Real-life prospective study on tocilizumab in severe COVID-19 infection

The outcomes of tocilizumab (recombinant monoclonal antibody inhibiting IL-6) in SARS-CoV-2 infection have been variable, with REMAP-CAP and RECOVERY being the largest trials to show benefits. In this prospective, observational study we compared tocilizumab plus standard care (dexamethasone) vs standard care alone in patients with severe COVID-19 infection. Eligibility criteria included patients (age >18 years) with radiological evidence of COVID-19 Pneumonia, PO2/FiO2 (PF) ratio of <300 mmHg and an inflammatory phenotype defined by raised CRP, IL-6 and Ferritin. The primary outcome was a composite of mechanical ventilation and death. A total of 36 patients were included in this study, 27 in the treatment group and 9 in the standard care group. The treatment arm received tocilizumab 8mg/kg (maximum 800mg) as a single infusion within the first 24 hours of respiratory deterioration (identified as worsening RR and PF ratio). Results showed significantly lower mortality rate in the tocilizumab group compared to standard care group (3% vs 33% respectively, p=0.013). Patients who received tocilizumab were also less likely to progress to mechanical ventilation, with only 3.7% of the treatment group requiring mechanical ventilation vs 44% in the control group (p=0.002). Our findings support the use of tocilizumab in severe COVID-19 infection when given early in respiratory deterioration. The predominant variant at the time of this study was the Alpha variant, and so further investigation is required into its effectiveness in newer variants. Limitations include small sample size.

Repeated transmission of SARS-CoV-2 in an overcrowded Irish emergency department elucidated by whole-genome sequencing.

AIM: To provide a detailed genomic-epidemiological description of a complex multi-ward SARS-CoV-2 outbreak, which originated in the crowded emergency department (ED) in our hospital during the third wave of the COVID-19 pandemic, and was elucidated promptly by local whole-genome sequencing (WGS). METHODS: SARS-CoV-2 was detected by reverse transcriptase real-time polymerase chain reaction on viral RNA extracted from nasopharyngeal swabs. WGS was performed using an Oxford MinION Mk1C instrument following the ARTIC v3 sequencing protocol. High-quality consensus genomes were assembled with the artic-ncov2019 bioinformatics pipeline and viral phylogenetic trees were built, inferred by maximum-likelihood. Clusters were defined using a threshold of 0-1 single nucleotide polymorphisms (SNPs) between epidemiologically linked sequences. RESULTS: In April 2021, outbreaks of COVID-19 were declared on two wards at University Hospital Limerick after 4 healthcare-associated SARS-CoV-2 infections were detected by post-admission surveillance testing. Contact tracing identified 12 further connected cases; all with direct or indirect links to the ED 'COVID Zone'. All sequences were assigned to the Pangolin B.1.1.7 lineage by WGS, and SNP-level analysis revealed two distinct but simultaneous clusters of infections. Repeated transmission in the ED was demonstrated, involving patients accommodated on trolleys in crowded areas, resulting in multiple generations of infections across three inpatient hospital wards and subsequently to the local community. These findings informed mitigation efforts to prevent cross-transmission in the ED. CONCLUSION: Cross-transmission of SARS-CoV-2 occurred repeatedly in an overcrowded emergency department. Viral WGS elucidated complex viral transmission networks in our hospital and informed infection, prevention and control practice.

Association between tocilizumab treatment of hyperinflammatory patients with COVID-19 in a critical care setting and elevated incidence of hospital-acquired bacterial and invasive fungal infections.

BACKGROUND: Tocilizumab is an interleukin-6 inhibitor that reduces mortality and the need for invasive mechanical ventilation, while increasing the possibility of successful hospital discharge for hyperinflammatory patients with severe coronavirus disease 2019 (COVID-19). No increase in adverse events or serious infections has been reported previously. AIM: To describe the characteristics and outcomes of patients with severe COVID-19 in critical care who received tocilizumab, and to compare mortality and length of hospital stay for patients who received tocilizumab (N=41) with those who did not (N=33). METHODS: Retrospective review of data related to patients with COVID-19 who received tocilizumab in a critical care setting from 1st January to 31st December 2021. FINDINGS: Amongst COVID-19 survivors, those who had received tocilizumab had longer intensive care unit (ICU) stays (median length 21 vs 9 days) and hospital stays (45 vs 34 days) compared with those who had not received tocilizumab. Thirty-day mortality (29% vs 36%; P=0.5196) and 60-day mortality (37% and 42%; P=0.6138) were not significantly lower in patients who received tocilizumab. Serious bacterial and fungal infections occurred at higher frequency amongst patients who received tocilizumab [odds ratio (OR) 2.67, 95% confidence interval (CI) 1.04-6.86; P=0.042], and at significantly higher frequency than in non-COVID-19 ICU admissions (OR 5.26, 95% CI 3.08-9.00; P<0.0001). CONCLUSIONS: In this single-centre study, patients in critical care with severe COVID-19 who received tocilizumab had a greater number of serious bacterial and fungal infections, but this may not have been a direct effect of tocilizumab treatment.