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Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

Infection and Immunity, <a href="https://journals.asm.org/toc/iai/0/ja">Volume 0, Issue ja</a>, -Not available-.

A previously healthy 42-year-old male from the upper Midwestern United States presented with a 1-day history of fever, fatigue, headache, myalgias, and arthralgias. He reported removing a “wood tick” the day of admission. His temperature was 38.4°C. No swollen joints, rash, or neurological abnormalities were noted on physical examination.

This study aimed to analyze the effect of discontinuation of antimicrobial stewardship program (ASP) activity on the usage pattern of antibiotics.

by Jonas Schmuck, Nina Hiebel, Milena Rabe, Juliane Schneider, Yesim Erim, Eva Morawa, Lucia Jerg-Bretzke, Petra Beschoner, Christian Albus, Julian Hannemann, Kerstin Weidner, Susann Steudte-Schmiedgen, Lukas Radbruch, Holger Brunsch, Franziska Geiser Introduction The COVID-19 pandemic resulted in severe detrimental effects on the mental well-being of health care workers (HCW). Consequently, there has been a need to identify health-promoting resources in order to mitigate the psychological impact of the pandemic on HCW. Objective Our objective was to investigate the association of sense of coherence (SOC), social support and religiosity with self-reported mental symptoms and increase of subjective burden during the COVID-19 pandemic in HCW. Methods Our sample comprised 4324 HCW of four professions (physicians, nurses, medical technical assistants (MTA) and pastoral workers) who completed an online survey from 20 April to 5 July 2020. Health-promoting resources were assessed using the Sense of Coherence Scale Short Form (SOC-3), the ENRICHD Social Support Inventory (ESSI) and one item on religiosity derived from the Scale of Transpersonal Trust (TPV). Anxiety and depression symptoms were measured with the PHQ-2 and GAD-2. The increase of subjective burden due to the pandemic was assessed as the retrospective difference between burden during the pandemic and before the pandemic. Results In multiple regressions, higher SOC was strongly associated with fewer anxiety and depression symptoms. Higher social support was also related to less severe mental symptoms, but with a smaller effect size, while religiosity showed minimal to no correlation with anxiety or depression. In professional group analysis, SOC was negatively associated with mental symptoms in all groups, while social support only correlated significantly with mental health outcomes in physicians and MTA. In the total sample and among subgroups, an increase of subjective burden was meaningfully associated only with a weaker SOC. Conclusion Perceived social support and especially higher SOC appeared to be beneficial for mental health of HCW during the COVID-19 pandemic. However, the different importance of the resources in the respective occupations requires further research to identify possible reasons.

by Lirane Elize Defante Ferreto, Stephanny Guedes, Fernando Braz Pauli, Samyra Soligo Rovani, Franciele Aní Caovilla Follador, Ana Paula Vieira, Renata Himovski Torres, Harnoldo Colares Coelho, Guilherme Welter Wendt The prevalence of hepatitis C virus (HCV) and the acquired immunodeficiency virus (HIV) is much higher in prisons than in community settings. Some explanatory factors for this burden include putative aspects of the prison environment, such as unprotected sexual relations and sexual violence, use of injectable drugs and syringe sharing. Nonetheless, efforts in better understanding the dynamics of both HCV and HIV are scarce in developing countries such as Brazil, which poses a risk not only to the inmates but to the community as well. In this investigation, we sought to determine the seroprevalence and sociodemographic and behavioral risk factors associated with HIV and anti-HCV antibodies among men detained at high-security institutions. This is an epidemiological, proportionally stratified observational study including 1,132 inmates aged 18 to 79 years-old (Mage = 32.58±10.18) from eleven high-security prisons located in the State of Paraná, Brazil. We found that HIV and anti-HCV prevalence were 1.6% (95% CI: 1.0–2.5) and 2.7% (95% CI: 1.0–2.5), respectively. Risk factors associated with HIV included not receiving intimate visits (OR = 8.80, 95% CI: 1.15–66.88), already having another sexually transmitted infection (OR = 3.89, 95% CI: 1.47–10.29), and reporting attendance in HIV preventive campaigns (OR = 4.24, 95% CI: 1.58–11.36). Moreover, anti-HCV seroprevalence was associated with higher age (OR = 4.03, 95% CI: 1.61–10.07), criminal recidivism (OR = 2.58, 95% CI 1.02–6.52), and the use of injectable drugs (OR = 7.32, 95% CI 3.36–15.92). Although prisons might increase the risk for acquiring and transmitting HIV and HCV, the adoption of permanent epidemiological surveillance programs could help reducing the circulation of viruses, involving strategies focusing on screening, treating, and preventing infections to assure proper prisoner health. Moreover, these policies need to take place inside and outside the prison environment to offer continued assistance to former prisoners once they leave the institution.

by Murielle Mary-Krause, Joel José Herranz Bustamante, Mégane Héron, Astrid Juhl Andersen, Tarik El Aarbaoui, Maria Melchior Background The outbreak of the COVID-19 epidemic lead to high levels of morbidity and mortality around the globe. Consequences of this outbreak and possible associated infection are an increase in mental health disorders and an increased likelihood of internalizing problems, particularly depression. However, to date few studies have tested this hypothesis while taking into account individuals’ preexisting mental health difficulties. Methods We used longitudinal data collected among 729 persons in the context of the French TEMPO cohort between March and June 2020 (7 waves of data collection). COVID-19-like symptoms as well as anxiety/depression (assessed by the Adult Self Report), were reported at each wave of data collection. To study the relationship between COVID-19-like symptoms and anxiety/depression, we used generalized estimation equation (GEE) models controlled for socio-demographic and health-related characteristics, including anxiety/depression prior to 2020. Results Overall, 27.2% of study participants reported anxiety/depression during lockdown. 17.1% of participants reported COVID-19-like symptoms during the course of follow-up, 7.3% after the beginning of lockdown, with an average number of 2.7 symptoms, and 3.6% reported respiratory distress. In multivariate analyses, nearly all the considered indicators of COVID-19-like symptoms were associated with higher odds of symptoms of anxiety/depression (symptoms Yes/No: OR = 1.66, 95% CI = 1.08–2.55; symptoms after the beginning of lockdown: OR = 1.91, 95% CI = 1.03–3.52; number of symptoms: OR for each additional symptom = 1.19, 95% CI = 1.02–1.39. This relationship exists after taking into account prior symptoms of anxiety/depression, which are associated with a 5-fold increased likelihood of psychological distress. And this impact is stronger among men than women. Conclusions Our study shows higher risk of anxiety/depression among persons who experienced COVID-19-like symptoms, even after accounting for prior mental health difficulties. COVID-19 infection could have both a direct and indirect impact on the occurrence of psychological difficulties, and this association should be studied in greater detail.

by Noa Furth, Shay Shilo, Niv Cohen, Nir Erez, Vadim Fedyuk, Alexander M. Schrager, Adina Weinberger, Amiel A. Dror, Asaf Zigron, Mona Shehadeh, Eyal Sela, Samer Srouji, Sharon Amit, Itzchak Levy, Eran Segal, Rony Dahan, Dan Jones, Daniel C. Douek, Efrat Shema The COVID-19 pandemic raises the need for diverse diagnostic approaches to rapidly detect different stages of viral infection. The flexible and quantitative nature of single-molecule imaging technology renders it optimal for development of new diagnostic tools. Here we present a proof-of-concept for a single-molecule based, enzyme-free assay for detection of SARS-CoV-2. The unified platform we developed allows direct detection of the viral genetic material from patients’ samples, as well as their immune response consisting of IgG and IgM antibodies. Thus, it establishes a platform for diagnostics of COVID-19, which could also be adjusted to diagnose additional pathogens.

by Anna Babicka-Wirkus, Lukasz Wirkus, Krzysztof Stasiak, Paweł Kozłowski The COVID-19 pandemic has changed the functioning of universities worldwide. In Poland, the transfer to online teaching was announced without prior warning, which radically changed students’ daily functioning. This situation clearly showed the students’ helplessness and difficulties with coping with this new, stressful situation, highlighted in many previous studies. A sudden and far-reaching change in daily functioning caused anxiety, depression, and stress in this group. Thus, from a pedagogical and psychological point of view, it is pertinent to examine the students’ strategies of coping with stress caused by the COVID-19 pandemic. To this end, in 2020, a sample of Polish students was anonymously measured using the Mini-COPE questionnaire. Data was gathered from 577 students from 17 universities. The statistical analysis showed that during the coronavirus pandemic, Polish students most often used the coping strategies of: acceptance, planning, and seeking emotional support. Such factors as age, gender, and place of residence influenced the choice of specific strategies of coping with stress during the COVID-19 pandemic. The results also showed that the youngest students had the lowest coping skills. The results allow for concluding that the students’ maladaptive strategies of coping with stress, especially during the pandemic, may result in long-term consequences for their psychophysiological health and academic achievements. Thus, based on the current results and on the participatory model of intervention, a support program for students is proposed which would involve psychological, organizational, and instrumental support.

by Xiaofeng Liu, Zubair Ahmad, Ahmed M. Gemeay, Alanazi Talal Abdulrahman, E. H. Hafez, N. Khalil Over the past few months, the spread of the current COVID-19 epidemic has caused tremendous damage worldwide, and unstable many countries economically. Detailed scientific analysis of this event is currently underway to come. However, it is very important to have the right facts and figures to take all possible actions that are needed to avoid COVID-19. In the practice and application of big data sciences, it is always of interest to provide the best description of the data under consideration. The recent studies have shown the potential of statistical distributions in modeling data in applied sciences, especially in medical science. In this article, we continue to carry this area of research, and introduce a new statistical model called the arcsine modified Weibull distribution. The proposed model is introduced using the modified Weibull distribution with the arcsine-X approach which is based on the trigonometric strategy. The maximum likelihood estimators of the parameters of the new model are obtained and the performance these estimators are assessed by conducting a Monte Carlo simulation study. Finally, the effectiveness and utility of the arcsine modified Weibull distribution are demonstrated by modeling COVID-19 patients data. The data set represents the survival times of fifty-three patients taken from a hospital in China. The practical application shows that the proposed model out-classed the competitive models and can be chosen as a good candidate distribution for modeling COVID-19, and other related data sets.

by Uday Narayan Yadav, Om Prakash Yadav, Devendra Raj Singh, Saruna Ghimire, Binod Rayamajhee, Sabuj Kanti Mistry, Lal Bahadur Rawal, ARM Mehrab Ali, Man Kumar Tamang, Suresh Mehta Background Coronavirus disease 2019 (COVID-19) has affected all age groups worldwide, but older adults have been affected greatly with an increased risk of severe illness and mortality. Nepal is struggling with the COVID-19 pandemic. The normal life of older adults, one of the vulnerable populations to COVID-19 infection, has been primarily impacted. The current evidence shows that the COVID-19 virus strains are deadly, and non-compliance to standard protocols can have serious consequences, increasing fear among older adults. This study assessed the perceived fear of COVID-19 and associated factors among older adults in eastern Nepal. Methods A cross-sectional study was conducted between July and September 2020 among 847 older adults (≥60 years) residing in three districts of eastern Nepal. Perceived fear of COVID-19 was measured using the seven-item Fear of COVID-19 Scale (FCV-19S). Multivariate logistic regression identified the factors associated with COVID-19 fear. Results The mean score of the FCV-19S was 18.1 (SD = 5.2), and a sizeable proportion of older adults, ranging between 12%-34%, agreed with the seven items of the fear scale. Increasing age, Dalit ethnicity, remoteness to the health facility, and being concerned or overwhelmed with the COVID-19 were associated with greater fear of COVID-19. In contrast, preexisting health conditions were inversely associated with fear. Conclusion Greater fear of the COVID-19 among the older adults in eastern Nepal suggests that during unprecedented times such as the current pandemic, the psychological needs of older adults should be prioritized. Establishing and integrating community-level mental health support as a part of the COVID-19 preparedness and response plan might help to combat COVID-19 fear among them.

by Assia Zemmour, Radia Dali-Yahia, Makaoui Maatallah, Nadjia Saidi-Ouahrani, Bouabdallah Rahmani, Nora Benhamouche, Hissa M. Al-Farsi, Christian G. Giske The purpose of the study was to characterize the resistome, virulome, mobilome and Clustered Regularly Interspaced Short Palindromic Repeats-associated (CRISPR-Cas) system of extended-spectrum β-lactamase producing Klebsiella pneumoniae (ESBL-KP) clinical isolates and to determine their phylogenetic relatedness. The isolates were from Algeria, isolated at the University Hospital Establishment of Oran, between 2011 and 2012. ESBL-KP isolates (n = 193) were screened for several antibiotic resistance genes (ARGs) using qPCR followed by Pulsed-Field Gel Electrophoresis (PFGE). Representative isolates were selected from PFGE clusters and subjected to whole-genome sequencing (WGS). Genomic characterization of the WGS data by studying prophages, CRISPR-Cas systems, Multi-Locus Sequence Typing (MLST), serotype, ARGs, virulence genes, plasmid replicons, and their pMLST. Phylogenetic and comparative genomic were done using core genome MLST and SNP-Based analysis. Generally, the ESBL-KP isolates were polyclonal. The whole genome sequences of nineteen isolates were taken of main PFGE clusters. Sixteen sequence types (ST) were found including high-risk clones ST14, ST23, ST37, and ST147. Serotypes K1 (n = 1), K2 (n = 2), K3 (n = 1), K31 (n = 1), K62 (n = 1), and K151 (n = 1) are associated with hyper-virulence. CRISPR-Cas system was found in 47.4%, typed I-E and I-E*. About ARGs, from 193 ESBL-KP, the majority of strains were multidrug-resistant, the CTX-M-1 enzyme was predominant (99%) and the prevalence of plasmid-mediated quinolone resistance (PMQR) genes was high with aac(6′)-lb-cr (72.5%) and qnr’s (65.8%). From 19 sequenced isolates we identified ESBL, AmpC, and carbapenemase genes: blaCTX-M-15 (n = 19), blaOXA-48 (n = 1), blaCMY-2 (n = 2), and blaCMY-16 (n = 2), as well as non-ESBL genes: qnrB1 (n = 12), qnrS1 (n = 1) and armA (n = 2). We found IncF, IncN, IncL/M, IncA/C2, and Col replicon types, at least once per isolate. This study is the first to report qnrS in ESBL-KP in Algeria. Our analysis shows the concerning co-existence of virulence and resistance genes and would support that genomic surveillance should be a high priority in the hospital environment.

by Alexandra Heidel, Christian Hagist, Christian Schlereth Objectives The objective of this paper is to study under which circumstances wearable and health app users would accept a compensation payment, namely a digital dividend, to share their self-tracked health data. Methods We conducted a discrete choice experiment alternative, a separated adaptive dual response. We chose this approach to reduce extreme response behavior, considering the emotionally-charged topic of health data sales, and to measure willingness to accept. Previous experiments in lab settings led to demands for high monetary compensation. After a first online survey and two pre-studies, we validated four attributes for the final online study: monthly bonus payment, stakeholder handling the data (e.g., health insurer, pharmaceutical or medical device companies, universities), type of data, and data sales to third parties. We used a random utility framework to evaluate individual choice preferences. To test the expected prices of the main study for robustness, we assigned respondents randomly to one of two identical questionnaires with varying price ranges. Results Over a period of three weeks, 842 respondents participated in the main survey, and 272 respondents participated in the second survey. The participants considered transparency about data processing and no further data sales to third parties as very important to the decision to share data with different stakeholders, as well as adequate monetary compensation. Price expectations resulting from the experiment were high; pharmaceutical and medical device companies would have to pay an average digital dividend of 237.30€/month for patient generated health data of all types. We also observed an anchor effect, which means that people formed price expectations during the process and not ex ante. We found a bimodal distribution between relatively low price expectations and relatively high price expectations, which shows that personal data selling is a divisive societal issue. However, the results indicate that a digital dividend could be an accepted economic incentive system to gather large-scale, self-tracked data for research and development purposes. After the COVID-19 crisis, price expectations might change due to public sensitization to the need for big data research on patient generated health data. Conclusion A continuing success of existing data donation models is highly unlikely. The health care sector needs to develop transparency and trust in data processing. An adequate digital dividend could be an effective long-term measure to convince a diverse and large group of people to share high-quality, continuous data for research purposes.

by John T. Connelly, Alfred Andama, Benjamin D. Grant, Alexey Ball, Sandra Mwebe, Lucy Asege, Martha Nakaye, Brianda Barrios Lopez, Helen V. Hsieh, David Katumba, Job Mukwatamundu, Mayimuna Nalubega, Victoria M. Hunt, Stephen Burkot, Harisha Ramachandraiah, Alok Choudhary, Lech Ignatowicz, Bernhard H. Weigl, Christine Bachman, Jerry Mulondo, Fred Semitala, William Worodria, Abraham Pinter, Beston Hamasur, David Bell, Adithya Cattamanchi, Akos Somoskovi Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51–69%) and specificity of 80% (95%CI 73–85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p<0.0001) and HIV-positive patients with CD4+ T-cell counts >200cells/μL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity.

by Chunxia Hou, Huiyuan Jiang Coronavirus disease 2019(COVID-19) has brought great disasters to humanity, and its influence continues to intensify. In response to the public health emergencies, prompt relief supplies are key to reduce the damage. This paper presents a method of emergency medical logistics to quick response to emergency epidemics. The methodology includes two recursive mechanisms: (1) the time-varying forecasting of medical relief demand according to a modified susceptible-exposed-infected- Asymptomatic- recovered (SEIAR) epidemic diffusion model, (2) the relief supplies distribution based on a multi-objective dynamic stochastic programming model. Specially, the distribution model addresses a hypothetical network of emergency medical logistics with considering emergency medical reserve centers (EMRCs), epidemic areas and e-commerce warehousing centers as the rescue points. Numerical studies are conducted. The results show that with the cooperation of different epidemic areas and e-commerce warehousing centers, the total cost is 6% lower than without considering cooperation of different epidemic areas, and 9.7% lower than without considering cooperation of e-commerce warehousing centers. Particularly, the total cost is 20% lower than without considering any cooperation. This study demonstrates the importance of cooperation in epidemic prevention, and provides the government with a new idea of emergency relief supplies dispatching, that the rescue efficiency can be improved by mutual rescue between epidemic areas in public health emergency.

by Sanath Kumar Janaka, Natasha M. Clark, David T. Evans, Huihui Mou, Michael Farzan, Joseph P. Connor Background The novel coronavirus SARS-CoV2 that causes COVID-19 has resulted in the death of more than 2.5 million people, but no cure exists. Although passive immunization with COVID-19 convalescent plasma (CCP) provides a safe and viable therapeutic option, the selection of optimal units for therapy in a timely fashion remains a barrier. Study design and methods Since virus neutralization is a necessary characteristic of plasma that can benefit recipients, the neutralizing titers of plasma samples were measured using a retroviral-pseudotype assay. Binding antibody titers to the spike (S) protein were also determined by a clinically available serological assay (Ortho-Vitros total IG), and an in-house ELISA. The results of these assays were compared to a measurement of antibodies directed to the receptor binding domain (RBD) of the SARS-CoV2 S protein (Promega Lumit Dx). Results All measures of antibodies were highly variable, but correlated, to different degrees, with each other. However, the anti-RBD antibodies correlated with viral neutralizing titers to a greater extent than the other antibody assays. Discussion Our observations support the use of an anti-RBD assay such as the Lumit Dx assay, as an optimal predictor of the neutralization capability of CCP.

by Davis T. Weaver, Benjamin D. McElvany, Vishhvaan Gopalakrishnan, Kyle J. Card, Dena Crozier, Andrew Dhawan, Mina N. Dinh, Emily Dolson, Nathan Farrokhian, Masahiro Hitomi, Emily Ho, Tanush Jagdish, Eshan S. King, Jennifer L. Cadnum, Curtis J. Donskey, Nikhil Krishnan, Gleb Kuzmin, Ju Li, Jeff Maltas, Jinhan Mo, Julia Pelesko, Jessica A. Scarborough, Geoff Sedor, Enze Tian, Gary C. An, Sean A. Diehl, Jacob G. Scott Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm−2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 μWcm−2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.

Introduction The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects. Objective Our primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens. Methods and analysis A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16–50 years with an injury severity score ≥16, will be recruited. Ethics and dissemination This protocol was approved by the West Midlands – Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences. Trial registration This trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158). Trial progression The study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.

Objective To analyse the epidemiological characteristics of family clusters of COVID-19 and the three stages of the comprehensive non-pharmaceutical interventions and measures implemented in Shenzhen. Methods The epidemic curve of COVID-19 was drawn and the impact of the comprehensive non-pharmaceutical interventions and measures was analysed by the different periods of the epidemic. Results A total of 427 cases (417 confirmed cases and 10 asymptomatic infectious cases) were reported in Shenzhen, of which 259 (60.7%) were clustered cases. 97 cluster events were drawn and most cluster events (97.3%) occurred in families. There were three stages of the COVID-19 epidemic in Shenzhen. The epidemic increased rapidly, but the peak lasted for a short time, while the decline in incidence was rapid and large. Conclusions Family clusters were the main feature of the COVID-19 outbreak in Shenzhen in 2020, and the Shenzhen government rolled out a quick response to the epidemic. Non-pharmaceutical interventions and measures were proven to have effectively contained community transmission, limit the transmission to aggregation and reduce the scale of transmission within a household.

Objective This systematic review aimed to describe the connection between the inspired oxygen fraction and pulmonary complications in adult patients, with the objective of determining a safe upper limit of oxygen supplementation. Methods MEDLINE and Embase were systematically searched in August 2019 (updated July 2020) for studies fulfilling the following criteria: intubated adult patients (Population); high fractions of oxygen (Intervention) versus low fractions of (Comparison); atelectasis, acute respiratory distress syndrome (ARDS), pneumonia and/or duration of mechanical ventilation (Outcome); original studies both observational and interventional (Studies). Screening, data extraction and risk of bias assessment was done by two independent reviewers. Results Out of 6120 records assessed for eligibility, 12 were included. Seven studies were conducted in the emergency setting, and five studies included patients undergoing elective surgery. Eight studies reported data on atelectasis, two on ARDS, four on pneumonia and two on duration of mechanical ventilation. There was a non-significant increased risk of atelectasis if an oxygen fraction of 0.8 or above was used, relative risk (RR): 1.37 (95% CI 0.95 to 1.96). One study showed an almost threefold higher risk of pneumonia in the high oxygen fraction group (RR: 2.83 (95% CI 2.25 to 3.56)). The two studies reporting ARDS and the two studies with data on mechanical ventilation showed no association with oxygen fraction. Four studies had a high risk of bias in one domain. Conclusions In this systematic review, we found inadequate evidence to identify a safe upper dosage of oxygen, but the identified studies suggest a benefit of keeping inspiratory oxygen fraction below 0.8 with regard to formation of atelectases. PROSPERO registration number CRD42020154242.

Introduction COVID-19 has a serious impact on people’s physical health and mental health. The COVID-19 pandemic forced college and university students to take online classes, which may have bad impacts on students’ learning. In addition, the students lost many job opportunities during the pandemic. Faced with employment and study pressure and worried about the epidemic, college and university students were prone to increased overall negative emotion, anxiety and depression. Therefore, this systematic review and meta-analysis will be conducted to explore the impact of the COVID-19 pandemic on the mental health and learning of college and university students. Methods and analysis We will conduct electronic literature search of the PubMed, Embase, Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure databases. Two researchers will independently screen the studies, extract data and assess the quality of the included studies. Any disagreement will be resolved by the third investigator. The Newcastle–Ottawa Scale and other tools will be used to assess the risk of bias, according to the study design of included studies. OR, risk ratio, mean difference and 95% CI will be considered as the effect size. Heterogeneity between studies will be assessed by subgroup and sensitivity analysis, and publication bias will be detected by funnel plots, Begg’s test and Egger’s test. Ethics and dissemination This systematic review and meta-analysis involves no patient contact and no interaction with healthcare providers or systems. We will disseminate the findings of this study through the presentation at scientific conferences and publication in a peer-reviewed journal. PROSPERO registration number CRD42020201132.

Objectives To understand how clinicians working in addiction services perceive their responsibilities for physical healthcare of clients who use opioids, and how physical healthcare could be improved for this group. Design Qualitative study comprising semistructured interviews. Participants 16 clinicians, including nurses and nurse practitioners, nurse consultants, addiction psychiatrists, specialist general practitioners and psychiatry specialty registrars. Setting Community-based drug and alcohol treatment services in the UK, with services including outpatient opioid agonist therapy. Results We identified three overarching themes. First, clients have unmet physical health needs that are often first identified in community drug and alcohol services. Participants reported attempts to improve their clients’ access to healthcare by liaising directly with health services and undertaking other forms of health advocacy, but report limited success, with many referrals ending in non-attendance. Second, most participants saw their role as supporting access to mainstream health services rather than providing physical healthcare directly, though sometimes reported frustration at being unable to provide certain treatments such as antibiotics for a respiratory infection. A minority of participants felt that people who use illicit opioids would be best served by an integrated ‘one-stop-shop’ model, but felt this model is currently unlikely to receive funding. Third, participants felt isolated from other health services, in part due to commissioning arrangements in which funding is provided through local government rather than the National Health Service. Conclusions Clinicians participating in this study serve a patient group with unmet physical health needs, but lack the resources to respond effectively to these needs.

Objectives Pharmacists are increasingly providing patient-focused services in community pharmacies, including in the area of sexual and reproductive health (SRH). Specific SRH areas have been the focus of research, but a broader perspective is needed to position pharmacists as SRH providers. This review explored research that described and evaluated professional pharmacy services across a broad range of SRH areas. Design Scoping review Data sources Medline, EMBASE, CINAHL, Web of Science, Scopus and Cochrane Library (January 2007–July 2020). Study selection Studies reporting on the description and evaluation of professional pharmacy SRH services provided by community pharmacists. Data extraction Two investigators screened studies for eligibility, and one investigator extracted the data. Data were analysed to primarily describe professional pharmacy services and intervention outcomes. Results Forty-one studies were included. The main SRH areas and professional pharmacy services reported were sexually transmitted and bloodborne infections (63%) and screening (39%), respectively. Findings showed that pharmacists’ delivery of SRH services was feasible, able to reach vulnerable and high-risk groups, and interventions were highly accepted and valued by users. However, integration into daily workflow, pharmacist remuneration, cost and reimbursement for patients, and policy regulations were some of the barriers identified to implementing SRH services. Studies were primarily in specific areas such as chlamydia screening or hormonal contraception prescribing, while studies in other areas (ie, medical abortion provision, long-acting reversible contraception prescribing and vaccine delivery in pregnant women) were lacking. Conclusion This scoping review highlights the expansion of pharmacists’ roles beyond traditional product-focused services in a number of SRH areas. Given the potential feasibility, users’ acceptability and reach, pharmacists are ideally situated to enhance SRH care access. Future research describing implementation and evaluation of professional pharmacy services in all SRH areas is needed to promote access to these services through community pharmacies and position pharmacists as SRH providers worldwide.

Objectives To determine the variation in SARS-CoV-2 seroprevalence in school children and the relationship with self-reported symptoms. Design Baseline measurements of a longitudinal cohort study (Ciao Corona) from June to July 2020. Setting 55 schools stratified by district in the canton of Zurich, Switzerland. Participants 2585 children (1339 girls; median age: 11 years, age range: 6–16 years), attending grades 1–2, 4–5 and 7–8. Main outcome measures Variation in seroprevalence of SARS-CoV-2 in children across 12 cantonal districts, schools and grades, assessed using Luminex-based test of four epitopes for IgG, IgA and IgM (Antibody Coronavirus Assay,ABCORA 2.0). Clustering of cases within classes. Association of seropositivity and symptoms. Comparison with seroprevalence in adult population, assessed using Luminex-based test of IgG and IgA (Sensitive Anti-SARS-CoV-2 Spike Trimer Immunoglobulin Serological test). Results Overall seroprevalence was 2.8% (95% CI 1.5% to 4.1%), ranging from 1.0% to 4.5% across districts. Seroprevalence in grades 1–2 was 3.8% (95% CI 2.0% to 6.1%), in grades 4–5 was 2.4% (95% CI 1.1% to 4.2%) and in grades 7–8 was 1.5% (95% CI 0.5% to 3.0%). At least one seropositive child was present in 36 of 55 (65%) schools and in 44 (34%) of 131 classes where ≥5 children and ≥50% of children within the class were tested. 73% of children reported COVID-19-compatible symptoms since January 2020, with the same frequency in seropositive and seronegative children for all symptoms. Seroprevalence of children and adults was similar (3.2%, 95% credible interval (CrI) 1.7% to 5.0% vs 3.6%, 95% CrI 1.7% to 5.4%). The ratio of confirmed SARS-CoV-2 cumulative incidence-to-seropositive cases was 1:89 in children and 1:12 in adults. Conclusions SARS-CoV-2 seroprevalence was low in children and similar to that in adults by the end of June 2020. Very low ratio of diagnosed-to-seropositive children was observed. We did not detect clustering of SARS-CoV-2-seropositive children within classes, but the follow-up of this study will shed more light on transmission within schools. Trial registration number NCT04448717.

Introduction One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. Methods and analysis This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. Ethics and dissemination Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. Trial registration number ACTRN12619001329156.

Bloodstream infections (BSI) are prevalent after solid organ transplantation (SOT). In this study, we aimed to investigate the incidence and risk factors for BSI in the first five years post-transplantation.

Abstract Background The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms. Methods The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. Results None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039). Conclusion Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients.

I would like to express gratitude for reader's interest in previously published manuscript entitled “Pneumonia in medical professionals during COVID-19 outbreak in cardiovascular hospital” in International Journal of Infectious Diseases (Ilic et al., 2021).

Abstract Background A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years. Methods The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2–4 years) and PedsQL™4.0 infant scales (0–2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions. Results Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children. Conclusion RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Objective To examine the value of health systems data as indicators of emerging COVID-19 activity. Design Observational study of health system indicators for the COVID Hotspotting Score (CHOTS) with prospective validation. Setting and participants An integrated healthcare delivery system in Northern California including 21 hospitals and 4.5 million members. Main outcome measures The CHOTS incorporated 10 variables including four major (cough/cold calls, emails, new positive COVID-19 tests, COVID-19 hospital census) and six minor (COVID-19 calls, respiratory infection and COVID-19 routine and urgent visits, and respiratory viral testing) indicators assessed with change point detection and slope metrics. We quantified cross-correlations lagged by 7–42 days between CHOTS and standardised COVID-19 hospital census using observational data from 1 April to 31 May 2020 and two waves of prospective data through 21 March 2021. Results Through 30 September 2020, peak cross-correlation between CHOTS and COVID-19 hospital census occurred with a 28-day lag at 0.78; at 42 days, the correlation was 0.69. Lagged correlation between medical centre CHOTS and their COVID-19 census was highest at 42 days for one facility (0.63), at 35 days for nine facilities (0.52–0.73), at 28 days for eight facilities (0.28–0.74) and at 14 days for two facilities (0.73–0.78). The strongest correlation for individual indicators was 0.94 (COVID-19 census) and 0.90 (new positive COVID-19 tests) lagged 1–14 days and 0.83 for COVID-19 calls and urgent clinic visits lagged 14–28 days. Cross-correlation was similar (0.73) with a 35-day lag using prospective validation from 1 October 2020 to 21 March 2021. Conclusions Passively collected health system indicators were strongly correlated with forthcoming COVID-19 hospital census up to 6 weeks before three successive COVID-19 waves. These tools could inform communities, health systems and public health officials to identify, prepare for and mitigate emerging COVID-19 activity.

Nature Medicine, Published online: 26 July 2021; doi:10.1038/s41591-021-01463-x Heterologous dosing with the adenovirus-based ChAdOx1 (AstraZeneca) vaccine followed by an mRNA vaccine induced stronger immune responses than did the homologous ChAdOx1 vaccine series, according to recent immunogenicity studies.

Nature Medicine, Published online: 26 July 2021; doi:10.1038/s41591-021-01464-w In healthy adults, booster vaccination with an mRNA vaccine, irrespective of the vaccine used for the first dose, was well tolerated and elicited higher levels of spike-specific antibodies and spike-specific T cells than booster vaccination with ChAdOx1 nCov-19.

Dear editor,…

Although the threat of a pandemic had been expected for years, Covid-19 triggered frantic and uncoordinated reactions worldwide (Independent Panel for Pandemic and Preparedness and Response, 2021; Paul et al., 2020b). Since being declared a public health emergency in January 2020, Covid-19 has been regarded as an exceptional disease, as if it came from outer space. For the first time in history, billions of people were locked down, denied the right to go to school or to earn their living, and/or to see their loved ones, while an unprecedented race for treatment and vaccine discovery was launched.

Dear Sir…

To assess the extent to which food items are a source of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) and ESBL-producing Klebsiella pneumoniae (ESBL-Kp) for humans in five European cities.

To assess the performance of antigen-based rapid diagnostic tests (Ag-RDTs) for SARS CoV-2 when implemented for large-scale universal screening of asymptomatic individuals.

The clinical and laboratory characterization of Strongyloides stercoralis infection at diagnosis and after treatment is still poorly defined.

Hospital-acquired infections caused by antibiotic-resistant opportunistic pathogens are on the rise worldwide and represent one of the greatest challenges to modern medicine. Infections due to antibiotic resistant pathogens cause suffering, incapacity and death, and impose an enormous financial burden on both, healthcare systems and on society in general. In 2019, the WHO estimated that each year 700,000 deaths are a direct consequence of multidrug-resistant infections [1].

It was in 1880 when diphtheria toxin was discovered and, shortly after, the treatment of this infectious diseases with the serum of convalescent patients was proposed for the first time(1). Since then, a long chapter has been written in the History of Medicine about the use of serum o plasma containing immunoglobulins for the treatment, pre-emptive therapy or prophylaxis of infectious diseases. In the pandemic of influenza virus infection in 1918, called the Spanish flu, convalescent human serum was used for patients with pneumonia(2).

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had caused the current Coronavirus Disease 2019 (COVID-19) pandemic. The pandemic had resulted in a significant disruption of social live and had a major economic impact. Countries around the globe had taken extra-ordinary measures to combat the disease. The results from phase III clinical trials showed that both Pfizer-BioNTech messenger RNA (mRNA) vaccine (BNT162b2) and the Oxford-AstraZeneca adenovirus vector vaccine, ChAdOx1-S, also known as Ad26.COV2.S, vaccines very effective in decreasing disease and mortality with a planned two-dose schedule (Polack et al., 2020).

Objective: To validate and implement an optimised screening method for detection of SARS-CoV-2 RNA combining use of self-collected raw saliva samples, single-step heat-treated virus inactivation and RNA extraction, and direct RT-qPCR.Methods: 3-phased study conducted in Barcelona (Spain) in June-October, 2020, including: i) analytical validation against standard RT-qPCR in saliva samples; ii) diagnostic validation against standard RT-qPCR using paired saliva-nasopharyngeal samples obtained from asymptomatic teenagers and adults in a sports academy; and iii) pilot screening of asymptomatic health workers in a tertiary hospital.