Around the tenth day after diagnosis, ∼20% of patients with coronavirus disease 2019 (COVID-19)−associated pneumonia evolve toward severe oxygen dependence (stage 2b) and acute respiratory distress syndrome (stage 3) associated with systemic inflammation often termed a “cytokine storm.” Because interleukin-1 (IL-1) blocks the production of IL-6 and other proinflammatory cytokines, we treated COVID-19 patients early in the disease with the IL-1 receptor antagonist, anakinra. We retrospectively compared 22 patients from three different centers in France with stages 2b and 3 COVID-19−associated pneumonia presenting with acute severe respiratory failure and systemic inflammation who received either standard-of-care treatment alone (10 patients) or combined with intravenous anakinra (12 patients). Treatment started at 300 mg⋅d−1 for 5 d, then tapered with lower dosing over 3 d. Both populations were comparable for age, comorbidities, clinical stage, and elevated biomarkers of systemic inflammation. All of the patients treated with anakinra improved clinically (P < 0.01), with no deaths, significant decreases in oxygen requirements (P < 0.05), and more days without invasive mechanical ventilation (P < 0.06), compared with the control group. The effect of anakinra was rapid, as judged by significant decrease of fever and C-reactive protein at day 3. A mean total dose of 1,950 mg was infused with no adverse side effects or bacterial infection. We conclude that early blockade of the IL-1 receptor is therapeutic in acute hyperinflammatory respiratory failure in COVID-19 patients.

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Objective A better understanding of immune response against SARS-CoV-2 infection is critical to predict its dynamics within general population and its impact on vaccination strategy. We assessed both neutralizing antibody (Nab) activity persistence and SARS-CoV-2 serology in serum samples of mild and asymptomatic patients nine months post symptom onset (PSO) in a primary care context among immunocompetent adults. Methods A longitudinal cohort of crewmembers (CM) exposed to COVID-19 during the SARS-CoV-2 outbreak on the French aircraft carrier in April 2020 was created. CM infected with COVID-19 and having a positive serology at the end of quarantine were tested at 9-months PSO. Samples were collected at 18 and 280-days PSO. For each patient, both serology and serum viral neutralizing activity were performed. Results We analyzed 86 CM. Samples were collected at 18 and 280-days PSO. The seroconversion rate was 100% and 93% (82/86) at 18 and 280 days, respectively, while 72.7% of patients exhibited Persistent Nab at 9 months, regardless of disease severity. Conclusion Nab persists up to 9 months following asymptomatic/mild COVID-19 among young adults regardless of serology results at that time.

Anaplastic thyroid carcinoma (ATC) are highly aggressive malignant tumors with poor overall prognosis despite multimodal therapy. As ATC are extremely rare, no randomized controlled study has been published for metastatic disease. Thyrosine kinase inhibitors, especially lenvatinib and immune checkpoint inhibitors such as pembrolizumab, are emerging drugs for ATC. Few studies have reported the efficacity of pembrolizumab and lenvatinib association, resulting in its frequent off-label use. In this review, we discuss rationale efficacy and safety evidence for the association of lenvatinib and pembrolizumab in ATC. First, we discuss preclinical rationale for pembrolizumab monotherapy, lenvatinib monotherapy and synergistic action of pembrolizumab and lenvatinib in the metastatic setting. We also discuss clinical evidence for immunotherapy and pembrolizumab in ATC through the analysis of studies evaluating immunotherapy, lenvatinib and pembrolizumab lenvatinib association in ATC. In addition, we discuss the safety of this association and potential predictive biomarkers of efficiency.

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