Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy) (preprint)

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously exposed to SARS-CoV-2 subjects and not exposed to SARS-CoV-2 subjects.Methods: We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated.Results: Both previously exposed and not exposed to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-exposed subjects in comparison to titers of not exposed subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously exposed to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ( =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose.Conclusions: The results showed that, as early as the first dose, SARS-CoV-2-exposed individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-exposed subjects. FC for previously exposed subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not exposed subjects, after the second dose, were = 3.8 in >45.0% of vaccinees, and ≤3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

Evaluation of the diagnostic accuracy of a new point-of-care rapid test for SARS-CoV-2 virus detection (preprint)

Background: The easy access to a quick diagnosis of coronavirus disease 2019 (COVID-19) is a key point to improve the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to contain its spread. Up to now, laboratory real-time PCR is the standard of care, but requires a fully equipped laboratory and significant infrastructure. Consequently, new diagnostic tools are required. Methods: In the present work, the diagnostic accuracy of the point-of-care rapid test "bKIT Virus Finder COVID-19" (Hyris Ltd) is evaluated by a retrospective and a prospective analysis on SARS CoV-2 samples previously assessed with an FDA “authorized for the emergency use - EUA” reference method. Descriptive statistics were used for the present study.Results: Results obtained with the Hyris Kit are the same as that of standard laboratory-based real time PCR methods for all the analyzed samples. In addition, the Hyris Kit provides the test results in less than 2 hours, a significantly shorter time compared to the reference methods, without the need of a fully equipped laboratory. Conclusions: To conclude, the Hyris kit represents a promising tool to improve the health surveillance and to increase the capacity of SARS-CoV-2 testing.

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)