Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. MethodsIn this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0•32 [95% CI 0•27-0•37]) and 82% at 8 weeks (0•18 [0•14-0•23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

No abstract

Within the Zermatt-Saas ophiolite zone of the western Alps a record of polystadial high-pressure metamorphism is well preserved. Early blueschist assemblages, retained as inclusions in garnets, were succeeded by eclogitic assemblages which in some rocks contained lawsonite, kyanite, talc and chloritoid. These eclogitic assemblages formed by prograde reaction from the early blueschists. Subsequently, reaction of these eclogites with a mixed H,O-CO, vapour phase led to the replacement of kyanite by paragonite and the partial replacement of omphacite-garnet paragenses by assemblages containing glaucophane, paragonite and ankerite. High-pressure, eo-alpine metamorphism took place under conditions of 550-600°C and 17.5-20 kbar. Values of aH,O between 0.55 and 1 are high enough to accommodate equilibration with a water-rich vapour phase under the highestgrade conditions. The presence of such a fluid phase is locally indicated by the presence of quartz-rich veins containing omphacite and kyanite. This vapour phase was absorbed during retrogression. Later, rehydration is limited to areas close to albite veins, tectonic contacts and bodies of metasediment.The metamorphic conditions determined for the Zermatt-Saas zone are compatible with those suggested for over-and under-lying units. These conditions, and the P-T path inferred by comparing the reaction histories with a petrogenetic grid for the system Na,0-Ca0-Mg0-A1,0,-SiO~-H20, suggest that metamorphism occurred during subduction to depths of between 60 and 70 km and subsequent exhumation during the Alpine orogeny.

Background Streptococcus pneumoniae coinfection with influenza results in synergistic lethality, but there are limited data on pneumococcal coinfection with SARS-CoV-2. Methods Public Health England conducts invasive pneumococcal disease (IPD) and SARS-CoV-2 surveillance in England. IPD trends during 2000/01-2019/20 were analysed and cases between during February-June 2020 were linked with laboratory-confirmed SARS-CoV-2 infections. Multivariable logistic regression was used to assess risk factors for death. Results IPD incidence in 2019/20 (7.6/100,000; n=3,964) was 30% (IRR 0.70, 95%CI, 0.18-2.67) lower compared to 2018/19 (10.9/100,000; n=5,666) with large reductions observed across all age-groups during March-June 2020. The serotypes responsible for IPD during 2019/20 were similar to previous years. There were 160,886 SARS-CoV-2 and 1,137 IPD cases during February-June 2020, including 40 IPD/COVID-19 (0.025% [95%sCI, 0.018-0.034] of SARS-CoV-2 infections; 3.5% [95%CI, 2.5-4.8] of IPD cases), 21 with COVID-19 diagnosed 3-27 days after IPD and 27 who developed COVID-19 ≥28 days after IPD. Case-fatality rates (CFR) were 63.2% (25/40), 47.6% (10/21) and 33.3% (9/27), respectively (p<0.001). In addition to an independent association with increasing age and pneumococcal serotype group, CFR was 7.8-fold (95% CI, 3.8-15.8) higher in those with IPD/COVID-19 co-infection and 3.9-fold (95% CI, 1.4-10.7) higher in patients who developed COVID-19 3-27 days after IPD compared to patients with IPD only. Conclusions Large declines in IPD were observed following COVID-19 lockdown in England. IPD/COVID-19 confections were rare but associated with high CFR, mainly in older adults. The rarity, age distribution and serotype distribution of IPD/SARS-CoV-2 coinfections does not support wider extension of pneumococcal vaccination.

Background Invasive Pneumococcal Disease (IPD) is a major public health concern. The effectiveness of 23-valent polysaccharide pneumococcal vaccine (PPV23) against IPD in older age-groups is not fully understood. We measured PPV23 effectiveness against IPD and interpreted changes in IPD incidence between 2000 and 2017. Methods Public Health England conducts enhanced national IPD surveillance in England and Wales. The indirect cohort method was used to estimate PPV23 effectiveness against IPD in individuals aged ≥ 65 years eligible for PPV23 vaccination during 2012–2016. IPD incidence in 2016/17 was compared to rates during 2000–2003, when neither PPV23 nor pneumococcal conjugate vaccines (PCVs) were routinely used in England and Wales. Findings PPV23 effectiveness, irrespective of time since vaccination, was 27% (95% CI, 17–35) after adjusting for age, co-morbidity and year of infection. Vaccine effectiveness reduced non-significantly (p = 0.13) with time since vaccination, from 41% (95% CI, 23–54) for those vaccinated within two years, to 34% (95% CI, 16–48) for those vaccinated 2–4 years previously, and 23% (95% CI, 12–32) for those vaccinated ≥ 5 years previously. Vaccine effectiveness did not vary significantly by age but was highest in previously healthy individuals (45%; 95%CI, 27–59). IPD incidence for PPV23 serotypes not included in the PCVs did not decrease after routine PPV23 use but increased significantly since PCV introduction in 2006. Interpretation PPV23 offers moderate short-term protection against IPD in older adults. PPV23 serotypes comprise an increasing proportion of IPD cases in older adults because of serotype replacement following routine PCV use in children. Funding European Union's Horizon 2020.

BackgroundChanges over the last 5 years (2013–18) in the serotypes implicated in adult pneumococcal pneumonia and the patient groups associated with vaccine-type disease are largely unknown.MethodsWe conducted a population-based prospective cohort study of adults admitted to two large university hospitals with community-acquired pneumonia (CAP) between September 2013 and August 2018. Pneumococcal serotypes were identified using a novel 24-valent urinary monoclonal antibody assay and from blood cultures. Trends in incidence rates were compared against national invasive pneumococcal disease (IPD) data. Persons at risk of vaccine-type pneumonia (pneumococcal conjugate vaccine (PCV)13 and pneumococcal polysaccharide vaccine (PPV)23) were determined from multivariate analyses.FindingsOf 2934 adults hospitalised with CAP, 1075 (36.6%) had pneumococcal pneumonia. The annual incidence of pneumococcal pneumonia increased from 32.2 to 48.2 per 100 000 population (2013–18), predominantly due to increases in PCV13non7-serotype and non-vaccine type (NVT)-serotype pneumonia (annual incidence rate ratio 1.12, 95% CI 1.04 to 1.21 and 1.19, 95% CI 1.10 to 1.28, respectively). Incidence trends were broadly similar to IPD data. PCV13non7 (56.9% serotype 3) and PPV23non13 (44.1% serotype 8) serotypes were identified in 349 (32.5%) and 431 (40.1%) patients with pneumococcal pneumonia, respectively. PCV13-serotype pneumonia (dominated by serotype 3) was more likely in patients in the UK pneumococcal vaccination clinical risk group (adjusted OR (aOR) 1.73, 95% CI 1.31 to 2.28) while PPV23-serotype pneumonia was more likely in patients outside the clinical risk group (aOR 1.54, 95% CI 1.13 to 2.10).InterpretationThe incidence of pneumococcal CAP is increasing, predominantly due to NVT serotypes and serotype 3. PPV23-serotype pneumonia is more likely in adults outside currently identified clinical risk groups.

No abstract

Despite its inclusion in pneumococcal conjugate vaccine 13 (PCV13), Streptococcus pneumoniae serotype 3 remains a major cause of invasive pneumococcal disease in England and Wales. Previous studies have indicated that there are distinct lineages within serotype 3 clonal complex 180 and the clade distributions have shifted in recent years with the emergence of clade II. We undertook whole genome sequencing and genomic analysis of 616 serotype 3 isolates from England and Wales between 2003 and 2018, including invasive and carriage isolates. Our investigations showed that clade II has expanded since 2014 and now represents 50% of serotype 3 invasive pneumococcal disease (IPD) isolates in England and Wales. Genomic analysis of antibiotic resistance and protein antigen genes showed that distinct profiles are present within the clades which could account for the recent emergence of this clade. This investigation highlights the importance and utility of routine whole genome sequencing and its ability to identify new and emerging variation at the single nucleotide level which informs surveillance and will impact future vaccine development.