The COVID-19 pandemic as an opportunity for unravelling the causative association between respiratory viruses and pneumococcus-associated disease in young children: a prospective study.

BACKGROUND: In young children, rates of lower respiratory infections (LRI) and invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumonia and pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of these disease endpoints has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. METHODS: This prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were previously collected in multiple ongoing prospective surveillance programs and include: hospital visits for community-acquired alveolar pneumonia (CAAP), non-CAAP LRI; nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; and nationwide, all-ages COVID-19 episodes and IPD in children <5 years. A hierarchical statistical model was developed to estimate the proportion of the different clinical endpoints attributable to each virus from monthly time series data, stratified by age and ethnicity. A separate model was fit for each endpoint, with covariates that included a linear time trend, 12-month harmonic variables to capture unexplained seasonal variations, and the proportion of tests positive for each virus in that month. FINDINGS: During 2016 through 2021, 3,204, 26,695, 257, and 619 episodes of CAAP, non-CAAP LRI, pneumococcal bacteremic pneumonia and non-pneumonia IPD, respectively, were reported. Compared to 2016-2019, broad declines in the disease endpoints were observed shortly after the pandemic surge, coincident with a complete disappearance of all PDA-viruses and continued circulation of rhinovirus (RhV) and adenovirus (AdV). From April 2021, off-season and abrupt surges of all disease endpoints occurred, associated with similar dynamics among the PDA-viruses, which re-emerged sequentially. Using our model fit to the entire 2016-2021 period, 82% (95% CI, 75-88%) of CAAP episodes in 2021 were attributable to the common respiratory viruses, as were 22%-31% of the other disease endpoints. Virus-specific contributions to CAAP were: RSV, 49% (95% CI, 43-55%); hMPV, 13% (10-17%); PIV, 11% (7-15%); flu, 7% (1-13%). RhV and AdV did not contribute. RSV was the main contributor in all endpoints, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. INTERPRETATION: RSV and hMPV play a critical role in the burden of CAAP and pneumococcal disease in children. Interventions targeting these viruses could have a secondary effect on the burden of disease typically attributed to bacteria. FUNDING: There was no funding for this study.

Barriers and facilitators to vaccination uptake against COVID-19, influenza, and pneumococcal pneumonia in immunosuppressed adults with immune-mediated inflammatory diseases: A qualitative interview study during the COVID-19 pandemic.

OBJECTIVES: To explore barriers and facilitators to COVID-19, influenza, and pneumococcal vaccine uptake in immunosuppressed adults with immune-mediated inflammatory diseases (IMIDs). METHODS: Recruiting through national patient charities and a local hospital, participants were invited to take part in an in-depth, one-to-one, semi-structured interview with a trained qualitative researcher between November 2021 and January 2022. Data were analysed thematically in NVivo, cross-validated by a second coder and mapped to the SAGE vaccine hesitancy matrix. RESULTS: Twenty participants (75% female, 20% non-white) were recruited. Barriers and facilitators spanned contextual, individual/group and vaccine/vaccination-specific factors. Key facilitators to all vaccines were higher perceived infection risk and belief that vaccination is beneficial. Key barriers to all vaccines were belief that vaccination could trigger IMID flare, and active IMID. Key facilitators specific to COVID-19 vaccines included media focus, high incidence, mass-vaccination programme with visible impact, social responsibility, and healthcare professionals' (HCP) confirmation of the new vaccines' suitability for their IMID. Novel vaccine technology was a concern, not a barrier. Key facilitators of influenza/pneumococcal vaccines were awareness of eligibility, direct invitation, and, clear recommendation from trusted HCP. Key barriers of influenza/pneumococcal vaccines were unaware of eligibility, no direct invitation or recommendation from HCP, low perceived infection risk, and no perceived benefit from vaccination. CONCLUSIONS: Numerous barriers and facilitators to vaccination, varying by vaccine-type, exist for immunosuppressed-IMID patients. Addressing vaccine benefits and safety for IMID-patients in clinical practice, direct invitation, and public-health messaging highlighting immunosuppression as key vaccination-eligibility criteria may optimise uptake, although further research should assess this.

Effectiveness of influenza and pneumococcal vaccines on chronic obstructive pulmonary disease exacerbations.

BACKGROUND AND OBJECTIVE: Single-study evidence of separate and combined effectiveness of influenza and pneumococcal vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To fill this gap, we studied the effectiveness of trivalent seasonal influenza vaccine (TIV) and 23-valent pneumococcal polysaccharide vaccine (PPSV23), separately and together, at preventing adverse COPD outcomes. METHODS: Our study used a self-controlled, before-and-after cohort design to assess the effectiveness of TIV and PPSV23 in COPD patients. Patients were recruited from hospitals in Tangshan City, Hebei Province, China. Subjects self-selected into one of the three vaccination schedules: TIV group, PPSV23 group and TIV&PPSV23 group. We used a physician-completed, medical record-verified questionnaire to obtain data on acute exacerbations of COPD (AECOPD), pneumonia and related hospitalization. Vaccine effectiveness was determined by comparing COPD outcomes before and after vaccination, controlling for potential confounding using Cox regression. RESULTS: We recruited 474 COPD patients, of whom 109 received TIV, 69 received PPSV23 and 296 received TIV and PPSV23. Overall effectiveness for preventing AECOPD, pneumonia and related hospitalization were respectively 70%, 59% and 58% in the TIV group; 54%, 53% and 46% in the PPSV23 group; and 72%, 73% and 69% in the TIV&PPSV23 group. The vaccine effectiveness without COVID-19 non-pharmaceutical intervention period were 84%, 77% and 88% in the TIV group; 63%, 74% and 66% in the PPSV23 group; and 82%, 83% and 91% in the TIV&PPSV23 group. CONCLUSION: Influenza vaccination and PPSV23 vaccination, separately and together, can effectively reduce the risk of AECOPD, pneumonia and related hospitalization. Effectiveness for preventing AECOPD was the greatest.

Impact of vaccination on the epidemiology and prognosis of pneumonia.

Adults with lung diseases, comorbidities, smokers, and elderly are at risk of lung infections and their consequences. Community-acquired pneumonia happen in more than 1% of people each year. Possible pathogens of community-acquired pneumonia include viruses, pneumococcus and atypicals. The CDC recommend vaccination throughout life to provide immunity, but vaccination rates in adults are poor. Tetravalent and trivalent influenza vaccine is designed annually during the previous summer for the next season. The available vaccines include inactivated, adjuvant, double dose, and attenuated vaccines. Their efficacy depends on the variant of viruses effectively responsible for the outbreak each year, and other reasons. Regarding the pneumococcal vaccine, there coexist the old polysaccharide 23-valent vaccine with the new conjugate 10-valent and 13-valent conjugate vaccines. Conjugate vaccines demonstrate their usefulness to reduce the incidence of pneumococcal pneumonia due to the serotypes present in the vaccine. Whooping cough is still present, with high morbidity and mortality rates in young infants. Adult's pertussis vaccine is available, it could contribute to the control of whooping cough in the most susceptible, but it is not present yet in the calendar of adults around the world. About 10 vaccines against SARS-CoV-2 have been developed in a short time, requiring emergency use authorization. A high rate of vaccination was observed in most of the countries. Booster doses became frequent after the loss of effectiveness against new variants. The future of this vaccine is yet to be written.

CT features of community-acquired pneumonia at the emergency department.

BACKGROUND: Chest computed tomography (CT) was reported to improve the diagnosis of community-acquired pneumonia (CAP) as compared to chest X-ray (CXR). The aim of this study is to describe the CT-patterns of CAP in a large population visiting the emergency department and to see if some of them are more frequently missed on CXR. MATERIALS AND METHODS: This is an ancillary analysis of the prospective multicenter ESCAPED study including 319 patients. We selected the 163 definite or probable CAP based on adjudication committee classification; 147 available chest CT scans were reinterpreted by 3 chest radiologists to identify CAP patterns. These CT-patterns were correlated to epidemiological, biological and microbiological data, and compared between false negative and true positive CXR CAP. RESULTS: Six patterns were identified: lobar pneumonia (51/147, 35%), including 35 with plurifocal involvement; lobular pneumonia (43/147, 29%); unilobar infra-segmental consolidation (24/147, 16%); bronchiolitis (16/147, 11%), including 4 unilobar bronchiolitis; atelectasis and bronchial abnormalities (8/147, 5.5%); interstitial pneumonia (5/147, 3.5%). Bacteria were isolated in 41% of patients with lobar pneumonia-pattern (mostly Streptococcus pneumoniae and Mycoplasma pneumonia) versus 19% in other patients (p = 0.01). Respiratory viruses were equally distributed within all patterns. CXR was falsely negative in 46/147 (31%) patients. Lobar pneumonia was significantly less missed on CXR than other patterns (p = 0.003), especially lobular pneumonia and unilobar infra-segmental consolidation, missed in 35% and 58% of cases, respectively. CONCLUSION: Lobar and lobular pneumonias are the most frequent CT-patterns. Lobar pneumonia is appropriately detected on CXR and mainly due to Streptococcus pneumoniae or Mycoplasma pneumoniae. Chest CT is very useful to identify CAP in other CT-patterns. Prior the COVID pandemic, CAP was rarely responsible for interstitial opacities on CT.

Aetiology of lobar pneumonia determined by multiplex molecular analyses of lung and pleural aspirate specimens in the Gambia: findings from population-based pneumonia surveillance.

OBJECTIVES: To determine the causes of lobar pneumonia in rural Gambia. DESIGN AND SETTING: Population-based pneumonia surveillance at seven peripheral health facilities and two regional hospitals in rural Gambia. 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in August 2009 and replaced by PCV13 from May 2011. METHODS: Prospective pneumonia surveillance was undertaken among all ages with referral of suspected pneumonia cases to the regional hospitals. Blood culture and chest radiographs were performed routinely while lung or pleural aspirates were collected from selected, clinically stable patients with pleural effusion on radiograph and/or large, dense, peripheral consolidation. We used conventional microbiology, and from 8 April 2011 to 17 July 2012, used a multiplex PCR assay on lung and pleural aspirates. We calculated proportions with pathogens, associations between coinfecting pathogens and PCV effectiveness. PARTICIPANTS: 2550 patients were admitted with clinical pneumonia; 741 with lobar pneumonia or pleural effusion. We performed 181 lung or pleural aspirates and multiplex PCR on 156 lung and 4 pleural aspirates. RESULTS: Pathogens were detected in 116/160 specimens, the most common being Streptococcus pneumoniae(n=68), Staphylococcus aureus (n=26) and Haemophilus influenzae type b (n=11). Bacteria (n=97) were more common than viruses (n=49). Common viruses were bocavirus (n=11) and influenza (n=11). Coinfections were frequent (n=55). Moraxella catarrhalis was detected in eight patients and in every case there was coinfection with S. pneumoniae. The odds ratio of vaccine-type pneumococcal pneumonia in patients with two or three compared with zero doses of PCV was 0.17 (95% CI 0.06 to 0.51). CONCLUSIONS: Lobar pneumonia in rural Gambia was caused primarily by bacteria, particularly S. pneumoniae and S. aureus. Coinfection was common and M. catarrhalis always coinfected with S. pneumoniae. PCV was highly efficacious against vaccine-type pneumococcal pneumonia.

Porphyromonas gingivalis Components/Secretions Synergistically Enhance Pneumonia Caused by Streptococcus pneumoniae in Mice.

Streptococcus pneumoniae is an important causative organism of respiratory tract infections. Although periodontal bacteria have been shown to influence respiratory infections such as aspiration pneumonia, the synergistic effect of S. pneumoniae and Porphyromonas gingivalis, a periodontopathic bacterium, on pneumococcal infections is unclear. To investigate whether P. gingivalis accelerates pneumococcal infections, we tested the effects of inoculating P. gingivalis culture supernatant (PgSup) into S. pneumoniae-infected mice. Mice were intratracheally injected with S. pneumoniae and PgSup to induce pneumonia, and lung histopathological sections and the absolute number and frequency of neutrophils and macrophages in the lung were analyzed. Proinflammatory cytokine/chemokine expression was examined by qPCR and ELISA. Inflammatory cell infiltration was observed in S. pneumoniae-infected mice and S. pnemoniae and PgSup mixed-infected mice, and mixed-infected mice showed more pronounced inflammation in lung. The ratios of monocytes/macrophages and neutrophils were not significantly different between the lungs of S. pneumoniae-infected mice and those of mixed-infected mice. PgSup synergistically increased TNF-α expression/production and IL-17 production compared with S. pneumoniae infection alone. We demonstrated that PgSup enhanced inflammation in pneumonia caused by S. pneumoniae, suggesting that virulence factors produced by P. gingivalis are involved in the exacerbation of respiratory tract infections such as aspiration pneumonia.

Pneumonia Following Symptomatic Influenza Infection Among Nicaraguan Children Before and After Introduction of the Pneumococcal Conjugate Vaccine.

Influenza is associated with primary viral and secondary bacterial pneumonias; however, the dynamics of this relationship in populations with varied levels of pneumococcal vaccination remain unclear. We conducted nested matched case-control studies in 2 prospective cohorts of Nicaraguan children aged 2-14 years: 1 before pneumococcal conjugate vaccine introduction (2008-2010) and 1 following introduction and near universal adoption (2011-2018). The association between influenza and pneumonia was similar in both cohorts. Participants with influenza (across types/subtypes) had higher odds of developing pneumonia in the month following influenza infection. These findings underscore the importance of considering influenza in interventions to reduce global pneumonia burden.

Pneumococcal pneumonia among shipyard workers: Inside the features of disease onset.

BACKGROUND: Several outbreaks of pneumococcal pneumonia among shipyard workers have been described. In this study, following a previous report of grouped cases, we aimed to elucidate the features of disease onset. METHODS: We compared the population characteristics of shipyard workers with a confirmed diagnosis of pneumococcal pneumonia (N = 38) to those of workers without pneumonia (N = 53). We compared nine S. pneumoniae strains isolated from patients with pneumonia by capsular serotyping, multi-locus sequence typing, and whole genome sequencing. RESULTS: Shipyard workers with Streptococcus pneumoniae pneumonia were more frequently from Italy (P = 0.016), had at least one underlying condition (P = 0.024), lived on-board the ship (P = 0.009). None of these factors was independent by multivariate analysis. While capsular serotyping enabled us to identify four different serotypes: 4 (n = 5), 8 (n = 2), 9 N (n = 1), and 3 (n = 1), by sequence typing, we distinguished five sequence types (STs): ST801 (n = 4), ST205 (n = 2), ST1220 (n = 1), ST1280 (n = 1), and ST66 (n = 1). Whole genome sequencing confirmed the results obtained by MLST. Genomes of isolates of the same sequence type were similar with ≤80 single-nucleotide polymorphisms. CONCLUSIONS: We confirmed that the onset of pneumococcal infection among shipyard workers was attributable to both a person-to-person spread of single strains of S. pneumoniae and a shift of different strains from commensal to pathogen under favourable conditions (professional exposure, viral infections). Control measures should therefore be implemented by taking into account these features.

Pneumococcal Conjugate Vaccine Protection against Coronavirus-Associated Pneumonia Hospitalization in Children Living with and without HIV.

In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, P < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, P = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that Streptococcus pneumoniae infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes.IMPORTANCE SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.

A Retrospective Study of Coinfection of SARS-CoV-2 and Streptococcus pneumoniae in 11 Hospitalized Patients with Severe COVID-19 Pneumonia at a Single Center.

BACKGROUND A lethal synergism between the influenza virus and Streptococcus pneumoniae has been identified. However, bacterial coinfection is considered relatively infrequent in hospitalized patients with COVID-19, and the co-prevalence of Streptococcus pneumoniae is low. MATERIAL AND METHODS We retrospectively analyzed the clinical characteristics and outcomes of patients subsequently admitted to AMITA Health Saint Francis Hospital between March 1 and June 30, 2020, with documented SARS-CoV-2 and S. pneumoniae coinfection. RESULTS We identified 11 patients with S. pneumoniae coinfection. The median age was 77 years (interquartile range [IQR], 74-82 years), 45.5% (5/11) were males, 54.5% (6/11) were white, and 90.9% (10/11) were long-term care facility (LTCF) residents. The median length of stay was 7 days (IQR, 6-8 days). Among 11 patients, 4 were discharged in stable condition and 7 had died, resulting in an inpatient mortality rate of 64%. CONCLUSIONS At our center, 11 patients with COVID-19 pneumonia who had confirmed infection with SARS-CoV-2 were diagnosed with Streptococcus pneumoniae infection while in hospital. All patients had pneumonia confirmed on imaging and a nonspecific increase in markers of inflammation. The in-hospital mortality rate of 64% (7 patients) was higher in this group than in previous reports. This study highlights the importance of monitoring bacterial coinfection in patients with viral lung infection due to SARS-CoV-2.

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.