GRAd-COV2 vaccine provides potent and durable immunity in a randomised placebo-controlled phase 2 trial (COVITAR) (preprint)

Background. SARS-CoV-2 ongoing pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccines portfolio. We report safety and immunogenicity of GRAd-COV2, a novel gorilla adenovirus-based COVID-19 vaccine, in a phase 2 trial aimed at identifying the appropriate dose and schedule. Method. 917 eligible adults aged 18 years or older, including participants with co-morbidities, were randomised to receive, 21 days apart, a single vaccine administration at 2x1011 viral particles (vp) followed by placebo, or repeated vaccine administration at 1x1011 vp, or two doses of placebo. Primary endpoints were the incidence of local and systemic solicited AEs for 7 days post each dose and the post-treatment (35 days after the first dose), geometric mean titers (GMTs) and geometric mean fold rise (GMFRs) of ELISA antibody responses to Spike protein. Additional humoral and cellular immune response parameters were monitored for up to six months. Results. The safety profile of GRAd-COV2 was characterized by short-term, mild-to-moderate pain and tenderness at injection site, fatigue, headache, malaise, and myalgia. Neither related SAEs nor deaths were reported. Humoral (binding and neutralizing) Ab responses peaked at day 35 after a single administration, were boosted by a second vaccination, were sustained until day 57 to then decline at day 180. Potent, VOC cross-reactive T cell responses peaked already after first dose with high frequencies of long-lived CD8 T cells. Conclusion. GRAd-COV2 was safe, and induced robust immune responses after a single immunization; the second administration increased humoral but not cellular immune responses.

Severe Acute Respiratory Syndrome Coronavirus 2 Monoclonal Antibody Combination Therapy in Patients With Coronavirus Disease 2019 and Primary Antibody Deficiency.

BACKGROUND: Previous reports highlighted the efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific monoclonal antibodies (mAbs) against coronavirus disease 2019. METHODS: We conducted a prospective study on the clinical outcome and antiviral effects of mAbs added to standard of care therapy in SARS-CoV-2-infected patients with primary antibody defects. RESULTS: Median time of SARS-CoV-2 quantitative polymerase chain reaction (qPCR) positivity was shorter in 8 patients treated with mAbs (22 days) than in 10 patients treated with standard of care therapy only (37 days, P=.026). Median time of SARS-CoV-2 qPCR positivity from mAb administration was 10 days. CONCLUSIONS: The SARS-CoV-2 mAbs treatment was effective and well tolerated in patients with primary antibody defects.

Blood Glucose and Epicardial Adipose Tissue at the Hospital Admission as Possible Predictors for COVID-19 Severity (preprint)

Purpose: to study the possible association of CT-derived quantitative Epicardial Adipose Tissue (EAT) and glycemia at the admission, with severe outcomes in patients with COVID-19.Methods: 229 patients consecutively hospitalized for COVID-19 from March 1st to June 30th2020 were studied.Non contrast chest CT scans, to confirm diagnosis of pneumonia, were performed. EAT volume (cm3) and attenuation (Hounsfield units) were measured using a CT post-processing software. The primary outcome was acute respiratory distress syndrome (ARDS) or in-hospital death.Results: The primary outcome occurred in 56,8% patients. Fasting blood glucose was significantly higher in the group ARDS/death than in the group with better prognosis [114 (98-144) vs 101 (91-118) mg/dl, p=0,001]. EAT volume was higher in patients with vs without the primary outcome [103 (69,25;129,75) vs 78,95 (50,7;100,25) cm3, p <0,001] and it was positively correlated with glycemia, PCR, fibrinogen, P/F ratio. In the multivariable logistic regression analysis, age and EAT volume were independently associated with ARDS/death. Glycemia and EAT attenuation were risk factor for ARDS/death with a trend of statistical significance.Conclusions: Our findings suggest that both blood glucose and EAT, measurable and modifiable targets, could allow the early identification of subjects at greater risk of developing severe complications.

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)