Changes of respiratory pathogen and clinical features of in acute exacerbation of chronic obstructive pulmonary disease after COVID-19 pandemic (preprint)

Respiratory infections are common causes of acute exacerbation of chronic obstructive lung disease (AECOPD). We explored whether the pathogens causing AECOPD and clinical features changed from before to after the coronavirus disease 2019 (COVID-19) outbreak. We reviewed the medical records of patients hospitalized with AECOPD at four university hospitals between January 2017 and December 2018 and between January 2021 and December. We evaluated 1,180 patients with AECOPD for whom medication histories were available. After the outbreak, the number of patients hospitalized with AECOPD was almost 44% lower compared with before the outbreak. Patients hospitalized with AECOPD after the outbreak were younger (75 vs. 77 years, p = 0.003) and more often stayed at home (96.6% vs. 88.6%, p < 0.001) than patients of AECOPD before the outbreak. Hospital stay was longer after the outbreak than before the outbreak (10 vs. 8 days. p < 0.001). After the COVID-19 outbreak, the identification rates of S. pneumoniae (15.3 vs. 6.2%, p < 0.001) and Hemophilus influenzae (6.4 vs. 2.4%, p = 0.002) decreased, whereas the identification rates of P. aeruginosa (9.4 vs. 13.7%, p = 0.023), Klebsiella pneumoniae (5.3 vs. 9.8%, p = 0.004), and methicillin-resistant Staphylococcus aureus (1.0 vs. 2.8%, p = 0.023) increased. After the outbreak, the identification rate of influenza A decreased (10.4 vs. 1.0%, p = 0.023). After the outbreak, the number of patients hospitalized with AECOPD was lower and the identification rates of community-transmitted pathogens tended to decrease, whereas the rates of pathogens capable of chronic colonization tended to increase. During the period of large-scale viral outbreaks that require quarantine, patients with AECOPD should consider treatment against strains that can colonize chronic respiratory disease rather than community acquired pathogens.

Invasive Haemophilus influenzae disease: A report of 14 cases one year after the COVID-19 pandemic outbreak. / Enfermedad invasiva por Haemophilus influenzae: reporte de 14 casos luego de un año de iniciada la pandemia por COVID-19.

Haemophilus influenzae (Hi) causes invasive disease. There are encapsulated strains, such as serotype b (Hib), and non-typeable strains (NTHi). One year after the outbreak of the COVID-19 pandemic, the number of cases increased. In this report we describe the clinical and epidemiological characteristics of children hospitalized with invasive Hi disease (July 2021-July 2022). There were 14 cases; 12 were previously healthy children. Isolations: Hib (n = 6), Hi serotype a (n = 2), NTHi (n = 5); 1 case was not typified. Median age: 8.5 months (IQR: 4­21). Manifestations: meningitis (n = 5), pneumonia (n = 6), cellulitis (n = 2), arthritis (n = 1). Incomplete Hib immunization was observed in 9 children. Invasive Hi disease increased 2.5 times from previous years. These data suggest the reemergence of Hib due to a decline in vaccination coverage and an increase in other non-b-type Hi serotypes.

El Haemophilus influenzae (Hi) causa enfermedad invasiva (EI). Se distinguen cepas capsuladas, como el serotipo b (Hib), y cepas no tipificables (HNT). Al año de declarada la pandemia por COVID-19, observamos un aumento de casos. Se describen las características clínico-epidemiológicas de niños con EI por Hi internados en el hospital (julio 2021-julio 2022). Hubo 14 casos; 12 previamente sanos. Aislamientos: Hib (n = 6), Hi serotipo a (n = 2), HNT (n = 5), 1 no se tipificó. Mediana de edad: 8,5 meses (RIC 4-21). Manifestaciones: meningitis (n = 5), neumonía (n = 6), celulitis (n = 2), artritis (n = 1). Nueve presentaron vacunación incompleta para Hib. Observamos un incremento de EI por Hi de 2,5 veces respecto a años previos. Estos datos sugieren el resurgimiento de Hib por la caída de las coberturas de vacunación y porque otras cepas de Hi no b están en aumento.

Variability in mRNA SARS-CoV-2 BNT162b2 vaccine immunogenicity is associated with differences in the gut microbiome and habitual dietary fibre intake (preprint)

Objective: Little is known about the interplay between gut microbiome and SARS-CoV-2 vaccine immunogenicity. In this prospective observational study, we investigated associations between the gut microbiome, habitual dietary fibre intake, and mRNA vaccine-elicited immune responses, including anti-Spike IgG, avidity, and ACE-2 competition (surrogate neutralization). Design: 16S rRNA sequencing and short-chain fatty acid analyses were undertaken using stool samples collected from 48 healthy individuals at baseline and twelve-weeks after 1st BNT162b2 SARS-CoV-2 vaccine dose. Associations between gut microbiome data and SARS-CoV-2 spike and RBD IgG levels, competitive binding antibodies, and anti-SARS-CoV-2 spike total relative fractional avidity assays were evaluated. A validated dietary fibre intake food frequency questionnaire was also used to correlate habitual dietary fibre intakes with vaccine responses. Results: Our data revealed several baseline bacterial taxa, including Prevotella, Haemophilus and Veillonella (p<0.01), associated with BNT162b2 vaccine responses. Several Bacteroides spp. (p<0.01) as well as Bifidobacterium animalis, (p=0.003), amongst others, were positively associated with antibody avidity. Conversely, concentrations of isovaleric and isobutyric acid were higher in individuals with the lowest SARS-CoV-2 vaccine responses (p<0.01). Classifying participants based on habitual dietary fibre intake identified distinct avidity responses. Conclusion: We showed associations between baseline gut microbiota composition and immunogenicity of BNT162b2 vaccine responses, particularly avidity maturation. We also demonstrate that branched-chain fatty acids and habitual dietary fibre intakes are associated with BNT162b2 vaccine immunogenicity. Together these findings indicate a link between gut microbiome, diet and antibody immunity to SARS-CoV-2 spike protein, suggesting interventions which modulate the gut microbiome could enhance COVID-19 vaccine responses.

Analysis of 16S rRNA gene sequence of nasopharyngeal exudate from healthy donors reveals changes in key microbial communities associated with aging (preprint)

ABSTRACT Background Functional or compositional perturbations of the microbiome can occur at different sites of the body and this dysbiosis has been linked to various diseases. Changes in the nasopharyngeal microbiome are associated to patient’s susceptibility to multiple viral infections, including COVID-19, supporting the idea that the nasopharynx may be playing an important role in health and disease. Most studies on the nasopharyngeal microbiome have focused on a specific component in the lifespan, such as infanthood or the elderly, or have other limitations such as low sample sizes. Therefore, detailed studies analyzing the age- and sex-associated changes in the nasopharyngeal microbiome of healthy people across their whole life are essential to understand the relevance of the nasopharynx in the pathogenesis of multiple diseases, particularly viral infections such as COVID-19. Results 120 nasopharyngeal samples from healthy subjects of all ages and both sexes were analyzed by 16s rRNA sequencing. Nasopharyngeal bacterial alpha diversity did not vary in any case between age or sex groups. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant phyla in all the age groups, with several sex-associated differences probably due to the different levels of sex hormones between both sexes. Acinetobacter, Brevundimonas, Dolosigranulum, Finegoldia, Haemophilus, Leptotrichia, Moraxella, Peptoniphilus, Pseudomonas, Rothia , and Staphylococcus were the only 11 bacterial genera that presented significant age-associated differences. Other bacterial genera such as Anaerococcus, Burkholderia, Campylobacter, Delftia, Prevotella, Neisseria, Propionibacterium, Streptococcus, Ralstonia, Sphingomonas , and Corynebacterium appeared in the population with a very high frequency, suggesting that their presence might be biologically relevant. Conclusions In contrast to other anatomical areas such as the gut, bacterial diversity in the nasopharynx of healthy subjects remains very stable and resistant to perturbations throughout the whole life and in both sexes. Age-associated changes in taxonomic composition were observed at phylum, family, and genus levels, as well as several sex-associated changes probably due to the different levels of sex hormones present in both sexes at certain ages. Our results provide a complete and valuable dataset that will be useful for future research aiming for studying the relationship between changes in the nasopharyngeal microbiome and susceptibility to or severity of multiple diseases, including COVID-19.

Estimating the global and regional burden of meningitis in children caused by Haemophilus influenzae type b: A systematic review and meta-analysis.

Background: Haemophilus influenzae Type B (Hib) meningitis caused significant public health concern for children. Recent assessment in 2015 suggests vaccination has virtually eliminated invasive Hib diseases. However, many countries launched their programs after 2010, and few are yet to establish routine Hib immunisations. We therefore aimed to update the most recent global burden of Hib meningitis before the impact of COVID-19 pandemic, from 2010 to 2020, in order to aid future public health policies on disease management and prevention. Methods: Epidemiological data regarding Hib meningitis in children <5 years old were systematically searched and evaluated from PubMed and Scopus in August, 2020. We included studies published between 2010 and 2019 that reported incidence, prevalence, mortality, or case-fatality-ratio (CFR), and confirmation of meningitis by cerebrospinal fluid culture, with a minimum one year study period and ten cases. Each data was stratified by one study-year. Median study-year was used if information was not available. Quality of all studies were assessed using our adapted assessment criteria from Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Study Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from National Heart, Lung and Blood Institute (NHLBI). We constructed and visually inspected a funnel plot of standard error by the incidence rate and performed an Egger's regression test to statistically assess publication bias. To ascertain incidence and CFR, we performed generalised linear mixed models on crude individual study estimates. Heterogeneity was assessed using I-squared statistics whilst further exploring heterogeneity by performing subgroup analysis. Results: 33 studies were identified. Pooled incidence of global Hib meningitis in children was 1.13 per 100 000-child-years (95% confidence interval (CI) = 0.80-1.59). Southeast Asian Region (SEAR) of World Health Organisation (WHO) region reported the highest incidence, and European Region (EUR) the lowest. Considering regions with three or more data, Western Pacific Region (WPR) had the highest incidence rate of 5.22 (95% CI = 3.12-8.72). Post-vaccination incidence (0.67 cases per 100 000-child-years, 95% CI = 0.48-0.94) was dramatically lower than Pre-vaccination incidence (4.84 cases per 100 000-child-years, 95% CI = 2.95-7.96). Pooled CFR in our meta-analysis was 11.21% (95% CI = 7.01-17.45). Eastern Mediterranean Region (EMR) had the highest CFR (26.92, 95% CI = 13.41-46.71) while EUR had the lowest (4.13, 95% CI = 1.73-9.54). However, considering regions with three or more data, African Region (AFR) had the highest CFR at 21.79% (95% CI = 13.65-32.92). Before the coronavirus disease 2019 (COVID-19) impact, the estimation for global Hib meningitis cases in 2020 is 7645 and 857 deaths. Conclusions: Global burden of Hib meningitis has markedly decreased, and most regions have implemented vaccination programs. Extrapolating population-at-risk from studies has possibly led to an underestimation. Continuous surveillance is necessary to monitor vaccination impact, resurgence, vaccine failures, strain variance, COVID-19 impact, and to track improvement of regional and global Hib meningitis mortality.

Increase in invasive disease caused by Haemophilus influenzae b, the Netherlands, 2020 to 2021.

The incidence of most respiratory-transmitted diseases decreased during the COVID-19 pandemic as a result of containment measures. In contrast, in the Netherlands we noted an increase in invasive disease caused by Haemophilus influenzae b (Hib) (from < 0.3/100,000 before 2019 to 0.39 and 0.33/100,000 in 2020 and 2021) in vaccinated and unvaccinated age groups. We did not find a change in vaccine effectiveness against Hib invasive disease (effectiveness > 90%). We discuss factors that may have contributed to this rise.

COVID-19 severity and complications associated with low diversity, dysbiosis and predictive metagenome features of the oropharyngeal microbiome. (preprint)

Coronavirus 2 (SARS-CoV-2) infection and the resulting COVID-19 illness vary from asymptomatic disease, mild upper respiratory tract infection, pneumonia1, to a life-threatening multi-organ failure with case fatality rates ranging from 0.27–13.4%2,3. Despite increasing knowledge of the clinical and immunological features underlying COVID-191,4−6, biological variables explaining the course of infection and its severity remain elusive. At the entry site of SARS-CoV2, the oropharyngeal microbiome represents a hub integrating viral and immune signals at the start of the infection7–10. To evaluate the role of the oropharyngeal microbiome in COVID-19, we performed a multi-center, cross-sectional clinical study analyzing the oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate and severe COVID-19 encompassing a total of 345 participants. Significantly reduced microbiome diversity and high dysbiosis were observed in hospitalized patients with severe COVID-19, which was further associated with a loss of microbial genes and metabolic pathways. In this cohort, diversity measures were also associated with need for intensive care treatments as major clinical parameters in COVID-19. We further applied random forest machine learning to unravel microbial features for segregating clinical outcomes in hospitalized cases, and observed oropharyngeal microbiome abundances of Haemophilus or Streptococcus species as most important features. These findings provide insights into the role of the oropharyngeal microbiome in SARS-CoV-2 infection, and may suggest new biomarkers for COVID-19 severity.

A model for the incremental burden of invasive Haemophilus influenzae type b due to a decline of childhood vaccination during the COVID-19 outbreak: A dynamic transmission model in Japan.

BACKGROUND: The current coronavirus disease 2019 (COVID-19) outbreak has caused a persistent decline in childhood vaccination coverage, including Haemophilus influenzae type b (Hib) vaccine, in some countries. Our objective was to evaluate the impact of decreased Hib vaccination due to COVID-19 on invasive Hib disease burden in Japan. METHODS: Using a deterministic dynamic transmission model (susceptible-carriage-infection-recovery model), the incidence rates of invasive Hib disease in under 5 year olds in rapid vaccination recovery and persistent vaccination declined scenarios were compared for the next 10 years after 2020. The national Hib vaccination rate after the impact of COVID-19 reduced to 87% and 73% in 2020 from approximately 97% each in 2013-2019 for primary and booster doses. RESULTS: While the persistent decline scenarios revealed an increase in invasive Hib disease incidence to 0.50/100,000 children under 5 years old, the incidence of the rapid recovery scenario slightly increased with a consistent decline of incidence after 2021. The shorter the duration of the decline in vaccination rate was, the smaller the incremental disease burden observed in the model. Compared to the rapid recovery scenario, the permanent decline scenario showed a 296.87 cumulative incremental quality-adjusted life years (QALY) loss for the next 10 years. CONCLUSIONS: The persistent decline of Hib vaccination rate due to COVID-19 causes an incremental disease burden irrespective of the possible decline of Hib transmission rate by COVID-19 mitigation measures. A rapid recovery of vaccination coverage rate can prevent this possible incremental disease burden.

Transmission of respiratory tract infections at mass gathering events.

PURPOSE OF REVIEW: Mass gathering events bring people from across all continents increasing the risk of spread of aerosol transmissible respiratory tract infections. Respiratory tract infections for instance in pilgrims attending the world's largest recurring annual pilgrimage, the Hajj are common. We review recent literature on viral and bacterial infectious diseases with special focus on the Hajj. RECENT FINDINGS: The prevalence of bacterial and viral infections continue to increase, because of the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus during Hajj. Whilst MERS-CoV continues to circulate in the Middle East, no cases of MERS-CoV have yet been identified in pilgrims during Hajj. SUMMARY: Respiratory tract infections are a major cause of morbidity in pilgrims attending mass gathering events. The management of severe respiratory infections should consider investigation and empirical coverage for the most likely agents based on syndromic surveillance data from hosting country and /or other relevant exposure history during events. Pneumococcal and Pertussis vaccines should be recommended for Hajj pilgrims.

Impact of COVID-19 pandemic and the lockdown on invasive meningococcal disease (preprint)

Objective: Few data are available on the association between SARS-CoV-2 and secondary bacterial infections. Such an association was described for flu and invasive meningococcal disease (IMD). We aimed exploring such a correlation between COVID-19and IMD.Results: We compared IMD cases received at the French National Reference Centre for meningococci and Haemophilus influenzae that are sent as part of the mandatory reporting of IMD. We compared these data during the period 01 January-15 May 2020 to those from the same period in 2019. IMD cases that were associated with respiratory presentations significantly increased in 2020, involved elderly and were due to unusual isolates. However, usual IMD cases due to highly transmissible isolates decreased during the lockdown. Enhancing IMD surveillance and anti-meningococcal vaccination in elderly should to be addressed.