Severe high-molecular-weight kininogen deficiency: clinical characteristics, deficiency–causing KNG1 variants, and estimated prevalence

Background: Severe high-molecular-weight kininogen (HK) deficiency is a poorly studied autosomal recessive contact system defect caused by pathogenic, biallelic KNG1 variants. Aim: We performed the first comprehensive analysis of diagnostic, clinical, genetic, and epidemiological aspects of HK deficiency. Methods: We collected clinical information and blood samples from a newly detected HK-deficient individual and from published cases identified by a systematic literature review. Activity and antigen levels of coagulation factors were determined. Genetic analyses of KNG1 and KLKB1 were performed by Sanger sequencing. The frequency of HK deficiency was estimated considering truncating KNG1 variants from GnomAD. Results: We identified 48 cases of severe HK deficiency (41 families), of these 47 have been previously published (n = 19 from gray literature). We genotyped 3 cases and critically appraised 10 studies with genetic data. Ten HK deficiency-causing variants (one new) were identified. All of them were truncating mutations, whereas the only known HK amino acid substitution with a relevant phenotype instead causes hereditary angioedema. Conservative estimates suggest an overall prevalence of severe HK deficiency of approximately one case per 8 million population, slightly higher in Africans. Individuals with HK deficiency appeared asymptomatic and had decreased levels of prekallikrein and factor XI, which could lead to misdiagnosis. Conclusion: HK deficiency is a rare condition with only few known pathogenic variants. It has an apparently good prognosis but is prone to misdiagnosis. Our understanding of its clinical implications is still limited, and an international prekallikrein and HK deficiency registry is being established to fill this knowledge gap. Keywords: blood coagulation disorders; diagnosis; epidemiology; high-molecular-weight; kallikrein-kinin system; kininogen; partial thromboplastin tim

Perceived risk of infection and death from COVID-19 among community members of low- and middle-income countries: A cross-sectional study [version 1; peer review: awaiting peer review]

Background: Risk perceptions of coronavirus disease 2019 (COVID-19) are considered important as they impact community health behaviors. The aim of this study was to determine the perceived risk of infection and death due to COVID-19 and to assess the factors associated with such risk perceptions among community members in low- and middle-income countries (LMICs) in Africa, Asia, and South America. Methods: An online cross-sectional study was conducted in 10 LMICs in Africa, Asia, and South America from February to May 2021. A questionnaire was utilized to assess the perceived risk of infection and death from COVID-19 and its plausible determinants. A logistic regression model was used to identify the factors associated with such risk perceptions. Results: A total of 1,646 responses were included in the analysis of the perceived risk of becoming infected and dying from COVID-19. Our data suggested that 36.4% of participants had a high perceived risk of COVID-19 infection, while only 22.4% had a perceived risk of dying from COVID-19. Being a woman, working in healthcare-related sectors, contracting pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, as well as seeing or reading about individuals infected with COVID-19 on social media or TV were all associated with a higher perceived risk of becoming infected with COVID-19. In addition, being a woman, elderly, having heart disease and pulmonary disease, knowing people in the immediate social environment who are or have been infected with COVID-19, and seeing or reading about individuals infected with COVID-19 on social media or TV had a higher perceived risk of dying from COVID-19. Conclusions: The perceived risk of infection and death due to COVID-19 are relatively low among respondents; this suggests the need to conduct health campaigns to disseminate knowledge and information on the ongoing pandemic

c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans

Background Severe prekallikrein deficiency (PK deficiency) is an autosomal‐recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Africans according to gnomAD (allele frequency 1.43%). Patients/Methods The most common African (c.451dupT) and European (c.1643G>A, p.Cys548Tyr) PK deficiency causing KLKB1 variants were analyzed in two population‐based collectives of 300 Nigerian and 300 German subjects. Genome databases were evaluated for variant frequencies and ethnicity of the subjects. The geographic origin of PK‐deficient cases due to 451dupT was assessed. Results Two of five patients with PK deficiency caused by homozygous 451dupT were African, one African American, one from Oman, and one of unknown origin. The frequency of 451dupT was 1.17% in the Nigerian collective (7/600 alleles); none had Cys548Tyr. Subjects with 451dupT were found among different Nigerian ethnicities. Both variants were absent in the European collective. Database research was compatible with these findings, even though mainly data of African Americans (451dupT: 1.12%‐1.78%) was accessible. A relevant number of non‐American Africans are included only in the 1000Genomes collective: 451dupT frequency was 1.29% in native Africans and 1.56% in African Caribbeans. Conclusions This study underlines the higher prevalence of PK deficiency among people with African descent compared to Europeans. In order to avoid delay of necessary surgical procedures in patients of African origin, diagnostic algorithms for isolated, unexplained, activated partial thromboplastin time prolongation in these subjects should include PK deficiency screening

Acceptance of COVID-19 vaccination at different hypothetical efficacy and safety levels in ten countries in Asia, Africa, and South America

Vaccine hesitancy, defined as the reluctance or rejection in receiving a vaccine despite its availability, represents a major challenge to global health efforts aiming to control the ongoing COVID-19 pandemic. Understanding the possible factors correlated with COVID-19 vaccine hesitancy using a refined well-informed approach can be helpful to address the phenomenon. The current study aimed to evaluate COVID-19 vaccine acceptance rates using four hypothetical scenarios of varying levels of vaccine efficacy and safety profiles in ten Asian, African and South American countries. These scenarios included: 95% efficacy and 20% side effects (Vaccine A), 75% efficacy and 5% side effects (Vaccine B); 75% efficacy and 20% side effects (Vaccine C) and 50% efficacy and 5% side effects (Vaccine D). This study used a self-administered online survey that was distributed during February–May 2021. The total number of study respondents was 1337 with countries of residence as follows: India (21.1%), Pakistan (12.9%), Sudan (11.2%), Nigeria (9.3%), Iran (8.2%), Bangladesh and Brazil (7.9%), Chile (7.7%), Tunisia (7.6%), and Egypt (6.2%). The overall acceptance rates for COVID-19 vaccination were variable based on varying degrees of safety and efficacy as follows: 55.6% for Vaccine C, 58.3% for Vaccine D, 74.0% for Vaccine A and 80.1% for Vaccine B. The highest levels of COVID-19 vaccine acceptance were observed in Brazil followed by Chile across the four different safety and efficacy scenarios. The lowest COVID-19 vaccine acceptance rates were reported in Egypt and Tunisia for the low safety scenarios (20% side effects), and the low efficacy scenario (50% efficacy). The study revealed the potential effect of vaccine safety and efficacy on the intention to get COVID-19 vaccination. At the same efficacy level, higher possibility of side effects caused a large drop in COVID-19 vaccine acceptance rate. This indicates the importance of accurate communication regarding vaccine safety and efficacy on attitude towards the vaccine and intentions to get vaccinated. Regional differences in COVID-19 vaccine acceptance were observed with the Middle East/North African countries showing the lowest rates and the South American countries displaying the highest vaccine acceptance rates

Vaccine hesitancy among communities in ten countries in Asia, Africa, and South America during the COVID-19 pandemic

Vaccine hesitancy is considered one of the greatest threats to the ongoing coronavirus disease 2019 (COVID-19) vaccination programs. Lack of trust in vaccine benefits, along with concerns about side effects of the newly developed COVID-19 vaccine, might significantly contribute to COVID-19 vaccine hesitancy. The objective of this study was to determine the level of vaccine hesitancy among communities in particular their belief in vaccination benefits and perceived risks of new vaccines. An online cross-sectional study was conducted in 10 countries in Asia, Africa, and South America from February to May 2021. Seven items from the WHO SAGE Vaccine Hesitancy Scale were used to measure a construct of belief in vaccination benefit, and one item measured perceived riskiness of new vaccines. A logistic regression was used to determine which sociodemographic factors were associated with both vaccine hesitancy constructs. A total of 1,832 respondents were included in the final analysis of which 36.2% (range 5.6–52.2%) and 77.6% (range 38.3–91.2%) of them were classified as vaccine hesitant in terms of beliefs in vaccination benefits and concerns about new vaccines, respectively. Respondents from Pakistan had the highest vaccine hesitancy while those from Chile had the lowest. Being females, Muslim, having a non-healthcare-related job and not receiving a flu vaccination during the past 12 months were associated with poor beliefs of vaccination benefits. Those who were living in rural areas, Muslim, and those who did not received a flu vaccination during the past 12 months had relatively higher beliefs that new vaccines are riskier. High prevalence of vaccine hesitancy in some countries during the COVID-19 pandemic might hamper COVID-19 vaccination programs worldwide. Programs should be developed to promote vaccination in those sociodemographic groups with relatively high vaccine hesitancy

Willingness-to-pay for COVID-19 vaccine in ten low-middle-income countries in Asia, Africa and South America: A cross-sectional study

Vaccine hesitancy is considered as one of the greatest challenges to control the ongoing coronavirus disease 2019 (COVID-19) pandemic. A related challenge is the unwillingness of the general public to pay for vaccination. The objective of this study was to determine willingness-to-pay (WTP) for COVID-19 vaccine among individuals from ten low-middle-income countries (LMICs) in Asia, Africa, and South America. Data were collected using an online questionnaire distributed during February - May 2021 in ten LMICs (Bangladesh, Brazil, Chile, Egypt, India, Iran, Nigeria, Pakistan, Sudan, and Tunisia). The major response variable of in this study was WTP for a COVID-19 vaccine. The assessment of COVID-19 vaccine hesitancy was based on items adopted from the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) vaccine hesitancy scale constructs. In this study, 1337 respondents included in the final analysis where the highest number of respondents was from India, while the lowest number was from Egypt. A total of 88.9% (1188/1337) respondents were willing to pay for the COVID-19 vaccination, and 11.1% (149/1337) were not. The average WTP for COVID-19 vaccination was 87.9 US dollars ($), (range:$5-$200). The multivariate model analysis showed that the country, monthly household income, having a history of respiratory disease, the agreement that routine vaccines recommended by health workers are beneficial and having received the flu vaccination within the previous 12 months were strongly associated with the WTP. Based on the country of origin, the highest mean WTP for COVID-19 vaccine was reported in Chile, while the lowest mean WTP for the vaccine was seen among the respondents from Sudan. The availability of free COVID-19 vaccination services appears as a top priority in the LMICs for successful control of the ongoing pandemic. This is particularly important for individuals of a lower socio-economic status. The effects of complacency regarding COVID-19 extends beyond vaccine hesitancy to involve less willingness to pay for COVID-19 vaccine and a lower value of WTP for the vaccine

Willingness-to-pay for COVID-19 vaccine in ten low-middle-income countries in Asia, Africa and South America: A cross-sectional study

Vaccine hesitancy is considered as one of the greatest challenges to control the ongoing coronavirus disease 2019 (COVID-19) pandemic. A related challenge is the unwillingness of the general public to pay for vaccination. The objective of this study was to determine willingness-to-pay (WTP) for COVID-19 vaccine among individuals from ten low-middle-income countries (LMICs) in Asia, Africa, and South America. Data were collected using an online questionnaire distributed during February - May 2021 in ten LMICs (Bangladesh, Brazil, Chile, Egypt, India, Iran, Nigeria, Pakistan, Sudan, and Tunisia). The major response variable of in this study was WTP for a COVID-19 vaccine. The assessment of COVID-19 vaccine hesitancy was based on items adopted from the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) vaccine hesitancy scale constructs. In this study, 1337 respondents included in the final analysis where the highest number of respondents was from India, while the lowest number was from Egypt. A total of 88.9% (1188/1337) respondents were willing to pay for the COVID-19 vaccination, and 11.1% (149/1337) were not. The average WTP for COVID-19 vaccination was 87.9 US dollars ($), (range:$5-$200). The multivariate model analysis showed that the country, monthly household income, having a history of respiratory disease, the agreement that routine vaccines recommended by health workers are beneficial and having received the flu vaccination within the previous 12 months were strongly associated with the WTP. Based on the country of origin, the highest mean WTP for COVID-19 vaccine was reported in Chile, while the lowest mean WTP for the vaccine was seen among the respondents from Sudan. The availability of free COVID-19 vaccination services appears as a top priority in the LMICs for successful control of the ongoing pandemic. This is particularly important for individuals of a lower socio-economic status. The effects of complacency regarding COVID-19 extends beyond vaccine hesitancy to involve less willingness to pay for COVID-19 vaccine and a lower value of WTP for the vaccine