ABSTRACT
Canadian Respiratory Therapist COVID-19 vaccination uptake rates and responses were investigated with a look at the reasons behind any delays or non-vaccinations as well as other demographics, attitudes, or factors that may be shown to play a role. An anonymous survey using SurveyMonkey® on vaccination uptake rates, responses, and attitudes was available to Student, Graduate, and Registered Respiratory Therapists in Canada from July to October of 2021. A total of 1066 surveys (8.4% of target population) were started, 983 in English and 83 in French with 1013 completed fully and included in the data analysis. Canadian RT Vaccination uptake rates were compared to those of all Canadian healthcare workers which showed that 90.42% of the surveyed RT population in Canada received their vaccination right away compared to the posted rate at the time of 86.27% for all Canadian Healthcare Workers. Pearson Chi-Square Tests were performed to evaluate association between vaccination status and other categorical parameters evaluated in the survey. There was a significant (P = 0.013) association between early vaccination and age, a significant (P = 0.036) association between vaccination status and participants’ response on whether or not they have a family member or know someone who has had COVID-19, a significant (P < 0.001) association between vaccination status and attitudes towards trusting science to develop safe, effective, new vaccines, and a significant (P < 0.001) association between vaccination status and attitudes towards trusting the Ministry of Health to ensure that vaccines are safe. There was no significant association between vaccination status and gender, province/territory of residency/work, level of education, level of involvement with COVID-19 patients. The results suggest that the RT groups across Canada had higher early vaccination uptake rates than the general Healthcare worker groups and that age, relationship to people with COVID-19 and trust in science played a significant role in their vaccination uptake rates.
ABSTRACT
RATIONALE: Patients with idiopathic pulmonary fibrosis (IPF) have worse outcomes following COVID-19. SARS-CoV-2 (2019-nCoV) spike protein (S1) harbors an RGD motif in its receptor-binding domain (RBD). Although SARS-CoV-2 is to exploit human Angiotensin Converting Enzyme-2 (ACE2) receptors for cell entry. Single Cell RNA-seq showed that normal lung expresses low levels of ACE2 with very low expression (1.5%) in Alveolar type 2 epithelial cells. It is possible that SARS-CoV-2 needs a cellular co-receptor, which could include integrins, to promote alveolar cell internalization and pneumonitis.METHODS: Solid-phase binding assays were used to investigate S1 binding to ACE2 or αv containing integrins. Pseudovirus entry assays were used to measure the internalization of SARS-CoV-2 into Human embryonic kidney 293T cells expressing different combinations of potential receptors. RNAscope was used to visualize the co-localization of SARS-CoV-2, ACE2, and integrin mRNAs. Immunohistochemistry was used to evaluate the expression of αvβ6 integrins and ACE2 in lung tissue.RESULTS: Binding assays demonstrated that the RGD containing αvβ3 and αvβ6 integrins bound robustly to the SARS-CoV-2 S1 subunit of Spike protein and overexpression of the αvβ6 integrin modestly augments ACE2 mediated SARS-CoV-2 pseudoviral entry into epithelial cells. In COVID-19 damaged lung ACE2 levels are low but the αvβ6 integrin levels are increased in alveolar epithelium whereas both ACE2 and αvβ6 integrin are increased in lung sections from idiopathic pulmonary fibrosis compared with normal lung samples. CONCLUSION: The SARS-CoV-2 S1 subunit can bind αvβ6 integrins augmenting ACE2-dependent internalization of pseudovirus. In IPF patients, ACE2 levels and αvβ6 integrin levels are increased. Increased binding of the SARS-CoV-2 to ACE2 and the αvβ6 integrin within fibrotic lung may explain the increased risk of severe COVID in patients with IPF.