Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial.

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).

Diagnostic Performance of Chest X-Ray for COVID-19 Pneumonia During the SARS-CoV-2 Pandemic in Lombardy, Italy.

Chest x-ray (CXR) can play a role in diagnosing patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but only few small-scale studies are available. We assessed the diagnostic performance of CXR in consecutive patients presenting at the emergency room at the Policlinico San Donato, Milan, Italy from February 24 to April 8, 2020 for suspected SARS-CoV-2 infection. The results of CXR were classified as positive or negative according to the original prospective radiologic reports. To overcome the limitations of reverse transcriptase-polymerase chain reaction (RT-PCR) swab, especially oscillating sensitivity, we added the information obtained from phone calls to discharged patients with negative initial RT-PCR. Thus, we included 535 patients with concomitant CXR and RT-PCR on admission (aged 65±17 y; 340 males, 195 females), resulting in 408 RT-PCR positive and 127 negative patients at the composite reference standard. Original CXR reports showed an 89.0% sensitivity (95% confidence intervals [CI], 85.5%-91.8%), 60.6% specificity (95% CI, 51.6%-69.2%), 87.9% positive predictive value (95% CI, 84.4%-90.9%), and 63.1% negative predictive value (95% CI, 53.9%-71.7%). The adoption of CXR alongside RT-PCR to triage patients with suspected SARS-CoV-2 infection could foster a safe and efficient workflow, counteracting possible false negative RT-PCR results.