ABSTRACT
Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1-3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.
Subject(s)
Gastrointestinal Microbiome , Intestine, Large , Symbiosis , Trypsin , Administration, Oral , Animals , Bacterial Secretion Systems , Bacterial Vaccines/administration & dosage , Bacterial Vaccines/immunology , Bacteroidetes/isolation & purification , Bacteroidetes/metabolism , COVID-19/complications , Citrobacter rodentium/immunology , Diarrhea/complications , Feces/microbiology , Gastrointestinal Microbiome/genetics , Humans , Immunoglobulin A/metabolism , Intestine, Large/metabolism , Intestine, Large/microbiology , Mice , Murine hepatitis virus/metabolism , Murine hepatitis virus/pathogenicity , Proteolysis , SARS-CoV-2/pathogenicity , Trypsin/metabolism , Virus InternalizationABSTRACT
BACKGROUND: We have reported the vaccine effectiveness of inactivated influenza vaccine in children aged 6 months to 15 years between the 2013/14 and 2018/19 seasons. Younger (6-11 months) and older (6-15 years old) children tended to have lower vaccine effectiveness. The purpose of this study is to investigate whether the recent vaccine can be recommended to all age groups. METHODS: The overall adjusted vaccine effectiveness was assessed from the 2013/14 until the 2020/21 season using a test-negative case-control design based on rapid influenza diagnostic test results. Vaccine effectiveness was calculated by influenza type and by age group (6-11 months, 1-2, 3-5, 6-12, and 13-15 years old) with adjustments including influenza seasons. RESULTS: A total of 29,400 children (9347, 4435, and 15,618 for influenza A and B, and test-negatives, respectively) were enrolled. The overall vaccine effectiveness against influenza A, A(H1N1)pdm09, and B was significant (44% [95% confidence interval (CI), 41-47], 63% [95 %CI, 51-72], and 37% [95 %CI, 32-42], respectively). The vaccine was significantly effective against influenza A and B, except among children 6 to 11 months against influenza B. The age group with the highest vaccine effectiveness was 1 to 2 years old with both influenza A and B (60% [95 %CI, 55-65] and 52% [95 %CI, 41-61], respectively). Analysis for the 2020/21 season was not performed because no cases were reported. CONCLUSIONS: This is the first report showing influenza vaccine effectiveness by age group in children for several seasons, including immediately before the coronavirus disease (COVID-19) era. The fact that significant vaccine effectiveness was observed in nearly every age group and every season shows that the recent vaccine can still be recommended to children for the upcoming influenza seasons, during and after the COVID-19 era.
Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Adolescent , COVID-19/epidemiology , COVID-19/prevention & control , Case-Control Studies , Child , Child, Preschool , Humans , Infant , Influenza A Virus, H3N2 Subtype , Influenza B virus , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Seasons , Vaccination , Vaccines, InactivatedABSTRACT
INTRODUCTION: The risk factors in pediatric influenza immediately before the COVID-19 era are not well understood. This study aims to evaluate the risk factors for hospitalization in pediatric influenza A and B for the recent seasons. METHODS: Children with a fever of ≥38 °C and laboratory-confirmed influenza at 20 hospitals in outpatient settings in Japan in the 2013/14 to 2019/20 seasons were retrospectively reviewed. Possible risk factors, including gender, age, comorbidities, nursery school or kindergarten attendance, earlier diagnosis, no immunization, lower regional temperature, earlier season, and period of onset, were evaluated using binary logistic regression methods. RESULTS: A total of 13,040 (type A, 8861; B, 4179) children were evaluated. Significant risk factors (p < 0.05) in multivariate analyses were young age, lower regional temperature, earlier season, respiratory illness (adjusted odds ratio [aOR]:2.76, 95% confidence interval [CI]:1.84-4.13), abnormal behavior and/or unusual speech (aOR:2.78, 95% CI:1.61-4.80), and seizures at onset (aOR:16.8, 95% CI:12.1-23.3) for influenza A; and young age, lower regional temperature, respiratory illness (aOR:1.99, 95% CI:1.00-3.95), history of febrile seizures (aOR:1.73, 95% CI:1.01-2.99), and seizures at onset (aOR:9.74, 95% CI:5.44-17.4) for influenza B. CONCLUSIONS: In addition to previously known factors, including young age, seizures, and respiratory illness, abnormal behavior and/or unusual speech and lower regional temperature are new factors. Negative immunization status was not a risk factor for hospitalization. A better understanding of risk factors may help improve the determination of indications for hospitalization during the future co-circulation of influenza and COVID-19.