Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans (preprint)

Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae. Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

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.

Streptococcus pneumoniae re-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021 (preprint)

BackgroundThe COVID-19 pandemic and the associated containment measures had a substantial impact on pathogens causing pneumonia in adults. The objective of this study was to determine the etiology of hospitalized community-acquired pneumonia (CAP) among adults in Germany in 2021, the second year of the COVID-19 pandemic. MethodsSince January 2021, this on-going, prospective, population-based surveillances study enrolled adult patients with clinically and radiographically confirmed CAP at three hospitals in Thuringia, Germany, serving a population of approximately 280,000. Urine samples were collected from patients and tested for S. pneumoniae using the pneumococcal urinary antigen test (PUAT, BinaxNOW S. pneumoniae) and the proprietary serotype-specific urinary antigen detection (UAD) assays. Nasopharyngeal swabs were tested for 10 respiratory viruses by PCR. ResultsA total of 797 patients were enrolled, of whom 760 were included in the analysis. The median age of patients with CAP was 67 years; in-hospital case-fatality rate was 8.4%. A respiratory pathogen was detected in 553 (72.8%) patients. The most common pathogen was SARS-CoV-2 (n=498, 68.2%), followed by S. pneumoniae (n=40, 6.4%). Serotypes contained in the 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccine were detected in 42.5%, 45.0%, and 70.0% of the pneumococcal CAP cases. Between the first and second half of 2021, the proportion of CAP cases associated with S. pneumoniae increased from 1.1% to 5.6% in patients aged 18-59 years and from 2.5% to 12.4% in those aged [≥]60 years; coinfection of SARS-CoV-2 and S. pneumoniae among COVID-19 patients increased from 0.7% (2/283 cases) to 6.0% (13/215) in patients aged [≥]18 years, and from 1.0% (2/195) to 8.7% (11/127) in those aged [≥]60 years. ConclusionIn Germany, the proportion of CAP cases associated with S. pneumoniae rebounded to a near-pandemic level in the second half of 2021 and many pneumococcal infections occurred in patients with COVID-19. Vaccination uptake against respiratory pathogens, including S. pneumoniae, should be strengthened.

The COVID-19 Pandemic as an Opportunity for Unravelling the Causative Association between Respiratory Viruses and Pneumococcus-Associated Disease in Young Children: A Prospective Cohort Study (preprint)

BACKGROUNDIn young children, rates of community-acquired alveolar pneumonia (CAAP) or invasive pneumococcal disease (IPD) have been associated with respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (flu), and parainfluenza (PIV) (collectively termed here as pneumococcal disease-associated viruses [PDA-viruses]). However, their contribution to the pathogenesis of pneumococcal-associated disease has not yet been elucidated. The COVID-19 pandemic provided a unique opportunity to examine the question. METHODSThis prospective study comprised all children <5 years, living in southern Israel, during 2016 through 2021. The data were derived from multiple ongoing prospective cohort surveillance programs and include: hospital visits for CAAP, non-CAAP lower respiratory infections (LRI); nasopharyngeal pneumococcal carriage (<3 years of age); respiratory virus activity; all-ages COVID-19 episodes; and IPD in children <5 years (nationwide) A hierarchical negative binominal regression model was developed to estimate the proportion of the disease outcomes attributable to each of the viruses from monthly time series data, stratified by age and ethnicity. A separate model was fit for each outcome, 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. FINDINGSDuring 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 outcomes 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 outcomes 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 outcomes. 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 outcomes, especially in infants. Pneumococcal carriage prevalence remained largely stable throughout the study. INTERPRETATIONRSV 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 disease burden typically attributed to bacteria. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSCommunity-acquired alveolar pneumonia (CAAP) and invasive pneumococcal disease (IPD) in young children have often been associated with specific respiratory viruses, namely respiratory syncytial virus (RSV) human metapneumovirus (hMPV) influenza viruses (flu), and parainfluenza viruses (PIV) (termed in the current article pneumococcal disease-associated viruses [PDA-viruses]). However, their causative role as co-pathogens has not yet been fully elucidated. Pneumococcal conjugate vaccines (PCVs) significantly reduce hospitalization for viral lower respiratory infections (LRIs), suggesting that viral-pneumococcal coinfections are common and play a role in the pathogenesis of pneumococcal respiratory infections. However, in theory, the strongest demonstration of the causative role of respiratory viruses on pneumococcus-associated diseases would derive from measuring the impact of elimination of one or more of the respiratory viruses during the expected respiratory season. Shortly after the start of the COVID-19 pandemic, multiple reports have demonstrated reduced IPD and LRI rates among young children, coincident with dramatically reduced rates of the PDA-viruses globally. Initially, the reduced pneumococcal disease rates were attributed to non-pharmaceutical interventions that might reduce pneumococcal transmission in the community. However, continuous, virtually unchanged pneumococcal carriage rates were reported in multiple studies, strongly suggesting the reduced circulation of S. pneumoniae was not significantly contributing to disease reduction. Surprisingly, pneumococcus-associated diseases and PDA-viruses simultaneously re-emerged in 2021 during the off-season. In contrast to PDA-viruses, other viruses, such as adenovirus and rhinovirus did not show any of the patterns discussed above. We searched PubMed on June 1st, 2022, for studies since 2012 using the following terms: ("COVID-19" or "SARS-Cov-2") and ("S. pneumoniae" or "pneumococcus" or "IPD" or "respiratory virus" or respiratory syncytial virus" or "hMPV" or "influenza" or "parainfluenza" or "adenovirus" or "rhinovirus" or "lower respiratory infection"). The search was for English literature and unrestricted by date. Added value of this studyThree unique characteristics of the COVID-19 pandemic-induced abnormal dynamics, coupled with multiple ongoing cohort studies in young children, contributed to the historic opportunity to model and quantify the attributable role of the various common respiratory viruses to four pneumococcus-associated disease outcomes (CAAP, non-CAAP LRIs, pneumococcal bacteremic pneumonia and non-pneumonia IPD): First, the full seasonal disappearance of all PDA-viruses shortly after the start of the pandemic, in the presence of continuous, uninterrupted pneumococcal carriage and continuous unchanged rhinovirus and adenovirus activity. Second, the off-season resurgence of the PDA-viruses in 2021. Third, the sequential, rather than simultaneous, re-emergence of the PDA-viruses. The analysis in this study suggests that several of the respiratory viruses, particularly RSV and hMPV, play an important causative role in the pathogenesis of pneumococcal diseases and related conditions. Furthermore, the proportion attributable to each of the PDA-viruses for each of the four studied disease outcomes, and each of the age groups (<1, 1, and 2-4 years of age) could be demonstrated. Implication of all the available findingsOur findings add evidence about the absolute and relative contribution of common respiratory viruses to the burden of pneumococcal diseases and related conditions in young children, likely to be caused, at least in part, by virus-pneumococcus interaction or coinfections. The strong predominance of RSV contribution compared to other viruses in all studied disease outcomes suggests that interventions that target viruses could have secondary effects on the burden of diseases typically attributed to bacteria.

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.

Bacteraemic pneumococcal pneumonia and SARS-CoV-2 pneumonia: differences and similarities.

OBJECTIVE: To analyse differences in clinical presentation and outcome between bacteraemic pneumococcal community-acquired pneumonia (B-PCAP) and sSvere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pneumonia. METHODS: This observational multi-centre study was conducted on patients hospitalized with B-PCAP between 2000 and 2020 and SARS-CoV-2 pneumonia in 2020. Thirty-day survival, predictors of mortality, and intensive care unit (ICU) admission were compared. RESULTS: In total, 663 patients with B-PCAP and 1561 patients with SARS-CoV-2 pneumonia were included in this study. Patients with B-PCAP had more severe disease, a higher ICU admission rate and more complications. Patients with SARS-CoV-2 pneumonia had higher in-hospital mortality (10.8% vs 6.8%; P=0.004). Among patients admitted to the ICU, the need for invasive mechanical ventilation (69.7% vs 36.2%; P<0.001) and mortality were higher in patients with SARS-CoV-2 pneumonia. In patients with B-PCAP, the predictive model found associations between mortality and systemic complications (hyponatraemia, septic shock and neurological complications), lower respiratory reserve and tachypnoea; chest pain and purulent sputum were protective factors in these patients. In patients with SARS-CoV-2 pneumonia, mortality was associated with previous liver and cardiac disease, advanced age, altered mental status, tachypnoea, hypoxaemia, bilateral involvement, pleural effusion, septic shock, neutrophilia and high blood urea nitrogen; in contrast, ≥7 days of symptoms was a protective factor in these patients. In-hospital mortality occurred earlier in patients with B-PCAP. CONCLUSIONS: Although B-PCAP was associated with more severe disease and a higher ICU admission rate, the mortality rate was higher for SARS-CoV-2 pneumonia and deaths occurred later. New prognostic scales and more effective treatments are needed for patients with SARS-CoV-2 pneumonia.

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.

[Vaccination against community acquired pneumonia in adults. Update 2021 of the position paper by Neumoexpertos en Prevención Group]. / Vacunación frente a la neumonía adquirida en la comunidad del adulto. Actualización 2021 del posicionamiento del Grupo de Neumoexpertos en Prevención.

Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the practical prevention guide for CAP through vaccination in Spain developed in 2016 and updated in 2018, based on available vaccines and evidence through bibliographic review and expert opinion. The arrival of COVID-19 as a new cause of CAP and the recent availability of safe and effective vaccines constitutes the most significant change. Vaccines against pneumococcus, influenza, pertussis and COVID-19 can help to reduce the burden of disease from CAP and its associated complications. The available evidence supports the priority indications established in this guide, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice.

Decline in pneumococcal disease in young children during the COVID-19 pandemic associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: A prospective cohort study (preprint)

Background: Invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from non-pharmacological interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis. Methods: The first SARS-CoV-2 cases were detected in February-2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), non-alveolar lower respiratory infections necessitating chest X-rays (NA-LRI), nasopharyngeal pneumococcal carriage in non-respiratory visits, nasopharyngeal respiratory virus detection (by PCR), and nationwide invasive pneumococcal disease (IPD). Monthly rates (January-2020 through February-2021 vs. mean monthly rates 2016-2019 [expected rates]) adjusted for age and ethnicity, were compared. Findings: CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios, [IRRs] 0.07 and 0.19, respectively); NA-LRI and non-pneumonia IPD were also reduced, with a lesser magnitude (IRRs, 0.46 and 0.42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced and density of colonization and pneumococcal serotype distributions were similar to previous years. The pneumococcus-associated disease decline was temporally associated with a full suppression of RSV, influenza viruses, and hMPV, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. Interpretation: Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic were not predominantly related to reduced pneumococcal transmission and carriage but were strongly associated with the complete disappearance of specific respiratory viruses. Funding: Partially funded by Pfizer, Inc.

Streptococcus pneumoniae colonisation associates with impaired adaptive immune responses against SARS-CoV-2 (preprint)

Although recent epidemiological data suggest that pneumococci may contribute to the risk of SARS-CoV-2 disease, secondary pneumococcal pneumonia has been reported as infrequent. This apparent contradiction may be explained by interactions of SARS-CoV-2 and pneumococcus in the upper airway, resulting in the escape of SARS-CoV-2 from protective host immune responses. Here, we investigated the relationship of these two respiratory pathogens in two distinct cohorts of a) healthcare workers with asymptomatic or mildly symptomatic SARS-CoV-2 infection identified by systematic screening and b) patients with moderate to severe disease who presented to hospital. We assessed the effect of co-infection on host antibody, cellular and inflammatory responses to the virus. In both cohorts, pneumococcal colonisation was associated with diminished anti-viral immune responses, which affected primarily mucosal IgA levels among individuals with mild or asymptomatic infection and cellular memory responses in infected patients. Our findings suggest that S. pneumoniae modulates host immunity to SARS-CoV-2 and raises the question if pneumococcal carriage also enables immune escape of other respiratory viruses through a similar mechanism and facilitates reinfection occurrence.

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 pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.