Few studies have examined access to cigarettes among adolescents. To address this, we aimed to examine cigarette access and purchase patterns among adolescent cigarette smokers based on the most recent data from the Global Youth Tobacco Surveys (GYTS).We used the most recent school-based GYTS data (2010-2018) on 49 856 adolescent cigarette smokers aged 12-16 years in 140 countries/territories (hereafter “countries”) to examine cigarette access and purchase patterns among adolescent smokers.Over half (51.2%) of adolescent smokers bought cigarettes from commercial vendors  and one-third of smokers (32.7%) got cigarettes from private persons . Males , older adolescents (vs younger ones), and adolescent smokers from low-income countries (vs those from middle- or high-income countries) were more likely to buy cigarettes from commercial vendors. Younger adolescents (vs older ones) and adolescent smokers from low-income countries (vs those from middle- or high-income countries) were more likely to get cigarettes from private persons. As many as 39.6% of adolescent smokers reported that they were not denied buying cigarettes from commercial vendors due to age restrictions, especially among males , among older adolescents (vs younger ones), and among adolescent smokers from upper-middle-income or high-income countries (vs those from low-income countries). Purchasing cigarettes as single sticks was more likely to occur in males , in older adolescents (vs younger ones), and in adolescent smokers from low-income countries (vs those from upper-middle-income or high-income countries), with inverse findings for purchasing cigarettes in full packs.Adolescent smokers often obtained cigarettes from commercial vendors or private persons. Additionally, adolescent smokers often purchased cigarettes in packs and as individual sticks. These findings emphasize the need to strengthen measures to reduce the supply of cigarettes to minors. Tobacco use is a leading preventable cause of morbidity and mortality ,2, with Tobacco use usually starts in childhood or adolescence and tracks into adulthood due to the addictive nature of nicotine . A recenOnly three studies have examined how adolescents obtain cigarettes in different regions -15. One We used the most recent data 2010-2018 GYTS data from 140 countries to examine how adolescent smokers aged 12-16 years purchased cigarettes, particularly whether they got cigarettes from commercial vendors vs private persons, and in pack vs as individual sticks.We obtained data from the most recent GYTS 2010-2018) conducted in each included country among school-attending students aged 12-16 years. If a country conducted more than one survey between 2010 and 2018, we used only the latest one. The same sampling strategy and standardized questionnaire methodology allow for a direct comparison of data across countries and over time. A detailed description of the GYTS is available from the websites of the US Centers for Disease Control and Prevention (CDC) and WHO [ conducteOne question assessed on how adolescents obtained cigarettes , with responses including bought from stores/shops/supermarkets/gas station shops, street vendors/un-established vendors/kiosks, a vending machine, someone else , or from other ways  . Another2 test to examine differences in proportions between groups. We used the “pwr” package in R to calculate the statistical power based on the sample size and proportion with α = 0.05. The statistical power was higher than 0.80 for most subgroups  using the “Complex Samples” module in SPSS (version 16.0). Subgroup analyses were performed according to sex, age, WHO region, and World Bank income. We calculated pooled estimates in the total population and in population subgroups by meta-analyses using STATA version 11.0 with random-effects models due to high heterogeneity between countries and used the χTable S2 in the As shown in The proportion of adolescent smokers purchasing cigarettes from commercial vendors varied largely across countries, ranging from 4.7% in Tokelau to 91.1% in the United Republic of Nevis  or as individual sticks (37.1%). The proportion of adolescent smokers purchasing cigarettes per pack was highest in the European region, whereas the proportion of adolescents purchasing cigarettes as individual sticks was the highest in the South-East Asian region. The proportion of adolescent smokers purchasing cigarettes in packs was higher in upper-middle-income and high-income countries compared to lower-middle-income countries, with an inverse trend found for purchasing cigarettes as individual sticks. The proportion of adolescent smokers purchasing cigarettes in packs (As shown in P < 0.01) and private persons (P < 0.01). Males, older adolescents, and adolescents from upper-middle-income or high-income countries were more likely to not be denied buying cigarettes due to age restrictions . Males, older adolescents, and those from low-income countries were more likely to purchase cigarettes as individual sticks (P < 0.001).As shown in In 49 856 adolescent cigarette smokers aged 12-16 years from 140 countries, over half obtained cigarettes from commercial vendors, and approximately one-third obtained cigarettes from private persons during the past 30 days. Males, older age, and persons with low income were associated with buying cigarettes from commercial vendors, while younger age persons and those of low income were associated with getting cigarettes from private persons. Two-fifths of adolescent smokers were not denied buying cigarettes from commercial vendors, and this occurred more among males, older adolescents, and those in upper-middle-income or high-income countries. Nearly half (46.3%) of adolescent smokers purchased cigarettes in packs and 37.1% as single sticks. Males, older adolescents, and those in low-income countries were more likely to buy cigarettes as single sticks.Our findings update previous results from a study based on 45 countries from the GYTS between 2013 and 2014, which similarly showed that nearly half of the adolescent smokers aged 13-15 years got cigarettes from a store, street vendor, or kiosk ). It wasIn this study, 46.3% of adolescent smokers purchased cigarettes in packs, especially in the European region (68.5%) and in high-income countries (58.7%), while 37.1% purchased cigarettes as individual sticks, and the proportion buying cigarettes as individual sticks was higher in regions of South-East Asia (57.2%) and Africa (48.5%), and in low-income (45.4%) and lower-middle-income countries (48.0%) compared to other countries. A previous study based on GYTS conducted between 2013 and 2014 in 45 countries similarly showed that nearly 40% of adolescent smokers purchased individual cigarettes in most countries in regions of South-East Asia and Africa, and approximately 50% of adolescent smokers purchased cigarettes in packs in most countries in the European region [Overall, our findings suggest that tobacco control measures recommended by the WHO FCTC  should bWe found that the main sources of cigarette access were commercial vendors and private persons across countries, which may guide the development and enforcement of public policies and programmes on prevention and control of cigarette access, according to national circumstances. The proportion differences in sex, age, WHO region, and income level may also contribute to more specific and efficient strategies. When the bans and regulations are strongly enforced, adolescents possibly smoke less as a result. Previous studies have confirmed the adverse effect of cigarette use on health outcomes, such as cardiovascular diseases . We specThis study has several strengths. First, we used the most recent available data from 140 nationally representative surveys using a standardized methodology, which makes the results broadly generalizable and comparable across countries. Second, we quantified access to cigarettes and purchase patterns among adolescent smokers by age, sex, country, region, and national income level. However, this study also has several limitations. First, data came from a self-reported questionnaire and may be subject to over- or under-reporting. However, the use of the GYTS questions has been shown to have good reliability for different domains ,21. SecoThis study assessed various channels through which adolescent smokers accessed cigarettes in many countries. Our findings highlight the need to strengthen measures to limit the access to cigarettes among adolescents, including enforcement of age checking by cigarettes retailers, ensuring that cigarettes are sold only through licensed vendors, and banning the sale of cigarettes by units, as advised by the WHO Framework Convention on Tobacco Control.


Reduced aerobic capacity, fatigue and living in a city also increased the odds of low life satisfaction. As people with post-COVID-19 report several long-term consequences, this suggests that there is a need for targeted care for this group. The results of this study can serve as guidance for healthcare authorities regarding important long-term consequences that should be considered in rehabilitation programs directed toward post-COVID-19.A significant number of individuals experience post-COVID-19 symptoms, but knowledge of perceived consequences and life satisfaction is lacking. Here, we investigate perceived consequences regarding everyday life, health, physical activity and work post-COVID-19 and factors associated with low life satisfaction. A total of 766 people  experiencing post-COVID-19 symptoms at least two months after infection (mean 13 months) responded to an online survey. A majority (≥77%) perceived physical fatigue, mental fatigue, dizziness, reduced work ability, low life satisfaction and a reduced level of aerobic capacity. In the final logistic regression model (Nagelkerke R Square 0.296,  According to the World Health Organization (WHO) there have now been about 600 million confirmed cases of COVID-19 worldwide . Most pePost-COVID-19 is defined as a condition that occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, with symptoms that last for at least two months and cannot be explained by an alternative diagnosis . The mecThe severity of the acute COVID-19 infection, comorbidities and advanced age have been identified as risk factors for post-COVID-19 ,8,9. HowAs long-term disability can impact life satisfaction negatively , it is iCurrently, there is a lack of knowledge of perceived consequences and life satisfaction with post-COVID-19. Increased knowledge can improve the ability of welfare authorities and the healthcare system to support these people. The aim of the study was, therefore, to investigate perceived consequences regarding everyday life, health, physical activity and work post-COVID-19 and the factors associated with low life satisfaction.This study had a cross-sectional design and was part of a larger project on life after COVID-19 (The LAC project) investigating different aspects of the long-term consequences of COVID-19 and their impact on life.Recruitment of participants was conducted by means of an announcement on social media, posted between the 21 October and the 13 November 2021. Persons 18 years or older, able to read and understand Swedish and having had a COVID-19 infection with remaining symptoms, were invited to participate. The current study included people with remaining symptoms for at least 2 months after the acute infection.A Facebook page with information about the project was targeted to persons in the three most populated regions of Sweden  but could also be shared with users outside these areas. The link to the invitation was also posted on Instagram and Twitter. The project webpage was hosted at Lund University and included general project information, a participant information sheet, and a link to the survey. The survey was open until 12 February 2022, which resulted in a total of 867 persons participating in the survey. Of those, 52 persons did not meet the inclusion criteria on remaining post-COVID-19 symptoms for at least 2 months, and 49 persons were excluded due to not completing the mandatory background questions, giving a total of 766 participants who were included in the study.Data collection was completed using REDCap (Research Electronic Data Capture), a secure, web-based application designed to support data capture for research studies ,28. OutcThe online survey included sociodemographic questions regarding age, sex (man or woman), family situation , residential community characteristics  and level of education , provision  and comorbidities (yes or no). The participants answered questions on the acute COVID-19 infection  and post-COVID-19 condition (duration and symptoms). They also responded to questionnaires on the perceived consequences of COVID-19.Physical fatigue was assessed with the Fatigue Severity Scale (FSS) , which hMental fatigue was assessed with the Mental Fatigue Scale (MFS) . The MFSPerceived dizziness and balance impairment related to COVID-19 were assessed by a single question (yes or no) that has been used in previous studies of dizziness .Level of dependence on another person in daily activities (ADL) was assessed by the ADL Staircase  that hasCurrent perceived aerobic capacity was assessed by the Rating of Perceived Capacity scale (RPC) . RPC is Work ability was measured with the Work Ability Score (WAS) . The WASLife satisfaction was rated using the Life Satisfaction Questionnaire (LiSat-11) ,22. The Statistical analyses were performed with SPSS version 28.0 . Probability values less than 0.05 were considered statistically significant. For descriptive data, means , frequencies and medians  were calculated.The proportion of participants with low life satisfaction (LiSat-11 score 1–4) was presented for each item of LiSat-11 and compared to the proportion of satisfied persons in the Swedish reference sample  by meansThe association of potential explanatory factors with life satisfaction was investigated with logistic regression analyses. Life as a whole (item 1 in LiSat-11) was used as an overall measure of perceived life satisfaction (dependent variable) and dichotomized into low and high life satisfaction. Potential explanatory independent variables added in the regression building were sociodemographic factors that, in previous studies, have been shown to impact life satisfaction ,24,25,26p-value were calculated. A generous inclusion criterion (p ≤ 0.20) was used to ensure that no potential variable was omitted in the following multivariate regression analysis. The variable with the lowest p-value (if ≤ 0.20) from the univariate analysis was included in the model. Thereafter, the other factors were tentatively added, one at a time. The model with the highest explanatory value and the two independent variables with the lowest p-values (if both p ≤ 0.20) were kept. Thereafter, the remaining factors were again added, one at a time, and the model with the highest explanatory value and variables with the lowest p-values (if p ≤ 0.20) were retained. Thus, in each step, one variable was added to the model. This procedure was continued as long as the p-value of all the included variables in the model was p ≤ 0.20 and the explanatory value increased.The associations with overall life satisfaction  were evaluated for each explanatory factor separately using univariate logistic regression analyses. The odds ratio, 95% confidence interval (CI), explanatory value (Nagelkerke R Square) and All participants gave their consent to participate in the study by clicking on a link that directed them to the online survey. The study was approved by the Swedish Ethical Review Authority (Dnr 2020-02776), and the principles of the Declaration of Helsinki were followed.There were 766 persons who completed the survey, but as the participants could choose not to answer a question/questionnaire, the number of answers varies (see detailed information for each variable in the tables).Most participants were middle-aged , women (89%), highly educated (72%), working (69%) and approximately equally distributed in terms of their residential community , see Thirty-nine percent reported comorbidities such as asthma (27%), thyroid dysfunction (19%), allergies (12%) and hypertension (11%). A majority developed their acute COVID-19 infection during the second wave (autumn and winter of 2020–2021), and most persons were not in need of hospital care (89%). The most commonly reported acute COVID-19 symptoms were fatigue (88%), fever (74%), headache (73%) and anosmia/ageusia (67%). The remaining COVID-19 symptoms (for at least two months) were fatigue (79%), joint and muscle pain (45%), anosmia/ageusia (42%), dyspnea (39%), chest pain (35%) and cough (18%). The mean duration of post-COVID-19 was 13 months (SD 5), According to the questionnaires on perceived consequences of COVID-19, a majority of the participants experienced physical fatigue (85%), mental fatigue (84%), dizziness (84%) and balance impairments (56%); see Overall life satisfaction  showed a median of 4 (IQR 3–4), whereof 77% of the participants perceived low satisfaction with Life as a whole . For 87%p < 0.001) except for Economy (p = 0.096); see For the domain-specific items (2–11), a large proportion of the participants perceived low satisfaction with Physical health (91%) and Leisure (89%), and a majority experienced low satisfaction with the other items (51–79%) except for ADL (33%) and Partner relationship (48%). Compared to the Swedish reference values , a signip < 0.001) (see p ≤ 0.20) for being included in the multivariate model building.Work ability had the strongest univariate association with low satisfaction of Life as a whole  see , and thep < 0.001) and had an explanatory value, Nagelkerke R Square, of 0.177. The Nagelkerke R Square value is a pseudo R-square value that demonstrates how well the model explains the dependent variable from 0 to 1. Aerobic capacity added 0.063 to the Nagelkerke R Square value of the total model, mental fatigue added another 0.028, residential community added 0.021 and physical fatigue added 0.007. The final model had a total Nagelkerke R Square value of 0.296 (p < 0.001) (n = 619).In the final multivariate regression model , work abThe aim of this study was to investigate perceived consequences regarding everyday life, health, physical activity and work post-COVID-19 and factors associated with low life satisfaction. We found that a majority of our sample with post-COVID-19 experienced physical fatigue, mental fatigue, dizziness, balance impairments, reduced aerobic capacity and work ability. In addition, most perceived low satisfaction with Life as a whole, and all but one of the domain-specific items of LiSat-11 showed a higher proportion with low satisfaction relative to reference values. Poor work ability was the most important factor for perceiving low overall life satisfaction. Reduced aerobic capacity, mental fatigue, living in a city and physical fatigue were factors that also increased the odds of experiencing low life satisfaction in post-COVID-19.The results of the present study showed that post-COVID-19 may persist long after recovery from the acute COVID-19 infection, even in this sample of younger patients with milder initial infection. The most commonly reported consequence of post-COVID-19 was fatigue , which is in accordance with previous studies ,14,15,16The most strenuous activity that could be sustained for at least 30 min was walking or cycling slowly (median RPC = 5), which is considerably lower compared to levels of physical activity reported in a Swedish study among adults during the first wave of the pandemic . In thatFurthermore, our results showed that many of the participants perceived reduced work ability. This is in line with a previous study where a majority of the respondents with remaining COVID-19 symptoms reported working fewer hours or were in need of a reduced work schedule. In addition, many perceived that the worsening of COVID-19 symptoms could be triggered by stress and mental exertion at work . This emA majority (77%) of our participants perceived low satisfaction with Life as a whole, and almost all responded that they perceived a deterioration in life satisfaction due to COVID-19. The percentage of low satisfaction in the present study was considerably higher than in the Swedish reference sample  and in cEconomy was the only domain-specific item of LiSat-11 that did not differ significantly in the proportion of persons with low satisfaction in comparison with the reference values . This miIn the multivariate regression model, poor work ability showed the highest odds of perceiving low satisfaction with Life as a whole. This result demonstrates the importance of work for well-being. In a recent cohort study, workplace modifications have been found to be the most important factor in supporting the return to work for persons with post-COVID-19 . TherefoAerobic capacity and mental and physical fatigue were also included in our final logistic model. Those who reported lower aerobic capacity and a high level of fatigue generally had higher odds of perceiving low satisfaction with Life as a whole. However, the explanatory values of these variables were relatively low, probably due to their relation to work ability. Adapted rehabilitation interventions focusing on increasing physical activity levels and reducing fatigue may have a positive effect on life satisfaction post-COVID-19.The logistic regression model also showed that persons living in cities compared to less densely populated areas in towns and villages had higher odds of perceiving low life satisfaction. In previous studies, similar findings have demonstrated that a higher population density can affect life satisfaction negatively ,25. The Interestingly, comorbidity was not significantly associated with low life satisfaction, despite the fact that comorbidity is a risk factor for developing post-COVID-19 and that comorbidity might increase post-COVID-19 , while hA strength of the current study was that validated questionnaires were used to assess the perceived consequences of post-COVID-19, and the large sample size allowed for the use of multivariate regression analyses. However, the study has some limitations that should be regarded when interpreting the results. By recruiting via social media, the study attracted a selected group of mostly well-educated women that are more frequent on Facebook, Instagram, etc. Nevertheless, the fact that more women participated may partly be because post-COVID-19 is twice as common in women younger than 60 ,56. FurtThis study has important healthcare implications. As people with post-COVID-19 report a wide range of long-term consequences, this may have a large impact on their return to normal life, including previous levels of physical activity and work. Recovery may also be negatively affected by stress and exertion that can worsen or cause a relapse of symptoms. In addition, our findings imply that post-COVID-19 has a major negative impact on general well-being. Post-COVID-19 may, therefore, increase the burden on the healthcare system and also have a wider economic impact on society. Thus, people with long-term consequences post-COVID-19 may need comprehensive assessments of their physical and cognitive function, ability to manage daily life, work and quality of life. Person-centered multidisciplinary rehabilitation ought to be provided by healthcare professionals that have a thorough understanding of the post-COVID-19 condition and knowledge of how to optimize recovery.This study has shown that physical and mental fatigue, dizziness, balance impairments, reduced aerobic capacity, poor work ability and low life satisfaction are commonly perceived consequences of post-COVID-19. Work ability, aerobic capacity and fatigue are factors associated with low life satisfaction. The results of this study can serve as guidance for healthcare authorities regarding important long-term consequences that should be considered in rehabilitation programs directed toward post-COVID-19. Future studies should focus on how post-COVID-19 consequences change over time and evaluate the efficacy of rehabilitation protocols for persons with post-COVID-19.


In Georgia, an upper-middle income European country, the COVID-19 vaccine rollout began on 15 March 2021 with health workers (HWs), a priority group for vaccination. We assessed the factors associated with COVID-19 vaccination among HWs at six large hospitals in the early stages of the vaccine rollout (March–July 2021). Among 1533 HWs, 274 (17.9%) had received one dose of the COVID-19 vaccine. Strong independent predictors of early vaccine uptake were age > 40 years, especially 50–59 years old , considering the vaccine as “somewhat effective” or “very effective” rather than “not effective” , and previous vaccination against seasonal influenza . Previous SARS-CoV-2 infection was negatively associated with receiving the vaccine . Compared to physicians, nurses/midwives , administrative staff , and ancillary staff  were less likely to have received the COVID-19 vaccine. Tailoring the COVID-19 vaccine communications campaign to younger and non-physician HWs, and emphasizing the benefits of the COVID-19 vaccine, could help further increase vaccine coverage among HWs in Georgia. COVID-19 vaccine uptake has been variable among health workers (HWs) in Europe; rates of vaccine coverage among HWs have been particularly low in some middle- and low-income countries in the eastern part of the European region .While lack of vaccine availability has partly contributed to this low uptake, vaccine hesitancy among HWs continues to be a challenge ,4,5. DifHWs play a critical role in the pandemic response. They are at high risk of infection due to occupational exposure and, furthermore, infected HWs who come to work can transmit the virus to vulnerable patients . In addiIn the Republic of Georgia, an upper-middle income country of 3.7 million people, the COVID-19 vaccine rollout began in Georgia on 15 March 2021 . The plaIn March 2021, the National Center for Disease Control and Public Health of Georgia (NCDC) and the World Health Organization (WHO) initiated a prospective cohort study to measure the effectiveness of the COVID-19 vaccine among hospital-based HWs . We analThe study was initially a one-year (March 2021–April 2022) prospective cohort study among HWs at six large hospitals in Tbilisi and Batumi, to evaluate the effectiveness of the COVID-19 vaccine in preventing laboratory-confirmed SARS-CoV-2 infection . The stuFrom 19 March–16 July 2021, we invited all HWs  over 18 years old who were employed at the study sites and eligible to receive the COVID-19 vaccine to participate in the study. HWs could enroll voluntarily in the study regardless of whether they had already received a dose of the COVID-19 vaccine and regardless of their intention to get vaccinated. At the time of enrolment, contra-indications to the COVID-19 vaccine in Georgia included having a previous SARS-CoV-2 infection <120 days ago, and acute febrile illness [The primary outcome for this study was vaccination status  on the day of enrolment, irrespective of vaccine brand. Independent variables were self-reported socio-demographic characteristics, clinical and behavioral factors, and knowledge and attitudes about the COVID-19 vaccination.We excluded participants with unknown vaccination status and participants who were not eligible for vaccination before their enrolment in the study due to a SARS-CoV-2 infection in the previous 120 days.We computed descriptive statistics as frequency and percentage for categorical variables, or as median and inter-quartile range for continuous variables. We conducted a univariable analysis using a chi-squared test for independence or Wilcoxon rank sum test, as appropriate, followed by logistic regression modeling to measure crude associations between each independent variable and the outcome of vaccination status at enrolment.p-value < 0.2 in the univariable analysis, and sequentially removed the least significant variable until only significant variables remained. We selected the best fit model by examining the Bayesian Information Criterion (BIC) score of successive nested models and retaining the model with the lowest BIC score. We calculated crude and adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI). We conducted a collinearity diagnostic using the variance inflation factor (VIF).We then conducted a backward multivariable analysis to assess factors associated with early COVID-19 vaccine uptake, adjusting for socio-demographic, clinical, and behavioral factors, and knowledge and attitudes about the COVID-19 vaccine. The hospital study site was included a priori. We included in the initial model all independent variables with a For the descriptive and univariable analysis, we included all available observations. However, we performed a complete case analysis in the multivariable models, excluding 4 (0.3%) observations with missing data.To further investigate factors associated with vaccine uptake among non-physicians, we conducted a similar but separate analysis with subjects restricted to nurses and midwives.Analyses were conducted in R statistical software  .Of the 1606 participants enrolled in the study, we included 1533 participants in this analysis. We excluded 73 (4.5%) participants because of unknown vaccination status (n = 16), or ineligibility to receive the COVID-19 vaccine due to a previous SARS-CoV-2 infection <120 days before enrolment (n = 55) or at an unknown date (n = 2).Characteristics of participants, both overall and stratified by vaccination status, with crude and adjusted measures of associations are presented in Most participants were female , and the median age was 41 years old (interquartile range: 29–53 years); 617 (40.2%) were nurses or midwives, 314 (20.5%) were physicians, 241 (15.7%) were ancillary workers, and 227 (14.8%) were administrative staff. Over half of the participants provided direct medical care to patients . Most participants reported being “well informed”  or “extremely well informed”  about the COVID-19 vaccination, but less than a third  said that the COVID-19 vaccination is “very effective” at preventing COVID-19 disease, and only half  “mostly agreed” or “totally agreed” that COVID-19 vaccination is safe.Overall, 274 (17.9%) participants had received one vaccine dose at enrolment; 172 (62.8%) received Pfizer-BioNTech vaccine, 50 (18.2%) received Sinovac, 33 (12.0%) received Sinopharm, and 19 (6.9%) received AstraZeneca.After controlling for hospital study site in the multivariable analysis, occupation, seasonal influenza vaccination, age groups, and opinion about the effectiveness of COVID-19 vaccination remained significantly associated with vaccination status. However, sex, underlying medical condition, regular contact with pregnant women or infants at work, providing direct care to a patient, performing respiratory procedures, and other behaviors and knowledge and attitudes about the COVID-19 vaccine were not retained in the final model. Non-physicians were less likely to be vaccinated compared to physicians, particularly nurses , administrative staff , and ancillary staff . Participants who had a previous SARS-CoV-2 infection were less likely to have received a vaccine compared to those who had not been infected . In contrast, having received the seasonal influenza vaccine during the 2020–2021 influenza season , judging the COVID-19 vaccine as “somewhat effective” or “very effective” , and being in an age group > 40 years old, especially 50–59 years old , were strong independent predictors of COVID-19 vaccine uptake.Results from the final model restricted to nurses and midwives remained consistent with findings from the overall cohort . Nurses In both models , the variance inflation factor showed low correlations among the investigated variables (VIF < 2).In this analysis of enrolment data collected from HWs participating in a COVID-19 vaccine effectiveness cohort study at six large hospitals in Georgia, only 17.9% HWs were vaccinated against COVID-19 with one dose at the time of enrolment, during March–July 2021, a period that overlapped with the first months of the national vaccination campaign. To our knowledge, this is the first study to examine factors associated with early uptake of COVID-19 vaccine in HWs in Georgia.We found that non-physicians and HWs who had been previously infected with SARS-CoV-2 were significantly less likely to have received the COVID-19 vaccine, whereas older HWs, those who had received seasonal influenza vaccine (winter 2020/2021), and HWs who considered the COVID-19 vaccine highly effective were more likely to have been vaccinated.Our findings are consistent with previous studies that have reported lower vaccination coverage among non-physicians ,9,10,11.We found that concerns about vaccine safety and vaccine effectiveness, and insufficient knowledge about COVID-19 vaccines were associated with lower COVID-19 vaccine uptake in our study population, findings that have been reported among HWs elsewhere in the world . Our finData from a public opinion survey, conducted in Georgia by NGOs between late April 2020 and February 2021 suggested that intention to get vaccinated in the general population was low and highlighted a general lack of trust in the quality of the COVID-19 vaccine ,23. FurtFinally, our study corroborates other known factors associated with COVID-19 vaccine uptake in HWs in other settings, such as older age and seasonal influenza vaccination, and those associated with a decrease in COVID-19 vaccine receipt, such as a prior SARS-CoV-2 infection ,9,10,11.Receipt of seasonal influenza vaccine in the 2020–2021 influenza season was found to be a positive predictor of COVID-19 vaccine uptake in our study. This finding suggests that investment and promotion of annual influenza vaccination among HWs might positively affect COVID-19 vaccine acceptance.We did not find any significant difference in vaccine uptake by sex, occupational exposure, such as care provision or regular contact with vulnerable patient groups at work, or other behavioral factors with respect to public health and social health measures, such as the use of facemasks, physical distancing, and social interactions.Our study has a number of strengths. We enrolled a large number of HWs—over 1500—from six hospitals in Georgia, and enrolment data were complete for nearly all questions. In addition, we were able to validate all self-reported vaccination data using a comprehensive national vaccine registry.This study has some limitations. First, the study may suffer from selection bias; while all eligible HWs were invited to participate in the vaccine effectiveness study, the study was voluntary, and participants who chose to participate in the study may not be representative of all HWs at their institutions. In addition, our analysis only included HWs working in hospitals in Tbilisi and Batumi, which may not be representative of HWs in the rest of the country. However, by the end of June 2021, uptake among HWs across Georgia was approximately 19% , which iWe observed low COVID-19 vaccine uptake among HWs in the first few months that the COVID-19 vaccine was available in Georgia. Older HWs, those previously vaccinated against seasonal influenza, and HWs who considered COVID-19 vaccines highly effective were more likely to have been vaccinated early, whereas HWs who were not physicians, and HWs who had been previously infected with SARS-CoV-2 were significantly less likely to have received the vaccine. Community engagement and a tailored communication campaign addressing non-physicians and younger HWs are critical to increasing vaccine uptake among HWs in Georgia, particularly in light of the continued relatively low rates of COVID-19 vaccine coverage well over a year after the vaccine was first offered in the country. In addition, public health messaging emphasizing the safety and the individual and collective benefits of vaccination could help increase vaccine coverage in a timely manner.


The coronavirus disease (COVID-19) breakout had an unimaginable worldwide effect in the 21st century, claiming millions of lives and putting a huge burden on the global economy. The potential developments in vaccine technologies following the determination of the genetic sequence of SARS-CoV-2 and the increasing global efforts to bring potential vaccines and therapeutics into the market for emergency use have provided a small bright spot to this tragic event. Several intriguing vaccine candidates have been developed using recombinant technology, genetic engineering, and other vaccine development technologies. In the last decade, a vast amount of the vaccine development process has diversified towards the usage of viral vector-based vaccines. The immune response elicited by such vaccines is comparatively higher than other approved vaccine candidates that require a booster dose to provide sufficient immune protection. The non-replicating adenoviral vectors are promising vaccine carriers for infectious diseases due to better yield, cGMP-friendly manufacturing processes, safety, better efficacy, manageable shipping, and storage procedures. As of April 2022, the WHO has approved a total of 10 vaccines around the world for COVID-19 (33 vaccines approved by at least one country), among which three candidates are adenoviral vector-based vaccines. This review sheds light on the developmental summary of all the adenoviral vector-based vaccines that are under emergency use authorization (EUA) or in the different stages of development for COVID-19 management. The coronavirus disease COVID-19), which was discovered for the first time in Wuhan, China, in December 2019, was declared a pandemic by the WHO on March 11, 2020 9, which , but latFollowing the announcement of the SARS-CoV-2 genetic sequence, intensive worldwide R&D activities were performed to create a vaccine to curtail the pandemic ,13,14. SVaccines usually uses natural or synthetic viral antigenic material to induce immunity in the host against the virus, however, the procedure remains different with diverse vaccine platforms. On the other hand, vaccines based on viral vectors use a viral vector that, when injected, activates the machinery of the host cell to create the viral antigen ,22. The Viruses are used as replicating  or non-replicating vectors in this vaccine platform ,27. ReplAdenovirus has gained considerable consideration as an important therapeutic vector, and it was the initial DNA virus to undergo rigorous medical intervention, owing to its very suitable biology, stable genes, better transduction efficiency, and ease of mass production ,31. AdenCommonly used human adenoviruses i.e., Ad5, and Ad26 have a genomic size of 36 kb . The DNAIn this generation of adenovirus, E1 and E3 genes are deleted, which disables the adenovirus’ ability to replicate on its own. The cloning capacity is restricted to 8.2 Kb (kilobyte) with higher immunogenicity .These generations of adenovirus were designed to have higher cloning capacity up to 12 Kb with a low level of immunogenicity. Besides E1 and E3, additional regulator genes i.e., E2 and E4 are also omitted .The Ad vectors of this generation have high cloning capacity up to 36 Kb with negligible toxicity. The vectors are deprived of regulatory genes rather than having genetic elements such as ITR and packing signals ,53.E. coli (Escherichia coli) cells [The creation of the vector genome generally encompasses the straight cloning recombination or transportation technique in i) cells . There aThe most classical way to obtain E1-deleted AdVs involves the utilization of homologous recombination of two DNA vectors . One of To overcome the limitation of method 1, Cre-lox site-specific recombination was established which involves three elements . (a) A rE. coli clone, particularly, by introducing expression cassettes into the E1 region. After purification of recombinant plasmid DNA, it releases the viral chromosome and is relevantly transfected in the cell line [E. coli rather than mammalian cells due to presence of the homologous machinery of bacteria [This method utilizes HEK 293 cells so that the issue of homologous recombination can be reduced by utilizing recombination in microbes such as yeast and bacterial cells . E.g., Aell line . The sysbacteria ,59.To obtainobtain a virion for sufficient packaging, the genome size should fall within the range of 27.7 kb–37 kb . HoweverPositive-stranded RNA viruses known as coronaviruses have a nucleocapsid (N) protein that houses the genome and is encircled by the proteins that make up the envelope (E), membrane (M), and spike (S) . TargetiSix adhesive SARS-CoV-2 proteins have been predicted by Vaxign analysis viz. nsp3, nsp8, nsp9, nsp10, 3CL-PRO and S protein. Adhesin is involved in the virus attaching to the host genome and enabling virus entrance into the host genome, and it has a direct correlation to vaccine-induced immunity. S protein was anticipated to be the adhesin in SARS-CoV-2, which matches its key role in viral entry . DesigniOwing to their nanoscopic structure, it is easy for the viruses to invade the host cell, and such is the case with adenovirus. Rowe, along with his company, first attempted to culture adenoid tissue in a lab more than half a century ago. Since then, many have played their part in adenovirology . The fieIn the case of SARS-CoV-2, when the AdV vector-based vaccine is administered, a virus with the gene for S protein attaches itself to the host cell surface receptor . By the The nuclear pore then disassembles, and DNA is released into the nucleus along with some histones. The DNA now undergoes transcription to produce mRNA inside the nucleus. The formed mRNA is released into the cytoplasm where ribosomes are found. In the translation process, mRNA is attached to ribosomes and produces S proteins. Endosomes inside the cytoplasm chop and break these S proteins into fragments. The fragments of S protein are loaded up on major histocompatibility complex 1 or 2 (MHC-I and -II) which help in the presentation of S proteins on the cell surface . All theAdenovirus comes in both replicating and non-replicating forms. Replication-competent vectors vary from replication-defective vectors in that only the E3 region is removed. As a consequence, they have a smaller clone potential than replication-defective Ad, which is 3–4 kb. Furthermore, they require doses that are at least 2–3 logs lower compared to those of non-replicating AdV vectors. This dose-sparing impact is attributed to the virus particles’ subsequent reproduction in the cells. It was discovered that a replication-competent adenovirus vector influenza vaccine exhibits long-lasting mucosal and systemic immunity in an investigation on adenovirus-type-4-expressing influenza virus H5 HA (Ad4-H5-Vtn) to test the strength and persistence of the immune response of a replicating vaccine .The vaccine against Ebola virus (ERVEBO) developed by Merck in collaboration with IAVI is another example of a replication-competent vector. The vaccine against replication-competent vesicular stomatitis virus vectors also offers defense against illnesses linked to SARS-CoV-2. It was found to be effective in mice  and reseDiscussion of the outcome of the virus entering non-antigen presenting cells, the possible systemic release of the encoded antigen.All of the body’s nucleated cell types are non-professional antigen-presenting cells. To display endogenous peptides on the cell membrane, they bind an MHC class I molecule to beta-2 microglobulin . The infAs of 22 April 2022, more than 507 million individuals have been infected and among them 6.2 million lost their lives during this coronavirus pandemic . DiffereUniversity of Oxford and AstraZeneca manufactured AZD1222, which consists of a ChAdOx1 adenoviral vector and the gene of the S protein of coronavirus administered via the IM route. In AZD1222, the coding sequence has not been changed in order to stabilize the expressed S protein in the prefusion conformation; instead, the SARS-CoV-2 S immunogen is expressed in the vaccine in the trimeric prefusion conformation . The SerA phase ½ single blind, randomized controlled trial carried out with 1090 participants in the 18–55 age group showed good safety and immune response . A phaseSeveral medicinal agencies such as The Australian Therapeutic Goods Administration and The European Medicines Agency (EMA) have permitted the Covishield vaccine . AdditioThe Gamaleya Research Institute developed Sputnik V, or Gam-COVID-vac, which consists of Ad26 and Ad5 vectors with S protein genes of SARS-CoV-2. The Sputnik V vaccine from Gamaleya, which encodes natural S, does not appear to use 2P spike mutations . Phase IJanssen Pharmaceutical prepared the Ad26Cov2-S vaccine using an Ad26 vector including the genes of coronavirus. It expresses the S protein and contains K986P and V987P alterations (2P) in a loop that abuts the S2’ membrane fusion machinery’s core helix. Higher titers of neutralizing antibodies are produced as a result of the alteration, which traps the spike in a prefusion conformation. It also features a deletion at the location where furin cleaves . The vacThe Lancet [CanSino Biologics developed Convidecia (AD5-nCOV) using an Ad5 vector with genome of S protein of SARS-CoV-2. It is a single dose vaccine. A phase I dose escalation trial was carried out in healthy volunteers, 108 of which were in the 18–60 age group, and results showed a safe and good tolerability profile . Phase Ie Lancet . Apart fe Lancet . City ofe Lancet . TMV-083e Lancet . Table 1Intranasal vaccination can be considered as the most attractive way of vaccination from all mucosal routes owing to greater patient compliance . A stronThe method provides complete sterility in the nose that is the foremost entrance point for the virus. Trained personnel are also not required; self-administration is possible. Along with that, the method is adapted to affiliate global needs. Several studies have shown that the viral S Protein is the major cause of viral attachment and engaging the cell surface receptor ACE-2 ,124,125.+ killer T cells are detected in the lungs that confirm cellular immunity. Data from clinical trials, however, has shown that AdCOVIDTM did not sufficiently activate immunity. As a result, Altimmune, Inc. announced that AdCOVIDTM development will no longer be pursued.Altimmune has developed AdCOVID™, which is characterized as a needle-free intranasal single dose non-replicating Ad-5-vectored vaccine. AdCOVID™ strongly generates humoral and cellular immune response . GeneralChAdOx1/AZD1222 is formulated as an IM injection and has also been assessed for the intranasal route in non-human primates . The outThe advance of the SARS-CoV-2 vaccine (BBV154) relies on chimpanzee adenovirus as has been established by Washington University, School of Medicine in association with Bharat Biotech. For defensive action at the lower and upper respiratory tract a single dose intranasal vaccination exhibited higher neutralizing antibody action . The intIn the early 2020s, CanSino Biologics Inc. and the Beijing Institute of Biotechnology developed Ad5-nCoV, a human adenovirus serotype 5 vaccine. It is an Ad5-derived first-generation E1/E3-deleted vector that expresses the whole SARS-CoV-2 spike glycoprotein in full length. In mice and ferrets, where SARS-CoV-2 infection exclusively occurs in the upper respiratory tract as opposed to the lungs, Ad5-nCoV’s efficacy was examined. The upper and lower respiratory tracts of mice were totally shielded from SARS-CoV-2 when the intranasal (IN) and intramuscular (IM) injection routes were contrasted. However, because of issues with IN administration in individuals with asthma, IM was chosen for Ad5-nCoV immunization in early human clinical research. . Ad5-nCoThe emergence of new vaccinations against potentially more virulent SARS-CoV-2 strains has sparked new research attempts. Concerns about the potential return of a viral variation resistant to the protection generated by the currently available vaccinations are particularly highlighted by the D614G spike protein mutation ,136. TheThe Omicron variant, which carries mutations, has recently increased dramatically, raising worries about immune evasion even in those who have received all of the recommended vaccinations. The latest research has looked at the effectiveness of booster vaccinations given after CoronaVac/AZD1222 prime to produce T-cell activation and neutralizing antibodies (NAbs) towards BA.1 and BA.2 omicron. A number of 167 subjects were recruited to obtain BNT162b2, AZD1222, or mRNA-1273 as a third dosage after being immunized with heterologous CoronaVac/AZD1222 for 4–5 months. Total interferon responses, reactogenicity, immunogenicity, and the NAb titers towards BA.1 and BA.2 were all measured. After 4–5 months from the administration of the heterologous CoronaVac/AZD1222, a noteworthy loss in neutralizing potency to the omicron variant was discovered. Without any severe adverse effects, reactogenicity was mild to moderate. A dramatic rise in associating antibodies and neutralizing activity against the delta and omicron variants was seen after a booster immunization. The greatest titers for omicron BA.1 and BA.2 neutralization were obtained following mRNA-1273-boosted dose, then BNT162b2 and AZD1222. In contrast to those who received AZD1222 as a booster, those who received messenger RNA (mRNA) vaccinations acquire a T-cell response to the spike protein .Over the last few days, novel subvariants of Omicron BA.5, including BA.5.1.7 and BF.7, were found throughout China. The two novel subvariants are extremely contagious and spread quickly.Emerging Microbes and Infections. Aerosolized vaccine injection in the respiratory mucosa can produce local mucosal IgA antibodies and a higher level of antibody count against the Omicron variations in blood, which may effectively treat the Omicron variant BA.5 [The research shows that inhaling the COVID-19 vaccine after receiving two doses of the inactivated vaccine raises levels of neutralizing antibodies against a number of variants, including BA.5. It was published on October 5, 2022 in the prestigious infectious diseases journal ant BA.5 .The potential for interaction between the viral gene and the host genome needs to be carefully examined before entry and throughout clinical progress. Most of these worries about safety are considerable, and they could cause clinical research to be delayed in the event of a pandemic ,141. It Pre-existing immunity is one of many challenges that need to be tackled by all Ad vector-based vaccine manufacturers. The unique serotype of adenovirus that is hardly exposed to humans can be an option for those who are infected by adenovirus ,143,144.Ad5 is a common type of AdV. If one uses Ad5 for vaccine production, Ad5-based vaccines will be less effective. Adenovirus is a virus that naturally exists and mainly infects our upper respiratory tract, rendering individuals with some immunity against adenovirus ,149. ThuSputnik V COVID-19 vaccine uses Ad26 for the priming dose and Ad5 for boosting/second dose as a vector . HoweverThe best way to overcome pre-existing immunity is oral immunization. However, this only produces a response against neutralizing antibodies and it fails to produce a response against T cells . An intrThe lentivirus vector has a tropism for both dividing and non-dividing cells . By makiSome observations show that cross-reactivity is present between non-related pathogens. This is called heterologous immunity. Heterologous immunity can either increase or decrease the response of a vaccine. Heterologous immunity mainly forms due to cross-reactivity of T-cells or neutralizing antibodies . HeterolBecause of reports of unusual blood clots, such as heparin-induced thrombocytopenia (HIT), linked to the COVID-19 vaccinations, the introduction of the Oxford/AstraZeneca and Johnson & Johnson vaccines was halted in many countries in the middle of 2021. However, the vaccination was resumed after a review of the data, except in Denmark, which is the only country where the Oxford/AstraZeneca vaccine is still not being administered ,168. OneCoronaviruses mutate at a slower rate than influenza viruses. The existing vaccinations appear to be significantly less effective against many of the new viral variants, this does not necessarily imply that vaccinations will need to be modified each year as they do with flu . A boostThe technology that underpins these vaccinations is also distinct. Unlike conventional influenza vaccines, which are created by cultivating flu viruses in chicken eggs and then extracting and deactivating them, the authorized COVID-19 vaccines are created by inserting the genetic instructions for generating the coronavirus spike protein into the human cells, or into an innocuous adenovirus, which further transports this information into our cells ,69,121. The Omicron version is naturally resistant to being neutralized by plasma from both recovering patients and those who have received one of the four COVID-19 vaccinations that have been widely rolled out . Even serum from those who had been immunized and boosted with mRNA-based vaccines had significantly reduced neutralizing antibody efficacy against the Omicron variant . There iPatients with autoimmune diseases and primary/secondary immunodeficiency disorders including rheumatoid arthritis, psoriasis, and inflammatory bowel diseases would be significantly impacted by the COVID-19 pandemic. Several anti-COVID-19 immunizations are safe and effective in treating individuals with immune-compromising diseases, including those using medications that influence the immune system, according to numerous clinical experimental studies . InactivPerceiving all the coronavirus outbreaks in 21st century , this can be assumed that similar outbreaks are likely to occur in the future. However, to limit the current COVID-19 outbreak, the speedy development of a safe, reliable, and effective vaccine is crucial along with efficacious treatment . RegardlViral vectors can produce the viral protein of interest with high titers, which serve as the foundation for advanced vaccine development. For identifying virulent antigens, varieties of viral vector expression systems were explored by the researchers. Non-replicating Ad vectors are promising vaccine carriers for infectious diseases due to better yield, cGMP friendly manufacturing processing, safe to use, high efficacy during clinical trials, and manageable shipping and storage procedures. Ad26Cov2.S and/or Ad5-nCoV single-dose vaccines use an inactivated common cold virus as a vector for delivering the viral spike protein gene into the cells, which is subsequently expressed by the host cell with a cascade of immune reactions post-protein expression. Apart from that, they are a better carrier option for mucosal vaccine delivery that provides localized immune protection to the individual and helps in the prevention of viral spread .In India, as per data from the Ministry of Health and Family Welfare, the total number of vaccinations until 9 February 2022 was 1.58 billion. As per the WHO source as of 9 February 2022, 28 vaccines are approved for use. Among these approved vaccines six candidates are Ad vector-based vaccines. Furthermore, a good number of vector-based vaccines are in the clinical and preclinical stages of research. This vaccine platform will be crucial in mitigating the current pandemic situation. Investigational outcomes in non-human primates showed clear favorable protection of virus assembly and shedding resulting in the generation of mucosal immune reaction (sIgA) in the human respiratory tract, as well as sturdy systemic and humoral immune responses. An IM prime accompanied by a booster immunization would almost certainly result in a more well-rounded immune reaction, along with viral replication inhibition (or strong reduction) in the human respiratory tracts. In short, Ad viral vector-based vaccine platform has a lot of potential to be delivered by various routes of administration to generate sufficient immune protection against different viral variants. Various foreign funding agencies, on the other hand, should galvanize and step up to support the vaccine advancement program by overcoming obstacles and amassing the COVID-19 vaccine.


Adults of low socioeconomic status (SES) had lower vaccination rates compared to those of high SES . Adults aged 20–59 years had a lower vaccination rate than those ≥60 years . Multivariate analysis identified five independent variables that were significantly (p < 0.001) associated with low vaccination rates: minority groups of the ultra-Orthodox sector and Arab population, and underlying conditions of asthma, smoking and diabetes mellitus . Specific targeted public health interventions towards these subpopulations with significantly lower rates of vaccination are suggested.We aimed to examine rates of COVID-19 vaccination to elucidate the need for targeted public health interventions. We retrospectively reviewed the electronic medical files of all adults registered in a central district in Israel from 1 January 2021 to 31 March 2022. The population was characterized by vaccination status against COVID-19 and the number of doses received. Univariate and multivariable analyses were used to identify predictors of low vaccination rates that required targeted interventions. Of the 246,543 subjects included in the study, 207,911 (84.3%) were vaccinated. The minority groups of ultra-Orthodox Jews and Arabs had lower vaccination rates than the non-ultra-Orthodox Jews (68.7%, 80.5% and 87.7%, respectively,  Coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on 11 March 2020 .Vaccination against the causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the leading strategy to control the COVID-19 pandemic worldwide . A COVIDBecause of waning immunity and the development of SARS-CoV-2 mutants, on 30 July 2021, Israel was the first country to make a third dose (“booster dose”) of the BNT162b2 Pfizer vaccine available to all individuals aged ≥60 years who had been vaccinated at least 5 months earlier . Later oA large observational study conducted by Barda et al., using nationwide mass vaccination data in Israel, showed that a third dose of the BNT162b2 mRNA COVID-19 vaccine is effective in preventing severe COVID-19-related outcomes. Adding a third vaccine dose was estimated as being 93% effective in preventing COVID-19-related hospitalization, 92% in preventing severe disease, and 81% in preventing COVID-19-related death, as of ≥7 days after the third dose .The aim of our study was to explore factors associated with low acceptance of the COVID-19 vaccine in adults, in order to improve public health-targeted interventions in subpopulations with low vaccination rates. In this manuscript, we describe the study population and the methodology used and then report univariate and multivariate analyses of variables associated with vaccine acceptance.Clalit Health Services (CHS) insures approximately 54% of the Israeli population. It maintains a comprehensive computerized database, continuously updated with regard to subjects’ demographics, community and outpatient visits, laboratory tests, hospitalizations, and medications prescribed and purchased. During each physician’s visit, a diagnosis is recorded according to the International Classification of Diseases, ninth revision (ICD-9).The study population consisted of all subjects aged ≥20 years who were registered with CHS during the study period of 1 January 2021 to 31 March 2022 within the Dan-Petach Tikva administrative district. This district comprises about 500,000 members and includes large towns of mainly secular Jews, large towns of ultra-Orthodox Jews, and few Arab towns, with the majority being the non-ultra-Orthodox Jewish population. Israelis tend to live within neighborhoods based on this grouping.The study population was divided into two groups: unvaccinated and vaccinated with at least one dose of the vaccine, with further subgroupings according to the number of COVID-19 vaccine doses received. The data collected from the electronic database included demographic information , which was defined according to the classification of the Israeli Central Bureau of Statistics ); vaccinhttps://www.R-project.org, accessed on 18 July 2022).We extracted the study data into a central data table, which was anonymized for statistical analyses. Descriptive statistics were used to report the demographic and clinical variables of the vaccinated and unvaccinated study groups. Proportions were compared by a chi-square test or Fisher’s exact test, as appropriate, and continuous variables by Student’s t-test or a Mann–Whitney test, as appropriate. Variables associated with vaccine acceptance were first identified by univariate analysis. We then performed multivariate logistic regression to analyze the adjusted odds ratio of vaccination as the dependent variable, based on variables found significant in the univariate analysis. We drew vaccination uptake curves by sector adjusted for age and gender. We also drew a forest plot describing the adjusted relative association of the various variables on vaccine acceptance. Analysis was performed with R software  were female and 120,724 (49%) males; 230,546 (93.5%) were Jews and 15,997 (6.5%) Arabs.p < 0.001). Males were less often vaccinated than females . The minority groups of ultra-Orthodox Jews and Arabs had lower vaccination rates than the non-ultra-Orthodox Jews . Vaccination rates were also significantly related to SES: adults with low SES had lower vaccination rates compared to those with high SES . A higher COVID-19 vaccination rate was observed in adults who had received a previous seasonal influenza vaccine compared to those who did not .Of the 207,911 adults who were vaccinated against COVID-19, 7.5% received only one single dose of the vaccine, 16.5% received two doses and 76% received the recommended three doses .p < 0.001 for these three variables)  .p < 0.001) associated with low vaccination rates. Among the demographic variables were the minority groups of ultra-Orthodox Jews and the Arab population . Among the underlying conditions were individuals with asthma, smoking and diabetes mellitus . In contrast, obesity was significantly and independently associated with an increased vaccine acceptance .p < 0.001). A non-parametric forest plot describing the adjusted relative risks of the various variables on vaccine acceptance is shown in Gender differences were noted among the minority groups: Arab women were at risk of a low vaccination rate, whereas ultra-Orthodox women showed a relatively high vaccination rate compared to corresponding males , although they were still less likely to be vaccinated than the non-ultra-Orthodox Jewish population. In the non-ultra-Orthodox Jewish population, after adjustment for age, elderly women were significantly less likely to vaccinate than men. Lower SES was negatively associated with getting vaccinated , it is significantly lower among certain populations, including in groups at high risk of severe course and complications of COVID-19, such as those with comorbidities. Targeted public health interventions aimed at these populations are required with consideration of their special social characteristics and underlying conditions. Targeted delivery of key messages to the identified populations is currently possible, for example, by community/religious leaders, newsletters, specialized media and social media networks. It is suggested that health policymakers use the aid of experts in online health communication and social networking. Targeted needs of special populations such as those with low SES should also be planned, for example, by making vaccination sites more accessible .


We performed an exploratory analysis to identify patient and thrombus characteristics associated with early recanalization in large-vessel occlusion (LVO) stroke patients transferred for endovascular treatment (EVT) from a primary (PSC) to a comprehensive stroke center (CSC).We included patients with an LVO stroke of the anterior circulation who were transferred to our hospital for EVT and underwent repeated imaging between January 2016 and June 2019. We compared patient characteristics, workflow time metrics, functional outcome , and baseline thrombus imaging characteristics, which included: occlusion location, thrombus length, attenuation, perviousness, distance from terminus of intracranial carotid artery to the thrombus (DT), and clot burden score (CBS), between early-recanalized LVO (ER-LVO), and non-early-recanalized LVO (NER-LVO) patients.One hundred and forty-nine patients were included in the analysis. Early recanalization occurred in 32% of patients. ER-LVO patients less often had a medical history of hypertension , and more often had clinical improvement between PSC and CSC , compared with NER-LVO patients. Thrombolysis administration was similar in both groups . ER-LVO patients had no ICA occlusions , more often an M2 occlusion , longer DT , shorter thrombi , and higher CBS  at baseline imaging. ER-LVO patients had lower mRS scores .Early recanalization is associated with clinical improvement between PSC and CSC admission, more distal occlusions and shorter thrombi at baseline imaging, and better functional outcome. The imaging protocol to confirm the presence of an acute ischemic stroke (AIS) due to an intracranial large-vessel occlusion (LVO) generally includes non-contrast CT (NCCT) and CT angiography (CTA).We included adult patients with an LVO stroke of the anterior circulation who were presented to a PSC between January 2016 and June 2019, were subsequently transferred to our hospital  for EVT, and underwent repeated neuroimaging on arrival.This study was evaluated by the medical ethics review committee of our hospital, who waived the need for obtaining written informed consent. The procedures followed were all in accordance with institutional guidelines. A letter with detailed information about the study was sent to all patients meeting the inclusion criteria. The patient or legal representative had the opportunity to deny consent for use of their data via an opt-out form, conforming to the European Union General Data Protection Regulation.An LVO was defined as the occlusion of one of the major intracranial arteries. Early recanalization was defined as the dissolution of the thrombus, as confirmed with neuroimaging performed at the CSC. Non-early recanalization was defined as a persistent LVO either in the same vessel segment  or in a new vascular territory. Spontaneous early recanalization was defined as early recanalization without IVT administration.PSC and NIHSSCSC, respectively). The change in NIHSS score between presentation to the PSC and presentation to the CSC was also calculated (ΔNIHSS=NIHSSCSC – NIHSSPSC). A negative ΔNIHSS value means clinical improvement and a positive value implies clinical deterioration.Stroke severity at PSC and CSC admission was assessed using the National Institutes of Health Stroke Scale  to the thrombus (DT), thrombus length, thrombus attenuation, thrombus perviousness, and clot burden score (CBS). These characteristics were assessed on pre-IVT NCCT and/or CTA data from the PSC. If both NCCT and CTA were available, the scans were co-registered using Elastix rigid-registration.Thrombus location was re-assessed on CTA by a trained observer cognizant of the radiology report of the attending neuroradiologist, supported by the hyperdense artery sign if observed on NCCT, and was classified as internal carotid artery (ICA), middle cerebral artery , or anterior cerebral artery  occlusions.The DT was defined as the path length from the ICA-T to the most proximal thrombus border. Up to five markers were placed along the vessel centerline connecting the ICA-T to the proximal thrombus border using the software ITK-snap (version 3.4)Thrombus length was defined as the largest extension of lack of contrast filling shown on CTA, aided by the hyperdense artery sign if observed on NCCT. We placed five markers along the occluded vessel centerline using ITK-snap,Thrombus perviousness is a measure of the amount of contrast that has penetrated the thrombus in CTA, compared with NCCT. Both thrombus attenuation and perviousness were measured by manually placing three spherical regions of interests of 1 mm radius within the thrombus . ThrombuThe CBS is a 10-point score that assesses the thrombus extension in the anterior circulation. The CBS was assessed as reported previously.All measurements were performed using both co-registered scans simultaneously. If only NCCT was available, DT, thrombus length, thrombus perviousness, and CBS were measured solely based on the hyperdense artery sign (if present). If only CTA was available, DT, thrombus length, and CBS were measured based on the lack of contrast filling. All measurements were performed by three trained observers: NAT, AAEB, and ISJS.Workflow-related outcomes included time from stroke onset to initiation of IVT, time from stroke onset to arrival at the PSC, time from arrival at the PSC to initiation of IVT, and time from imaging at the PSC to imaging at the CSC. The time of stroke onset was defined as the time of witnessed symptom onset or, if unknown, as the time the patient was last seen well.Functional patient outcome was assessed using the modified Rankin Scale (mRS) at 90 days after stroke onset. Functional independence was defined as an mRS of 0–2.U test for continuous variables and χ2 and Fisher’s exact test for categorical variables. Statistical significance was set at P<0.05. All the analyses were performed with IBM SPPS Statistics package software (version 26.0).We performed an exploratory analysis and compared patient and thrombus characteristics of ER-LVO patients to those of NER-LVO patients. Data are presented as median and interquartile range (IQR) for continuous variables, and number and proportion (%) for categorical variables. Comparison between groups was done using the Mann–Whitney In total, 677 patients were transferred to our hospital for EVT between January 2016 and June 2019. Of these, 169/667 (25%) underwent repeated CT imaging on arrival. The reasons underlying repeated imaging in our study population have previously been reported:10.1136/neurintsurg-2021-017441.supp1Supplementary dataEarly recanalization occurred in 48/149 (32%) patients. Spontaneous early recanalization (without IVT) occurred in 6/48 (12%) ER-LVO patients. Among the NER-LVO patients, 48/101 (48%) patients had a persistent LVO in the same vessel segment, 11/101 (11%) patients had a distally migrated thrombus, and 1/101 (1%) patients had a thrombus in a new vascular territory. For 41/101 (40%) patients, the location of the persistent LVO was not explicitly reported. Among the NER-LVO patients, we did not identify any complete thrombus resolution on the first digital subtraction angiography (DSA) scan. In four NER-LVO patients, the location of the thrombus (as shown in the DSA scan) was too distal for EVT.CSC scores were lower for ER-LVO patients , and median ΔNIHSS score was −5 for ER-LVO patients  and 3 for NER-LVO patients  (P<0.01) . NIHSS(P<0.01) . IVT wasCSC scores and more often had clinical improvement between PSC and CSC admission.A subgroup analysis comparing the baseline characteristics of ER-LVO and NER-LVO patients that received IVT can be found in the NCCT and CTA acquired prior to IVT were both available in 133/149 patients. Scan co-registration succeeded in 100/133 patients: 71/100 with rigid-registration and 29/100 with affine-registration. Co-registration of the remaining patients was not successful due to poor quality scans (13/33), and other co-registration errors (20/33). In total, 63 NCCT scans were re-sliced.ER-LVO patients did not have ICA occlusions  and more often had M2 occlusions  . ER-LVO Among patients that had IVT administered, ER-LVO patients had more distal occlusions, shorter thrombi, and higher clot burden score than NER-LVO patients. This subgroup analysis can be found in the There were no significant differences in the time metrics between ER-LVO and NER-LVO patients .In ER-LVO patients, mRS at 90 days was lower  . ER-LVO Early recanalization occurred in 32% of repeated imaging patients transferred to a CSC. These patients had more distal occlusions and shorter thrombi at baseline CT imaging. Spontaneous early recanalization occurred in a small subgroup of patients that did not receive IVT. Patients with early recanalization more often had clinical improvement between PSC and CSC admission. Early recanalization was associated with better functional outcome.Our results are in accordance with previous findings. A systematic review of 26 studies has reported that the incidence of early recanalization after IVT is 33% (95% CI 27 to 40). Distal LVOs have been associated with less severe neurological deficit,PSC scores.CSC and the ΔNIHSS scores, which likely reflect the clinical improvement of the patient due to the thrombus resolution. Previous studies have also suggested that higher thrombus attenuation and partial occlusions are potential predictors of early recanalization.Other studies have shown that ER-LVO patients have lower NIHSSWe found that patients with a medical history of hypertension were less likely to have early recanalization. High blood pressure on hospital admission has been related to reducing the chances of early recanalization.Early recanalization is a factor to consider in the current debate on which treatment is more beneficial for AIS patients: bridging therapy (IVT together with EVT) or EVT alone. Some previous studies found that patients with bridging therapy have a better functional outcome,Our study has some limitations. First, the number of transferred patients who underwent repeated imaging is limited, and only one-third shows early recanalization. Therefore, any statistical analysis comparing both groups is also limited. In addition, 41% of mRS scores at 90 days' post-stroke were missing.Second, the requirements for measuring the thrombus imaging characteristics further reduced our sample size. The slice thickness exceeded 2.5 mm in 63 NCCT scans. The HU interpolation caused by the re-slicing led to the exclusion of several patients for the thrombus density and perviousness measurements. Moreover, defining the thrombus extension was challenging when both modalities were not available, especially in cases without collateral filling on CTA and in the absence of the hyperdense artery sign on NCCT, which in many cases prevent us from measuring thrombus length. In addition, the performed measurements are observer-dependent. An (semi-) automatized method that places the markers along the occluded vessel centerline would be less time-consuming and would reduce the observer-dependency.Finally, the decision to perform repeated imaging is not arbitrary.Patients with early recanalization are characterized by more distal occlusions and shorter thrombi at baseline CT imaging, and clinical improvement between presentation to the PSC and the CSC. Early recanalization is associated with better functional patient outcome and might therefore be an important factor to consider in treatment-planning of transferred stroke patients.


Coronavirus disease 2019 (COVID-19), leading to mild infection (MI), acute respiratory distress syndrome or death in different persons. Although the basis of these variabilities has not been fully elucidated, some possible findings have been encountered. In the present study, we aimed to reveal genes with different expression profiles by next-generation sequencing of RNA isolated from blood taken from infected patients to reveal molecular causes of different response.Two healthy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative control individuals (NCI), two SARS-CoV-2-positive patients who have MI, and two patients who have critical infection (CI) were included in the study. Total RNA was extracted from blood samples and sequenced. Raw RNA-Seq data were analyzed on Galaxy platform for the identification of differentially expressed genes and their pathway involvements.We found that 199 and 521 genes were downregulated in whole blood of COVID-19-positive CI patients compared to NCI and MI patients, respectively. We identified 21 gene ontology pathways commonly downregulated in CI patients compared to both NCI and MI, mostly associated with innate and adaptive immune responses. Three hundred and fifty-four and 600 genes were found to be upregulated compared to NCI and MI, respectively. Upregulated six pathways included genes that function in inflammatory response and inflammatory cytokine release.The transcriptional profile of CI patients deviates more significantly from that of MI in terms of the number of differentially expressed genes, implying that genotypic differences may account for the severity of SARS-CoV-2 infection and inflammatory responses through differential regulation of gene expression. Therefore, further studies that involve whole genome analysis coupled with differential expression analysis are required in order to determine the dynamics of genotype – gene expression profile associations. One of the main agents of the seasonal cold, human coronaviruses, is known to cause pneumonia. In 2019, a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) emerged, leading to acute respiratory distress syndrome, death, or asymptomatic infection in different persons [ persons . Advance persons , 5.Although the cause of the differential response to SARS-CoV-2 infection in different patients has not been fully elucidated, some possible findings have been encountered. For instance, a study showed that patients with severe SARS-CoV-2 infection exhibit a higher antibody response to spike and nucleocapsid proteins of SARS-CoV-2, and a higher memory B-cell response to spike protein . In a reIn the present work, we aimed to reveal differentially expressed genes in blood from SARS-CoV-2-infected individuals to identify the molecular causes underlying the variation in response to SARS-CoV-2 infection in different individuals.Ethical approval for the study was obtained from Istanbul Medeniyet University, Goztepe Training and Research Hospital Ethics Committee for Clinical Research . Two healthy non-infected control individuals (NCI), two SARS-CoV-2-positive patients who have mild infection (MI), and two SARS-CoV-2-positive patients who have critical infection (CI), as described before , were in•COVID-19 infection disease is heterogeneous and not predictable.•Innate and adaptive immunity were downregulated in CI.•Platelet activation and platelet degranulation pathways were exclusively upregulated in CI.•These factors may be the cause of immunothrombosis.Total RNA was extracted from blood samples using Zymo Quick-RNA™ Whole Blood , according to the manufacturer’s instructions with some modifications. For all three patient groups, 300 μl whole blood was used. After the DNase I treatment in column, RNA was eluted from the column with 15 μl RNase-free water. The quality and quantity of resulting total RNA samples were controlled by Nanodrop spectrophotometer (Thermo Scientific™ NanoDrop) and Qubit (Thermo Fischer Qubit™ 4 Fluorometer). The A260/A280 ratio of purified RNAs was between 1.8 and 2.0, and A260/A230 ratio ranged between 1.8 and 2.1. The RNA integrity number (RIN) was assessed using the Bioanalyzer  for all RNA samples. RNA samples with a RIN number >7 were subjected to cDNA library preparation protocol. The concentration of RNA was measured using the RNA-BR protocol of the Qubit 2.0 Fluorometer (Thermo Fischer Life Technologies).For the removal of mitochondrial and cytoplasmic rRNA from total RNA samples, Ribo-Zero Gold rRNA depletion protocol  was used. Depleted and purified samples (200 ng RNA) underwent enzymatic fragmentation. After the first and second strand cDNA synthesis, adenylation, adapter ligation, and amplification procedures were performed with some modifications in the TruSeq Stranded Total RNA protocol . For the adapter ligation step, IDT for Illumina TruSeq RNA unique dual indexes (UDIs) was used . Enrichment of the DNA fragments that have adapter sequences on both ends was carried out by 15 cycles of PCR. After the clean-up procedure of the amplified DNA with AMPure XP beads, the size and purity of the libraries were assessed with Bioanalyzer using the HS DNA Kit . To obtain optimum cluster densities and high-quality data, library quantification was performed by qPCR (KAPA Library Quantification Kits KK4601). The quantity of the libraries was controlled using three replications and two dilutions for each sample for accurate quantification. After the calculation, master pool was loaded onto the NovaSeq 6000 platform, using 150 bp paired ends sequencing and S1 flow cell. The quality score of the run (QC30) was 80.Raw RNA-Seq data were analyzed using Galaxy platform . TrimmomDifferential gene expression patterns of SARS-CoV-2 were obtained by RNA-Seq transcriptome sequencing performed on whole-blood RNA samples of each group. Differentially expressed genes in CI patients with respect to NCI and MI were determined based on a cutoff log2-fold change value of 2. Gene ontology (GO) terms were assigned to the differentially expressed genes and GO enrichment analysis was performed to determine the up- and down-regulated pathways with putative relations to SARS-CoV-2 infection response in CI patients.Six samples were evaluated in three groups abbreviated as CI, MI, and NCI . PatientWhen genes differentially upregulated in whole blood of CI patients were examined, 354 and 600 genes were found to be upregulated compared to NCI and MI, respectively , with 27Differentially expressed genes in CI patients compared to NCI and MI were identified as a result of the study. A log2-fold change value of 2 was used as a cutoff to accept genes as differentially expressed. It is feasible to adjust lower cutoff values, which would result in the identification of a higher number of genes as differentially expressed. However, it is useful to set high stringency statistical analysis conditions to compensate for the relatively narrow sample size in cases where sampling from a high number of individuals is not feasible. Nevertheless, a significantly high number of genes were found to be differentially expressed in CI patients compared to both NCI and MI individuals when differentially expressed genes were determined based on a statistically safe cutoff threshold. GO enrichment analysis determined the up- and down-regulated pathways. We identified 21 GO pathways commonly downregulated in CI patients compared to both NCI and MI. Downregulated 17 GO pathways were directly associated with innate and adaptive immune responses. Three hundred and fifty four and 600 genes were found to be upregulated compared to NCI and MI, respectively. Upregulated six pathways included genes that function in inflammatory response and inflammatory cytokine release.st week following symptoms and IgG antibodies follow that, mostly retaining a lifelong immunity [Immune responses to SARS-CoV-2 infection include tissue barriers, innate and adaptive cells, and mediators. Once the virus infects respiratory epithelial cells, viral peptides are presented through Class I major histocompatibility complex (MHC) proteins to CD8+ cytotoxic T cells, leading to the activation and development of virus-specific effector and memory T cells. In short time, virus is recognized by antigen-presenting cells which present viral peptides to CD4+ T cells through MHC-Class-II molecules, while B cells can directly recognize the virus and interact with CD4+ T cells. Immunoglobulin (Ig) M virus-specific antibody response is observed within the 1immunity .A wide variety of mild, moderate, severe, and rapidly progressive clinical findings are observed in patients with SARS-CoV-2 . SARS-CoThrombosis is reported to contribute significantly to the severity of COVID-19 symptoms –30. Our Limitations of this study are limited number of patients and that the study design was cross sectional. Gene expression regulation is actually highly dynamic and gene expression profiles of both CI and MI patients may change during the period of COVID-19 infection in both groups. Following changes in gene expression, patterns with periodic recurrent tests can be useful to reveal infection phase-dependent differences in gene expression between CI and MI patients. Age differential may affect the observed gene expression differences, on the other hand, the fact that majority of downregulated genes in CI patients belong to pathways associated with immune responses imply the effect of glucocorticoid therapy on gene expression. Yet, regardless of age and differences in therapeutic applications, the pool of differentially expressed genes detected in this study unquestionably includes genes that are associated with severe disease symptoms. It is important to note that Favipravir was administered to both CI and NCI patients, which also would cause changes in gene expression regulation. Yet, the gene expression profile of CI patients deviates more significantly from the MI patients compared to NCI individuals. Thus, gene expression differences observed in the present work result from not only differential drug treatments but also differential disease severity in CI and MI individuals.Overall, it is noteworthy that the transcriptional profile of CI patients deviates more significantly from that of MI in terms of the number of differentially expressed genes. These results imply that genotypic differences may account for the severity of SARS-CoV-2 infection responses. In addition, upregulated blood ACE2 expression in CI patients was observed only compared to MI, supporting the putative role of genotypic differences in disease severity. To resolve genotype – disease susceptibility associations, combined studies that involve both genomic and transcriptomic analyses are essential.Differential transcriptomic analysis highlights the necessity of genomic association studies, therefore, further work involving the genotyping of large groups of asymptomatic and symptomatic individuals as well as transcriptomic analyses would help determine genotypic associations with the severity of COVID-19 symptoms.