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The COVID-19 pandemic poses a historical challenge to society. The profusion of data requires machine learning to improve and accelerate COVID-19 diagnosis, prognosis and treatment. However, a global and open approach is necessary to avoid pitfalls in these applications.

In the last decade Open Science principles have been successfully advocated for and are being slowly adopted in different research communities. In response to the COVID-19 pandemic many publishers and researchers have sped up their adoption of Open Science practices, sometimes embracing them fully and sometimes partially or in a sub-optimal manner. In this article, we express concerns about the violation of some of the Open Science principles and its potential impact on the quality of research output. We provide evidence of the misuses of these principles at different stages of the scientific process. We call for a wider adoption of Open Science practices in the hope that this work will encourage a broader endorsement of Open Science principles and serve as a reminder that science should always be a rigorous process, reliable and transparent, especially in the context of a pandemic where research findings are being translated into practice even more rapidly. We provide all data and scripts at https://osf.io/renxy/ .

ObjectivesWe conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19 and to estimate the proportion of deaths attributable to these conditions.MethodsRelevant observational studies were identified by searches in the PubMed, Cochrane library and Embase databases through 14 November 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% CIs. Certainty of evidence was assessed using the Cochrane methods and the Grading of Recommendations, Assessment, Development and Evaluations framework.ResultsA total of 186 studies representing 210 447 deaths among 1 304 587 patients with COVID-19 were included in this analysis. The SRR for death in patients with COVID-19 was 1.54 (95% CI 1.44 to 1.64, I2=92%, n=145, low certainty) for diabetes and 1.42 (95% CI 1.30 to 1.54, I2=90%, n=127, low certainty) for hypertension compared with patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI 1.31 to 1.61, I2=91%, n=54, high certainty) for patients with BMI ≥30 kg/m2 compared with those with BMI <30 kg/m2 and 1.12 (95% CI 1.07 to 1.17, I2=68%, n=25) per 5 kg/m2 increase in BMI. There was evidence of a J-shaped non-linear dose–response relationship between BMI and mortality from COVID-19, with the nadir of the curve at a BMI of around 22–24, and a 1.5–2-fold increase in COVID-19 mortality with extreme obesity (BMI of 40–45). The SRR was 1.28 (95% CI 1.17 to 1.40, I2=74%, n=28, low certainty) for ever, 1.29 (95% CI 1.03 to 1.62, I2=84%, n=19) for current and 1.25 (95% CI 1.11 to 1.42, I2=75%, n=14) for former smokers compared with never smokers. The absolute risk of COVID-19 death was increased by 14%, 11%, 12% and 7% for diabetes, hypertension, obesity and smoking, respectively. The proportion of deaths attributable to diabetes, hypertension, obesity and smoking was 8%, 7%, 11% and 2%, respectively.ConclusionOur findings suggest that diabetes, hypertension, obesity and smoking were associated with higher COVID-19 mortality, contributing to nearly 30% of COVID-19 deaths.Trial registration numberCRD42020218115.

The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS‐2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020‐000936‐23) randomly assigned to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS‐2 score lower than 3 (in patients with NEWS‐2 <7 at hospitalization) or 5 (in patients with NEWS‐2 ≥7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS‐2. However, simulations predicted that antiviral activity greater than 99% could reduce by 2 days the time to clinical improvement in patients with high viral load, irrespective of the NEWS‐2 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.

Background Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 h. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. Methods In this prospective study, we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheter (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital: the medical and infectious diseases ICU, the surgical ICU, and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotic changes they would have made if the M-PCR results had been available. Results We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 h (IQR 4.4–5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95% CI, 73–88%) and specificity of 99% (95% CI 99–100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) ( p  = 0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. Conclusions Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics.

The COVID-19 pandemic has led health schools to cancel many on-site training and exams. Teachers were looking for the best option to carry out online OSCEs, and Zoom was the obvious choice since many schools have used it to pursue education purposes. Methods: We conducted a feasibility study during the 2020-2021 college year divided into six pilot phases and the large-scale eOSCEs on Zoom on June 30th, 2021. We developed a specific application allowing us to mass create Zoom meetings and built an entire organization, including a technical support system (an SOS room and catching-up rooms) and teachers' training sessions. We assessed satisfaction via an online survey. Results: On June 30th, 531/794 fifth-year medical students (67%) participated in a large-scale mock exam distributed in 135 Zoom meeting rooms with the mobilization of 298 teachers who either participated in the Zoom meetings as standardized patients (N =135, 45%) or examiners (N =135, 45%) or as supervisors in the catching-up rooms (N =16, 6%) or the SOS room (N =12, 4%). In addition, 32/270 teachers (12%) experienced difficulties connecting to their Zoom meetings and sought the help of an SOS room member. Furthermore, 40/531 students (7%) were either late to their station or had technical difficulties and declared those issues online and were welcomed in one of the catching-up rooms to perform their eOSCE stations. Additionally, 518/531 students (98%) completed the entire circuit of three stations, and 225/531 students (42%) answered the online survey. Among them, 194/225 (86%) found eOSCES helpful for training and expressed their satisfaction with this experience. Conclusion: Organizing large-scale eOSCEs on Zoom is feasible with the appropriate tools. In addition, eOCSEs should be considered complementary to on-site OSCEs and to train medical students in telemedicine.

Controversy remains regarding the transmission routes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To review current evidence on air contamination with SARS-CoV-2 in hospital settings and the factors associated with contamination, including viral load and particle size. The MEDLINE, Embase, and Web of Science databases were systematically queried for original English-language articles detailing SARS-CoV-2 air contamination in hospital settings between January 1 and October 27, 2020. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The positivity rate of SARS-CoV-2 viral RNA and culture were described and compared according to the setting, clinical context, air ventilation system, and distance from patients. The SARS-CoV-2 RNA concentrations in copies per meter cubed of air were pooled, and their distribution was described by hospital areas. Particle sizes and SARS-CoV-2 RNA concentrations in copies or median tissue culture infectious dose (TCID50) per meter cubed were analyzed after categorization as less than 1 μm, from 1 to 4 μm, and greater than 4 μm. Among 2284 records identified, 24 cross-sectional observational studies were included in the review. Overall, 82 of 471 air samples (17.4%) from close patient environments were positive for SARS-CoV-2 RNA, with a significantly higher positivity rate in intensive care unit settings (intensive care unit, 27 of 107 [25.2%] vs non-intensive care unit, 39 of 364 [10.7%]; P < .001). There was no difference according to the distance from patients (≤1 m, 3 of 118 [2.5%] vs >1-5 m, 13 of 236 [5.5%]; P = .22). The positivity rate was 5 of 21 air samples (23.8%) in toilets, 20 of 242 (8.3%) in clinical areas, 15 of 122 (12.3%) in staff areas, and 14 of 42 (33.3%) in public areas. A total of 81 viral cultures were performed across 5 studies, and 7 (8.6%) from 2 studies were positive, all from close patient environments. The median (interquartile range) SARS-CoV-2 RNA concentrations varied from 1.0 × 103 copies/m3 (0.4 × 103 to 3.1 × 103 copies/m3) in clinical areas to 9.7 × 103 copies/m3 (5.1 × 103 to 14.3 × 103 copies/m3) in the air of toilets or bathrooms. Protective equipment removal and patient rooms had high concentrations per titer of SARS-CoV-2 (varying from 0.9 × 103 to 40 × 103 copies/m3 and 3.8 × 103 to 7.2 × 103 TCID50/m3), with aerosol size distributions that showed peaks in the region of particle size less than 1 μm; staff offices had peaks in the region of particle size greater than 4 μm. In this systematic review, the air close to and distant from patients with coronavirus disease 2019 was frequently contaminated with SARS-CoV-2 RNA; however, few of these samples contained viable viruses. High viral loads found in toilets and bathrooms, staff areas, and public hallways suggest that these areas should be carefully considered.

An Emergency Use Authorization was issued in the United States and in Europe for a monoclonal antibody monotherapy to prevent severe COVID-19 in high-risk patients. This study aimed to assess the risk of emergence of mutations following treatment with a single monoclonal antibody. Bamlanivimab was administered at a single dose of 700 mg in a one-hour IV injection in a referral center for the management of COVID-19 in France. Patients were closely monitored clinically and virologically with nasopharyngeal RT-PCR and viral whole genome sequencing. Six patients were treated for a nosocomial SARS-CoV-2 infection, all males, with a median age of 65 years and multiple comorbidities. All patients were infected with a B.1.1.7 variant, which was the most frequent variant in France at the time, and no patients had E484 mutations at baseline. Bamlanivimab was infused in the six patients within 4 days of the COVID-19 diagnosis. Four patients had a favorable outcome, one died of complications unrelated to COVID-19 or bamlanivimab, and one kidney transplant patient treated with belatacept died from severe COVID-19 more than 40 days after bamlanivimab administration. Virologically, four patients cleared nasopharyngeal viral shedding within one month after infusion, while two presented prolonged viral excretion for more than 40 days. The emergence of E484K mutants was observed in five out of six patients, and the last patient presented a Q496R mutation potentially associated with resistance. CONCLUSIONS: These results show a high risk of emergence of resistance mutants in COVID-19 patients treated with monoclonal antibody monotherapy.

The correlation between real-time PCR (rt-PCR) cycle threshold (Ct) values for respiratory viruses and clinical outcomes remains unclear. This study evaluates the association between Ct values and clinical outcomes in patients tested via point-of-care testing upon emergency department (ED) admission. This is a retrospective analysis of adults admitted to a French university hospital ED for suspected lower respiratory tract infections (LRTI) requiring oxygen therapy between 2019 and 2020. Ct values were assessed for their association with symptom duration and clinical outcomes (hospital length of stay (LOS), Intensive Care Unit (ICU) admission, and 28-day mortality) using zero-inflated negative binomial regression (ZINB) and logistic regression models, adjusted for age, sex, co-infection, and symptom duration. A total of 410 patients were included, with 37 (9%) having co-infections with two pathogens and 2 (0.5%) with three pathogens. The most common pathogens were human rhinovirus/enterovirus (HRV/EV) (26.3%), influenza A (24.9%), and SARS-CoV-2 (21.9%). Median symptom duration was 3 days [IQR: 2-7]. Of the patients, 308 (75.1%) were hospitalized, 74 (18%) required ICU care, and the 28-day mortality rate was 11.7% (n = 48). Multivariable analysis showed that higher Ct values for SARS-CoV-2 were associated with reduced odds of hospitalization (OR = 0.75, p = 0.04) and shorter LOS (x0.96 days per Ct unit increase, p = 0.04). Similar trends for shorter LOS were observed for HRV/EV and RSV but did not reach statistical significance. Conversely, higher influenza A Ct values were linked to longer LOS (x1.05 days per Ct unit increase, p = 0.025). Higher Ct values for SARS-CoV-2 were also associated with lower 28-day mortality (OR = 0.87, p = 0.049). Ct values were not associated with ICU admission for any virus. This study supports the association of higher Ct values with shorter LOS and lower mortality for SARS-CoV-2. In contrast, higher Ct values for influenza A were linked to longer LOS. Ct values were not predictive of ICU admission, underscoring the complexity of the relationship between viral load and clinical outcomes.

Background Healthcare services across the world have been deeply impacted by the COVID-19 pandemic. In primary care, community pharmacists have had an important role in the frontline healthcare response to the pandemic. Objectives This study aimed to explore the experiences, contributions and perceived challenges of community pharmacists regarding the provision of healthcare services during the COVID-19 pandemic. Methods Semi-structured qualitative interviews were conducted with community pharmacists in France. Participants were recruited through a professional organization of pharmacists combined with a snowballing technique. Interviews were transcribed and then analyzed using thematic analysis. Results A total of 16 community pharmacists participated in the interviews. Study participants described providing a range of novel services in response to the pandemic on top of continuing their usual services. All participants described providing preventative services to reduce and mitigate the spread of SARS-CoV-2, such as education on hygiene and social distancing, delivery of face masks and hand sanitizer and adjusting pharmacy premises. Most respondents also described being involved in SARS-CoV-2 detection through screening and performing antigen testing in pharmacies. Participants reported being actively involved in COVID-19 vaccination by educating the general public about vaccines, facilitating their distribution to general practitioners as well as administering vaccines. Over half the respondents described rapidly changing guidelines and service users’ anxiety as challenges to the provision of healthcare services during the pandemic. Conclusions This study suggests that community pharmacists have significantly contributed to the response to the COVID-19 pandemic by ensuring continuity of pharmaceutical services and providing novel screening, testing and vaccination services. Their roles and responsibilities during the COVID-19 health crisis indicate that they can play an important role in the management of emerging infectious diseases.