Impact of vaccination on the presence and severity of symptoms in hospitalized patients with an infection of the Omicron variant (B.1.1.529) of the SARS-CoV-2 (subvariant BA.1).

OBJECTIVES: The emergence of SARS-CoV-2 variants raised questions about the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalized patients. METHODS: We conducted an international, multi-centric, retrospective study in 14 centres (Bulgaria, Croatia, France, and Turkey). We collected data on patients hospitalized for ≥24 hours between 1 December 2021 and 3 March 2022 with PCR-confirmed infection at a time of exclusive Omicron circulation and hospitalization related or not related to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least two injections of either mRNA and/or ChAdOx1-S or one injection of Ad26.CoV2-S vaccines. RESULTS: Among 1215 patients (median age, 73.0 years; interquartile range, 57.0-84.0; 51.3% men), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (Odds Ratio [95% Confidence Interval] (OR [95CI]) = 0.50 [0.32-0.77]), intensive care unit admission (OR [95CI] = 0.40 [0.26-0.62]), and oxygen requirement (OR [95CI] = 0.34 [0.25-0.46]), independent of age and comorbidities. When co-analysing these patients with Omicron infection with 948 patients with Delta infection from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (OR [95CI] = 0.53 [0.37-0.76]), intensive care unit admission (OR [95CI] = 0.19 [0.12-0.28]), and oxygen requirements (OR [95CI] = 0.50 [0.38-0.67]), independent of age, comorbidities, and vaccination status. DISCUSSION: Originally designed vaccines have remained effective on the severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independent of vaccination and patient characteristics.

Coadministration of seasonal influenza and COVID-19 vaccines: A systematic review of clinical studies.

The lifting of non-pharmaceutical measures preventing transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources and fears of an increased number of cases of influenza and COVID-19. For the 2021-2022 influenza season, the WHO and >20 European countries promoted coadministration of influenza and COVID-19 vaccines. Recently, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign for healthcare professionals and people at risk of severe COVID-19. The present systematic review examines published data on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. The results should reassure vaccinees and vaccinators in case of coadministration and increase vaccine coverage. Healthcare systems promoting coupled campaigns must provide the necessary means for successful coadministration.

The lifting of non-pharmaceutical measures recommended to prevent transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources, already under pressure. It also raises fears of an increase in the number of cases of influenza or COVID-19 infection during the winter season. For the 2021­2022 influenza season, the World Health Organization and several European countries promoted concomitant administration in distinct anatomic sites (i.e., coadministration) of influenza and COVID-19 vaccines to avoid additional stress on healthcare systems. In May 2022, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022­2023 influenza vaccination campaign (i.e., starting COVID-19 vaccination at the date of influenza vaccination) for healthcare professionals and people at risk of severe COVID-19, in case of epidemic wave. Coadministration of influenza and COVID-19 vaccines is one of the factors of success for a coupled campaign. The present systematic review examines all published data (articles or reports, clinical trials, or surveys) on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. The PRISMA method was used to collect information. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. Acceptability and acceptance were good but could be improved. By reassuring vaccinees and vaccinators, these results are expected to favor coadministration and ultimately increase vaccine coverage, thus offering better protection. Healthcare systems promoting coupled campaigns with coadministration must provide the necessary means for their successful implementation.

Immunogenicity and reactogenicity of heterologous and homologous mRNA-1273 and BNT162b2 vaccination: A multicenter non-inferiority randomized trial.

Background: Although effective mRNA vaccines for SARS-CoV-2 infection have been deployed worldwide, their interchangeability could facilitate the scale-up of vaccination programs. The objective of the trial was to assess whether the immune response induced by a heterologous SARS-CoV-2 mRNA primo vaccination is non-inferior to that of a homologous mRNA vaccination. Methods: We conducted a multicenter, randomized, open-label trial in adults 18 years of age and older who received a first dose of SARS-CoV-2 mRNA vaccine. Participants were randomly assigned in a 1:1 ratio to receive a second dose of BNT162b2 or mRNA-1273, 28 to 49 days after the first dose. Randomization was stratified on the vaccine received at the first vaccination. The primary endpoint was the anti-spike IgG antibodies titer measured 28 days after the second vaccine dose. This study is registered with ClinicalTrials.gov, Trial, NCT04900467. Findings: Of the 414 randomized participants recruited from May 28 to July 2, 2021, 390 were included in the per protocol analysis: 94 participants in group 1 (BNT162b2/BNT162b2), 96 in group 2 (BNT162b2/mRNA-1273), 97 in group 3 (mRNA-1273/mRNA-1273), and 103 in group 4 (mRNA-1273/BNT162b2). The geometric mean titers ratios of anti-spike IgG antibodies for each heterologous regimen relative to the corresponding homologous regimen were 1·37 (two-sided 95% CI, 1·10 to 1·72) in the groups 1 and 2 and 0·67 (two-sided 95% CI, 0·55 to 0·82) in the groups 3 and 4. Levels of neutralizing antibodies to the main circulating SARS-Cov-2 viral strains were higher with the vaccine regimen containing mRNA-1273. Participants who received mRNA-1273 as a second dose experienced a higher rate of local adverse reactions and general symptoms than those who received BNT162b2 (p < 0·0001). Interpretation: The two SARS-CoV-2 mRNA vaccines could be used with flexibility for the second dose of COVID-19 primo vaccination. Tolerance remains good regardless of vaccine sequence although mRNA-1273 was more reactogenic. Funding: French Ministries of Solidarity and Health and Research. BNT162b2 was provided by Pfizer/BioNTech. mRNA-1273 was provided by Moderna.

Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection.

OBJECTIVES: The diffusion of the SARS-CoV-2 Delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status. METHODS: We performed a retrospective observational study on patients hospitalised in 10 centres with a SARS-CoV-2 infection (Delta variant) from July to November 2021 by including all patients who had completed their primary vaccination at least 14 days before hospital admission and the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression. RESULTS: We included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older (75.0 [63.25-84.0] vs. 55.0 [38.0-73.0]; p < 0.001), more frequently males (55.1% (261/474) vs. 46.4% (223/481); p = 0.009), and had more comorbidities (2.0 [1.0-3.0] vs. 1.0 [0.0-2.0]; p < 0.001). Vaccinated patients were less often admitted for Covid-19 (59.3% (281/474) vs. 75.1% (361/481); p < 0.001), had less extended lung lesions (≤25%: 64.3% (117/182) vs. 38.4% (88/229); p < 0.001), required oxygen less frequently (57.5% (229/398) vs. 73.0% (270/370); p < 0.001), at a lower flow (3.0 [0.0-8.7] vs. 6.0 [2.0-50.0] L/min, p < 0.001), and for a shorter duration (3 [0.0-8.0] vs. 6 [2.0-12.0] days, p < 0.001)., and required less frequently intensive care unit admission (16.2% (60/370) vs. 36.0% (133/369); p < 0.001) but had comparable mortality in bivariate analysis (16.7% (74/443) vs. 12.2% (53/433); p = 0.075). Multivariate logistic regression showed that vaccination significantly decreased the risk of death (0.38 [0.20-0.70](p = 0.002), ICU admission (0.31 [0.21-0.47](p < 0.001) and oxygen requirement (0.16 [0.10-0.26](p < 0.001), even among older patients or with comorbidities. CONCLUSIONS: Among patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Vaccination for Respiratory Infections in Patients with Heart Failure.

Bronchopulmonary infections are a major trigger of cardiac decompensation and are frequently associated with hospitalizations in patients with heart failure (HF). Adverse cardiac effects associated with respiratory infections, more specifically Streptococcus pneumoniae and influenza infections, are the consequence of inflammatory processes and thrombotic events. For both influenza and pneumococcal vaccinations, large multicenter randomized clinical trials are needed to evaluate their efficacy in preventing cardiovascular events, especially in HF patients. No study to date has evaluated the protective effect of the COVID-19 vaccine in patients with HF. Different guidelines recommend annual influenza vaccination for patients with established cardiovascular disease and also recommend pneumococcal vaccination in patients with HF. The Heart Failure group of the French Society of Cardiology recently strongly recommended vaccination against COVID-19 in HF patients. Nevertheless, the implementation of vaccination recommendations against respiratory infections in HF patients remains suboptimal. This suggests that a national health policy is needed to improve vaccination coverage, involving not only the general practitioner, but also other health providers, such as cardiologists, nurses, and pharmacists. This review first summarizes the pathophysiology of the interrelationships between inflammation, infection, and HF. Then, we describe the current clinical knowledge concerning the protective effect of vaccines against respiratory diseases (influenza, pneumococcal infection, and COVID-19) in patients with HF and finally we propose how vaccination coverage could be improved in these patients.

Deterioration of vaccine-induced immune thrombotic thrombocytopenia treated by heparin and platelet transfusion: Insight from functional cytometry and serotonin release assay.

We report a case of a 62-year-old man who developed cerebral venous sinus thrombosis with subarachnoid hemorrhage and concomitant thrombocytopenia, which occurred 13 days after ChAdOx1 nCov-19 injection. The patient died in the intensive care unit after heparin infusion and platelet transfusion. The key clinical purpose of this case report is to better understand how to confirm vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT diagnosis was made using 14C-serotonin release and flow cytometry evaluating activation and platelet microvesicles on washed platelets. Four control patients were examined: a patient with heparin-induced thrombocytopenia (HIT), two patients with thrombotic events without thrombocytopenia after ChAdOx1 nCov-19 or BNT162b2, and a patient with suspected HIT and an excluded diagnosis. We evidenced in the VITT case a high level of IgG anti-platelet factor 4-heparin antibodies associated with a high level of platelet activation in the absence of heparin. Conversely, the functional assays were negative in the patients with thrombosis without thrombocytopenia.

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France.

Vaccination programs against COVID-19 are being scaled up. We aimed to assess the effects of vaccine characteristics on vaccine hesitancy among healthcare workers in a multi-center survey conducted within French healthcare facilities from 1 December 2020 to 26 March 2021. We invited any healthcare workers naïve of COVID-19 vaccination to complete an online self-questionnaire. They reported on their socio-demographic characteristics, as well as their perception and beliefs towards vaccination. We measured their willingness to get vaccinated in eight scenarios for candidates' vaccines presented sequentially (1 to 4-point scale). Candidates' vaccines varied for efficacy (25%, 50%, 100%), length of immunization (1 year or lifetime), frequency (<1/100, <1/10,000), and severity (none, moderate, severe) of adverse events. We analyzed 4349 healthcare workers' responses with interpretable questionnaires. The crude willingness to get vaccinated was 53.2% and increased over time. We clustered the trajectories of responses using an unsupervised classification algorithm (k-means) and identified four groups of healthcare workers: those willing to get vaccinated in any scenario (18%), those not willing to get vaccinated at all (22%), and those hesitating but more likely to accept (32%) or reject (28%) the vaccination depending on the scenario. In these last two subgroups, vaccine acceptance was growing with age, educational background and was higher among men with condition. Compared to an ideal vaccine candidate, a 50% reduced efficacy resulted in an average drop in acceptance by 0.8 (SD ± 0.8, -23.5%), while it was ranging from 1.4 (SD ± 1.0, -38.4%) to 2.1 (SD ± 1.0, -58.4%) in case of severe but rare adverse event. The acceptance of a mandatory immunization program was 29.6% overall and was positively correlated to the willingness to get vaccinated, ranging from 2.4% to 60.0%. Even if healthcare workers represent a heterogeneous population, most (80%) could accept the vaccination against COVID-19. Their willingness to get the vaccine increased over time and as immunization programs became available. Among hesitant professionals, the fear of adverse events was the main concern. Targeted information campaigns reassuring about adverse events may increase vaccine coverage, in a population with a strong opinion about mandatory immunization programs.

Family medicine practitioners' stress during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: The COVID-19 pandemic has shaken the world in early 2020. In France, General Practitioners (GPs) were not involved in the care organization's decision-making process before and during the first wave of the COVID-19 pandemic. This omission could have generated stress for GPs. We aimed first to estimate the self-perception of stress as defined by the 10-item Perceived Stress Score (PSS-10), at the beginning of the pandemic in France, among GPs from the Auvergne-Rhône-Alpes, a french administrative area severely impacted by COVID-19. Second, we aimed to identify factors associated with a self-perceived stress (PSS-10 ≥ 27) among socio-demographic characteristics of GPs, their access to reliable information and to personal protective equipment during the pandemic, and their exposure to well established psychosocial risk at work. METHODS: We conducted an online cross-sectional survey between 8th April and 10th May 2020. The self-perception of stress was evaluated using the PSS-10, so to see the proportion of "not stressed" (≤20), "borderline" (21 ≤ PSS-10 ≤ 26), and "stressed" (≥27) GPs. The agreement to 31 positive assertions related to possible sources of stress identified by the scientific study committee was measured using a 10-point numeric scale. In complete cases, factors associated with stress (PSS-10 ≥ 27) were investigated using logistic regression, adjusted on gender, age and practice location. A supplementary analysis of the verbatims was made. RESULTS: Overall, 898 individual answers were collected, of which 879 were complete. A total of 437 GPs (49%) were stressed (PSS-10 ≥ 27), and 283 GPs (32%) had a very high level of stress (PSS-10 ≥ 30). Self-perceived stress was associated with multiple components, and involved classic psychosocial risk factors such as emotional requirements. However, in this context of health crisis, the primary source of stress was the diversity and quantity of information from diverse sources (614 GPs (69%, OR = 2.21, 95%CI [1.40-3.50], p < 0.001). Analysis of verbatims revealed that GPs felt isolated in a hospital-based model. CONCLUSION: The first wave of the pandemic was a source of stress for GPs. The diversity and quantity of information received from the health authorities were among the main sources of stress.

Trajectories of Hospitalization in COVID-19 Patients: An Observational Study in France.

Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20-65 year-olds to 4.5 in the >80 year-olds (p < 0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age: fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care.

Trajectories of Hospitalization in COVID-19 Patients: An Observational Study in France

Describing the characteristics of COVID-19 patients in the hospital is of importance to assist in the management of hospital capacity in the future. Here, we analyze the trajectories of 1321 patients admitted to hospitals in northern and eastern France. We found that the time from onset to hospitalization decreased with age, from 7.3 days in the 20-65 year-olds to 4.5 in the >80 year-olds (p <0.0001). Overall, the length of stay in the hospital was 15.9 days, and the death rate was 20%. One patient out of four was admitted to the intensive care unit (ICU) for approximately one month. The characteristics of trajectories changed with age: fewer older patients were admitted to the ICU and the death rate was larger in the elderly. Admission shortly after onset was associated with increased mortality (odds-ratio (OR) = 1.8, Confidence Interval (CI) 95% [1.3, 2.6]) as well as male sex (OR = 2.1, CI 95% [1.5, 2.9]). Time from admission within the hospital to the transfer to ICU was short. The age- and sex-adjusted mortality rate decreased over the course of the epidemic, suggesting improvement in care over time. In the SARS-CoV-2 epidemic, the urgent need for ICU at admission and the prolonged length of stay in ICU are a challenge for bed management and organization of care.