Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

The reactivation of latent tuberculosis (TB) is a major complication of tumor necrosis factor (TNF)-alpha inhibitors. Screening for TB infection is recommended before anti-TNF therapy is initiated; however, the use of tuberculin skin testing (TST) is controversial, due to the high rate of false-negative results in patients receiving immunosuppressive treatment. To compare the performance of two commercial interferon (IFN)-gamma release assays (IGRA), T-SPOT.TB (TS-TB) and QuantiFERON-TB Gold "In-tube" (QFT-GIT), with TST for the detection of TB infection in patients due to start anti-TNF therapy, 69 human immunodeficiency virus (HIV)-negative Italian patients (mean age: 45.2 +/- 12.6 years; male=39) were enrolled between September 2005 to August 2006. Patients affected by rheumatoid arthritis (n = 18), psoriatic arthritis (n = 26), ulcerous rectocolitis (n = 6), and Crohn's disease (n = 19) were tested simultaneously with TST, TS-TB, and QFT-GIT. Overall, 26% of patients were positive by TST, 30.4% by TS-TB, and 31.8% by QFT-GIT. Agreement with TST was similar (kappa = 0.21, p = 0.0002 and kappa = 0.26, p < 0.001, respectively). In 11 TST-negative cases, IFN-gamma release assays were positive. In addition, in seven Mantoux-positive cases with no TB risk factors, TST result agreement was achieved with at least one blood test. Indeterminate results were detected in 5.8% and 2.8% of cases, respectively, with TS-TB and with QFT-GIT (p = not significant [ns]). In conclusion, our results suggest that IGRAs may be helpful for screening purposes in patient candidates for anti-TNF therapy to confirm positive TST results and in selected cases when false-negative results are suspected. The utility of blood tests in patients with low or no TB risk remains to be assessed.

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The RT-PCR dot-blot analysis of CEA mRNA in blood cells seems to be a promising tool for the early detection of micrometastatic circulating cells in patients with lung cancer.

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