The Dysregulation of the Monocyte-Dendritic Cell Interplay Is Associated with In-Hospital Mortality in COVID-19 Pneumonia (preprint)

Background: The monocyte-phagocyte system (MPS), including monocytes/macrophages and dendritic cells (DCs), plays a key role in anti-viral immunity. We aimed to analyze the prognostic value of the MPS components on in-hospital mortality in a cohort of 58 patients (M/F ; mean ageSD years) with COVID-19 pneumonia and 22 age- and sex-matched healthy controls. Methods: We measured frequencies and absolute numbers of peripheral blood CD169+ monocytes, conventional CD1c+ and CD141+ (namely cDC2 and cDC1), and plasmacytoid CD303+ DCs by means of multi-parametric flow cytometry. A gene profile analysis of 770 immune-inflammatory related human genes and 20 SARS-CoV-2 genes was also performed. Results: Median frequencies and absolute counts of CD169-expressing monocytes were significantly higher in COVID-19 patients than in controls (p 0.04 and p 0.01, respectively). Conversely, percentages and absolute numbers of all DC subsets were markedly depleted in patients (p

The Clinical and Translational Research Activities at the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy) during the COVID-19 Pandemic (preprint)

COVID-19 pandemic following the outbreak in China and Western Europe, where it finally lost the momentum, is now devastating North and South America. It has not been identified the reason and the molecular mechanisms of the two different patterns of the pulmonary host responses to virus from a minimal disease in young subjects to a severe distress syndrome (ARDS) in older subjects, particularly those with previous chronic diseases (including diabetes) and Cancer. The Management of the Istituto Nazionale Tumori - IRCCS “Fondazione Pascale” in Naples [INT-Pascale], along with all Health professionals decided not to interrupt the treatment of those hospitalized and to continue, even if after a careful triage in order not to allow SARS-CoV-2 positive subjects to access, to take care of cancer patients with serious conditions. Although very few (n=3) patients developed a symptomatic COVID-19 and required the transfer to a COVID-19 area of the Institute, no patients died during the Hospitalization and completed their oncology treatment. Besides monitoring of the patients, all employees of the Institute (physicians, nurses, researchers, lawyers, accountants, gatekeepers, guardians, janitors) have been tested for a possible exposure. Personnel identified as positive, has been promptly subjected to home quarantine and subdued to health surveillance. One severe case of respiratory distress has been reported in a positive employees and one death of a family member. Further steps to home monitoring of COVID-19 clinical course have been taken with the development of remote Wi-Fi connected digital devices for the detection of early signs of respiratory distress, including heart rate and oxygen saturation.In conclusion cancer care has been performed and continued safely also during COVID-19 pandemic and further remote home strategies are in progress to ensure the appropriate monitoring of cancer patients.

Tocilizumab for patients with COVID-19 pneumonia. The TOCIVID-19 phase 2 trial (preprint)

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. MethodsA multicentre, single-arm, hypothesis-driven phase 2 trial was planned to study the effect of Tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints). A cohort of patients consecutively enrolled after phase 2 was used as a validation dataset. A multivariable logistic regression was performed to generate hypotheses, while controlling for possible confounders. Resultsout of 301 patients in phase 2 intention-to-treat (ITT) analysis, 180 (59.8%) received tocilizumab. With 67 death events, lethality rates were 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. Lethality rates were lower in the validation dataset, including 920 patients. No signal of specific drug toxicity was reported. The multivariable logistic regression suggests tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Also, it supports a positive effect on lethality rate of the use of corticosteroids. ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Such result support the use of tocilizumab while waiting for ongoing phase 3 trials. RegistrationEudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)