COVID-19 impact on EuroTravNet infectious diseases sentinel surveillance in Europe.

BACKGROUND: The COVID-19 pandemic resulted in a sharp decline of post-travel patient encounters at the European sentinel surveillance network (EuroTravNet) of travellers' health. We report on the impact of COVID-19 on travel-related infectious diseases as recorded by EuroTravNet clinics. METHODS: Travelers who presented between January 1, 2019 and September 30, 2021 were included. Comparisons were made between the pre-pandemic period (14 months from January 1, 2019 to February 29, 2020); and the pandemic period (19 months from March 1, 2020 to September 30, 2021). RESULTS: Of the 15,124 visits to the network during the 33-month observation period, 10,941 (72%) were during the pre-pandemic period, and 4183 (28%) during the pandemic period. Average monthly visits declined from 782/month (pre-COVID-19 era) to 220/month (COVID-19 pandemic era). Among non-migrants, the top-10 countries of exposure changed after onset of the COVID-19 pandemic; destinations such as Italy and Austria, where COVID-19 exposure peaked in the first months, replaced typical travel destinations in Asia (Thailand, Indonesia, India). There was a small decline in migrant patients reported, with little change in the top countries of exposure (Bolivia, Mali). The three top diagnoses with the largest overall decreases in relative frequency were acute gastroenteritis (-5.3%), rabies post-exposure prophylaxis (-2.8%), and dengue (-2.6%). Apart from COVID-19 (which rose from 0.1% to 12.7%), the three top diagnoses with the largest overall relative frequency increase were schistosomiasis (+4.9%), strongyloidiasis (+2.7%), and latent tuberculosis (+2.4%). CONCLUSIONS: A marked COVID-19 pandemic-induced decline in global travel activities is reflected in reduced travel-related infectious diseases sentinel surveillance reporting.

Age-related changes in plasma biomarkers and their association with mortality in COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19. METHODS: We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort. RESULTS: 464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively). CONCLUSIONS: Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19.

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial

Objectives To test whether BCG vaccination would reduce the incidence of COVID-19 and other respiratory tract infections in older adults with one or more comorbidities. Methods Community-dwelling adults over 60 years old with one or more underlying comorbidities and no contra-indications for BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for six months. The primary endpoint was self-reported test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTI (i.e. RTI including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine and Gray regression, accounting for competing events. Results A total of 6,112 participants with a median age of 69 years (inter-quartile range 65-74) and median of 2 (inter-quartile range 1-3) comorbidities were randomized to BCG (n=3,058) or placebo (n=3,054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients (hazard ratio (HR) 1.12;95% confidence interval (CI) 0.87-1.44). COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR 0.86;95% CI 0.46-1.61). During the study period 13 BCG recipients compared to 18 placebo recipients died (HR 0.71;95% CI 0.35 - 1.43) of which 11 deaths (35%) were COVID-19 related six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR 0.92;95% CI 0.66-1.28). Conclusion BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization or clinically relevant RTI.

Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial.

OBJECTIVES: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities. METHODS: Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events. RESULTS: A total of 6112 participants with a median age of 69 years (interquartile range, 65-74) and median of 2 (interquartile range, 1-3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87-1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46-1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35-1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66-1.28). DISCUSSION: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.

A hot topic at the environment-health nexus: investigating the impact of climate change on infectious diseases.

CLIMATE CHANGE - THE ULTIMATE CHALLENGE OF OUR TIME: COVID-19 pandemic aside, climate change is the ultimate challenge of our time. However, to date, there has been insufficient political thrust to make that much-needed climate action a reality. CLIMATE CHANGE AND INFECTIOUS DISEASES: Infectious diseases represent only one facet of the threats arising from climate change. Direct impacts from climate change include the more frequent occurrence and increased magnitude of extreme weather events, as well as changing temperatures and precipitation patterns. For climate-sensitive infectious diseases, these changes implicate a shift in geographical and temporal distribution, seasonality, and transmission intensity. SIZING UP THE PROBLEM: Susceptibility to the deleterious effects of climate change is a net result of the interplay of not only environmental factors, but also human, societal, and economic factors, with social inequalities being a major determinant of vulnerability. The global South is already disproportionately affected by the climate crisis. The financial capacity to pursue adaptation options is also limited and unevenly distributed. CONCLUSIONS: Climate change-induced mortality and morbidity from both infectious and non-infectious diseases, among other adverse scenarios, are expected to rise globally in the future. The coming decade will be crucial for using all remaining opportunities to develop and implement adequate mitigation and adaptation strategies.

On prioritising global health's triple crisis of sepsis, COVID-19 and antimicrobial resistance: a mixed-methods study from Malawi.

Sepsis causes 20% of global deaths, particularly among children and vulnerable populations living in developing countries. This study investigated how sepsis is prioritised in Malawi's health system to inform health policy. In this mixed-methods study, twenty multisectoral stakeholders were qualitatively interviewed and asked to quantitatively rate the likelihood of sepsis-related medium-term policy outcomes being realised. Respondents indicated that sepsis is not prioritised in Malawi due to a lack of local sepsis-related evidence and policies. However, they highlighted strong linkages between sepsis and maternal health, antimicrobial resistance and COVID-19, which are already existing national priorities, and offers opportunities for sepsis researchers as policy entrepreneurs. To address the burden of sepsis, we recommend that funding should be channelled to the generation of local evidence, evidence uptake, procurement of resources and treatment of sepsis cases, development of appropriate indicators for sepsis, adherence to infection prevention and control measures, and antimicrobial stewardship.

Acute hepatitis A in international travellers: a GeoSentinel analysis, 2008-2020.

BACKGROUND: Non-immune international travellers are at risk of acquiring hepatitis A. Although hepatitis A vaccination is recommended for unvaccinated travellers to high or intermediate hepatitis A virus endemicity, compliance with this recommendation is not universal.The main objective was to describe the demographic and travel characteristics of international travellers infected with hepatitis A during travel. METHODS: Available data on travellers with confirmed (positive molecular test) or probable (symptomatic individuals with a single positive IgM test) hepatitis A diagnosed during and after travel from January 2008 to December 2020 were obtained from the GeoSentinel Surveillance Network database. We analysed demographic and travel characteristics of infected travellers. RESULTS: Among 254 travellers with hepatitis A (185 confirmed and 69 probable), the median age was 28 years (interquartile range: 19-40), 150 (59%) were male, and among 54 travellers with information available, 53 (98%) were unvaccinated. The most common reasons for travel included tourism (n = 120; 47%) and visiting friends or relatives (VFR; n = 72; 28%). About two-thirds of VFR travellers with hepatitis A (n = 50; 69%) were younger than 20 years old. Hepatitis A was acquired most frequently in South-Central Asia (n = 63; 25%) and sub-Saharan Africa (n = 61; 24%), but 16 travellers (6%) acquired hepatitis A in regions with low endemicity including Western Europe (n = 7; 3%), the Caribbean (n = 6; 2%) and North America (n = 3; 1%). Median duration from illness onset to GeoSentinel site presentation was ~7 days (interquartile range : 4-14 days). Among 88 travellers with information available, 59% were hospitalized. CONCLUSIONS: Despite availability of highly effective vaccines, travellers still acquire hepatitis A, even when traveling to low-endemicity destinations. Providing pre-departure hepatitis A vaccine to susceptible travellers is crucial to reducing travel-associated hepatitis A and should be offered to all travellers as part of the pre-travel consultation, regardless of destination.

Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial.

BACKGROUND: Additional safe and efficacious vaccines are needed to control the COVID-19 pandemic. We aimed to analyse the efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate. METHODS: HERALD is a randomised, observer-blinded, placebo-controlled, phase 2b/3 clinical trial conducted in 47 centres in ten countries in Europe and Latin America. By use of an interactive web response system and stratification by country and age group (18-60 years and ≥61 years), adults with no history of virologically confirmed COVID-19 were randomly assigned (1:1) to receive intramuscularly either two 0·6 mL doses of CVnCoV containing 12 µg of mRNA or two 0·6 mL doses of 0·9% NaCl (placebo) on days 1 and 29. The primary efficacy endpoint was the occurrence of a first episode of virologically confirmed symptomatic COVID-19 of any severity and caused by any strain from 15 days after the second dose. For the primary endpoint, the trial was considered successful if the lower limit of the CI was greater than 30%. Key secondary endpoints were the occurrence of a first episode of virologically confirmed moderate-to-severe COVID-19, severe COVID-19, and COVID-19 of any severity by age group. Primary safety outcomes were solicited local and systemic adverse events within 7 days after each dose and unsolicited adverse events within 28 days after each dose in phase 2b participants, and serious adverse events and adverse events of special interest up to 1 year after the second dose in phase 2b and phase 3 participants. Here, we report data up to June 18, 2021. The study is registered at ClinicalTrials.gov, NCT04652102, and EudraCT, 2020-003998-22, and is ongoing. FINDINGS: Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0-61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7% (95% CI 42·5-86·1; CVnCoV 12 cases in 1735·29 person-years, placebo 37 cases in 1569·87 person-years). In participants aged 18-60 years, vaccine efficacy against symptomatic disease was 52·5% (95% CI 36·2-64·8; CVnCoV 71 cases in 1591·47 person-years, placebo, 136 cases in 1449·23 person-years). Too few cases occurred in participants aged 61 years or older (CVnCoV 12, placebo nine) to allow meaningful assessment of vaccine efficacy. Solicited adverse events, which were mostly systemic, were more common in CVnCoV recipients (1933 [96·5%] of 2003) than in placebo recipients (1344 [67·9%] of 1978), with 542 (27·1%) CVnCoV recipients and 61 (3·1%) placebo recipients reporting grade 3 solicited adverse events. The most frequently reported local reaction after any dose in the CVnCoV group was injection-site pain (1678 [83·6%] of 2007), with 22 grade 3 reactions, and the most frequently reported systematic reactions were fatigue (1603 [80·0%] of 2003) and headache (1541 [76·9%] of 2003). 82 (0·4%) of 19 783 CVnCoV recipients reported 100 serious adverse events and 66 (0·3%) of 19 746 placebo recipients reported 76 serious adverse events. Eight serious adverse events in five CVnCoV recipients and two serious adverse events in two placebo recipients were considered vaccination-related. None of the fatal serious adverse events reported (eight in the CVnCoV group and six in the placebo group) were considered to be related to study vaccination. Adverse events of special interest were reported for 38 (0·2%) participants in the CVnCoV group and 31 (0·2%) participants in the placebo group. These events were considered to be related to the trial vaccine for 14 (<0·1%) participants in the CVnCoV group and for five (<0·1%) participants in the placebo group. INTERPRETATION: CVnCoV was efficacious in the prevention of COVID-19 of any severity and had an acceptable safety profile. Taking into account the changing environment, including the emergence of SARS-CoV-2 variants, and timelines for further development, the decision has been made to cease activities on the CVnCoV candidate and to focus efforts on the development of next-generation vaccine candidates. FUNDING: German Federal Ministry of Education and Research and CureVac.

Recommendations for Antimalarial Prophylaxis

Gegenwartig werden vielfach die Regelungen zur Eindammung der SARS-CoV-2-Pandemie wieder zuruckgenommen, auch mit dem Wunsch, Urlaubsreisen als Wirtschaftsfaktor wiederzubeleben. Dabei werden Kreuzfahrten besonders kritisch beurteilt, was die Gefahrdung von Passagieren und Crew durch COVID-19 angeht. Das liegt zum einen an der relativen Enge der Unterbringung und Versorgung an Bord, zum anderen an dem unglucklichen Beispiel der Diamond Princess", der ab 03.02.2020 in Yokohama/Japan trotz COVID-19-Fallen an Bord keine Evakuierung samtlicher Passagiere gestattet wurde .