COVID-19 clusters in a teaching hospital during the second wave of the SARS-CoV-2 pandemic in France: A descriptive study and lessons learned for waves to come.

A total of 92 coronavirus disease 2019 clusters involving 1,156 individuals (729 patients and 427 healthcare workers) occurred in Lyon University Hospital between September 1, 2020 and March 31, 2021, mostly on medical and geriatric wards. The number of clusters was closely correlated to the trend in coronavirus disease 2019 community incidence over time; in-hospital clusters did not persist when community incidence decreased. Recommended preventive measures were not fully applicable due to specific ward-associated determinants and patient characteristics.

Protocol for a prospective quasi-experimental study on SARS-CoV-2 transmission during outdoor sports events in France: the COVID-ESO project.

INTRODUCTION: The spread of SARS-CoV-2 and its variants in the community remains a major concern despite the application of control measures including the banning of mass sporting events. The circulation of SARS-CoV-2 within the general population, and potentially within the population practicing outdoor sports activities, suggests contexts conducive to the transmission of the virus. We hypothesise that outdoor sports events (OSEs) do not present a higher risk of SARS-CoV-2 contamination. The objective of the COVID-ESO project is to measure if individuals participating in OSE present a similar risk of SARS-CoV-2 transmission compared with individuals not participating in OSE, in France. METHODS AND ANALYSIS: The COVID-ESO project is a prospective, quasi-experimental study to be conducted in volunteer individuals likely to participate in OSE. Six events are targeted across France to be included. Three sport trials will be eligible for the study: running, cycling and triathlon. Each individual participating in the OSE will choose one of his or her usual training partner to be eligible for the unexposed control group. Individuals will be matched (1:1) on age, sex and the district of residence. Individuals assigned to the exposed group will participate in the OSE, whereas individuals assigned to the unexposed group will not participate in the OSE. All individuals will be asked to perform saliva tests on the day of the event and 7 days after the event. A questionnaire including sociodemographic, clinical and exposure data to SARS-CoV-2 will be sent by email for both groups on the day before the event and 7 days after the event. Differences in SARS-CoV-2 infection rates between the exposed versus the unexposed group will be analysed by fitting a conditional logistic regression model, adjusted for potential confounders. As the sport events unfold, data will be analyzed by performing sequential meta-analyses. ETHICS AND DISSEMINATION: This protocol has been approved by the ethical committee. Ethical approval has been obtained for the Clinical research and committee of South West of France, 10 June 2021. COMITE DE PROTECTION DES PERSONNES DU SUD-OUEST ET OUTRE-MER 4 under the reference number 21.03.23.71737/CPP2021-04-045 a COVID/2021-A00845-36. Findings generated from this study will be shared to national health and sport authorities.

Undernourished patients do not have increased risk of severe COVID-19 outcomes.

Background: Undernutrition has been previously identified as a deleterious factor in acute infections. In covid-19 infection, obesity is a risk-factor of severe evolution, but initial undernutrition has not been evaluated yet. Methods: We retrospectively analyzed correlation between nutritional status at admission and severe outcomes (intensive care unit admission, invasive mechanical ventilation requirement and death) of patients hospitalized for confirmed covid-19 infection. Results: Risk of intensive care unit admission and invasive mechanical ventilation requirement was not significantly different between undernutrition and normoweight sub-groups, but increased in excessive weight sub-group (ODDR (IC 95%) 1.048 (1.011-1.086), p = 0.011). Risk of death was the same in all sub-groups. Conclusion: Undernutrition didn't appear as a factor of severe outcomes in covid-19 infection.

Baseline clinical features of COVID-19 patients, delay of hospital admission and clinical outcome: A complex relationship.

INTRODUCTION: Delay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission. METHODS: The present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis. RESULTS: Data from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (p<0.01), had higher body mass index (p<0.01), and were more frequently admitted to intensive care unit (p<0.01). Their plasma levels of C-reactive protein were also significantly higher (p<0.01). The crude in-hospital fatality rate was lower in this group (13.3% versus 27.6%), p<0.01. Multiple analysis with correction for multiple testing showed that age ≥75 years was associated with a short delay between symptom onset and hospital admission (≤5 days) (aOR: 0.47 95% CI (0.34-0.66)) and CRP>100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32-2.55)). DISCUSSION: Delay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Tobacco smoking and severity of COVID-19: Experience from a hospital-based prospective cohort study in Lyon, France.

Information gathered so far from published studies attest the existence of a complex relationship between tobacco smoking and the severity of COVID-19. We investigated the association between smoking habits and the severity of COVID-19 in patients hospitalized in university-affiliated hospitals in Lyon, France. Baseline sociodemographic, clinical and biological characteristics of adult COVID-19 hospitalized patients presenting from the community were prospectively collected and analyzed. Tobacco exposure was documented at admission. Characteristics of patients hospitalized in medical wards to those admitted or transferred to intensive care units (ICUs) were compared using Mann-Whitney and Χ2 or Fisher's exact test. A composite endpoint including admission or transfer to ICU or death was created as a proxy for severe outcome. Adjusted odds ratio (aOR) and 95% confidence interval (95% CI) were calculated to identify variables independently associated with a severe outcome. Of the 645 patients with documented information on smoking habits, 62.6% were never-smokers, 32.1% ex-smokers, and 5.3% active smokers. Past tobacco use was independently associated with an increased risk of severe outcome (aOR: 1.71; 95% CI: 1.12-2.63), whereas a nonsignificant protective trend was found for active smoking. The results suggest that past smoking is associated with enhanced risk of progressing toward severe COVID-19 disease in hospitalized patients.

Protocol for a prospective, observational, hospital-based multicentre study of nosocomial SARS-CoV-2 transmission: NOSO-COR Project.

INTRODUCTION: The newly identified SARS-CoV-2 can cause serious acute respiratory infections such as pneumonia. In France, mortality rate in the general population was approximately 10% and could reach higher levels at the hospital. In the current context of high incidence rates of SARS-CoV-2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to estimate the prevalence and incidence of suspected or confirmed cases of nosocomial SARS-CoV-2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals. METHODS AND ANALYSIS: This will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients and healthcare professionals in France and hospitals affiliated with the GABRIEL network. Demographic and clinical data will be collected using case report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV-2 by reverse-transcriptase PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV-2 infections relative to all patients with syndromes suggestive of SARS-CoV-2 infection, will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset. ETHICS AND DISSEMINATION: This study was approved by the clinical research and committee of all participating countries. The findings will be submitted to peer-reviewed journal for publication and shared with national health authorities. TRIAL REGISTRATION NUMBER: NCT04290780.

The incubation period of COVID-19: A meta-analysis.

OBJECTIVES: A valid measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incubation period is needed for case definitions and for adapting appropriate isolation measures but is challenging in an emergency context. Our objective was to systematically review recent literature reporting estimates of the distribution of the incubation period of SARS-CoV-2 and describe the distribution and its variability and dispersion through a meta-analysis. METHODS: A systematic review was carried out on studies published from 1 January 2020 to 10 January 2021 reporting the SARS-CoV-2 incubation period. Individual mean and standard deviation were used to produce the pooled estimate. Sources of heterogeneity were explored by age, gender and study design using a meta-regression. RESULTS: In total, 99 studies were eligible for analysis in our meta-analysis. The pooled estimate of the mean incubation period across the studies was 6.38 days, 95% CI (5.79; 6.97). CONCLUSION: Calculation of the mean incubation period will help with the identification of time of exposure, however, determinants of its variations/range might be explored for potential links with the clinical outcome or pathogenic steps at the early stage of infection. A real-time meta-analysis, named the InCoVid Lyon, is proposed following this initial analysis.

Factors associated with admission to intensive care units in COVID-19 patients in Lyon-France.

INTRODUCTION: A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the determinants associated with admission in intensive care units (ICUs) in hospitalized COVID-19 patients. PATIENTS AND METHODS: In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients presenting from the community for their first admission were prospectively collected and analysed. Characteristics of patients hospitalized in medical ward to those admitted in ICU were compared using Mann-Whitney and Chi-square or Fisher exact test when appropriate. Univariate logistic regression was first used to identify variables on admission that were associated with the outcome i.e. admission to an ICU versus total hospital stay in a medical ward. Forward selection was then applied beginning with sex, age and temperature in the multivariable logistic regression model. RESULTS: Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of ICU hospitalization with temperature (OR, 1.56 [95% CI, 1.06-2.28] per degree Celsius increase), oxygen saturation <90% (OR, 12.45 [95% CI, 5.27-29.4]), abnormal lung auscultation on admission (OR, 3.58 [95% CI, 1.58-8.11]), elevated level of CRP (OR, 2.7 [95% CI, 1.29-5.66for CRP>100mg/L vs CRP<10mg/L). and monocytopenia (OR, 3.28 [95% CI, 1.4-7.68]) were also associated with increasing odds of ICU hospitalization. Older patients were less likely to be hospitalized in ICU (OR, 0.17 [95%CI, 0.05-0.51]. CONCLUSIONS: Age and delay between onset of symptoms and hospital admission were associated with the risk of hospitalisation in ICU. Age being a fixed variable, interventions that shorten this delay would improve the prognosis of Covid-19 patients.