COVID-19 vaccine uptake among healthcare workers in the fourth country to authorize BNT162b2 during the first month of rollout (preprint)

Background: The Kingdom of Saudi Arabia (KSA) was the fourth country in the world to authorize the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine, which it rolled out on December 17, 2020 and first targeted at healthcare workers (HCWs). This study assesses vaccine uptake among this group during the first month of its availability. Methods: A national cross-sectional, pilot-validated, self-administered survey was conducted among HCWs in the KSA between December 27, 2020 and January 3, 2021. The survey included sociodemographic details, previous contact with COVID-19 patients, previous infection with COVID-19, receiving (or registering with the Ministry of Health website to receive) the COVID-19 vaccine, sources of HCWs information on vaccines, awareness of emerging variants of concern, and anxiety level using the 7 item Generalized Anxiety Disorder assessment. A descriptive bivariate analysis and multivariate logistic binary regression analysis were performed. The primary evaluated outcome was vaccine uptake. Results: Of the 1,058 participants who completed the survey, 704 (66.5%) were female, and 626 (59.2%) were nurses. Of all the respondents, 352 (33.27%) were enrolled to receive or had already received the vaccine, while 706 (66.73%) had not registered. In a bivariate analysis, not enrolling for vaccination was more likely in females than males (78.5% vs. 21.5%, P < 0.001), HCWs between the ages of 20 and 40 years than those > 40 years (70.4% vs. 29.6%, P = 0.005), Saudi HCWs than expatriates (78% vs 22%, P < 0.001), and among HCWs who used social media as a source of information than those who did not (69.8% vs. 38.6%, P < 0.001) . In a multivariate analysis, independent factors for not enrolling to receive the vaccine included being female (aOR = 0.287, 95%CI = 0.206, 0.401, P < 0.001), being less than 40 years of age (aOR = 1.021, 95%CI = 1.002,1.040, P = 0.032), and using social media as a source of information (aOR = 0.207, 95%CI = 0.132,1.354, P = 0.001 ). Factors associated with uptake were being a Saudi national (aOR = 1.918, 95%CI = 1.363,2.698, P < 0.001), working in an intensive care unit (aOR = 1.495, 95%CI = 1.083,2.063, P = 0.014), and working at a university hospital (aOR = 1.867, 95%CI = 1.380,2.525, P < 0.001). Conclusions: A low level of vaccine uptake was observed especially in female HCWs, those younger than 40 years old, and those who used social media as their source of vaccine information. This survey provides important information for public health authorities in order to scale up vaccination campaigns targeting these HCWs to increase vaccine enrollment and uptake.

In vitro infection of human lung tissue with SARS-CoV-2: Heterogeneity in host defense and therapeutic response (preprint)

Cell lines are the mainstay in understanding the biology of COVID-19 infection, but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue allows for the in vitro study of the inter-individual heterogeneity of host response to SARS-CoV-2 infection, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 16 donors, most of whom had risk factors for severe illness from COVID-19. Cryopreserved tissues preserved 90% of cell viability and contained heterogeneous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infectible with HCoV-OC43 and SARS-CoV-2 coronavirus strains, and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL-6, CXCL8 and IFN{beta} in response to SARS-CoV-2 infection. Treatment of tissues with dexamethasone and the experimental drug, N-hydroxycytidine, suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted antiviral activity, suppressed viral replication in tissues from a subset of donors. In summary, we developed a novel system for the in vitro study of human SARS-CoV-2 infection using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 pathogenesis.

Evidence of ongoing recombination in SARS-CoV-2 through genealogical reconstruction (preprint)

The evolutionary process of genetic recombination has the potential to rapidly change the properties of a viral pathogen, and its presence is a crucial factor to consider in the development of treatments and vaccines. It can also significantly affect the results of phylogenetic analyses and the inference of evolutionary rates. The detection of recombination from samples of sequencing data is a very challenging problem, and is further complicated for SARS-CoV-2 by its relatively slow accumulation of genetic diversity. The extent to which recombination is ongoing for SARS-CoV-2 is not yet resolved. To address this, we use a parsimony-based method to reconstruct possible genealogical histories for samples of SARS-CoV-2 sequences, which enables the analysis of recombination events that could have generated the data. We propose a framework for disentangling the effects of recurrent mutation from recombination in the history of a sample, and hence provide a way of estimating the probability that ongoing recombination is present. We apply this to samples of sequencing data collected in England and in South Africa, and find compelling evidence of ongoing recombination.

SARS-CoV-2 B.1.1.7 lineage-related perceptions and travel worry among healthcare workers (preprint)

BackgroundHealthcare workers (HCWs) travel-related anxiety needs to be assessed in light of the emergence of SARS-CoV-2 mutations. MethodsAn online, cross-sectional questionnaire among HCWs between December 21, 2020 to January 7, 2021. The outcome variables were HCWs knowledge and awareness of the SARS-CoV-2 B.1.1.7 lineage, and its associated travel worry and Generalized Anxiety Disorder (GAD-7) score. ResultsA total of 1,058 HCWs completed the survey; 66.5% were female, 59.0% were nurses. 9.0% indicated they had been previously diagnosed with COVID-19. Regarding the B.1.1.7 lineage, almost all (97.3%) were aware of its emergence, 73.8% were aware that it is more infectious, 78.0% thought it causes more severe disease, and only 50.0% knew that current COVID-19 vaccines are effective in preventing it. Despite this, 66.7% of HCWs were not registered to receive the vaccine. HCWs most common source of information about the new variant was social media platforms (67%), and this subgroup was significantly more worried about traveling. Nurses were more worried than physicians (P=0.001). ConclusionsMost HCWs were aware of the emergence of SARS-CoV-2 B.1.1.7 variant and expressed substantial travel worries. Increased worry levels were found among HCWs who used social media as their main source of information, those with lower levels of COVID-19 vaccine uptake, and those with higher GAD-7 scores. The utilization of official social media platforms could improve accurate information dissemination among HCWs regarding the pandemics evolving mutations. Targeted vaccine campaigns are warranted to assure HCWs about the efficacy of COVID-19 vaccines toward SARS-CoV-2 variants.