Impact of long COVID-19 on posttraumatic stress disorder as modified by health literacy: an observational study in Vietnam
Article information
Abstract
Objectives
The prevalence of posttraumatic stress disorder (PTSD) has increased, particularly among individuals who have recovered from coronavirus disease 2019 (COVID-19) infection. Health literacy is considered a “social vaccine” that helps people respond effectively to the pandemic. We aimed to investigate the association between long COVID-19 and PTSD, and to examine the modifying role of health literacy in this association.
Methods
A cross-sectional study was conducted at 18 hospitals and health centers in Vietnam from December 2021 to October 2022. We recruited 4,463 individuals who had recovered from COVID-19 infection for at least 4 weeks. Participants provided information about their sociodemographics, clinical parameters, health-related behaviors, health literacy (using the 12-item short-form health literacy scale), long COVID-19 symptoms and PTSD (Impact Event Scale-Revised score of 33 or higher). Logistic regression models were used to examine associations and interactions.
Results
Out of the study sample, 55.9% had long COVID-19 symptoms, and 49.6% had PTSD. Individuals with long COVID-19 symptoms had a higher likelihood of PTSD (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.63–2.12; p<0.001). Higher health literacy was associated with a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97–0.99; p=0.001). Compared to those without long COVID-19 symptoms and the lowest health literacy score, those with long COVID-19 symptoms and a 1-point health literacy increment had a 3% lower likelihood of PTSD (OR, 0.97; 95% CI, 0.96–0.99; p=0.001).
Conclusion
Health literacy was found to be a protective factor against PTSD and modified the negative impact of long COVID-19 symptoms on PTSD.
Introduction
Traumatic events occur throughout our lives, and most will fade over time [1]. However, in some instances, individuals may experience persistent flashbacks, nightmares, avoidance of trauma-related stimuli, changes in emotion and cognition, and disruptions in daily functioning following a traumatic event. When these symptoms persist for at least 1 month, the individual may be diagnosed with posttraumatic stress disorder (PTSD) [2]. The etiology of PTSD remains elusive, with theories suggesting a combination of biological factors (such as genetics and neurobiology), psychological determinants, and socio-environmental influences as contributing to the development of PTSD [2,3]. PTSD can also lead to a range of other mental health issues, including depression, anxiety, suicidal thoughts or behaviors, substance abuse, and eating disorders [4–6], and physical health problems, such as cardiovascular or metabolic diseases [7–9]. In severe cases, PTSD can last for decades if untreated [10,11].
The coronavirus disease 2019 (COVID-19) pandemic continues to have severe consequences on human life [12,13]. While most patients with COVID-19 recover fully, some individuals experience persistent symptoms after the acute phase of the infection, known as long COVID-19. Long COVID-19 is an umbrella term for symptoms that continue for at least 4 weeks following the initial onset of COVID-19 [14,15] and can last for years [16]. Globally, 43% of individuals who have had COVID-19 report experiencing some degree of long COVID-19 symptoms [17]. Previous studies have reported an increased prevalence of symptoms such as anxiety, depression, cognitive impairment, memory loss, sleep disturbances, and PTSD in those affected by COVID-19 [18,19]. PTSD is prevalent in COVID-19 patients (15.45%), in the general population (17.24%), and even more so in healthcare workers (30.98%) [20]. The prevalence of PTSD is also high in survivors of previous pandemics; for instance, 43% of individuals who survived the Middle East respiratory syndrome exhibited clinical PTSD after 1 year, and 26% of severe acute respiratory syndrome survivors met the full criteria for a PTSD diagnosis after 30 months [21,22].
The COVID-19 pandemic has both direct and indirect effects on PTSD [23] and exacerbates other mental disorders [24]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human cells and causes systemic inflammation, immune dysfunction, invasion, and brain damage, which may contribute to the development of PTSD [25]. Additionally, a variety of measures were implemented during the pandemic to prevent viral spread. Adherence to these measures varied according to factors such as age, educational background, trust in social institutions, and perceptions of social actors [26,27]. These interventions significantly altered daily life and have been associated with deteriorating mental health [28]. Although the pandemic does not conform to existing models or diagnostic criteria for PTSD, it is nonetheless considered a traumatic stressor [24]. Moreover, individuals may be affected by COVID-19 either through susceptibility to infection or the traumatic experience of witnessing the sudden death of a loved one, both of which can lead to significant stress with potential traumatic implications [29]. COVID-19 survivors have more severe PTSD symptoms than healthy people [30]. Furthermore, PTSD has been termed the “second tsunami” of the pandemic due to its chronic symptoms, impairment of social functioning, and increased risk of suicide [31]. In addition, PTSD causes unfavorable COVID-19 outcomes [32]. Therefore, assessing and monitoring PTSD symptoms in COVID-19 patients is crucial for mitigating the severe effects of long COVID-19 and enhancing mental well-being.
Promoting health literacy is a global public health goal in contemporary healthcare [33]. Health literacy is defined as the capacity to access, comprehend, appraise, and apply information pertaining to health and disease [34,35]. The COVID-19 pandemic led to an “infodemic” of misinformation and rumors from unreliable sources, which caused fear and panic in the community [36]. The importance of health literacy has become increasingly recognized and emphasized for both communities and individuals when dealing with emergencies such as the COVID-19 pandemic [37]. Health literacy can enhance people's understanding of COVID-19 symptoms, foster adherence to measures aimed at curbing the virus's spread (including hygiene practices, physical distancing, and behavioral changes), and support the uptake of COVID-19 vaccines [38,39]. Moreover, numerous studies have shown that individuals with adequate health literacy are less likely to suffer from mental health issues during the COVID-19 pandemic, such as depression, anxiety, and sleep disturbances [40–42]. However, research on the impact of health literacy on PTSD, particularly among patients with long COVID-19, remains limited.
We aimed to investigate the association between long COVID-19 and PTSD and examine the modifying role of health literacy on this association in people who had recovered from COVID-19 infection for at least 4 weeks. We hypothesized that health literacy could modify the negative impact of long COVID-19 on PTSD.
Materials and Methods
Study Design and Setting
We conducted a cross-sectional study through an online survey at 18 health centers and hospitals in various regions of Vietnam, spanning from December 2021 to October 2022. Data collection took place at hospitals, field hospitals, and Centers for Disease Control and Prevention (CDC) sites, encompassing 9 health facilities in the north (including 3 settings in Thai Nguyen Province, 1 hospital in Hai Duong Province, 4 settings in Hai Phong City, and 1 hospital in Hanoi City), 3 facilities in the central region (located in Quang Tri Province, Thua Thien Hue Province, and CDC Da Nang), and 6 facilities in the south (in Ho Chi Minh City and Can Tho City).
Investigators at each facility trained research assistants (undergraduate and postgraduate students, nurses, and doctors) on how to administer the survey questionnaires. These research assistants then reached out to patients who had recovered from COVID-19, using the contact lists provided by their respective health facilities, to invite them to participate in the survey. Upon agreeing, participants were sent a survey link that included an online consent form and the questionnaire via SMS. It took participants approximately 30 minutes to complete the survey.
Participants
Out of the 11,626 individuals who had recovered from COVID-19 and were invited from 18 facilities to participate in the study, 5,977 patients agreed and provided their consent. A total of 4,466 eligible patients were aged 18 to 85 years, were able to read and understand Vietnamese, and had recovered from COVID-19 infection for at least 4 weeks. Those with missing data related to health literacy and PTSD measures were excluded from the survey (n=3). Consequently, a final sample of 4,463 eligible participants was analyzed in this study.
Variables
Outcome variable
The impact of event scale-revised (IES-R) was utilized to evaluate symptoms of PTSD following unexpected exposure to traumatic stress over the past 7 days [43]. This questionnaire consists of 22 self-reported items, corresponding to the Diagnostic and Statistical Manual of Mental Disorders–4th Edition (DSM-IV) symptoms of PTSD with 3 subscales: intrusion, avoidance, and hyperarousal. The scale was validated among Vietnamese during the pandemic [44]. Each item was scored from 0 (not at all) to 1 (a little bit), 2 (moderately), 3 (quite a bit), and 4 (extremely). The total IES-R score ranged from 0 to 88, with a higher score representing more severe PTSD symptoms. The IES-R score was also classified into 4 levels, from normal (0–23) to mild or clinical concern PTSD (24–32), a moderately probable diagnosis of PTSD (33–36), and severe PTSD (≥37) [43]. The IES-R demonstrated a strong diagnostic capability for traumatic stress reactions, with an overall diagnostic accuracy of 0.88 at a cut-off score of 33, a sensitivity of 0.9, and a specificity of 0.82 [43]. Therefore, for the purposes of this study, we classified an IES-R score below 33 as indicating no PTSD, and a score of 33 or higher as indicative of PTSD symptoms.
Independent variables
In this study, the independent variables included sociodemographic characteristics (age, sex, marital status, educational attainment, healthcare workers, the ability to pay for medications, social status, family members with COVID-19 infection), clinical parameters (body mass index [BMI], number of COVID-19 infections, long COVID-19 symptoms, comorbidities), health-related behaviors (balanced meals, physical activity), and health literacy. Health literacy was evaluated as a potential effect modifier.
Sociodemographic characteristics and clinical parameters
Participants provided information on their age, sex (male or female), marital status (never married or ever married), level of education (high school or below versus college or above), status as healthcare workers (no or yes), ability to pay for medication (very or fairly difficult vs. fairly or very easy), social status (low, middle, or high), weight (kg), height (m), number of family members infected with COVID-19 (1 person vs. ≥2 people), number of COVID-19 infections (first time or more), and presence of comorbidities (0 vs. 1 or more). We calculated BMI using participants' weight and height (kg/m2). BMI was categorized into 3 groups: underweight (less than 18.5 kg/m2), normal weight (18.5 kg/m2 to less than 23 kg/m2), and overweight (23 kg/m2 or greater).
Health-related behaviors
Health-related behaviors included whether meals were balanced (no vs. yes) and the physical activity of participants. The International Physical Activity Questionnaire–Short Form (IPAQ) is a widely used tool for assessing physical activity in adults [45,46]. We evaluated the participants' physical activity over the previous 7 days across 4 intensity levels: vigorous, moderate, walking, and sitting. We also recorded the number of days and minutes participants engaged in each activity. Metabolic equivalent of task (MET) values, expressed in minutes per week, were utilized to quantify overall physical activity [47]. Craig et al. [45] introduced the formula for the calculation of MET min/wk by multiplying the time spent on vigorous, moderate, walking, and setting activities by 8.0, 4.0, 3.0, and 1.0, respectively. The IPAQ has been validated in Vietnam [48].
Long COVID-19 assessment
According to the guidance from the National Institute for Health and Care Excellence, “long COVID-19” is defined as a condition characterized by signs and symptoms that persist for at least 4 weeks after the onset of a COVID-19 infection, with no other explanation [49]. People were classified as having or not having long COVID-19 symptoms based on whether they had any of the following symptoms: fever, cough, shortness of breath, altered sense of smell/taste, muscle soreness, fatigue/tiredness, sputum, chest pain, headache, sore throat, dizziness, confusion, …, diarrhea, nausea/vomiting [50].
Health literacy
To evaluate participants’ health literacy, we utilized the 12-item Short-Form Health Literacy Questionnaire (HLS-SF12) [51]. This questionnaire has been validated and used in Vietnam [51]. Participants responded to the questions on a 4-point Likert scale from 1 (very difficult) to 2 (fairly difficult), 3 (fairly easy), and 4 (very easy). The health literacy score was standardized to a uniform number from 0 to 50 and presented as an index according to the formula:
Index=(mean−1)×(50/3)
The mean is the average value of the evaluation items, 1 is the lowest mean, 3 is the mean range, and 50 is the maximum selected value. Higher health literacy index scores indicate higher health literacy [52].
Study sample size
The α level was 0.05, the power was 0.95, the estimated prevalence of PTSD in COVID-19 patients is 22.9% [53], and the prevalence of PTSD before the COVID-19 pandemic was 5.6% [54]. With these values, we used G*Power 3.1.9.7 (http://www.gpower.hhu.de/) to calculate the sample size for logistic regression [55]. Therefore, the required sample for analysis was 285 participants. In our study, the sample collected was 4,463 participants which was satisfactory for the statistical models.
Data Analysis
Categoral variables were expressed as frequency and percentage, while continuous variables were presented as mean and standard deviation. The chi-square and Mann-Whitney U tests were conducted to compare categorical and continuous variables. Simple and multiple logistic regression analyses were performed to identify potential factors associated with PTSD in individuals who had contracted COVID-19. For the multiple regression model, we included independent variables that had a p-value of less than 0.2 in the simple regression analysis [56]. We also conducted an interaction analysis to examine the potential modifying effect of health literacy on the relationship between long COVID-19 symptoms and PTSD, after adjusting for sociodemographic factors, other clinical parameters, and health-related behaviors. A p-value of less than 0.05 was considered statistically significant. All statistical analyses were carried out using IBM SPSS ver. 20.0 (IBM Corp.) [57].
Ethics Statement
The study was reviewed and approved by the Institutional Ethical Review Committee of Hanoi School of Public Health in Vietnam (No: 400/2021/YTCC-HD3 and 45/2022/YTCC-HD3). Patients were informed about the study’s purpose and provided consent to complete the survey questionnaire. The survey was conducted anonymously.
Results
Participants’ Characteristics
Among the participants, 2,213 individuals (49.6%) exhibited symptoms of PTSD, as indicated by an IES-R score of 33 or higher. Of the 4,463 participants, 72.5% were aged between 18 and 39 years, 55.7% were female, 72.3% had a college education or higher, 82.5% were from a middle social status, and 28% worked in healthcare. Clinically, 97.6% had experienced their first COVID-19 infection, 55.9% reported at least 1 long COVID-19 symptoms, and 28.1% had at least 1 comorbid disease. The average health literacy score was 31.23±8.54. Comparative analysis revealed that the prevalence of PTSD symptoms varied significantly across several demographics and clinical parameters. These included age, educational attainment, ability to pay for medication, social status, having a family member with a COVID-19 infection, presence of long COVID-19 symptoms, comorbidities, balanced diet, and physical activity (p<0.001 for all), as well as sex (p=0.008). Additionally, there was a significant difference in the mean health literacy scores between participants with PTSD symptoms and those without (p<0.001) (Table 1). However, the prevalence of PTSD did not significantly differ between healthcare workers and non-healthcare workers (p=0.392) (Table 1).
Factors Associated with PTSD
Multiple logistic regression showed that respondents who were middle-aged (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.69–0.97; p=0.019), had a college degree or higher educational attainment (OR, 0.84; 95% CI, 0.72–0.99; p=0.033), had a fairly or very easy ability to pay for medications (OR, 0.77; 95% CI, 0.67–0.88; p<0.001), had high social status (OR, 0.59; 95% CI, 0.41–0.85; p=0.004), had balanced meals (OR, 0.58; 95% CI, 0.5–0.66; p<0.001), and more physical activities (OR, 0.53; 95% CI, 0.47–0.63; p<0.001 for tertile 2 or OR, 0.58; 95% CI, 0.48–0.69; p<0.001 for tertile 3) had significantly lower odds of PTSD than their counterparts (Table 2). Individuals with a higher health literacy score had a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97–0.99; p=0.001). Those with 1 or more long COVID-19 symptoms had a higher likelihood of PTSD (OR, 1.86; 95% CI, 1.63–2.12; p<0.001) than those without long COVID-19. Additionally, having at least 2 family members with COVID-19 infection was associated with a higher likelihood of PTSD (OR, 1.24; 95% CI, 1.06–1.45; p=0.008) (Table 2).
Interaction between Long COVID-19 Symptoms and Health Literacy on PTSD
In comparison to individuals without long COVID-19 symptoms and the lowest health literacy scores, those with long COVID-19 and higher health literacy (1-score increment) had a lower likelihood of PTSD (adjusted OR, 0.973; 95% CI, 0.958–0.988; p=0.001) (Table 3).
Discussion
The principal finding of this study was that health literacy moderated the adverse effects of long COVID-19 symptoms on PTSD. Among the 4,463 participants deemed eligible, 49.6% exhibited symptoms of PTSD, and 55.9% had experienced at least 1 long COVID-19 symptoms. Individuals between the ages of 40 and 59 who had at least a college degree, reported ease in affording medications, had a high social status, consumed balanced meals, participated in regular physical activity, and exhibited higher levels of health literacy were less likely to have PTSD.
In our study, the prevalence of PTSD symptoms among individuals with COVID-19 is 49.6%, a figure significantly higher than the 15.4% reported among frontline healthcare workers in Taiwan [58]. Although frontline healthcare workers are also susceptible to PTSD during the COVID-19 pandemic, Lu et al. included both participants with confirmed COVID-19 cases and those without, and utilized a different instrument for assessing PTSD, namely the IES-6. These differences in study design and methodology likely account for the higher prevalence of PTSD observed in our study.
When compared to young adults, middle-aged individuals were found to have a significantly lower likelihood of experiencing PTSD. In line with previous research, older adults also showed a lower prevalence of PTSD than their younger counterparts [20,59,60]. Notably, it was predominantly middle-aged people who exhibited the lowest PTSD scores [60]. Factors contributing to the increased risk of PTSD among young people included feelings of isolation, fear of death, uncertainty about the future, and concerns regarding the long-term effects of COVID-19 on health [24,61]. Furthermore, middle-aged individuals demonstrated better adherence to COVID-19 preventive guidelines than young adults [62]. Na et al. suggested that older adults possess greater resilience and more effective stress-coping mechanisms [63]. However, older adults tend to experience more severe COVID-19 symptoms, complicated long COVID-19 symptoms, and higher mortality rates, which exacerbate comorbidities related to COVID-19 [64]. The increased burden on physical health among older adults pose a heightened risk for mental health problems. These findings suggest that variations in the study populations may contribute to the observed differences in PTSD risk across age groups.
Individuals with a college degree or higher are less likely to experience PTSD compared to those with only a high school diploma or less. Higher education is linked to stable socioeconomic status, better coping mechanisms, improved problem-solving skills, and a more optimistic outlook, as well as a healthier lifestyle [65,66]. The financial and socio-political uncertainties resulting from the COVID-19 pandemic have been found to exacerbate PTSD symptoms [67]. Moreover, a diet rich in nutrients and regular physical activity contribute to maintaining good mental health and managing mental disorders [68]. We found that individuals who regularly consumed balanced meals and engage in physical activity were at a reduced risk of developing PTSD. When the body is under stress, increased corticosteroids and insulin can stimulate appetite, and a balanced, nutritious diet can help alleviate stress [69]. In contrast, diets high in calories, saturated fat, and sodium are more likely to be associated with negative moods [70]. Furthermore, physical activity has been shown to reduce inflammatory activity [71], lower the risk of cardiovascular disease [72], and enhance mood [73].
Our findings also showed that people who had family members with COVID-19 and those with long COVID-19 symptoms had an increased potential for PTSD. Individuals with family members with COVID-19 in the intensive care unit had a higher prevalence of PTSD symptoms [74]. The presence of COVID-19 within a household increases the risk of infection for other members, which in turn heightens anxiety over contracting the disease and concerns for the health of loved ones. Those who contract COVID-19 often experience stigma and discrimination from their communities, resulting in lower social support and more psychological distress than healthy individuals [75]. The impact of COVID-19 extends beyond the physical and mental health of the individual; it also places long-term burdens on their family members' daily lives [76]. After recovering from COVID-19, some patients face the possibility of reinfection with SARS-CoV-2 or suffer from long COVID-19 symptoms. Those with long COVID-19 symptoms are burdened with worries about the future, fears of reinfection, concerns about their ability to return to work, and in some cases, suicidal thoughts [77]. We found that individuals with long COVID-19 symptoms had a higher likelihood of PTSD.
In our study, patients with comorbidities had a nonsignificantly higher likelihood of PTSD. However, robust evidence indicates that patients who have comorbidities and contract COVID-19 are more likely to develop severe symptoms or complicated sequelae of COVID-19 [78]. The prevalence of mental disorders was found to be high among cancer patients during the COVID-19 pandemic [79], and the COVID-19 pandemic has exerted a negative impact on the mental health of patients with chronic diseases [80]. Furthermore, the healthcare system has focused on the treatment of COVID-19, leading to inadequate treatment, insufficient support, and increased psychological distress for cancer patients [81]. Further research is warranted concerning PTSD and mental health among individuals with cancer or chronic diseases after COVID-19 infection.
This study found that individuals with higher health literacy were less likely to develop PTSD. Studies on the relationship between health literacy and mental problems during COVID-19 have also yielded consistent results. Alatawi et al. [82] reported a negative association between PTSD symptoms and a higher level of health literacy. Higher levels of health literacy could mitigate fear, depression, and anxiety, while concurrently enhancing overall quality of life [83]. Additionally, people with long COVID-19 symptoms who had higher health literacy exhibited a lower likelihood of PTSD. Health literacy is not only essential during the COVID-19 pandemic, but it will also be critical and urgent in post-COVID health crises [84,85]. People with a high level of health literacy will be more aware of their COVID-19 status, better understand COVID-19 symptoms, more accurately identify behaviors to prevent infection, and more readily accept COVID-19 vaccination [39,86]. The COVID-19 pandemic highlights the importance of developing health literacy for personal and community self-protection [84,87]. People with long COVID-19 symptoms who have higher health literacy will apply healthy behaviors and appropriate coping mechanisms to stress and adjust to life.
The study has several limitations. First, it was unable to determine the cause-and-effect relationship between long COVID-19 and PTSD. Second, the data were collected through an online survey using convenience sampling, which, while appropriate for the COVID-19 context in Vietnam, may result in sampling bias. Third, we could not assess the likelihood of PTSD among healthcare and non-healthcare workers due to insufficient information regarding the types of hospitals where healthcare workers were employed during the COVID-19 outbreak. Additionally, participants subjectively evaluated their meals' nutritional balance, which calls for further research to investigate the link between nutrition and PTSD. Fifth, the use of the IES-R for PTSD assessment, without a clinical interview, could lead to an overestimation of PTSD prevalence. Finally, we were unable to evaluate the direct impact of severe COVID-19 infection on PTSD. Despite these limitations, the study's findings indicate that individuals who have recovered from COVID-19 infection for at least 4 weeks may benefit from early interventions if they exhibit PTSD symptoms, potentially alleviating these symptoms and improving their overall quality of life.
Conclusion
Individuals with a higher health literacy score had a lower likelihood of PTSD. Notably, health literacy played a modifying role by reducing the adverse effects of long COVID-19 symptoms on PTSD. Consequently, promoting health literacy in the general population, particularly among those infected with COVID-19, may help alleviate the psychological impact of the COVID-19 pandemic and attenuate its long-term consequences.
HIGHLIGHTS
• A high prevalence of posttraumatic stress disorder (PTSD) was found among people with long coronavirus disease 2019 (COVID-19).
• A higher health literacy score was associated with a lower likelihood of PTSD.
• People with long COVID-19 symptoms and a higher health literacy score were less likely to have PTSD.
Notes
Ethics Approval
The study was approved by the Institutional Ethical Review Committee of Hanoi School of Public Health in Vietnam (No: 400/2021/YTCC-HD3 and 45/2022/YTCC-HD3) and performed in accordance with the principles of the Declaration of Helsinki. Patients were informed about the study’s purpose and provided consent to complete the survey questionnaire. The survey was conducted anonymously.
Conflicts of Interest
The authors have no conflicts of interest to declare.
Funding
This study was supported by Thai Nguyen National Hospital, Military Hospital 103, Can Tho University of Medicine and Pharmacy, and Taipei Medical University (TMU108-AE1-B37).
Availability of Data
The datasets are not publicly available but are available from the corresponding author upon reasonable request.
Authors’ Contributions
Conceptualization: all authors; Data curation: HTV, TTMP, TTPN, TVD; Formal analysis: HTV, TVD; Funding acquisition: TVD; Investigation: all authors; Methodology: all authors; Project administration: TTPN and TVD; Resources: all authors; Software: TTPN, TVD; Supervision: TVD; Validation: all authors; Visualization: TVD; Writing–original draft: HTV, TVD; Writing–review & editing: all authors. All authors read and approved the final manuscript.
Additional Contributions
The authors express their gratitude towards the doctors, nurses, and medical students who assisted in data collection. We also extend our thanks to the board of directors and medical staff in the 18 hospitals and health centers for providing the list of COVID-19 patients and facilitating data collection. The authors acknowledge and appreciate the COVID-19 patients who willingly participated in the survey and provided complete information without any commercial interest. The hospitals and health centers supported us in collecting data, including Thai Nguyen National Hospital, Gang Thep Hospital, Thai Nguyen Tuberculosis, and Lung Disease Hospital (Thai Nguyen Province), Hospital for Tropical Disease (Hai Duong Province), Kien Thuy District Health Center, Viet Tiep Friendship Hospital, Kien An Hospital, Hai Phong University of Medicine and Pharmacy Hospital (Hai Phong City), Military Hospital 103 (Hanoi City), Trieu Phong District Health Center in Quang Tri Province, Thua Thien Hue Centralized Isolation Facility (T2F0, T3F0), CDC Da Nang, (Thu Duc City Health Center, Military Hospital 175 (Ho Chi Minh City), Field Hospital No.1, Field Hospital No.2, Binh Thuy Field Hospital, Tuberculosis and Lung Disease Can Tho Hospital (Can Tho City).