated immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccination in hemodialysis patients. Here, we showed two doses of AZD1222 vaccines lead to high seroconversion rate of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies, and more than 80% patients acquired neutralizing antibodies against ancestral virus and delta variant. However, seldom did they obtain neutralizing antibodies against the omicron variant. The geometric mean 50% pseudovirus neutralization titer against the ancestral virus was 25.9-fold higher than that against the omicron variant. Also, there was a substantial decay in anti-RBD titers with time. Our findings provided evidence supporting that more protective measures, including additional/booster vaccinations, is warranted in these patients during the current COVID-19 pandemic.

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study.

Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.