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Despite the numerous articles published on the clinical characteristics and outcomes of COVID-19 with regard to high-income countries, little is known about patients in low- and middle-income countries (LMIC) in this context. The objective of this observational, prospective, hospital-based multicentric study was to describe clinical features and outcomes of laboratory-confirmed COVID-19 patients hospitalized in each of the participating centers in Bangladesh, Guinea, Ivory Coast, Lebanon, Madagascar, and Mali during the first year of the pandemic (March 5, 2020 to May 4, 2021). The study outcome was the clinical severity of COVID-19, defined as hospitalization in intensive care unit or death. Multivariate logistic regression models were performed to identify independent variables associated with disease severity. Overall, 1,096 patients were included. The median age was 49.0 years, ranging from 38.0 in Mali to 63.0 years in Guinea. The overall clinical severity of COVID-19 was 12.3%, ranging from 6.4% in Mali to 18.8% in Guinea. In both groups of patients <60 and ≥60 years old, cardiovascular diseases (adjusted odds ratio [aOR]: 1.99; 95% CI: 1.13-3.50, P = 0.02; aOR: 2.47; 95% CI: 1.33-4.57, P = 0.004) were independently associated with clinical severity, whereas in patients <60 years, diabetes (aOR: 2.13; 95% CI: 1.11-4.10, P = 0.02) was also associated with clinical severity. Our findings suggest that COVID-19-related severity and death in LMICs are mainly driven by older age. However, the presence of chronic diseases can also increase the risk of severity especially in younger patients.

(1) Background: A substantial proportion of COVID-19 patients continue to experience long-lasting effects that hamper their quality of life. The objectives of this study were (1) to report the prevalence of persistent clinical symptoms 6-12 months after the onset of COVID-19 and (2) to identify potential factors at admission associated with the occurrence of long COVID. (2) Methods: A prospective study was conducted among COVID-19 adult patients, hospitalized in four French university hospitals. Patients were invited to two ambulatory follow-up medical visits, 6-8 months (visit #1) and one year (visit #2) after the onset of their COVID-19. A multivariate logistic regression was performed to assess factors associated with long COVID. (3) Results: In total, 189 patients participated in this study (mean age of 63.4 years). BMI > 30 kg/m 2 (aOR 3.52), AST levels between 31 and 42 U/L (aOR 8.68), and AST levels > 42 U/L (aOR 3.69) were associated with persistent clinical symptoms at visit #1. Anosmia (aOR 13.34), AST levels between 31 and 42 U/L (aOR 10.27), stay in ICU (aOR 5.43), pain (aOR 4.31), and longer time before hospitalization (aOR 1.14) were significantly associated with persistent clinical symptoms at visit #2. Patients with ageusia (aOR 0.17) had a lower risk of long COVID. (4) Conclusions: This study showed that some patients experienced persistent clinical symptoms one year after COVID-19 onset that were associated with some determinants at the acute phase/stage.

Purpose of Review: This review provides an update on specificities of influenza in older adults (≥65-year-old), including epidemiology, burden in terms of hospitalization and mortality, extra-respiratory complications and specific challenges of prevention., Recent Findings: In the past 2 years, influenza activity was drastically reduced by barrier measures implemented during the COVID-19 pandemic. A recent French epidemiological study covering 2010-2018 epidemic seasons estimated that 75% of costs induced by influenza-associated hospitalizations and complications were attributable to older adults, a population bearing more than 90% of influenza-associated excess mortality.In addition to their age, comorbidities and reduced vaccine response, long-term facility residents are at risk for nosocomial outbreaks. Beyond respiratory complications, influenza triggers acute myocardial infarction and ischemic stroke. Influenza might drive significant functional loss in frail older adults, which can lead to "catastrophic" or severe disability in up to 10% of patients. Vaccination remains the cornerstone of prevention, with enhanced immunization strategies (i.e., high-dose or adjuvanted formulations) to be largely implemented in older adults. Efforts to increase influenza vaccination uptake during the COVID-19 pandemic should be consolidated., Summary: Burden of influenza in the elderly is largely under-recognized, especially the cardiovascular complications and the impact on functional status, justifying more effective preventive strategies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Detailed information are lacking on influenza transmissibility in hospital although clusters are regularly reported. In this pilot study, our goal was to estimate the transmission rate of H3N2 2012-influenza, among patients and health care professionals in a short-term Acute Care for the Elderly Unit by using a stochastic approach and a simple susceptible-exposed-infectious-removed model. Transmission parameters were derived from documented individual contact data collected by Radio Frequency IDentification technology at the epidemic peak. From our model, nurses appeared to transmit infection to a patient more frequently with a transmission rate of 1.04 per day on average compared to 0.38 from medical doctors. This transmission rate was 0.34 between nurses. These results, even obtained in this specific context, might give a relevant insight of the influenza dynamics in hospitals and will help to improve and to target control measures for preventing nosocomial transmission of influenza. The investigation of nosocomial transmission of SARS-COV-2 might gain from similar approaches., (© 2023. The Author(s).)

Objectives: Quantify the effects of characteristics of nursing homes and their surroundings on the spread of COVID-19 outbreaks and assess the changes in resident protection between the first 2 waves (March 1 to July 31 and August 1 to December 31, 2020)., Design: An observational study was carried out on data on COVID-19 outbreaks extracted from a database that monitored the spread of the virus in nursing homes., Setting and Participants: The study concerned all 937 nursing homes with >10 beds in Auvergne-Rhône-Alpes region, France., Methods: The rate of nursing homes with at least 1 outbreak and the cumulative number of deaths were modeled for each wave., Results: During the second (vs the first wave), the proportion of nursing homes that reported at least 1 outbreak was higher (70% vs 56%) and the cumulative number of deaths more than twofold (3348 vs 1590). The outbreak rate was significantly lower in public hospital-associated nursing homes than in private for-profit ones. During the second wave, it was lower in public and private not-for-profit nursing homes than in private for-profit ones. During the first wave, the probability of outbreak and the mean number of deaths increased with the number of beds (P < .001). During the second wave, the probability of outbreak remained stable in >80-bed institutions and, under proportionality assumption, the mean number of deaths was less than expected in >100-bed institutions. The outbreak rate and the cumulative number of deaths increased significantly with the increase in the incidence of hospitalization for COVID-19 in the surrounding populations., Conclusions and Implications: The outbreak in the nursing homes was stronger during the second than the first wave despite better preparedness and higher availabilities of tests and protective equipment. Solutions for insufficient staffing, inadequate rooming, and suboptimal functioning should be found before future epidemics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

BackgroundTo cope with the persistence of the COVID-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.AimWe wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.MethodsWe combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse immunological parameters before and after the third mRNA vaccine dose.ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18-3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72-1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.ConclusionThe advantage conferred by heterologous vaccination was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, β-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc ( p = 0.012) and β-carotene ( p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc ( p = 0.009), selenium ( p = 0.014), vitamin A ( p = 0.001), and β-carotene ( p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced T H 1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Objectives: We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults., Methods: Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized., Results: We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies., Conclusions: A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

BackgroundAs record cases of Omicron variant were registered in Europe in early 2022, schools remained a vulnerable setting undergoing large disruption.AimThrough mathematical modelling, we compared school protocols of reactive screening, regular screening, and reactive class closure implemented in France, in Baselland (Switzerland), and in Italy, respectively, and assessed them in terms of case prevention, testing resource demand, and schooldays lost.MethodsWe used a stochastic agent-based model of SARS-CoV-2 transmission in schools accounting for within- and across-class contacts from empirical contact data. We parameterised it to the Omicron BA.1 variant to reproduce the French Omicron wave in January 2022. We simulated the three protocols to assess their costs and effectiveness for varying peak incidence rates in the range experienced by European countries.ResultsWe estimated that at the high incidence rates registered in France during the Omicron BA.1 wave in January 2022, the reactive screening protocol applied in France required higher test resources compared with the weekly screening applied in Baselland (0.50 vs 0.45 tests per student-week), but achieved considerably lower control (8% vs 21% reduction of peak incidence). The reactive class closure implemented in Italy was predicted to be very costly, leading to > 20% student-days lost.ConclusionsAt high incidence conditions, reactive screening protocols generate a large and unplanned demand in testing resources, for marginal control of school transmissions. Comparable or lower resources could be more efficiently used through weekly screening. Our findings can help define incidence levels triggering school protocols and optimise their cost-effectiveness.

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., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased risk of death if VAP occurs in a patient) and attributable fraction (proportion of deaths that are attributable to an exposure) of VAP-related mortality compared with subjects without coronavirus disease (COVID-19). Objectives: Estimation of the attributable mortality of the VAP among patients with COVID-19. Methods: Using the REA-REZO surveillance network, three groups of adult medical ICU patients were computed: control group (patients admitted between 2016 and 2019; prepandemic patients), pandemic COVID-19 group (PandeCOV + ), and pandemic non-COVID-19 group (PandeCOV - ) admitted during 2020. The primary outcome was the estimation of attributable mortality and attributable fraction related to VAP in these patients. Using multistate modeling with causal inference, the outcomes related to VAP were also evaluated. Measurements and Main Results: A total of 64,816 patients were included in the control group, 7,442 in the PandeCOV - group, and 1,687 in the PandeCOV + group. The incidence of VAP was 14.2 (95% confidence interval [CI], 13.9 to 14.6), 18.3 (95% CI, 17.3 to 19.4), and 31.9 (95% CI, 29.8 to 34.2) per 1,000 ventilation-days in each group, respectively. Attributable mortality at 90 days was 3.15% (95%, CI, 2.04% to 3.43%), 2.91% (95% CI, -0.21% to 5.02%), and 8.13% (95% CI, 3.54% to 12.24%), and attributable fraction of mortality at 90 days was 1.22% (95% CI, 0.83 to 1.63), 1.42% (95% CI, -0.11% to 2.61%), and 9.17% (95% CI, 3.54% to 12.24%) for the control, PandeCOV - , and PandeCOV + groups, respectively. Except for the higher risk of developing VAP, the PandeCOV - group shared similar VAP characteristics with the control group. PandeCOV + patients were at lower risk of death without VAP (hazard ratio, 0.62; 95% CI, 0.52 to 0.74) than the control group. Conclusions: VAP-attributable mortality was higher for patients with COVID-19, with more than 9% of the overall mortality related to VAP.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In response to the coronavirus disease (COVID-19) outbreak that unfolded across Europe in 2020, the World Health Organisation (WHO) called for repurposing existing influenza surveillance systems to monitor COVID-19. This analysis aimed to compare descriptively the extent to which influenza surveillance systems were adapted and enhanced and how COVID-19 surveillance could ultimately benefit or disrupt routine influenza surveillance., Methods: We used a previously developed framework in France, Germany, Italy, Spain and the United Kingdom to describe COVID-19 surveillance and its impact on influenza surveillance. The framework divides surveillance systems into seven subsystems and 20 comparable outcomes of interest and uses five evaluation criteria based on WHO guidance. Information on influenza and COVID-19 surveillance systems were collected from publicly available resources shared by European and national public health agencies., Results: Overall, non-medically attended, virological, primary care and mortality surveillance were adapted in most countries to monitor COVID-19, although community, outbreak and hospital surveillance were reinforced in all countries. Data granularity improved, with more detailed demographic and medical information recorded. A shift to systematic notification for cases and deaths enhanced both geographic and population representativeness, although the sampling strategy benefited from the roll out of widespread molecular testing. Data communication was greatly enhanced, contributing to improved public awareness., Conclusions: Well-established influenza surveillance systems are a key component of pandemic preparedness, and their upgrade allowed European countries to respond to the COVID-19 pandemic. However, uncertainties remain on how both influenza and COVID-19 surveillance can be jointly and durably implemented., (© 2021 Sanofi Pasteur. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Studies involving the associations between vitamin D supplementation taken before the onset of COVID-19 infection and the clinical outcomes are still scarce and this issue remains controversial. This study aimed to assess the relationships between vitamin D (VitD) status and supplementation and coronavirus disease 2019 (COVID-19) severity in older adults (average age of 78 years) hospitalized for COVID-19. We conducted an observational retrospective cohort study with 228 older hospitalized patients during the first wave of the COVID-19 pandemic. The outcomes were in-hospital mortality secondary to COVID-19 or critically severe COVID-19. A logistic regression analysis was conducted to test whether pre-hospital VitD supplementation was independently associated with severity. In this study, 46% of patients developed a severe form and the overall in-hospital mortality was 15%. Sixty-six (29%) patients received a VitD supplement during the 3 months preceding the infection onset. Additionally, a VitD supplement was associated with fewer severe COVID-19 forms (OR = 0.426, p = 0.0135) and intensive care unit (ICU) admissions (OR = 0.341, p = 0.0076). As expected, age > 70 years, male gender and BMI ≥ 35 kg/m2 were independent risk factors for severe forms of COVID-19. No relationship between serum 25(OH)D levels and the severity of the COVID-19 was identified. VitD supplementation taken during the 3 months preceding the infection onset may have a protective effect on the development of severe COVID-19 forms in older adults. Randomized controlled trials and large-scale cohort studies are necessary to strengthen this observation.

Background: In critically ill COVID-19 patients, the initial response to SARS-CoV-2 infection is characterized by major immune dysfunctions. The capacity of these severe patients to mount a robust and persistent SARS-CoV-2 specific T cell response despite the presence of severe immune alterations during the ICU stay is unknown., Methods: Critically ill COVID-19 patients were sampled five times during the ICU stay and 9 and 13 months afterwards. Immune monitoring included counts of lymphocyte subpopulations, HLA-DR expression on monocytes, plasma IL-6 and IL-10 concentrations, anti-SARS-CoV-2 IgG levels and T cell proliferation in response to three SARS-CoV-2 antigens., Findings: Despite the presence of major lymphopenia and decreased monocyte HLA-DR expression during the ICU stay, convalescent critically ill COVID-19 patients consistently generated adaptive and humoral immune responses against SARS-CoV-2 maintained for more than one year after hospital discharge. Patients with long hospital stays presented with stronger anti-SARS-CoV-2 specific T cell response but no difference in anti-SARS-CoV2 IgG levels., Interpretation: Convalescent critically ill COVID-19 patients consistently generated a memory immune response against SARS-CoV-2 maintained for more than one year after hospital discharge. In recovered individuals, the intensity of SARS-CoV-2 specific T cell response was dependent on length of hospital stay., Funding: This observational study was supported by funds from the Hospices Civils de Lyon, Fondation HCL, Claude Bernard Lyon 1 University and Région Auvergne Rhône-Alpes and by partial funding by REACTing (Research and ACTion targeting emerging infectious diseases) INSERM, France and a donation from Fondation AnBer (http://fondationanber.fr/)., Competing Interests: Declaration of interests MB, CT, KBG, VC and MAC are bioMérieux's employees. This private company had no role in the study design, result analysis and decision to publish this study. PV received consulting fees and payment for a literature review from Pfizer and Astellas. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population., Design: Cohort exposed/nonexposed study among the REA-REZO surveillance network., Setting: Multicentric; ICUs in France., Patients: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1)., Interventions: None., Measurements and Main Results: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013)., Conclusions: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern., Competing Interests: Dr. Vanhems’ institution received funding from Anios; he received funding from Astellas and Sanofi. Drs. Vanhem and Friggeri received funding from Pfizer. Dr. Friggeri received funding from MSD. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Measuring vaccine effectiveness (VE) using real-life data is critical to confirm the effectiveness of licensed vaccine, which could strengthen vaccination adherence., Methods: We measured VE against adult COVID-19 hospitalization in five hospitals in France using a test negative design. We compared the odds of vaccinated patients hospitalized with COVID-19 with the odds of vaccinated patients hospitalized for the same symptoms with a negative test., Results: A total of 853 patients (463 cases and 390 controls) were included, with a total of 170 patients vaccinated (104 with one dose, 65 with two doses, and one with three doses). There were four cases of breakthrough infections, all in immunocompromised patients. The VE was 84.0% (CI 0.95 =[72.6; 90.6]) for one dose and 96.2% (CI 0.95 =[86.8; 98.9]) for two doses., Conclusion: Our results confirm the high VE of COVID-19 vaccine in France to prevent hospitalizations due to the alpha variant., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

COVID-19 vaccination has proven to be effective in preventing severe cases, reducing viral load, and transmissibility. The aim of this study was to evaluate the impact of vaccination 11 months after implementation on epidemiological indicators and the effective reproduction number in one French region. We plotted four indicators with vaccination coverage as the explaining variable and estimated the impact of vaccination using the reduction rates in infections and hospital admissions. A reduction of 98% in COVID-19-related hospitalisation 11 months after the vaccine campaign began in January 2021 has been reported while vaccine coverage increased over time. Those results do not make it possible to postulate a causal relationship but do support the effect of vaccination against multiple variants of concern. Non-pharmaceutical measures remain necessary to attain complete epidemic control. Open epidemiological data should be considered to monitor vaccine effectiveness wherever possible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Worldwide, COVID-19 outbreaks in nursing homes have often been sudden and massive. The study investigated the role SARS-CoV-2 virus spread in nearby population plays in introducing the disease in nursing homes., Material and Methods: This was carried out through modelling the occurrences of first cases in each of 943 nursing homes of Auvergne-Rhône-Alpes French Region over the first epidemic wave (March-July, 2020). The cumulative probabilities of COVID-19 outbreak in the nursing homes and those of hospitalization for the disease in the population were modelled in each of the twelve Départements of the Region over period March-July 2020. This allowed estimating the duration of the active outbreak period, the dates and heights of the peaks of outbreak probabilities in nursing homes, and the dates and heights of the peaks of hospitalization probabilities in the population. Spearman coefficient estimated the correlation between the two peak series., Results: The cumulative proportion of nursing homes with COVID-19 outbreaks was 52% (490/943; range: 22-70% acc. Département). The active outbreak period in the nursing homes lasted 11 to 21 days (acc. Département) and ended before lockdown end. Spearman correlation between outbreak probability peaks in nursing homes and hospitalization probability peaks in the population (surrogate of the incidence peaks) was estimated at 0.71 (95% CI: [0.66; 0.78])., Conclusion: The modelling highlighted a strong correlation between the outbreak in nursing homes and the external pressure of the disease. It indicated that avoiding disease outbreaks in nursing homes requires a tight control of virus spread in the surrounding populations., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: PV received grants and fees from Anios, Pfizer, Astellas, MSD, Gilead and Sanofi. These grants and fees were not related to this present manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. All other authors have no competing interest to declare.

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 Χ 2 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., (© 2021 Wiley Periodicals LLC.)

Background: With no vaccines or specific treatments, non-pharmaceutical interventions are the only tools for controlling the human-to-human transmission of the COVID-19 disease, which appeared in Wuhan, China last December and has spread globally since. Here we describe and compare the first-wave mitigation strategies and epidemiology of five Asia-Pacific countries that responded rapidly to the epidemic., Methods: From January to April 2020, mitigation measures and epidemiological data for Singapore, South Korea, Japan, Taiwan, Hong Kong were screened from official local government websites and a review of investigational studies was conducted. Daily case reports and mitigation measures information were extracted. Epidemiological estimates were calculated and compared between countries., Results: All five countries combined measures, focusing on contact tracing, testing, isolation efforts and healthcare management. Epidemiological data varied temporally and geographically: incubation period ranged 3.9-7.1 days, effective reproduction number at time t (Rt) ranged 0.48-1.5, with intensive care admissions 1-3% of hospitalised patients, and case fatality rates were 0.1-3%. Extrinsic estimates to the virus were lower than global estimates., Conclusion: Implemented mitigation strategies in these countries allowed a rapid and successful control or delay of the first COVID-19 pandemic wave. These are valuable examples to inform subsequent waves., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: The outbreak of coronavirus disease 2019 (COVID-19) in South Kivu, Democratic Republic of Congo raised concerns regarding additional morbidity and mortality. Updating these indicators before a second wave is essential in order to prepare for additional help., Methods: From mid-May to mid-December 2020, weekly surveys were undertaken in sampled streets from 10 health areas to quantify the use of barrier measures, and interview pedestrians about sickness and deaths in their households. Crude death rates (CDRs) were estimated., Results: Minimal use or no use of face masks was observed in at least half of the streets. From May to December 2020, the number of suspected cases of COVID-19 increased six-fold (P < 0.05). Of deaths within 30 days preceding the interviews, 20% were considered to be related to COVID-19. The monthly CDRs at the beginning and end of the study were approximately 5 and 25 per 1000 population, respectively (P < 0.05); that is, annual CDRs of 60 and 260 per 1000 population, respectively. Thus, during the first wave, the estimated mortality rate increased by 50% compared with previous years, and increased at least four-fold by the end of 2020., Conclusion: Despite possible overestimations, the excess mortality in South Kivu is extremely concerning. This crisis calls for a rapid response and increased humanitarian assistance., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: PV received grants and fees from Anios, Pfizer, Astellas, MSD, Gilead and Sanofi. These grants and fees were not related to this present manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. All other authors have no competing interest to declare.

To date, no specific estimate of R0 for SARS-CoV-2 is available for healthcare settings. Using interindividual contact data, we highlight that R0 estimates from the community cannot translate directly to healthcare settings, with pre-pandemic R0 values ranging 1.3-7.7 in 3 illustrative healthcare institutions. This has implications for nosocomial COVID-19 control., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The major economic and health consequences of COVID-19 called for various protective measures and mass vaccination campaigns. A previsional model was used to predict the future impacts of various measure combinations on COVID-19 mortality over a 400-day period in France. Calibrated on previous national hospitalization and mortality data, an agent-based epidemiological model was used to predict individual and combined effects of booster doses, vaccination of refractory adults, and vaccination of children, according to infection severity, immunity waning, and graded non-pharmaceutical interventions (NPIs). Assuming a 1.5 hospitalization hazard ratio and rapid immunity waning, booster doses would reduce COVID-19-related deaths by 50–70% with intensive NPIs and 93% with moderate NPIs. Vaccination of initially-refractory adults or children ≥ 5 years would half the number of deaths whatever the infection severity or degree of immunity waning. Assuming a 1.5 hospitalization hazard ratio, rapid immunity waning, moderate NPIs and booster doses, vaccinating children ≥ 12 years, ≥ 5 years, and ≥ 6 months would result in 6212, 3084, and 3018 deaths, respectively (vs. 87,552, 64,002, and 48,954 deaths without booster, respectively). In the same conditions, deaths would be 2696 if all adults and children ≥ 12 years were vaccinated and 2606 if all adults and children ≥ 6 months were vaccinated (vs. 11,404 and 3624 without booster, respectively). The model dealt successfully with single measures or complex combinations. It can help choosing them according to future epidemic features, vaccination extensions, and population immune status. [ABSTRACT FROM AUTHOR]

The outbreak of the SARS-CoV-2 virus, enhanced by rapid spreads of variants, has caused a major international health crisis, with serious public health and economic consequences. An agent-based model was designed to simulate the evolution of the epidemic in France over 2021 and the first six months of 2022. The study compares the efficiencies of four theoretical vaccination campaigns (over 6, 9, 12, and 18 months), combined with various non-pharmaceutical interventions. In France, with the emergence of the Alpha variant, without vaccination and despite strict barrier measures, more than 600,000 deaths would be observed. An efficient vaccination campaign (i.e., total coverage of the French population) over six months would divide the death toll by 10. A vaccination campaign of 12, instead of 6, months would slightly increase the disease-related mortality (+6%) but require a 77% increase in ICU bed–days. A campaign over 18 months would increase the disease-related mortality by 17% and require a 244% increase in ICU bed–days. Thus, it seems mandatory to vaccinate the highest possible percentage of the population within 12, or better yet, 9 months. The race against the epidemic and virus variants is really a matter of vaccination strategy. [ABSTRACT FROM AUTHOR]