ABSTRACT
The present work analyses in detail the published data on ChAdOx1 nCoV-19 vaccine and provides arguments for the involvement of anti-vector immunity and of SARS-CoV-2 variants on the efficacy of ChAdOx1 nCoV-19 vaccine. First, it is suggested that anti-vector immunity takes place as the regimen of homologous vaccination with ChAdOx1 nCoV-19 vaccine is applied and interferes with efficacy of the vaccine when the interval between prime and boost doses is less than three months. Second, longitudinal studies suggest that ChAdOx1 nCoV-19 vaccine provides sub-optimal efficacy against UK variant of SARS-CoV-2, which appears to have an increased transmissibility over the ancestral SARS-CoV-2 among vaccinated people. At the moment, ChAdOx1 nCoV-19 vaccine is able to reduce the severity of symptoms and transmissibility; however, if the vaccinated individuals do not maintain everyday preventive actions, they could turn into potential spreaders, thus accelerating the process of generation of new viral variants due to the selective pressure of immune response. Prediction and possible consequences of the SARS-CoV-2 evolution and repeated anti-SARS-CoV-2 vaccinations are discussed. Since the impact of emerging SARS-CoV-2 variants suggests that vaccines are unlikely to be effective in quickly solving the pandemic crisis, it is highlighted the need to keep searching for new and more efficacious pharmacotherapy for COVID-19, such as those targeting ACE2 and ADAM17 zinc-metalloprotease activities.
Subject(s)
COVID-19ABSTRACT
The objective of this retrospective cohort study was to determine the impact of a recent trauma on thyroid axis and adrenal activity in dogs and to assess the usefulness of urinary cortisol-to-creatinine ratio (UCCR), basal serum thyroid-stimulating hormone (TSH), total thyroxine (tT4), and free thyroxine (fT4) concentrations in predicting outcome in dogs traumatized by a road traffic accident (RTA). An RTA exposed group of 210 dogs was evaluated within 24 hours of the trauma. Their data were compared with data from a matched group of dogs with other diagnoses. UCCR was positively correlated with the trauma severity and was higher in the exposed group than in the nonexposed group (median 101.500 vs. 21.02;p <0.0001). tT4 values were statistically similar between the two groups, but were correlated with a trauma score, while TSH (median = 0.050 vs. 0.080 ng/mL;p <0.0001) and fT4 (median = 15.850 vs. 17.950 pmol/L;p = 0.0037) were significantly lower for the exposed group. Nonsurvivors in comparison to survivors presented and higher median UCCR (181.800 vs. 93.850 respectively;p = 0.020), and a lower serum fT4 (12.700 vs. 16.500 pmol/L, respectively;p = 0.0046). A similar pattern had been observed for tT4. TSH levels were not predictive of survival. This study provides insights into the endocrine characteristics of dogs suffering from acute trauma. UCCR was higher while fT4 and TSH were both lower in RTA-injured dogs than in dogs affected by other conditions. Furthermore low fT4 and tT4, and a high UCCR could be useful prognostic factors in dogs affected by RTA trauma.
ABSTRACT
Background: Multiple studies have been conducted to investigate Tocilizumab in patients with cOVID-19 pneumonitis. However, published reports show conflicting results, largely due to weak retrospective designs and heterogeneity in critical methodological issues. Methods: : This open-label trial was structured according to the Simon’s optimal two-stage design in order to clarify which patients could really benefit from anti-IL6 strategies and how a future randomized trial should be designed to provide reliable and unequivocal results. 46 patients received a single infusion of Tocilizumab. Inclusion criteria were: SARS-CoV2 infection diagnosed by rt-PCR, multifocal interstitial pneumonia, need of oxygen therapy (FiO2 50%) to maintain SO2 >93%, recent (within the last 24 hours) worsening of lung function. Clinical outcomes were established a priori to assess whether a patient responded to treatment. A low number of carefully chosen clinical and biological markers was measured in order to test their predictive values. Primary end point was early and sustained clinical response. Results: : Twenty-one (46%) patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 hours after tocilizumab infusion (p=0.049) and higher baseline values of PaO2/FiO2 (p=0.008) predicted a favorable clinical response. Patients not improving at 72 hours were also non-responder at day 7. 11/25 of non-responder patients were intubated and 7 died. High levels of vWF were detected in all sera, with a tendency towards higher concentrations in the non-responder group. Conclusions: : Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in selected patients with severe COVID-19 pneumonitis warrants investigations in randomized trials. Trial registration: NCT 04315480