Observational study on off-label use of tocilizumab in patients with severe COVID-19.

BACKGROUND: In December 2019 a novel coronavirus designated SARS-CoV-2 was identified, and the disease COVID-19 has caused many deaths. SARS-CoV-2 infection has been associated with the development of cytokine storm (including interleukin 6 (IL-6)), which can cause lung damage and lack of oxygen. Tocilizumab (TCZ) inhibits ligand binding to the IL-6 receptor and may be a potential treatment for the hyperinflammation symptoms of COVID-19. However, data regarding the efficacy of TCZ in COVID-19 are lacking. The rapid spread of the pandemic in France, especially in the Paris region, constrained us to the off-label use of TCZ in patients with severe clinical conditions. METHODS: A single-centre observational cohort study of 44 patients infected with COVID-19 was carried out between 6 April and 21 April 2020 in Groupe Hospitalier Intercommunal Le Raincy-Montfermeil (GHILRM). Twenty-two patients diagnosed with COVID-19 were treated with TCZ and were compared with 22 patients not treated with TCZ matched for age, gender and length of hospital stay for COVID-19. Respiratory rate and oxygen supplementation as well as laboratory parameters (such as C-reactive protein (CRP), aspartate aminotransferase and alanine aminotransferase) were collected at baseline and during 14 days of follow-up. Our primary objective was to assess the efficacy of TCZ on respiratory clinical conditions. FINDINGS: The average respiratory rate was lower in the TCZ group than in the control group (21.5 vs 25.5 breaths/min at day 14, 95% CI -7.5 to -0.4; p=0.03). Treated patients tended to be intubated less during the course of the disease (2/22 vs 6/22, 95% CI -0.4 to 0.1; p=0.12). In each group, 10 patients no longer required oxygen therapy. We found a significant decrease in CRP in treated patients on day 7 (p=0.04). TCZ caused cytolysis in more than half (14/22) of the patients but without clinical impact. INTERPRETATION: There was a significant difference in the respiratory rate on day 14 of follow-up, with a greater decrease observed in the treated group. Fewer patients required mechanical ventilation in the TCZ group, especially among patients with more extensive CT lung damage, than in the control group. The same number of patients were weaned off oxygen on day 14 in the two groups, while the patients in the TCZ group had more severe impairment at inclusion. We consider that TCZ showed significant control of the biological inflammatory syndrome, suggesting that it may limit the effect of the cytokine storm. Our study seems to indicate the efficacy of TCZ, particularly in patients with severe initial pulmonary impairment. Selecting the best candidates and the best timing for TCZ therapy needs to be determined in randomised clinical trials.

Trends in the risk of myocardial infarction among HIV-1-infected individuals relative to the general population in France: Impact of gender and immune status.

We examined trends in the MI incidence and age at MI diagnosis among adults living with HIV-1 between 2000 and 2009, by comparison with the French MI registries, by gender. Age standardized incidence rates and standardized incidence-ratios (SIRs) were estimated for individuals included in the French hospital database on HIV (n = 71 204, MI = 663) during three periods: 2000-2002, 2003-2005 and 2006-2009. Median ages at MI diagnosis were compared using the Brown-Mood test. Over the study periods, the absolute rate difference and relative risks were higher in women than in men in 2000-2002 and 2006-2009, with respective SIRs 1.99 (1.39-2.75) and 1.12 (0.99-1.27) in 2006-2009. The trends were different for men and women with a decreasing trend in SIRs in men and no change in women. In both sexes, among individuals with CD4 ≥500/µL and controlled viral-load on cART, the risk was no longer elevated. Age at MI diagnosis was significantly younger than in the general population, especially among women (-6.2 years, p<0.001; men: -2.1 years, p = 0.02). In HIV-1-positive adults, absolute rate difference and relative risks and trends of MI were different between men and women and there was no additional risk among individuals on effective cART.

Hemophagocytic Lymphohistiocytosis Associated With Bartonella henselae Infection in an HIV-Infected Patient.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome that often occurs in immunocompromised patients. We report the first case of HLH due to Bartonella henselae infection in a patient with human immunodeficiency virus infection. Early recognition of HLH and B. henselae through liver biopsy and serological tests led to the patient's recovery.

Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort.

BACKGROUND: The effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals. METHODS: Patients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox's proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated. RESULTS: Among 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights. CONCLUSION: The impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population.

Acute Plasmodium falciparum malaria following splenectomy for suspected lymphoma in 2 patients.

Two black African immigrants, with no history of recent travel outside France, received a diagnosis of a malignant lymphoproliferative disorder and splenomegaly, and they subsequently underwent splenectomy. A few weeks after surgery, both patients experienced an acute episode of Plasmodium falciparum malaria, so the initial diagnosis was corrected retrospectively and changed to hyperreactive malarial splenomegaly. These cases illustrate the difficulty in distinguishing hyperreactive malarial splenomegaly from malignant lymphoproliferative disorders and therefore underline the role of the spleen in the immune system's defense against malaria.