Tocilizumab versus anakinra in COVID-19: results from propensity score matching.

Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra. Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation. Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44). Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.

Anti-cardiolipin IgG autoantibodies associate with circulating extracellular DNA in severe COVID-19.

Whereas the detection of antiphospholipid autoantibodies (aPL) in COVID-19 is of increasing interest, their role is still unclear. We analyzed a large aPL panel in 157 patients with COVID-19 according to the disease severity. We also investigated a potential association between aPL and extracellular DNA (exDNA, n = 85) or circulating markers of neutrophil extracellular traps (NET) such as citrullinated histones H3 (CitH3, n = 49). A total of 157 sera of patients infected by SARS-CoV-2 were collected. A large aPL panel including lupus anticoagulant, anti-cardiolipin and anti-beta-2 glycoprotein I (IgG, IgM and IgA), anti-phosphatidylethanolamine IgA, anti-prothrombin (IgG and IgM) was retrospectively analyzed according to the disease severity. We found a total aPL prevalence of 54.8% with almost half of the cases having aCL IgG. Within an extended panel of aPL, only aCL IgG were associated with COVID-19 severity. Additionally, severe patients displayed higher CitH3 levels than mild patients. Interestingly, we highlighted a significant association between the levels of aCL IgG and exDNA only in aCL positive patients with severe disease. In conclusion, we showed a significant link between aPL, namely aCL IgG, and circulating exDNA in patients with severe form of COVID-19, that could exacerbate the thrombo-inflammatory state related to disease severity.

Factors associated with dexamethasone efficacy in COVID-19. A retrospective investigative cohort study.

Dexamethasone has demonstrated efficacy in reducing mortality in COVID-19. However, its practical use is badly defined. We aimed to investigate factors associated with dexamethasone efficacy in real life. Our retrospective study was conducted in two university hospitals between September and November 2020 and included all the consecutive hospitalized patients with a laboratory-confirmed SARS-CoV-2 infection assessed by RT-PCR, treated with intravenous dexamethasone (6 mg/day). Among 111 patients, 10.6% necessitated a transfer into the intensive care unit (ICU) and the 28-day mortality rate was 17.1%. The 28-day mortality rate was significantly lower in patients who demonstrated improvement at 48 h (hazard ratio [HR]: 0.17, 95% confidence interval [CI]: 0.04-0.78, p = 0.02) and 96 h (HR: 0.07, 95% CI: 0.02-0.31, p = 0.0005) after dexamethasone initiation. Apart from well-known risk factors (age, hypertension, active cancer, severe lesions on chest computed tomography [CT] scan), we found that a high viral load in nasopharyngeal swab (Cycle threshold <30) at dexamethasone initiation was associated with higher 28-day mortality (66.6% vs. 36.7%, p = 0.03). Patients who did not receive antibiotics at dexamethasone initiation had a higher rate of transfer into the ICU (55.6% vs. 23.5%, p = 0.045) with a trend towards higher mortality in case of severe or critical lesions on CT scan (75.0% vs. 25.0%, p = 0.053). Patients who did not improve within 2-4 days after steroid initiation have a bad prognosis and should receive additional anti-inflammatory drugs. Our data suggest better efficacy of dexamethasone in patients with a low or negative viral load, receiving broad-spectrum antibiotics.

Persistent IgG anticardiolipin autoantibodies are associated with post-COVID syndrome.

Persistence of various symptoms in patients who have recovered from coronavirus disease 2019 (COVID-19) was recently defined as 'long COVID' or 'post-COVID syndrome' (PCS). This article reports a case of a 58-year-old woman who, although recovering from COVID-19, had novel and persistent symptoms including neurological complications that could not be explained by any cause other than PCS. In addition to a low inflammatory response, persistence of immunoglobulin G anticardiolipin autoantibody positivity and eosinopenia were found 1 year after acute COVID-19 infection, both of which have been defined previously as independent factors associated with the severity of COVID-19. The pathophysiological mechanism of PCS is unknown, but the possibility of persistence of the virus, especially in the nervous system, could be suggested with a post-infectious inflammatory or autoimmune reaction.

Clinical characteristics and outcomes of patients with haematologic malignancies and COVID-19 suggest that prolonged SARS-CoV-2 carriage is an important issue.

Specificities of COVID-19 disease course in patients with haematologic malignancies are still poorly studied. So, we aimed to compare patients with haematologic malignancies to patients without malignancies, matched by sex and age and hospitalised for COVID-19 at the same time and in the same centre. Among 25 patients with haematologic malignancies, we found that mortality (40% versus 4%, p < 0.01), number of days with RT-PCR positivity (21.2 ± 15.9 days [range, 3-57] versus 7.4 ± 5.6 days [range, 1-24], p < 0.01), maximal viral load (mean minimal Ct, 17.2 ± 5.2 [range, 10-30] versus 26.5 ± 5.1 [range, 15-33], p < 0.0001) and the delay between symptom onset and clinical worsening (mean time duration between symptom onset and first day of maximum requirement in inspired oxygen fraction, 14.3 ± 10.7 days versus 9.6 ± 3.7 days, p = 0.0485) were higher than in other patients. COVID-19 course in patients with haematologic malignancies has a delayed onset and is more severe with a higher mortality, and patients may be considered as super-spreaders. Clinicians and intensivists need to be trained to understand the specificity of COVID-19 courses in patients with haematological malignancies.

Factors Associated With COVID-19 Hospitalizations and Deaths in French Nursing Homes.

OBJECTIVES: To describe the clinical characteristics and management of residents in French nursing homes with suspected or confirmed coronavirus disease 2019 (COVID-19) and to determine the risk factors for COVID-19-related hospitalization and death in this population. DESIGN: A retrospective multicenter cohort study. SETTING AND PARTICIPANTS: Four hundred eighty nursing home residents with suspected or confirmed COVID-19 between March 1 and May 20, 2020, were enrolled and followed until June 2, 2020, in 15 nursing homes in Marseille's greater metropolitan area. METHODS: Demographic, clinical, laboratory, treatment type, and clinical outcome data were collected from patients' medical records. Multivariable analysis was used to determine factors associated with COVID-19-related hospitalization and death. For the former, the competing risk analysis-based on Fine and Gray's model-took death into account. RESULTS: A total of 480 residents were included. Median age was 88 years (IQR 80-93), and 330 residents were women. A total of 371 residents were symptomatic (77.3%), the most common symptoms being asthenia (47.9%), fever or hypothermia (48.1%), and dyspnea (35.6%). One hundred twenty-three patients (25.6%) were hospitalized and 96 (20%) died. Male gender [specific hazard ratio (sHR) 1.63, 95% confidence interval (CI) 1.12-2.35], diabetes (sHR 1.69, 95% CI 1.15-2.50), an altered level of consciousness (sHR 2.36, 95% CI 1.40-3.98), and dyspnea (sHR 1.69, 95% CI 1.09-2.62) were all associated with a greater risk of COVID-19-related hospitalization. Male gender [odds ratio (OR) 6.63, 95% CI 1.04-42.39], thermal dysregulation (OR 2.64, 95% CI 1.60-4.38), falls (2.21 95% CI 1.02-4.75), and being aged >85 years (OR 2.36, 95% CI 1.32-4.24) were all associated with increased COVID-19-related mortality risk, whereas polymedication (OR 0.46, 95% CI 0.27-0.77) and preventive anticoagulation (OR 0.46, 95% CI 0.27-0.79) were protective prognostic factors. CONCLUSIONS AND IMPLICATIONS: Male gender, being aged >85 years old, diabetes, dyspnea, thermal dysregulation, an altered level of consciousness, and falls must all be considered when identifying and protecting nursing home residents who are at greatest risk of COVID-19-related hospitalization and death.