A Prospective Cohort Study of COVID-19: Evaluation of the Early Role of IL-1 and IL-6 Antagonists in Improving the Outcome of the Illness and Reduction in the Risk of Death.

The COVID-19 pandemic had a profound impact on global health, economies, and social systems. The crucial factor that determines the success of COVID-19 treatments is preventing the need for mechanical ventilation and intensive care admission. In the context of COVID-19, several treatments have been found to play a role in the disease's progression and severity. Interleukins (ILs) have been identified as key mediators of the cytokine storm that can occur in severe cases of COVID-19, leading to respiratory failure and other complications. For instance, IL-1 antagonist (anakinra) and IL-6 antagonist (tocilizumab) are supposed to be promising treatments as well as cortisones for COVID-19. This prospective study aims to evaluate the effectiveness of anakinra or tocilizumab in addition to cortisone in preventing the progression of mild to moderate COVID-19 cases to severe intensive care admission. Biochemical and hematological parameters, such as D-dimer, ferritin, LDH, CRP, and white blood cells (WBCs), were measured after treatment with either anakinra or tocilizumab in addition to cortisone or cortisone alone. The study also recorded the number of deaths and patients admitted to intensive care. The results indicate that anakinra significantly improved outcomes and decreased the number of intensive care admissions compared to tocilizumab or cortisone alone. Therefore, anakinra may play a vital role in controlling the progression of COVID-19, and its use in mild to moderate cases may prevent the worsening of the disease to severe stages.

Tocilizumab vs. baricitinib in hospitalized severe COVID-19 patients: results from a real-world cohort.

BACKGROUND: Tocilizumab and baricitinib are recommended treatment options for hospitalized COVID-19 patients requiring oxygen support. Literature about its efficacy and safety in a head-to-head comparison is scarce. METHODS: Hospitalized COVID-19 patients requiring oxygen were treated with tocilizumab or baricitinib additionally to dexamethasone. Tocilizumab was available from February till the 19th of September 2021 and baricitinib from 21st of September. The primary outcome was in-hospital mortality. Secondary outcome parameters were progression to mechanical ventilation (MV), length-of-stay (LOS) and potential side effects. RESULTS: 159 patients (tocilizumab 68, baricitinib 91) with a mean age of 60.5 years, 64% male were included in the study. Tocilizumab patients were admitted 1 day earlier, were in a higher WHO category at the time of inclusion and had a higher CRP level on admission and treatment initiation. Patients receiving Tocilizumab were treated with remdesivir more often and only patients in the baricitinib group were treated with monoclonal antibodies. Other characteristics did not differ significantly. In-hospital mortality (18% vs. 11%, p = 0.229), progression to MV (19% vs. 11%, p = 0.173) and LOS (13 vs. 12 days, p = 0.114) did not differ between groups. Side effects were equally distributed between groups, except ALAT elevation which was significantly more often observed in the tocilizumab group (43% vs. 25%, p = 0.021). CONCLUSIONS: In-hospital mortality, progression to MV and LOS were not significantly different in patients treated with tocilizumab or baricitinib additionally to standard of care. Both drugs seem equally effective but further head-to-head trials are needed.

Tocilizumab in patients with severe COVID-19: A single-center observational analysis.

Patients with coronavirus disease 2019 (COVID-19) may develop severe respiratory distress, thought to be mediated by cytokine release. Elevated proinflammatory markers have been associated with disease severity. Tocilizumab, an interleukin-6 receptor antagonist, may be beneficial for severe COVID-19, when cytokine storm is suspected. This is a retrospective single-center analysis of the records of patients diagnosed with COVID-19 who received tocilizumab. Outcomes, including clinical improvement, mortality and changes in oxygen-support at 24, 48, and 72 hours, and 7, 14, and 28 days post-tocilizumab, are reported. Patients were evaluated by baseline pre-tocilizumab oxygenation status and changes in proinflammatory markers within 7 days post-tocilizumab are reported. Sixty-six patients received tocilizumab at a mean dose of 724 mg (7.4 mg/kg), 3.7 days from admission. At baseline, 53% of patients were on ventilation support and all had elevated proinflammatory markers, including c-reactive protein (CRP). Common comorbidities were diabetes mellitus (43%) and hypertension (74%). Most patients received concomitant glucocorticoids and hydroxychloroquine. Seven days after tocilizumab, ten patients (15.2%) had clinical improvement in their oxygenation status, and there was a 95% decrease in CRP. Within 14 days of treatment, 29% of patients had clinical improvement, 20% had minimal or no improvement, 17% worsened, 27% died, and 7% were transferred to an outside hospital. Ultimately, 42% of all patients that received tocilizumab expired and 49% were discharged. This study found limited clinical improvement in patients that received tocilizumab in the setting of severe COVID-19. Clinical trials are ongoing to further evaluate tocilizumab's benefit in this patient population.