Background Although immune modulation is a promising therapeutic avenue in coronavirus disease 2019 (COVID-19), the most relevant targets remain to be found. COVID-19 has peculiar characteristics and outcomes, suggesting a unique immunopathogenesis. Methods Thirty-six immunocompetent non-COVID-19 and 27 COVID-19 patients with severe pneumonia were prospectively enrolled in a single center, most requiring intensive care. Clinical and biological characteristics (including T cell phenotype and function and plasma concentrations of 30 cytokines) and outcomes were compared. Results At similar baseline respiratory severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients (15 [7–22] vs. 4 (0–15) days; p = 0.0049). COVID-19 patients had lower levels of most classical inflammatory cytokines (G-CSF, CCL20, IL-1β, IL-2, IL-6, IL-8, IL-15, TNF-α, TGF-β), but higher plasma concentrations of CXCL10, GM-CSF and CCL5, compared to non-COVID-19 patients. COVID-19 patients displayed similar T-cell exhaustion to non-COVID-19 patients, but with a more unbalanced inflammatory/anti-inflammatory cytokine response (IL-6/IL-10 and TNF-α/IL-10 ratios). Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariate regression analysis confirmed that GM-CSF, CXCL10 and IL-10 levels were independently associated with the duration of mechanical ventilation. Conclusion We identified a unique cytokine response, with higher plasma GM-CSF and CXCL10 in COVID-19 patients that were independently associated with the longer duration of mechanical ventilation. These cytokines could represent the dysregulated immune response in severe COVID-19, as well as promising therapeutic targets. ClinicalTrials.gov: NCT03505281.

Introduction Obesity is commonly reported in COVID-19 patients and is associated with poorer outcomes. It is suggested that leptin could be the missing link between obesity and severe COVID-19. Our study aimed to unravel the link between adipokines, COVID-19 status, immune response, and outcomes in severe pneumonia. Methods In this prospective observational single-center study, 63 immunocompetent patients with severe pneumonia (36 non-COVID-19 and 27 COVID-19) were enrolled, most required intensive care. Clinical and biological characteristics (glucose metabolism, plasma adipokines, and cytokine concentrations) and outcomes were compared. Results At similar baseline severity, COVID-19 patients required mechanical ventilation for significantly longer than non-COVID-19 patients ( p = 0.0049). Plasma concentrations of leptin and adiponectin were respectively positively and negatively correlated with BMI and glucose metabolism (glycemia and insulinemia), but not significantly different between the two groups. Leptin levels were negatively correlated with IL-1β and IL-6, but the adipokines were not correlated with most other inflammatory mediators, baseline severity (SOFA score), or the duration of mechanical ventilation. Conclusion Adipokine levels were correlated with BMI but not with most inflammatory mediators, severity, or outcomes in severe pneumonia, regardless of the origin. The link between obesity, dysregulated immune response, and life-threatening COVID-19 requires further investigation. Clinical trial ClinicalTrials.gov: NCT03505281.

Influenza remains a major cause of illness and death in geriatric populations. While the influenza vaccine has successfully reduced morbidity and mortality, its effectiveness is suspected to decrease with age. The aim of this study was to assess the impact of influenza vaccination on all-cause mortality in very old ambulatory subjects. We conducted a prospective cohort study from 1 July 2016 to 31 June 2017 in a large unselected ambulatory population aged over 80 years. We compared all-cause mortality in vaccinated versus unvaccinated subjects after propensity-score matching, to control for age, sex and comorbidities. Among the 9149 patients included, with mean age 86 years, 4380 (47.9%) were vaccinated against influenza. In total, 5253 (57.4%) had at least one chronic disease. The most commonly vaccinated patients were those with chronic respiratory failure (76.3%) and the least commonly vaccinated were those suffering from Parkinson’s disease (28.5%). Overall, 2084 patients (22.8%) died during the study. After propensity score matching, the mortality was evaluated at 20.9% in the vaccinated group and 23.9% in the unvaccinated group (OR = 0.84 [0.75–0.93], p = 0.001). This decrease in mortality in the vaccinated group persisted whatever the age and Charlson Comorbidity index. In conclusion, nearly a half of this ambulatory elderly population received Influenza vaccine. After adjustment on comorbidities, influenza vaccination was associated with a significant decrease in all-cause mortality, even in the eldest multimorbid population. Improving immunization coverage in this frail older population is urgently needed.

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Funding : This work was supported by grants (MB) from the AOI (Appel d'Offre Interne)-COVID-2020 and Crowfunding (https://thellie.org/covid-19). Ethics approval and consent to participate : Oral consent was obtained from the patient or their legal representatives. Approval was obtained from the ethics committee (Comité de Protection des Personnes Sud-MEDITERRANEE V) (2017-A03404-49) and an amendment was obtained to include supplementary patients with COVID-19. Conflicts of interest: We declare no conflict of interest Acknowledgments: The authors acknowledge all investigators of the Lymphonie study group, the CIC-EC1432 (Alexandra Lamotte-Felin, Lydie Rossie and Delphine Pecqueur), the Intensive Care Medicine Research team (Solenne Villot, and Mathilde Audry), Serge Monier from the Cytometry core facility and Shaliha Bechoua from the CRB (Centre de Ressource Biologique). We thank the patients.