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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide disruption of global health putting healthcare workers at high risk. To reduce the transmission of SARS-CoV-2, in particular during treating the patients, our team aims to develop an optimized isolation chamber. The present study was conducted to evaluate the role of temperature elevation against SARS-CoV-2 viability, where the information would be used to build the isolation chamber. 0.6 mL of the Indonesian isolate of SARS-CoV-2 strain 20201012747 (approximately 10 13 PFU/mL) was incubated for one hour with a variation of temperatures: 25, 30, 35, 40, 45, 50, 55, 60, and 65°C in digital block heater as well as at room temperature (21-23°C) before used to infect Vero E6 cells. The viability was determined using a plaque assay. Our data found a significant reduction of the viral viability from 10 13 PFU/mL to 10 9 PFU/mL after the room temperature was increase to 40°C. Further elevation revealed that 55°C and above resulted in the total elimination of the viral viability. Increasing the temperature 40°C to reduce the SARS-CoV-2 survival could create mild hyperthermia conditions in a patient which could act as a thermotherapy. In addition, according to our findings, thermal sterilization of the vacant isolation chamber could be conducted by increasing the temperature to 55°C. In conclusion, elevating the temperature of the isolation chamber could be one of the main variables for developing an optimized isolation chamber for COVID-19 patients.

Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.

The available antiviral drugs against coronavirus disease 2019 (COVID-19) are limited. Oral drugs that can be prescribed to non-hospitalized patients are required. The 4′-fluoruridine, a nucleoside analog similar to remdesivir, is one of the promising candidates for COVID-19 oral therapy due to its ability to stall viral RdRp. Available data suggested that 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Although 4'-fluorouridine is considered as strong candidates, further studies are required to determine its efficacy in the patients and it’s genetic effects on humans. In this review, we the antiviral activity of 4′-fluorouridine is reviewed and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is compiled and discussed.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide disruption of global health putting healthcare workers at high risk. To reduce the transmission of SARS-CoV-2, in particular during treating the patients, our team aims to develop an optimized isolation chamber. The present study was conducted to evaluate the role of temperature elevation against SARS-CoV-2 viability, where the information would be used to build the isolation chamber. 0.6 mL of the Indonesian isolate of SARS-CoV-2 strain 20201012747 (approximately 1013 PFU/mL) was incubated for one hour with a variation of temperatures: 25, 30, 35, 40, 45, 50, 55, 60, and 65°C in digital block heater as well as at room temperature (21-23°C) before used to infect Vero E6 cells. The viability was determined using a plaque assay. Our data found a significant reduction of the viral viability from 1013 PFU/mL to 109 PFU/mL after the room temperature was increase to 40°C. Further elevation revealed that 55°C and above resulted in the total elimination of the viral viability. Increasing the temperature 40°C to reduce the SARS-CoV-2 survival could create mild hyperthermia conditions in a patient which could act as a thermotherapy. In addition, according to our findings, thermal sterilization of the vacant isolation chamber could be conducted by increasing the temperature to 55°C. In conclusion, elevating the temperature of the isolation chamber could be one of the main variables for developing an optimized isolation chamber for COVID-19 patients.

Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.

Background: The decrease of immunity acquired from COVID-19 vaccines is a potential cause of breakthrough infection. Understanding the dynamics of immune responses of vaccine-induced antibodies post-vaccination is important. This study aimed to measure the level of anti-SARS-CoV-2 receptor-binding domain (RBD) total antibody in individuals at different time points upon the receipt of the second dose of CoronaVac vaccine, as well as evaluate the plausible associated factors. Methods: A cross-sectional study was conducted among CoronaVac-vaccinated residents in Banda Aceh, Indonesia. The level of anti-SARS-CoV-2 RBD total antibody was measured using Elecsys immunoassay. A set of standardized and validated questionnaires were used to assess the demographics and other associated factors. Results: Our results showed waning anti-SARS-CoV-2 RBD total antibody titres over time post-vaccination. Compared to samples of the first month post-vaccination, the antibody titres were significantly lower than those of five-months (mean 184.6 vs. 101.8 U/mL, p = 0.009) and six-months post-vaccination (mean 184.6 vs. 95.59 U/mL, p = 0.001). This suggests that the length of time post-vaccination was negatively correlated with titre of antibody. A protective level of antibody titres (threshold of 15 U/mL) was observed from all the samples vaccinated within one to three months; however, only 73.7% and 78.9% of the sera from five- and six-months possessed the protective titres, respectively. The titre of antibody was found significantly higher in sera of individuals having a regular healthy meal intake compared to those who did not (mean 136.7 vs. 110.4 U/mL, p = 0.044), including in subgroup analysis that included those five to six months post-vaccination only (mean 79.0 vs. 134.5 U/mL, p = 0.009). Conclusions: This study provides insights on the efficacy of CoronaVac vaccine in protecting individuals against SARS-CoV-2 infection over time, which may contribute to future vaccination policy management to improve and prolong protective strategy.

Background: The decrease of immunity acquired from COVID-19 vaccines is a potential cause of breakthrough infection. Understanding the dynamics of immune responses of vaccine-induced antibodies post-vaccination is important. This study aimed to measure the level of anti-SARS-CoV-2 receptor-binding domain (RBD) total antibody in individuals at different time points upon the receipt of the second dose of CoronaVac vaccine, as well as evaluate the plausible associated factors. Methods: A cross-sectional study was conducted among CoronaVac-vaccinated residents in Banda Aceh, Indonesia. The level of anti-SARS-CoV-2 RBD total antibody was measured using Elecsys immunoassay. A set of standardized and validated questionnaires were used to assess the demographics and other associated factors. Results: Our results showed waning anti-SARS-CoV-2 RBD total antibody titres over time post-vaccination. Compared to samples of the first month post-vaccination, the antibody titres were significantly lower than those of five-months (mean 184.6 vs. 101.8 U/mL, p = 0.009) and six-months post-vaccination (mean 184.6 vs. 95.59 U/mL, p = 0.001). This suggests that the length of time post-vaccination was negatively correlated with titre of antibody. A protective level of antibody titres (threshold of 15 U/mL) was observed from all the samples vaccinated within one to three months; however, only 73.7% and 78.9% of the sera from five- and six-months possessed the protective titres, respectively. The titre of antibody was found significantly higher in sera of individuals having a regular healthy meal intake compared to those who did not (mean 136.7 vs. 110.4 U/mL, p = 0.044), including in subgroup analysis that included those five to six months post-vaccination only (mean 79.0 vs. 134.5 U/mL, p = 0.009). Conclusions: This study provides insights on the efficacy of CoronaVac vaccine in protecting individuals against SARS-CoV-2 infection over time, which may contribute to future vaccination policy management to improve and prolong protective strategy.

Background: To date, more than 10% of the global population is unvaccinated against the coronavirus disease 2019 (COVID-19), and the reasons why this population is not vaccinated are not well identified. Objectives: We investigated the prevalence of COVID-19 vaccine refusal and to assess the factors associated with COVID-19 vaccine refusal. Methods: A meta-analysis was conducted during August to November 2022 (PROSPERO: CRD42022384562). We searched articles investigating the refusal of COVID-19 vaccination and its potential associated factors in PubMed, Scopus, and the Web of Sciences. The quality of the articles was assessed using the Newcastle–Ottawa scale, and the data were collected using a pilot form. The cumulative prevalence of the refusal to vaccinate against COVID-19 was identified using a single-arm meta-analysis. The factors associated with COVID-19 vaccine refusals were determined using the Mantel-Haenszel method. Results: A total of 24 articles were included in the analysis. Our findings showed that the global prevalence of COVID-19 vaccine refusal was 12%, and the highest prevalence was in the general population, and the lowest prevalence was in the healthcare worker subgroup. Furthermore, individuals with a high socioeconomic status, history of previous vaccination, and medical background had a lower rate of COVID-19 vaccination refusal. Subsequently, the following factors were associated with an increased risk of COVID-19 vaccine refusal: being female, educational attainment lower than an undergraduate degree, and living in a rural area. Conclusion: Our study identified the prevalence of and factors associated with COVID-19 vaccine refusal. This study may serve as an initial reference to achieve global coverage of COVID-19 vaccination by influencing the population of COVID-19 vaccine refusal.

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.

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.

Background: Cases of myocarditis development have been reported after administration of messenger ribonucleic acid (mRNA)-based coronavirus disease (COVID-19) vaccines. However, the reports vary among the studies, and the types of mRNA vaccines with potential to cause myocarditis remain unidentified. The objective was to assess the cumulative prevalence of myocarditis and determine the association between myocarditis and mRNA-based COVID-19 vaccination. Methods: We performed a network meta-analysis by searching articles in PubMed, Scopus, and Web of Science. Information on the prevalence of myocarditis after the mRNA-based COVID-19 vaccination was collected from each study. Analysis was performed by calculating the pooled prevalence rate, and the association was determined using the Z-test. Data networking was performed using the Bayesian method. Results: A total of 18 papers was included in our analysis. We found that the cumulative prevalence of myocarditis was 1.7, 1.9, 1.2, and 1.1 per 100,000 population after vaccination with different types of mRNA-based COVID-19 vaccines, namely all mRNA COVID-19 vaccines, BNT162b1, mRNA-1273, and the combination of BNT162b1 and mRNA-1273, respectively. Moreover, the results revealed that BNT162b1 vaccination increased the risk of myocarditis by 1.64- and 1.71-folds compared to mRNA-1273 and the combination of BNT162b2 and mRNA-1273, respectively. Similar risks of developing myocarditis were observed after mRNA-1273 and the combination of BNT162b1 and mRNA-1273 vaccination. Conclusions: Our findings suggest the cumulative prevalence of myocarditis after mRNA-based COVID-19 vaccination with maximum prevalence was observed after BNT162b2 administration. BNT162b2 was associated with a higher risk of developing myocarditis than the other mRNA-based COVID-19 vaccines.

Background: Although vaccination is underway, antiviral drugs against coronavirus disease 2019 (COVID-19) are lacking. Remdesivir, a nucleoside analog that works by inhibiting the viral RNA-dependent RNA polymerase (RdRp), is the only fully approved antiviral for the treatment of COVID-19. However, it is limited to intravenous use and is usually recommended only for hospitalized patients with severe COVID-19; therefore, oral drugs that can be prescribed even to non-hospitalized patients are required. According to a recent study, 4′-fluoruridine, a nucleoside analog similar to remdesivir, is a promising candidate for COVID-19 oral therapy due to its ability to stall viral RdRp. Methods: We examined the antiviral activity of 4′-fluorouridine and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been compiled and discussed in this review. Results: The 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vitro studies have shown that SARS-CoV-2 is susceptible to 4'-fluorouridine, with the half-maximal effective concentration (EC 50) of 0.2 to 0.6 M, and that the 4′-fluorouridine derivative, 4′-fluorouridine-5′-triphosphate, inhibited RdRp via a mechanism distinct from that of the already approved COVID-19 oral drug, molnupiravir. In addition, an in vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Conclusions: Concerns about the genetic effects of molnupiravir may be resolved by the use of 4′-fluorouridine and its derivative, which, unlike molnupiravir, do not alter genetics, but inhibit RdRp instead. Although they are currently considered as strong candidates, further studies are required to determine the antiviral activity of 4′-fluorouridine and its derivative against SARS-CoV-2 and their genetic effects on humans.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide disruption of global health putting healthcare workers at high risk. To reduce the transmission of SARS-CoV-2, in particular during treating the patients, our team aims to develop an optimized isolation chamber. The present study was conducted to evaluate the role of temperature elevation against SARS-CoV-2 viability, where the information would be used to build the isolation chamber. 0.6 mL of the Indonesian isolate of SARS-CoV-2 strain 20201012747 (approximately 10 13 PFU/mL) was incubated for one hour with a variation of temperatures: 25, 30, 35, 40, 45, 50, 55, 60, and 65°C in digital block heater as well as at room temperature (21-23°C) before used to infect Vero E6 cells. The viability was determined using a plaque assay. Our data found a significant reduction of the viral viability from 10 13 PFU/mL to 10 9 PFU/mL after the room temperature was increase to 40°C. Further elevation revealed that 55°C and above resulted in the total elimination of the viral viability. Increasing the temperature 40°C to reduce the SARS-CoV-2 survival could create mild hyperthermia conditions in a patient which could act as a thermotherapy. In addition, according to our findings, thermal sterilization of the vacant isolation chamber could be conducted by increasing the temperature to 55°C. In conclusion, elevating the temperature of the isolation chamber could be one of the main variables for developing an optimized isolation chamber for COVID-19 patients.

Background: Query fever (Q fever), caused by Coxiella burnetii, is a highly infectious zoonotic infection to humans and livestock. Despite extensive efforts to develop effective vaccines against this disease, only one vaccine is licensed and available. The aim of this study was to investigate the global research trends, keystone bibliometric parameters, and network visualization mapping in Q fever vaccine from 1941 to 2021. Methods: A retrospective bibliometric followed by a visualized study was conducted. The searches were conducted in the Science Citation Index Expanded (SCI-E) Edition of Web of Science Core Collection (WoSCC). The following keywords were used: 'Q fever' OR 'Query fever' OR 'Coxiella burnetii' OR 'Coxiella-burnetii' OR 'C. burnetii' (Topic) AND 'Vaccin*' OR 'Immuniz*' OR 'Immunis*' (Topic) without any limitation. The data were plotted for co-authorship countries, co-occurrence keywords plus, and bibliographic coupling sources network visualization mapping. The VOSviewer version 1.6.17 was used for network visualization. Results: The bibliographical search resulted in a total of 478 publications which were included in this study. The publications were mainly published in English (n=436), while the major document types were articles (n=391). The most productive year was 2014 (n=33), while the most cited year was 2020 (n=1026). The extensively studied research areas were immunology and veterinary science, and the most used keywords plus were Q-fever and Coxiella-burnetii. Kazar J (n=17) was the leading author, while the famous journal was Acta Virologica (n=23). The most active institution was the Slovak Academy of Sciences (n=32), and the leading country was the US (n=129). Conclusion: A rapid increase has been observed in Q fever vaccine publications and citations in the past 20 years. This study might be of great interest to provide standard bibliographic information and keystones parameters in Q fever vaccine research.

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.

BACKGROUND: The COVID-19 vaccination program, which uses various types of vaccines, has been applied since the beginning of 2021. However, the efficacy in the context of seroconversion rate remains unclear. OBJECTIVE: To assess the seroconversion rates among different COVID-19 vaccines using a network meta-analysis approach. METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted during the study period. Data of interest, such as seroconversion rate and the type of COVID-19 vaccine, were extracted from each study. The analysis was performed using single-arm analysis by calculating the cumulative seroconversion rate. A network meta-analysis was conducted using the Bayesian method. RESULTS: A total of 31 RCTs were included in our analysis. Our pooled calculation revealed that the seroconversion rates of inactivated messenger ribonucleic acid (mRNA), protein subunit, and vector COVID-19 vaccines during the follow-up periods were 93.2%, 93.9%, 65.3%, and 54.7%, respectively, at ≤ 15 days; 96.0%, 94.8%, 91.2%, and 89.7%, respectively, between days 16–30; and 98.5%, 98.6%, 98.5%, and 96.2%, respectively, between days 31–60.The indirect comparison revealed that in the follow-up periods of ≤ 15 and 16–30 days, the inactivated and mRNA COVID-19 vaccines had superior seroconversion rates compared with those of the protein subunit and vector vaccines. In the follow-up period of 31–60 days, the highest seroconversion rates were found in the inactivated, mRNA, and protein subunit COVID-19 vaccines. CONCLUSION: This study provides valuable information regarding the comparison of seroconversion rates of COVID-19 vaccines.

Background: The decrease of immunity acquired from COVID-19 vaccines is a potential cause of breakthrough infection. Understanding the dynamics of immune responses of vaccine-induced antibodies post-vaccination is important. This study aimed to measure the level of neutralizing antibody (NAb) anti-SRBD in individuals at different time points upon the receipt of the second dose of CoronaVac vaccine, as well as evaluate the plausible associated factors. Methods: A cross-sectional study was conducted among CoronaVac-vaccinated residents in Banda Aceh, Indonesia. The level of NAb titre was measured using Elecsys Anti-SARS-CoV-2 S immunoassay. A set of standardized and validated questionnaires were used to assess the demographics and other plausible associated factors. Results: Our results showed waning SARS-Cov-2 NAb titres over time post-vaccination. Compared to samples of the first month post-vaccination, the levels of NAb titres were significantly lower than those of five-months (mean 184.6 vs. 101.8 IU/mL, p = 0.009) and six-months post-vaccination (mean 184.6 vs. 95.59 IU/mL, p = 0.001). This suggests that the length of time post-vaccination was negatively correlated with antibody anti-SRBD titre. A protective level of NAbs titres (threshold of 15 IU/mL) was observed from all the samples vaccinated within one to three months; however, only 73.7% and 78.9% of the sera from five- and six-months possessed the protective titres against SARS-CoV-2, respectively. The titre of NAb anti-SRBD was found significantly higher in sera of individuals having a regular healthy meal intake compared to those who did not (mean 136.7 vs. 110.4 IU/mL, p = 0.044), including in subgroup analysis that included those five to six months post-vaccination only (mean 79.0 vs. 134.5 IU/mL, p = 0.009). Conclusions: This study provides insights on the efficacy of CoronaVac vaccine in protecting individuals against SARS-CoV-2 infection over time, which may contribute to future vaccination policy management to improve and prolong protective strategy.

Introduction: Social distancing and wearing a face mask are highly recommended to mitigate the transmission of coronavirus disease 2019 (COVID-19). However, the success of these strategies relies on individuals’ adherence and public compliance. This study was conducted to assess the level of belief in social distancing and face mask practices in communities in low- and middle-income countries (LMICs) and to identify their possible determinants. Methods: A cross-sectional study was conducted in ten LMICs countries in Asia, Africa, and South America from February to May 2021. A questionnaire was used to assess the belief, practice, and their plausible determinants. Identification of the associated determinants was performed using a logistic regression model. Results: Our data revealed that only 62.6% and 66.9% of the participants had good beliefs in social distancing and good face mask practices, respectively. Residing in the Americas, having a healthcare-related job, knowing people in immediate social environment who are or have been infected and exposure to information of COVID-19 cases on social media or TV were factors significantly associated with good belief in social distancing. Residing country, gender, monthly household income, type of job and exposure to information of COVID-19 cases were significantly associated with face mask wearing practice. Conclusion: The proportion of participants having good beliefs in social distancing and good face mask practices is relatively low (

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.

Background: It is critical to understand the factors that could affect the acceptance of the coronavirus disease 2019 (COVID-19) vaccine in the community. The aim of this study was to determine factors that could possibly affect the acceptance of Indonesian citizens of COVID-19 vaccination using a Technology Acceptance Model (TAM), a model how users come to accept and use a technology. Methods: An online survey was conducted between the first and fifth of November, 2020. Participants were asked to respond to questions on acceptance, perceived usefulness, perceived ease of use, perceived religiosity towards, and amount of information about COVID-19. This study used the Technology Acceptance Model (TAM) as the framework to decide factors that affect vaccine acceptance. Structural Equation Model was employed to assess the correlation between all explanatory variables and vaccine acceptance. Mann-Whitney test and Kruskal-Wallis rank were employed to assess demographic factors associated with acceptance. Results: In total, 311 responses were included for analysis. Our TAM model suggested that high perceived usefulness significantly increased COVID-19 vaccine acceptance and high perceived ease of use significantly increased the perceived usefulness. Perceived religiosity did not substantially affect vaccine acceptance. The amount of information on COVID-19 also did not significantly affect vaccine acceptance. Our data suggested that vaccine acceptance was associated with age, type of occupation, marital status and monthly income to some degree. Conclusion: Since perceived usefulness affects vaccine acceptance, the government should focus on the usefulness of the vaccine when promoting the COVID-19 vaccine to Indonesian citizens. In addition, since perceived ease of use significantly affects users’ acceptance to COVID-19 vaccine, the easier to acquire the vaccine in the community, the higher chance that the citizens are willing to be vaccinated.

Background: The pathogenesis of herniated nucleus pulposus (HNP) is complex and may involve the wide variety of gene polymorphism. However, the reports from the existing studies are inconclusive. The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test. Results: We screened 3,067 unique studies for eligibility and three, two and nine case-control studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Background: The pathogenesis of herniated nucleus pulposus (HNP) is complex and may involve the wide variety of gene polymorphism. However, the reports from the existing studies are inconclusive. The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test. Results: We screened 3,067 unique studies for eligibility and three, two and nine case-control studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.

Background: It is critical to understand the factors that could affect the acceptance of the coronavirus disease 2019 (COVID-19) vaccine in the community. The aim of this study was to determine factors that could possibly affect the acceptance of Indonesian citizens of COVID-19 vaccination. Methods: An online survey was conducted between the first and fifth of November, 2020. Participants were asked to respond to questions on acceptance, perceived usefulness, perceived ease of use, perceived religiosity towards, and amount of information about COVID-19. This study used the Technology Acceptance Model (TAM) as the framework to decide factors that affect vaccine acceptance. Structural Equation Model was employed to assess the correlation between all explanatory variables and vaccine acceptance. Mann-Whitney test and Kruskal-Wallis rank were employed to assess demographic factors associated with acceptance. Results: In total, 311 responses were included for analysis. Our TAM model suggested that high perceived usefulness significantly increased COVID-19 vaccine acceptance and high perceived ease of use significantly increased the perceived usefulness. Perceived religiosity did not substantially affect vaccine acceptance. The amount of information on COVID-19 also did not significantly affect vaccine acceptance. Our data suggested that vaccine acceptance was associated with age, type of occupation, marital status and monthly income to some degree. Conclusion: Since perceived usefulness affects vaccine acceptance, the government should focus on the usefulness of the vaccine when promoting the COVID-19 vaccine to Indonesian citizens. In addition, since perceived ease of use significantly affects users’ acceptance to COVID-19 vaccine, the easier to acquire the vaccine in the community, the higher chance that the citizens are willing to be vaccinated.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified Jadad scale and Newcastle-Ottawa scale for randomized controlled trial (RCT) and non – RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and three RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without CCP had a 1.32 times higher risk of mortality than those treated with CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, could reduce the mortality rate among COVID-19 patients.

Background: The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test and presented as odd ratio (OR) and 95% confidence intervals (95%CI). Results: We screened 3,067 unique studies for eligibility and three, two and nine studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Background: This study aimed to determine the cumulative prevalence of prolonged gastrointestinal (GI) symptoms, including nausea, vomiting, diarrhea, lack of appetite, abdominal pain, and dysgeusia, in survivors of both mild and severe COVID-19 worldwide and to discuss the potential pathogenesis. Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for relevant articles up to January 30, 2021. Data on study characteristics, clinical characteristics during follow-up, the number of patients with prolonged GI symptoms, and total number of COVID-19 survivors were retrieved according to PRISMA guidelines. The quality of eligible studies was assessed using the Newcastle-Ottawa scale. The pooled prevalence of specific prolonged GI symptoms was calculated and the association between COVID-19 severity and the occurrence of prolonged GI symptoms was assessed if appropriate. Results: The global prevalence of prolonged nausea was 3.23% (95% CI: 0.54%–16.53%) among 527 COVID-19 survivors. Vomiting persisted in 93 of 2,238 COVID-19 survivors (3.19%, 95% CI: 1.62%–6.17%) and prolonged diarrhea was found in 34 of 1,073 survivors (4.12%, 95% CI: 1.07%–14.64%). A total of 156 patients among 2,238 COVID-19 survivors (4.41%, 95% CI: 1.91%–9.94%) complained of persistent decreased or loss of appetite. The cumulative prevalence of prolonged abdominal pain was 1.68% (95% CI: 0.84%–3.32%), whereas persistent dysgeusia was identified in 130 cases among 1,887 COVID-19 survivors (7.04%, 95% CI: 5.96%–8.30%). Data was insufficient to assess the relationship between COVID-19 severity and the occurrence of all prolonged GI symptoms. Conclusion: Persistent GI symptoms among COVID-19 survivors after discharge or recovery raises a concern regarding the long-term impact of the COVID-19 infection on the quality of life of the survivors. Despite several potential explanations proposed, studies that aim to follow patients after recovery from COVID-19 and determine the pathogenesis of the prolonged symptoms of COVID-19 survivors are warranted. PROSPERO registration: CRD42021239187.

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2 nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients (other respiratory viral infections), OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. PROSPERO registration: CRD42020210332 (28/09/2020)

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified jadad scale and Newcaste-ottawa scale for randomized controlled trial (RCT) and non – RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and two RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were involved.. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Four bibliographic databases and a preprint database were searched for potentially relevant articles. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 1,937 patients treated with CCP and 3,405 patients without CCP retrieved from 12 studies were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

Background: The present study aimed to determine the global prevalence of anosmia and dysgeusia in coronavirus disease 2019 (COVID-19) patients and to assess their association with severity and mortality of COVID-19. Moreover, this study aimed to discuss the possible pathobiological mechanisms of anosmia and dysgeusia in COVID-19. Methods: Available articles from PubMed, Scopus, Web of Science, and preprint databases (MedRxiv, BioRxiv, and Researchsquare) were searched on November 10th, 2020. Data on the characteristics of the study (anosmia, dysgeusia, and COVID-19) were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Newcastle–Ottawa scale was used to assess research quality. Moreover, the pooled prevalence of anosmia and dysgeusia were calculated, and the association between anosmia and dysgeusia in presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed using the Z test. Results: Out of 32,142 COVID-19 patients from 107 studies, anosmia was reported in 12,038 patients with a prevalence of 38.2% (95% CI: 36.5%, 47.2%); whereas, dysgeusia was reported in 11,337 patients out of 30,901 COVID-19 patients from 101 studies, with prevalence of 36.6% (95% CI: 35.2%, 45.2%), worldwide. Furthermore, the prevalence of anosmia was 10.2-fold higher (OR: 10.21; 95% CI: 6.53, 15.96, p < 0.001) and that of dysgeusia was 8.6-fold higher (OR: 8.61; 95% CI: 5.26, 14.11, p < 0.001) in COVID-19 patients compared to those with other respiratory infections or COVID-19 like illness. To date, no study has assessed the association of anosmia and dysgeusia with severity and mortality of COVID-19. Conclusion: Anosmia and dysgeusia are prevalent in COVID-19 patients compared to those with the other non-COVID-19 respiratory infections. Several possible mechanisms have been hypothesized; however, future studies are warranted to elucidate the definitive mechanisms of anosmia and dysgeusia in COVID-19. Protocol registration: PROSPERO CRD42020223204.

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I 2 =89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I 2 =94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched as of April 5, 2020. The quality of the included papers was appraised using the Newcastle-Ottawa scale (NOS). Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2 nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients with symptoms of other respiratory viral infections, OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. PROSPERO registration: CRD42020210332 (28/09/2020)

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I2=89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I2=94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched and extracted as of April 5, 2020. Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.

Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.

Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.

Background: Using immunohistochemical stains to target specific breast cancer markers has become indispensable for evaluation of small diagnostic tissue specimens, and therefore novel marker cocktails for specific breast cancers are required. This study was conducted to assess the immunoexpression of P63 and SOX2 in triple negative breast cancer (TNBC), and to evaluate the predictive diagnostic value of these markers for specific types of TNBC. Methods: Histological slides and paraffin blocks of TNBC cases were collected from Dr. Hasan Sadikin Hospital, Bandung, Indonesia from 5-years period (2011-2015). Each histological slide was subjected to immunohistochemical staining for P63 (nucleus and cytoplasm) and SOX2 (nucleus), with specific primer antibodies. Immunoexpression of P63 and SOX2 was evaluated using immunoreactivity scoring. Associations between P63 and SOX2 immunoexpression and TNBC types were assessed using Mann Whitney tests. In addition, the predictive diagnostic values of these markers were assessed. Results: Forty TNBC histological slides were included, and 23 (57.5%) were Basal-like type TNBC and 17 (42.5%) were Non basal-like type TNBC. Immunoexpression of P63 nucleus and SOX2 was not different between types of TNBC. However, immunoexpression of P63 in the cytoplasm in Basal-like type TNBC was significantly higher than in Non basal-like type TNBC ( p=0.021). Predictor diagnostic value analysis suggested that immunoexpression of P63 in cytoplasm had 56.5% sensitivity and 70.6% specificity for diagnosing Basal-like type TNBC, with area under curve of 0.64. Conclusions: Immunoexpression of P63 in the cytoplasm has a relatively weak diagnostic value to discriminate Basal-like and Non basal-like types of TNBC.