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.
7 March 2017 in Human Vaccines & Immunotherapeutics
HBV immunization is highly recommended in people infected with HIV. However, the classical schedule used in the general population has been shown to be insufficient in people living with HIV. This review summarizes the main studies dealing with HBV vaccination in people living with HIV, depending on their baseline status (in particular, never vaccinated, already vaccinated, or with an isolated anti-HBc serological profile). It shows that reinforced 40µg intramuscular HBV vaccination schedules are now frequently recommended, either initially in people never vaccinated, or in the lack of an anamnestic response in other situations. Adjuvants cannot be currently recommended. Anti-HBs titers have to be checked 1 to 2 months following the last vaccine dose, and annually thereafter a booster is necessary if antiHBs titers decrease below 10 mIU/mL. In patients with a CD4 cell count <200/µL, guidelines recommend starting the vaccination regimen as soon as possible after HAART has been started.
Current recommendations for empirical antimicrobial therapy in spontaneous bacterial peritonitis (SBP) are based on quite old trials. Since microbial epidemiology and the management of patients have changed, whether these recommendations are still appropriate must be confirmed.
To describe the characteristics of hepatitis B (HBV) infection in HIV-infected patients and the impact of anti-HBV treatments. All the patients with past or present chronic HBV infection seen in October 2005 in 17 French hospitals were included. Data were retrospectively collected from their first visit in a time-dependent manner, through a detailed standardized questionnaire. Among 477 HBV-infected patients, 261 (55%) were co-infected with HIV. The HBV-HIV co-infected patients underwent fewer serological, virological and histological evaluations. Initial positive HBe antigenemia (HBe Ag) was more frequent in these patients (57.9 versus 28.6%; P < 10), as was cirrhosis on the initial liver biopsy (17.9 versus 7.6%; P = 0.05). Throughout the mean 5-year follow-up, HBe Ag loss was less frequent (P = 0.04), as was HBe seroconversion (incidence rate 2.6 versus 10/100 patient-years; P < 10). HBe Ag loss was associated with fibrosis improvement (METAVIR score -0.5 +/- 0.4 versus +0.2 +/- 0.6 if persistent positive HBe Ag, P = 0.01). In co-infected patients on tenofovir, adefovir or interferon, HBe seroconversions were seen in patients on combined HBV treatment, the use of which is increasing (58% in 2005). Nevertheless, no significant difference in virological, immunological or biochemical evolution was observed between these different treatments. In HBV-HIV co-infected patients, the assessment of HBV infection still needs to be improved, the HBV wild-type remains predominant, and HBe Ag loss is rare and associated with a better histological evolution. There is insufficient evidence of the superiority of combined HBV treatment, and this still needs be demonstrated in long term studies.
(1) Background: Several smaller studies have shown that COVID-19 patients with cancer are at a significantly higher risk of death. Our objective was to compare patients hospitalized for COVID-19 with cancer to those without cancer using national data and to study the effect of cancer on the risk of hospital death and intensive care unit (ICU) admission. (2) Methods: All patients hospitalized in France for COVID-19 in March–April 2020 were included from the French national administrative database, which contains discharge summaries for all hospital admissions in France. Cancer patients were identified within this population. The effect of cancer was estimated with logistic regression, adjusting for age, sex and comorbidities. (3) Results: Among the 89,530 COVID-19 patients, we identified 6201 cancer patients (6.9%). These patients were older and were more likely to be men and to have complications (acute respiratory and kidney failure, venous thrombosis, atrial fibrillation) than those without cancer. In patients with hematological cancer, admission to ICU was significantly more frequent (24.8%) than patients without cancer (16.4%) (p < 0.01). Solid cancer patients without metastasis had a significantly higher mortality risk than patients without cancer (aOR = 1.4 [1.3–1.5]), and the difference was even more marked for metastatic solid cancer patients (aOR = 3.6 [3.2–4.0]). Compared to patients with colorectal cancer, patients with lung cancer, digestive cancer (excluding colorectal cancer) and hematological cancer had a higher mortality risk (aOR = 2.0 [1.6–2.6], 1.6 [1.3–2.1] and 1.4 [1.1–1.8], respectively). (4) Conclusions: This study shows that, in France, patients with COVID-19 and cancer have a two-fold risk of death when compared to COVID-19 patients without cancer. We suggest the need to reorganize facilities to prevent the contamination of patients being treated for cancer, similar to what is already being done in some countries.