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).

Background Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is the most Serious Cutaneous Adverse Reaction (SCAR) often with a fatal outcome. Coronavirus Disease (COVID-19) is caused by Severe Acute Respiratory Syndrome–Coronavirus—2 (SARS-COV2) and is an emergent pandemic for which no cure exist at the moment. Several drugs have been tried often with scant clinical evidence and safety. Case presentation Here we report the case of 78-years-old woman with cardiometabolic syndrome and COVID-19. A multidrug regimen including others hydroxychloroquine, antibiotics, dexamethasone and paracetamol, low-molecular-weight-heparin and potassium canrenoate was started. After almost 3 weeks, the patient started to display a violaceous rash initially involving the flexural folds atypical targetoid lesions and showing a very fast extension, blister formation and skin detachments of approximately 70% of the total body surface area and mucous membranes involvement consistent with toxic epidermal necrolysis (TEN). The ALDEN algorithm was calculated inserting all drugs given to the patient in the 28 days preceding the onset of the skin manifestations. The highest score retrieved was for hydroxychloroquine. Other less suspicious drugs were piperacillin/tazobactam, ceftriaxone and levofloxacin. Conclusions To our knowledge, this is the first case of TEN in a patient suffering from COVID-19 probably associated with hydroxychloroquine. Given the activation of the immune system syndrome induced by the virus and the widespread off-label use of this drug, we suggest a careful monitoring of skin and mucous membranes in all COVID-19 positive patients treated with hydroxychloroquine in order to early detect early signs of toxicities.

A female patient in her seventies affected by a signet-ring cell carcinoma G3pT4N3 (24/29), with lymphovascular invasion, HER2-negative. After completing three cycles of first-line systemic treatment in combination with cisplatin (CDDP) + 5-fluorouracil (5FU), a new systemic therapy line with paclitaxel + Cyramza (ramucirumab) was planned. On the day after the first administration the patient manifested a Standford type A aortic dissection (AD), with a diameter of around 6.5 cm and dissection flap originating in the ascending aorta below the brachiocephalic trunk, extended to the whole descending aorta until the carrefour.The causal relationship between adverse drug reactions and Cyramza, calculated using the Naranjo algorithm, led to a result of 'probable' correlation between ramucirumab and AD. The endothelial dysfunction associated with vascular endothelial growth factor pathway inhibitors (VPIs) would seem to be the most plausible explanation for such events: it causes thromboembolic events and cardiovascular complications.

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged.For clarity, all collaborators are listed in this correction article.

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