Further positive reports from tocilizumab to treat COVID-19
Two new publications provide additional reports of positive outcomes from using the anti-IL-6 monoclonal antibody tocilizumab to treat COVID-19.
The largest of these is a retrospective analysis of 544 patients hospitalised with severe COVID-19. Results were reported by Giovanni Guaraldi from University of Modena on 24 June in Lancet Rheumatology. 
Median age was 67 years (IQR: 56 to 77) and 359 (66%) men, with more severe baseline characteristics in participants who received tocilizumab.
Overall, 179/544 participants received open-label tocilizumab and 365/544 received standard of care. Of these, a similar percentage progressed to need mechanical ventilation: 57 (16%) vs 33 (18%), p=0.41, for the SoC and tocilizumab groups respectively. These results were similar for both intravenous (n=88) and subcutaneous (n=91) formulations of tocilizumab.
However, mortality was significantly higher in people just receiving SoC: 73 (20%) vs 13 (7%) in SoC vs tocilizumab, p<0·0001).
In multivariate analysis, adjusting for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab was associated with a significantly reduced risk of invasive mechanical ventilation or death (adj. HR 0·61, 95% CI: 0.40 to 0.92; p=0·020).
Tocilizumab was also associated with significantly fewer new infections: 24/179 (13%) vs 14/365 (4%), p<0·0001).
The second report was from an observational US cohort of 27 people hospitalised with SARS-CoV-2 pneumonia who received tocilizumab. Median age was 63 years (IQR: 51 to 75 years) and 23/27 were men. Seventeen patients (63%) had a significant comorbidity, including hypertension in 12/17. 
Participants received a 400 mg intravenous dose of tocilizumab as part of a compassionate access programme at a single site in Los Angeles. Participants also received hydroxychloroquine and azithromycin, with 7/27 on blinded placebo-controlled remdesivir study.
At baseline, all participants were already receiving oxygen support with oxygen levels <90%, with most (21/27) on mechanical intubation. All showed IL-6 as the predominant cytokine.
Although tocilizumab was associated with significant rapid reductions in temperature and CRP, 4/27 showed no response, and 3/4 progressed with poorer outcomes. The paper discussed whether the non-responses might have been different with higher dosing.
Two deaths, at days 3 and 11, were not judged to be linked to tocilizumab.
The report concluded that these results were significantly better than historical reports with hypothetical mechanism for reducing elevated IL-6 that is associated with severe COVID-19 and poor prognosis.
Although small retrospective analyses, these results add to the growing number of studies that have reported potentially positive results with tocilizumab. Four earlier studies were reviewed in a recent earlier issue of HIV and COVID-19. 
Many other prospective studies are already ongoing, including the large UK RECOVERY study, using a randomised design. 
Based on limited success with all approaches based on monotherapy, combination approaches should be prioritised, with at least one study already using tocilizumab plus remdesivir. 
- Guaraldi G et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. The Lancet Rheumatology, DOI: 10.1016/S2665-9913(20)30173-9. (24 June 2020).
- Jordan SC et al. Compassionate use of tocilizumab for treatment of SARS-CoV-2 pneumonia. Clinical Infectious Diseases, ciaa812, DOI: 10.1093/cid/ciaa812. (23 June 2020).
- Collins S, Potential for tocilizumab to treat moderate to severe COVID-19. HTB (14 May 2020).
- RECOVERY study.
- Tocilizumab and remdesivir in new dual therapy study. (1 June 2020).