Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial.

OBJECTIVE: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. METHODS: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. RESULTS: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). CONCLUSION: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

COVID-19 infection among patients with autoinflammatory diseases: a study on 117 French patients compared with 1545 from the French RMD COVID-19 cohort: COVIMAI - the French cohort study of SARS-CoV-2 infection in patient with systemic autoinflammatory diseases.

OBJECTIVE: There is little known about SARS-CoV-2 infection in patients with systemic autoinflammatory disease (SAID). This study aimed to describe epidemiological features associated with severe disease form and death. Mortality between patients with and without SAID hospitalised for SARS-CoV-2 infection was compared. METHODS: A national multicentric prospective cohort study was conducted from the French Rheumatic and Musculoskeletal Diseases (RMD) COVID-19 cohort. Patients with SAID were matched with patients with non-SAID on age±7 years, gender and number of comorbidities to consider important confounding factors. Impact of SAID on severity of SARS-CoV-2 infection was analysed using multinomial logistic regression for severity in three classes (mild, moderate and severe with mild status as reference). Fine-Gray regression model for length of hospital stay and binomial logistic regression model for risk of death at 30 days. RESULTS: We identified 117 patients with SAID (sex ratio 0.84, 17 children) and compared them with 1545 patients with non-autoinflammatory immune-mediated inflammatory disorders (non-SAID). 67 patients had a monogenic SAID (64 with familial Mediterranean fever). Other SAIDs were Behçet' disease (n=21), undifferentiated SAID (n=16), adult-onset Still disease (n=9) and systemic-onset juvenile idiopathic arthritis (n=5). Ten adults developed severe form (8.6%). Six patients died. All children had a benign disease. After matching on age±7 years, sex and number of comorbidities, no significant difference between the two groups in length of stay and the severity of infection was noted. CONCLUSION: As identified in the whole French RMD COVID-19 cohort, patients with SAID on corticosteroids and with multiple comorbidities are prone to develop more severe COVID-19 forms.

Follow-up of adults with noncritical COVID-19 two months after symptom onset.

OBJECTIVES: To describe the clinical evolution and predictors of symptom persistence during 2 months' follow-up in adults with noncritical coronavirus disease 2019 (COVID-19). METHODS: We performed descriptive clinical follow-up (day (D) 7, D30 and D60) of 150 patients with noncritical COVID-19 confirmed by real-time reverse transcriptase PCR at Tours University Hospital from 17 March to 3 June 2020, including demographic, clinical and laboratory data collected from the electronic medical records and by phone call. Persisting symptoms were defined by the presence at D30 or D60 of at least one of the following: weight loss ≥5%, severe dyspnoea or asthenia, chest pain, palpitations, anosmia/ageusia, headache, cutaneous signs, arthralgia, myalgia, digestive disorders, fever or sick leave. RESULTS: At D30, 68% (103/150) of patients had at least one symptom; and at D60, 66% (86/130) had symptoms, mainly anosmia/ageusia: 59% (89/150) at symptom onset, 28% (40/150) at D30 and 23% (29/130) at D60. Dyspnoea concerned 36.7% (55/150) patients at D30 and 30% (39/130) at D60. Half of the patients (74/150) at D30 and 40% (52/130) at D60 reported asthenia. Persistent symptoms at D60 were significantly associated with age 40 to 60 years old, hospital admission and abnormal auscultation at symptom onset. At D30, severe COVID-19 and/or dyspnoea at symptom onset were additional factors associated with persistent symptoms. CONCLUSIONS: Up to 2 months after symptom onset, two thirds of adults with noncritical COVID-19 had complaints, mainly anosmia/ageusia, dyspnoea or asthenia. A prolonged medical follow-up of patients with COVID-19 seems essential, whatever the initial clinical presentation.