Prevalence of post-traumatic stress disorder (PTSD) in survivors following the first SARS-CoV epidemic of 2003: A systematic review and meta-analysis

Prevalence of post-traumatic stress disorder (PTSD) in survivors following the first SARS-CoV epidemic of 2003: A systematic review and meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Prevalence of post-traumatic stress disorder (PTSD) in survivors following the first SARS-CoV epidemic of 2003: A systematic review and meta-analysis Frédéric Dutheil, Minh Nam Henry Thai, Georges Brousse, Julien S Baker, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6345541/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Drawing lessons from the past may help us to face long term mental health consequences of pandemic. The systematic review and meta-analysis examine the prevalence of post-traumatic stress disorder (PTSD) in survivors of the first SARS-CoV epidemic in 2003. PubMed, Embase, Science Direct, PsycInfo and Cochrane were searched until March 2025, for articles reporting prevalence or scores of PTSD in survivors following the SARS-CoV-1 epidemic. Random-effects meta-analysis were stratified by time of follow-up. We included 10 studies for the systematic review and 8 for the meta-analysis, i.e. a total of 1769 survivors (39.4 years old, 65% women). Overall prevalence of PTSD was 25% (95CI 19 to 32%). The longest follow-up was 46 months after the epidemic, with a PTSD prevalence of 42% in survivors. Younger patients and female were more at risk of PTSD following a SARS-CoV-1 infection (coefficient − 0.64 per 10-year, 95CI -0.93 to -0.33; and − 0.20 per 10%-male, 95CI -0.24 to -0.08, respectively). Prevalence of PTSD in survivors was high (25%) during the first SARS-CoV-1 epidemic in 2003 and remained high in long-term. Exploring the SARS-CoV-1 epidemic’s effects on mental health may help us to build efficient preventive strategies to face the long-term consequences of the COVID-19 pandemic. Health sciences/Diseases/Infectious diseases/Viral infection Biological sciences/Psychology/Human behaviour Public health mental health occupation infection predictive strategy stress disorders Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Post-traumatic stress disorder (PTSD) is a public health problem ( 1 ). It affects approximately 5–10% of individuals in the general population at some point during their lifetime ( 2 ). It is a serious and often debilitating condition that can occur after exposure to possibly life-threatening traumatic events; symptoms include distressing and intrusive memories and nightmares of the trauma, irritability, hypervigilance, difficulty sleeping, poor concentration and emotional withdrawal ( 1 – 3 ). PTSD is associated with psychiatric comorbidity ( 3 ), increases the risk of suicide ( 4 ), and leads to a considerable economic and social burden ( 5 , 6 ). Infectious disease outbreaks, such as the SARS-CoV-2 pandemic, can be considered as a traumatic event, and may well be followed by a wave of PTSD ( 7 ). Several scores were developed to assess PTSD, such as the Impact Event Scale (IES) ( 8 , 9 ), or its revised version (IES-R) ( 10 ). Studying the prevalence of PTSD following previous similar epidemics may help evaluate the psychological and psychiatric consequences of the SARS-CoV-2 pandemic ( 7 , 11 ). The first SARS-CoV (SARS-CoV-1) epidemic took place in 2003, rapidly spreading in southeast Asia and Canada, and affected 8422 people, with a death rate of 11% (916 deaths) ( 12 ). PTSD has been reported in survivors of the SARS-CoV-1 epidemic, however the consequences of the 2003 epidemic are not consensual ( 13 ). Factors such as age at trauma, gender, education or previous trauma have been linked to PTSD ( 14 ), but no robust conclusions were made after the SARS-CoV-1 outbreak. Although several studies described the issue, we did not find any systematic review and meta-analysis about the prevalence of PTSD in SARS-CoV-1 survivors. Therefore, we aimed to conduct a systematic review of the prevalence of PTSD in SARS-CoV-1 survivors. Secondary objectives were to determine whether the time elapsed since the epidemic and some sociodemographic were risk factors to develop a PTSD Methods Literature search We reviewed all studies assessing PTSD in survivors from the SARS-CoV-1 epidemic in 2003. PubMed, Embase, Cochrane, PsycInfo, and ScienceDirect databases were searched using the following keywords: (“PTSD” OR “post-traumatic stress disorder”) AND (“SARS” OR “SARS-CoV” OR “SARS-CoV-1” NOT “COVID” NOT “SARS-CoV-2”) until March 2025. Studies had to describe our main primary outcome, i.e. to describe the prevalence of PTSD (or reporting data allowing the calculation of the prevalence) in SARS survivors during or following the 2003 epidemic to be included. All articles compatible with our inclusion criteria were included, regardless of years of publication. Our research was limited to articles written in English. Studies had to be primary research. No limitation on regional origin was imposed. Furthermore, reference lists from all publication meeting our inclusion criteria were manually searched to identify any further studies that were not found with the electronic research. We also completed ancestry search on previous reviews to detect other potentially eligible primary studies. Two authors (Minh Nam Henry Thai and Jean-Baptiste Bouillon-Minois) conducted the literature searches, reviewed the abstracts and articles independently, checked suitability for inclusion, and extracted the data. When necessary, disagreements were solved with a third author (Frédéric Dutheil) (Fig. 1 ). Data extraction The primary outcome was the pooled prevalence of PTSD in the SARS-CoV-1 epidemic in 2003 survivors. The data collected included the name of the first author, year of publication, study design, main and secondary outcomes of each study, as well as inclusion and exclusion criteria, demographic (sample size, age, percentage of males, marital status, percentage of patients with chronic disease, percentage of healthcare workers, other), measures and prevalence of PTSD (number of patients suffering from PTSD, tool assessment and related scores, time from the epidemic). Quality of assessment We checked the quality of included articles used two grids: the Newcastle-Ottawa Scale (NOS) ( 15 , 16 ) and the “STrengthening the Reporting of OBservational studies in Epidemiology” (STROBE) ( 17 , 18 ). The NOS scales for cross-sectional studies (7 items) and for cohort studies (8 items) share several items regarding representativeness, ascertainment of the exposure, comparability, and assessment of the outcome. Some items are specific: sample size justification, non-respondents’ rate, and statistical test for cross-sectional studies; and selection of the non-exposed, demonstration that the outcomes were not present at the start of the study, follow-up long enough for the outcome to occur and adequacy of follow-up (details of dropouts) for cohort studies. Each item is scored “Yes” (1 point), “No” (0 point), or “Can’t say” (0 point) (Fig. 2 and Figure S1 ). The STROBE has 22 items (each scored 0 or 1 point), assessing the title, abstract, introduction, methods, results, discussion, and funding sections of articles (Figure S1 ). For both grids (NOS and STROBE), points converted into an overall percentage assessing the quality of each article. Statistical considerations We used Stata software (v16, StataCorp, College Station, US) for the statistical analysis ( 19 – 21 ). For each included study, data were summarized as number (%) for categorical variables and mean ± standard deviation (SD) for continuous variables. When data were sufficient and could be pooled, we conducted random effects meta-analyses using the DerSimonian and Laird approach to assess the prevalence of PTSD in SARS-CoV-1 survivors ( 22 – 24 ). We stratified our results by time from the epidemic: less than one year, one to two years after the end of the epidemic, two to three years after the end of the epidemic, three to four years after the epidemic. We repeated the meta-analysis on scores used to assess PTSD such as on IES and its dimension (IES-total, IES-intrusive, IES-avoidance and IES-hyperarousal). When possible (sufficient sample size), we computed meta-regressions to assess the relation between prevalence (or score) of PTSD, and sociodemographic (such as age, gender, marital status), and health condition before the start of the epidemic (such as chronic disease). Results were expressed as prevalence (%) or scores and 95% confidence intervals (95CI) for meta-analysis, and as regression coefficients and 95CI for meta-regressions. P-values less than 0.05 were considered statistically significant. Finally, results heterogeneity of the meta-analysis was evaluated by examining forest plots, 95CI and I-squared (I 2 ). I 2 is commonly used to assess heterogeneity between studies. I 2 ranges from 0 to 100%: I 2 50% for high heterogeneity. We also assessed publication bias by examining metafunnels of previous meta-analyses and aimed to verify the strength of our results by conducting further meta-analyses after exclusion of studies not evenly distributed around the base of the metafunnels. Results An initial search produced a possible 367 articles (Fig. 1 ). Removal of duplicates and use of the selection criteria reduced the number of articles reporting PTSD in survivors of the SARS-CoV-1 epidemic to 10 articles ( 25 – 34 ) for the systematic review and 8 articles for the meta-analysis – we excluded two studies because there was no prevalence or scores of PTSD ( 29 , 34 ). All included articles were written in English. All studies are described in Table 1 , and we will only refer to the studies included in our meta-analysis below. Table 1 Characteristics of included studies Study Country Design n Age, Sex, PTSD Measurement years % men n Scale Time 70 38.5 ± 12.3 32.9 28 2 months 61 NA NA 25 7 months Hong 2009 Beijing Cohort 57 NA NA 22 IES 10 months 57 NA NA 23 20 months 57 NA NA 24 46 months Kwek 2006 Singapore Cross-sectional 63 34.8 ± 10.5 20.6 26 IES 3 months Lam 2009 Hong-Kong Cross-sectional 181 43.3 ± 13.7 29.6 42 IES-R 41 months Lau 2006 Hong-Kong Cross-sectional 818 n per age group 49.8 129 IES-R 6 months Mak 2009 Hong-Kong Cohort 90 41.1 ± 12.1 37.8 23 SCID, IES-R 30 months Mak 2010 Hong-Kong Cohort 90 41.1 ± 12.1 37.8 23 SCID 30 months Wu 2005a Hong-Kong Cross-sectional 131 41.8 ± 14.0 44 6 IES-R 1 month 44 7 IES-R 3 months Wu 2005b Hong-Kong Cross-sectional 195 41.5 ± 14.0 43 11 IES-R 1 month Quality and study design of included studies All studies were cross-sectional except three cohort studies ( 25 , 30 , 31 ). Using the NOS scales, the overall quality of the included articles was good. The mean score was 80 ± 16% for cross-sectional studies ( 26 – 28 , 32 , 33 ), ranging from 62.5 ( 32 , 33 ) to 100% ( 27 , 28 ). They performed worst for selection bias, more specifically sample size, and representativeness. The three cohort studies ( 25 , 30 , 31 ) had a score of 87.5%, and performed worst for the selection of the non-exposed cohort (Fig. 2 and Figure S1 ). Using the STROBE checklist, the quality was also good, with a mean score of 71.0 ± 6.1%, ranging from 65.6 ( 32 , 33 ) to 81.3% ( 27 ). How missing data was addressed, the absence of flow-chart, and addressing potential bias were poorly reported (Figure S1 ). All studies were conducted in South-East Asia and were published from 2005 to 2010. Aims of included articles All studies shared the main objective of assessing the psychological or psychiatric impact of the SARS-CoV-1 epidemic of 2003 in survivors, except one study in which it was the secondary objective ( 28 ) – the main objective of this study was to investigate how the Hong Kong population perceived the SARS epidemic and would react to a possible resurgence ( 28 ). More specifically, four studies aimed to assess the psychological impact of the SARS-CoV-1 epidemic ( 25 , 26 , 28 , 32 ), three studies assessed the psychiatric morbidity of the 2003 epidemic ( 27 , 30 , 33 ), and one study aimed to identify predictors of chronic PTSD ( 31 ). Inclusion and exclusion criteria of included studies All studies included SARS-CoV-1 survivors, on a voluntary basis. Only four studies had exclusion criteria: age 65 years old or being abroad ( 26 ), neurological or pituitary disease ( 27 ), and severe communication problems or being treated and followed for SARS-CoV-1 in different hospitals ( 30 , 31 ). Population Sample size ranged from 63 ( 26 ) to 818 ( 28 ) survivors, for a total of 1769 survivors. Age was reported in all studies but one ( 28 ); mean age was 39.4 years old (95CI 29.5 to 49.2). Gender was reported in all studies; proportion of men was 35% (25 to 46%), ranging from 16 ( 27 ) to 50% ( 28 ). Marital status was described in four studies ( 27 , 28 , 30 , 31 ). Other parameters were reported in less than three studies, or differently between studies, precluding further analysis: duration of hospitalization ( 26 , 30 , 33 ), education level ( 25 , 27 , 28 , 31 – 33 ), chronic disease ( 26 , 30 – 33 ), percentage of health-care workers ( 26 , 30 – 32 ), and steroids treatment ( 27 , 30 – 32 ). Other parameters were only reported in one study. Assessment of PTSD PTSD was measured by self-reported questionnaires in all studies. Questionnaires were administered on hospital grounds during the follow-up of the SARS-CoV-1 infection in four studies ( 25 , 27 , 30 , 31 ), via postal survey in three studies ( 26 , 32 , 33 ), and via telephone in one study ( 28 ). Patients were also interviewed by clinicians in the four studies on hospital grounds ( 25 , 27 , 30 , 31 ). Seven of the included studies assessed PTSD with the IES scale (15 items) ( 25 , 26 ) or its revised version (IES-R) (22 items) ( 27 , 28 , 30 , 32 , 33 ). The IES assesses two dimensions: intrusion i.e. ideas disturbing the normal thinking, and avoidance i.e. actions to avoid a situation. The IES-R added a third dimension: hyperarousal i.e. trouble concentrating, anger, irritability, and hypervigilance. All items were scored on a 5-point Likert scale ranging from 0 (“not at all”) to 4 (“extremely”). Total score is the sum of all items, thus ranging from 0 to 60 for the IES, and from 0 to 88 for the IES-R; whereas score for each dimension is the average score, thus from 0 to 4. The higher the IES score, the higher the PTSD risk, but cut-off for PTSD is under debate and varied between included studies: total score > 26 ( 26 ), the three dimension > 2 ( 30 , 32 , 33 ), or not reported ( 25 , 27 , 28 , 31 ). Two of the included studies assessed PTSD using the Structured Clinical Interview for DSM-IV (SCID) ( 30 , 31 ). The SCID is a semi-structured and clinician-administered interview coding each symptom reported in the DSM-IV as present, subthreshold, or absent. A diagnosis of PTSD is made following the PTSD diagnostic algorithm. The study that used both the IES-R and the SCID retained the SCID to diagnose PTSD ( 30 ). All studies reported prevalence of SARS-CoV-1 survivors suffering from PTSD (six using the IES/IES-R and two using the SCID), two reported the mean IES scores ( 25 , 26 ), and four reported the mean IES subscale scores ( 26 , 27 , 32 , 33 ). Time from the epidemic Time from the epidemic was reported in all studies: less than one year after the epidemic ( 25 , 26 , 28 , 32 , 33 ), one to two years after the epidemic ( 25 ), two to three years after the epidemic ( 30 , 31 ) and three to four years after the epidemic ( 25 , 27 ). The longest follow-up in included studies was 46 months ( 25 ). Meta-analysis of prevalence of PTSD in survivors The overall prevalence of PTSD was 25% (95CI 19 to 32%) in SARS-CoV-1 survivors, with a high heterogeneity between studies (I²=94%). More specifically, the prevalence was 22% (14 to 29%) less than a year after the epidemic, 40% (28 to 53%) between one and two years after the epidemic, 26% (19 to 32%) between two and three years after the epidemic, and 27% (21 to 32%) between three and four years after the epidemic (Fig. 3 ). Meta-analysis of IES score in survivors All studies that reported a total score at IES used a 0 to 60 scale. IES total score was 39.1 (95CI 26.5 to 51.7). More specifically, IES total was 38.7 (24.2 to 53.1) less than one year after the epidemic, 41.2 (8.66 to 73.7) one to two years after the epidemic, 39.0 (-1.96 to 80.0) three to four years after the epidemic. If the two studies that used IES reported only total score (from 0 to 60), the five studies using the IES-R reported only score by dimensions (from 0 to 4) and not the total score (from 0 to 88). One study summed the score of each item for each dimension ( 26 ); we converted these scores on a 0 to 4 scale to pool data with other studies. IES avoidance score was 1.08 (95CI -0.09 to 2.26) less than one year after the epidemic: 0.93 (-0.42 to 2.28) one month after the epidemic ( 33 ), 1.55 (-0.80 to 3.90) three months after the epidemic ( 26 ). IES intrusive score was 1.09 (0.32 to 1.86), less than one year after the epidemic: 1.11 (-0.30 to 2.52) ( 33 ) and 1.12 (-0.31 to 2.55) ( 32 ) one month after the epidemic, and 0.91 (-0.52 to 2.34) ( 32 ) and 1.36 (-0.83 to 3.54) ( 26 ) three months after the epidemic. IES hyperarousal score was 0.97 (95CI 0.10 to 1.85) less than one year after the epidemic: 1.05 (-0.50 to 2.60) ( 32 ) and 1.04 (-0.53 to 2.61) ( 33 ) one month after the epidemic, 0.85 (-0.60 to 2.30) three months after the epidemic ( 32 ). IES total was not reported between two and three years after the epidemic, and IES avoidance, IES intrusive and IES hyperarousal were never reported more than one year after the epidemic. All I 2 were null (Figure S2 and 3). Meta-regression and sensitivity analyses PTSD following SARS-CoV-1 infection was more frequent in younger (Coefficient − 0.64 per 10 years, 95CI -0.93 to -0.33, p < 0.001), and in female patients (-0.20, -0.24 to – 0.08, p < 0.001). There was no significant effect of marital status (0.02, -0.02 to 0.05, p = 0.133) or chronic disease before the outbreak (-0.03, -0.12 to 0.05, p = 0.284) (Fig. 4 ). There was no significant effect of time, age, gender, marital status, or chronic disease before the epidemic on IES scores (total, intrusive, avoidance, hyperarousal) (Figure S4). Because of lacking data, meta regressions on PTSD in healthcare workers, education level and duration of hospitalization were impossible. The funnel plots for these meta-analyses demonstrated a high heterogeneity, precluding any sensitivity analyses (Fig. 5 and Figure S5). Discussion The main findings were that the prevalence of PTSD after the SARS-CoV-1 epidemic in 2003 among survivors is high, around 25%. Prevalence remained high even more than one year after the end of the epidemic. Younger age and female survivors seem to be more at risk of PTSD. PTSD in survivors: a public health issue We found a 25% prevalence of PTSD in survivors from the SARS-CoV-1 epidemic, which is higher than the prevalence in the general population, usually reported to be around 5 and 10% ( 2 ). This is an issue that needs to be considered, given the ongoing COVID-19 pandemic ( 35 ). The intensity and duration of the current pandemic are much more important than the 2003 epidemic, which may result in a higher rate of PTSD in survivors ( 7 ). Healthcare systems in several countries may be at risk after the Covid-19 pandemic ( 36 , 37 ). PTSD is an underlying mechanism of the development of several psychiatric and medical consequences, such as neurocognitive disorders ( 38 ) and dementia ( 39 ), inflammation ( 40 ) and cardiometabolic diseases ( 41 ). Strokes have been described even in younger patients ( 42 , 43 ). Considering the probably high prevalence of PTSD following the pandemic ( 44 ), management of survivors should not solely focus on treating the infection, but also on prevention, detection and management of psychological sequalae of infectious disease outbreaks. PTSD is treatable, with psychological therapies such as trauma-focused cognitive behavioural therapy or eye movement desensitisation ( 45 ), or pharmacological treatment such as selective serotonin reuptake inhibitors ( 2 ). Mental health professionals should be part of multidisciplinary teams that assess and manage infectious outbreaks ( 7 ). Although several meta-analysis being previously published ( 46 , 47 ), they focused on the Covid pandemic or covered a wide range of psychological disorders without detailing temporal, sociodemographic and other characteristics that could have influenced the onset of PTSD (meta-regression). In their general overview, they also did not analyze scores of PTSD, both in short- nor long term. Long-term PTSD Long-term PTSD has initially been described in traumatism caused by war, terrorism, or environmental catastrophes. For example, 15% of veterans still suffered from PTSD fifty years after the Korean war ( 48 ); 39% of survivors of terrorist attacks still had PTSD two years after the events ( 49 ), 14.1% in residents of restricted access areas in Fukushima eighteen months after the nuclear accident ( 50 ). Our study found a high prevalence of PTSD in SARS-CoV-1 survivors up to four years after the epidemic ( 25 ). These findings complement those in the literature about the long-term psychological impact of infectious diseases. A longitudinal study of survivors of Legionnaires’ disease reported that 15% of patients had PTSD seventeen months after the disease ( 51 ). Another study of survivors of acute respiratory distress syndrome found that 24% still had PTSD during an eight year follow-up ( 52 ). PTSD is reported between 30% ( 53 ) and 35% ( 54 ) of HIV patients six to fourteen months after receiving the diagnosis. PTSD can become a lifelong disorder ( 3 ), as it can remain high up to decades after the initial trauma ( 55 ). A third of patients with PTSD may experience a chronic form that can last for years ( 5 ). The consequences of PTSD are very costly both to healthcare systems and to society ( 56 ). The onset of PTSD can be delayed ( 57 , 58 ), and thus be overlooked in the acute stage of epidemics ( 30 ). Gender and age: risk factors for PTSD Gender and age were the two only factors which had a significant effect on the prevalence of PTSD in our study. Females were more likely to have PTSD, which is consistent with other studies. The prevalence of PTSD is approximately twice that found in men ( 59 – 61 ). This is observed both across nations and cultures ( 62 ). Besides being more prevalent, PTSD in females seems to be more severe, chronic, and have higher comorbidity rates ( 63 – 66 ). Gender and sex both affect trauma and PTSD in different ways, including combinations of genetic predisposition and hormonal influences and fluctuations along with individual gender-roles. Most of these different areas and functions seem to put women at a particular risk of PTSD ( 66 ). In our study, PTSD was more common in younger patients. This is consistent with other findings in literature ( 52 , 67 – 69 ). Younger age could also be a risk factor for PTSD in Covid-19 survivors ( 70 ). Age at trauma is a risk factor for some populations, but not for others ( 14 ). Among factors listed in our meta-analysis, we did not find any significant effect of marital status and chronic disease on prevalence of PTSD. Marital status is not linked with PTSD in some studies ( 67 , 71 ), whereas in others married women are less likely to develop PTSD ( 72 , 73 ). Chronic disease is associated with PTSD in some cases ( 74 ). No conclusive evidence was found to support the co-occurrence of PTSD and COPD, although there was evidence implicating PTSD as an important comorbidity affecting COPD management ( 75 ). Chronic pain and PTSD can be considered as mutually maintaining conditions, ( 76 ), and personality may also be a risk factor for PTSD ( 77 ). Other influencing factors for PTSD Besides aforementioned factors that were analysed in our meta-analysis, other factors have been reported in the literature to influence the prevalence of PTSD. Due to the massive number of Covid-19-related hospitalizations in the current pandemic, healthcare workers, more specifically in emergency care settings, are particularly exposed to the highly stressful work-related situations, therefore are at risk of developing PTSD ( 78 , 79 ). PTSD rates of 10 to 20% have been reported ( 80 – 83 ) for healthcare workers, with an even higher rate (13 to 40%) in Intensive Care Unit staff ( 84 – 86 ). The unprecedented numbers of critically ill patients, with an often-unpredictable course of the disease, high mortality rates and lack of effective treatment, or initial treatment guidelines may increase the risk of developing PTSD for healthcare workers ( 87 , 88 ). It is likely that healthcare workers involved in the diagnosis, care and treatment of SARS-CoV patients are at risk of developing PTSD ( 89 , 90 ). Marital status and pre-existing chronic disease didn’t have a significant effect on PTSD prevalence in our study. Obesity frequently accompanies PTSD ( 91 – 93 ), and is associated with emotional eating among veterans seeking treatment for overweight/obesity ( 94 ). While physical activity may not cure PTSD, it has a positive impact on the severity of its symptoms ( 95 ) and may be a useful adjunct to usual care to improve the health of people with PTSD ( 96 ). Exposure to trauma and PTSD are risk factors for smoking ( 97 ), and there is a two-to five-fold increased risk of PTSD or nicotine dependence given the occurrence of the other ( 98 ). Patients with PTSD smoke more heavily, experience more severe withdrawal symptoms, and have lower quit rates than those without PTSD ( 97 , 99 – 101 ); they may attempt to self-medicate PTSD symptoms (hyperarousal, re-experiencing) ( 98 ) or reduce negative affect ( 102 ) by smoking. Smoking among patients with PTSD contributes to their poorer physical health and greater healthcare costs ( 103 , 104 ). Limitations Our study has some limitations. We conducted our meta-analyses only on published articles, which theoretically exposes our results to publication bias. Meta-analyses inherit the limitations of each study of which they are composed: varying quality of studies and multiple variations in study protocols and evaluation ( 105 ). Both the selection procedure and literature search may have introduced biases, as we only studied articles written in English. The sample size may seem low, but the first epidemic of SARS-CoV-1 took place mostly in South-East Asia and Canada ( 12 ), which renders generalizability of our results impossible. Most included studies were based on self-report questionnaires, which induce declarative bias ( 106 ), with only two using a clinician-administered interviews ( 30 , 31 ). However, self-report questionnaires enable comparisons between studies. It is possible that some survivors were included twice, as several authors published two studies ( 30 – 33 ), which might introduce some bias. Selection bias is likely present, as most survivors were females ( 107 ). Response rate within those studies was heterogeneous, and ranged from 27.5% ( 32 ) to 96.8% ( 30 , 31 ). Data collection and inclusion/exclusion criteria were similar but not identical between studies, which may have affected our results. Most studies were cross-sectional, giving us data only at a precise point in time. The lack of data for long-term prevalence for PTSD suggest implementing longitudinal studies for several years to assess psychological impact on long term. Conclusion The overall prevalence of PTSD was high (25%) in survivors after the 2003 SARS-CoV-1 epidemic and remained high in the following years (27% between three and four years after the epidemic). Females and younger patients seem to be more impacted. Considering the current Covid-19 pandemic and the massive number of subsequent hospitalisations, worldwide, this article may be a warning for long-term psychological and psychiatric aftermath in severe infectious diseases survivors. Declarations Acknowledgments We are very thankful to Ms Nathalie Piñol-Domenech who helped us to retrieve articles through all the databases. Author contributions Frederic Dutheil : Conceptualization, Investigation, Project Administration, Resources, Supervision, Validation, Writing - Original Draft Preparation. Henry Thai : Data Curation, Formal Analysis, Methodology, Software, Visualization, Writing - Original Draft Preparation. Georges Brousse : Data Curation, Investigation, Writing - Review & Editing. Julien Baker : Validation, Writing - Review & Editing. Martial Mermillod : Methodology, Investigation, Writing - Review & Editing. Marek Zak : Methodology, Writing - Review & Editing. Ukadike Chris Ugbolube : Validation, Writing - Review & Editing. Reza Bagheri : Formal analysis, Validation, Software, Writing - Review & Editing. Jean-Baptiste Bouillon-Minois : Data curation, Methodology, Validation, Writing - Review & Editing. Luc Vialatte : Validation, Visualization, Writing - Original Draft Preparation. Data availability statement All relevant data, including the studies, datasets, and any additional supporting information that contributed to the analysis, have been compiled from publicly available sources, previously published studies, and databases. The raw data used and/or analysed in this study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding statements This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Declaration of ethics This meta-analysis is based solely on data from published studies, all of which have followed the appropriate ethical guidelines. 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A comparison of interview and self-report methods for the assessment of borderline personality disorder criteria. Psychol Assess. 2008;20(1):81‑5. Mark DH. Interpreting the term selection bias in medical research. Fam Med. 1997;29(2):132‑6. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Grenoble Alpes, Univ. Savoie Mont Blanc, CNRS, LPNC","correspondingAuthor":false,"prefix":"","firstName":"Martial","middleName":"","lastName":"Mermillod","suffix":""},{"id":452141833,"identity":"0d55a7aa-754b-47bb-a328-0b43264c824f","order_by":5,"name":"Marek Zak","email":"","orcid":"","institution":"Jan Kochanowski University","correspondingAuthor":false,"prefix":"","firstName":"Marek","middleName":"","lastName":"Zak","suffix":""},{"id":452141834,"identity":"a4517d3e-9647-488d-9471-a70a48a39f59","order_by":6,"name":"Ukadike Chris Ugbolube","email":"","orcid":"","institution":"University of the West of Scotland, University of Strathclyde","correspondingAuthor":false,"prefix":"","firstName":"Ukadike","middleName":"Chris","lastName":"Ugbolube","suffix":""},{"id":452141835,"identity":"c7ac0aba-b633-4031-ab2d-9546b04d98bc","order_by":7,"name":"Reza Bagheri","email":"","orcid":"","institution":"University of Isfahan","correspondingAuthor":false,"prefix":"","firstName":"Reza","middleName":"","lastName":"Bagheri","suffix":""},{"id":452141836,"identity":"bc82308d-b0c2-4db4-be9a-68e8a74128a0","order_by":8,"name":"Jean-Baptiste Bouillon-Minois","email":"","orcid":"","institution":"Université Clermont Auvergne, CNRS, CHU Clermont-Ferrand","correspondingAuthor":false,"prefix":"","firstName":"Jean-Baptiste","middleName":"","lastName":"Bouillon-Minois","suffix":""},{"id":452141837,"identity":"f8fcf684-00d8-42ec-b4e3-9635e84742a2","order_by":9,"name":"Luc Vialatte","email":"","orcid":"","institution":"Université Clermont Auvergne, CHU Clermont-Ferrand, Preventive and occupational medicine, AIST La Prevention Active","correspondingAuthor":false,"prefix":"","firstName":"Luc","middleName":"","lastName":"Vialatte","suffix":""}],"badges":[],"createdAt":"2025-03-31 14:08:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6345541/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6345541/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82311703,"identity":"e5d11fff-0969-419e-9979-465be49c6368","added_by":"auto","created_at":"2025-05-09 02:00:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":142377,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/50e11eded5bd1b5defe73e56.png"},{"id":82311702,"identity":"eac29c04-1cd1-4bc1-9a73-83ef13902668","added_by":"auto","created_at":"2025-05-09 02:00:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":102798,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of risk of bias. (SIGN)\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/78a288c4ae366e9cfb17d9f4.png"},{"id":82311704,"identity":"3b17bec8-9498-48d2-b212-1fb31cb12133","added_by":"auto","created_at":"2025-05-09 02:00:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":274901,"visible":true,"origin":"","legend":"\u003cp\u003eMeta-analysis on prevalence of post-traumatic stress disorder following the SARS-Co-V1 epidemic of 2003.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/580ac959a47993eaa0cf90d8.png"},{"id":82310517,"identity":"0366b8e3-29cb-4147-b585-29ae21898239","added_by":"auto","created_at":"2025-05-09 01:52:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":254594,"visible":true,"origin":"","legend":"\u003cp\u003eFactors influencing (meta-regressions) the prevalence of post-traumatic stress disorder following the SARS-Co-V1 epidemic of 2003.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/b77086965c4fcd2b35c515c0.png"},{"id":82311706,"identity":"69b4e16a-5639-41a2-8d0a-88c842fbd2e3","added_by":"auto","created_at":"2025-05-09 02:00:09","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":185802,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot with pseudo-95% confidence limits on prevalence.\u003c/p\u003e","description":"","filename":"Figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/4def6602cca4382a7fc6dc31.png"},{"id":84972230,"identity":"0be0a21a-1fd1-4b5c-89a0-e13498657b1e","added_by":"auto","created_at":"2025-06-19 11:17:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2002147,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/398b3303-a8a8-4e12-bf7b-4fc35d829e6f.pdf"},{"id":82310516,"identity":"4364236c-8ffd-4b4f-800b-20ccd2109d51","added_by":"auto","created_at":"2025-05-09 01:52:09","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2324138,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-6345541/v1/b72fd4aa32b334e3cbf8f8de.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence of post-traumatic stress disorder (PTSD) in survivors following the first SARS-CoV epidemic of 2003: A systematic review and meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePost-traumatic stress disorder (PTSD) is a public health problem (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It affects approximately 5\u0026ndash;10% of individuals in the general population at some point during their lifetime (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It is a serious and often debilitating condition that can occur after exposure to possibly life-threatening traumatic events; symptoms include distressing and intrusive memories and nightmares of the trauma, irritability, hypervigilance, difficulty sleeping, poor concentration and emotional withdrawal (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). PTSD is associated with psychiatric comorbidity (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), increases the risk of suicide (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), and leads to a considerable economic and social burden (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Infectious disease outbreaks, such as the SARS-CoV-2 pandemic, can be considered as a traumatic event, and may well be followed by a wave of PTSD (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Several scores were developed to assess PTSD, such as the Impact Event Scale (IES) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), or its revised version (IES-R) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Studying the prevalence of PTSD following previous similar epidemics may help evaluate the psychological and psychiatric consequences of the SARS-CoV-2 pandemic (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). The first SARS-CoV (SARS-CoV-1) epidemic took place in 2003, rapidly spreading in southeast Asia and Canada, and affected 8422 people, with a death rate of 11% (916 deaths) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). PTSD has been reported in survivors of the SARS-CoV-1 epidemic, however the consequences of the 2003 epidemic are not consensual (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Factors such as age at trauma, gender, education or previous trauma have been linked to PTSD (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), but no robust conclusions were made after the SARS-CoV-1 outbreak. Although several studies described the issue, we did not find any systematic review and meta-analysis about the prevalence of PTSD in SARS-CoV-1 survivors.\u003c/p\u003e \u003cp\u003eTherefore, we aimed to conduct a systematic review of the prevalence of PTSD in SARS-CoV-1 survivors. Secondary objectives were to determine whether the time elapsed since the epidemic and some sociodemographic were risk factors to develop a PTSD\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eLiterature search\u003c/h2\u003e \u003cp\u003eWe reviewed all studies assessing PTSD in survivors from the SARS-CoV-1 epidemic in 2003. PubMed, Embase, Cochrane, PsycInfo, and ScienceDirect databases were searched using the following keywords: (\u0026ldquo;PTSD\u0026rdquo; OR \u0026ldquo;post-traumatic stress disorder\u0026rdquo;) AND (\u0026ldquo;SARS\u0026rdquo; OR \u0026ldquo;SARS-CoV\u0026rdquo; OR \u0026ldquo;SARS-CoV-1\u0026rdquo; NOT \u0026ldquo;COVID\u0026rdquo; NOT \u0026ldquo;SARS-CoV-2\u0026rdquo;) until March 2025. Studies had to describe our main primary outcome, i.e. to describe the prevalence of PTSD (or reporting data allowing the calculation of the prevalence) in SARS survivors during or following the 2003 epidemic to be included. All articles compatible with our inclusion criteria were included, regardless of years of publication. Our research was limited to articles written in English. Studies had to be primary research. No limitation on regional origin was imposed. Furthermore, reference lists from all publication meeting our inclusion criteria were manually searched to identify any further studies that were not found with the electronic research. We also completed ancestry search on previous reviews to detect other potentially eligible primary studies. Two authors (Minh Nam Henry Thai and Jean-Baptiste Bouillon-Minois) conducted the literature searches, reviewed the abstracts and articles independently, checked suitability for inclusion, and extracted the data. When necessary, disagreements were solved with a third author (Fr\u0026eacute;d\u0026eacute;ric Dutheil) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the pooled prevalence of PTSD in the SARS-CoV-1 epidemic in 2003 survivors. The data collected included the name of the first author, year of publication, study design, main and secondary outcomes of each study, as well as inclusion and exclusion criteria, demographic (sample size, age, percentage of males, marital status, percentage of patients with chronic disease, percentage of healthcare workers, other), measures and prevalence of PTSD (number of patients suffering from PTSD, tool assessment and related scores, time from the epidemic).\u003c/p\u003e\n\u003ch3\u003eQuality of assessment\u003c/h3\u003e\n\u003cp\u003eWe checked the quality of included articles used two grids: the Newcastle-Ottawa Scale (NOS) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) and the \u0026ldquo;STrengthening the Reporting of OBservational studies in Epidemiology\u0026rdquo; (STROBE) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The NOS scales for cross-sectional studies (7 items) and for cohort studies (8 items) share several items regarding representativeness, ascertainment of the exposure, comparability, and assessment of the outcome. Some items are specific: sample size justification, non-respondents\u0026rsquo; rate, and statistical test for cross-sectional studies; and selection of the non-exposed, demonstration that the outcomes were not present at the start of the study, follow-up long enough for the outcome to occur and adequacy of follow-up (details of dropouts) for cohort studies. Each item is scored \u0026ldquo;Yes\u0026rdquo; (1 point), \u0026ldquo;No\u0026rdquo; (0 point), or \u0026ldquo;Can\u0026rsquo;t say\u0026rdquo; (0 point) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The STROBE has 22 items (each scored 0 or 1 point), assessing the title, abstract, introduction, methods, results, discussion, and funding sections of articles (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). For both grids (NOS and STROBE), points converted into an overall percentage assessing the quality of each article.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eStatistical considerations\u003c/h3\u003e\n\u003cp\u003eWe used Stata software (v16, StataCorp, College Station, US) for the statistical analysis (\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). For each included study, data were summarized as number (%) for categorical variables and mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for continuous variables. When data were sufficient and could be pooled, we conducted random effects meta-analyses using the DerSimonian and Laird approach to assess the prevalence of PTSD in SARS-CoV-1 survivors (\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). We stratified our results by time from the epidemic: less than one year, one to two years after the end of the epidemic, two to three years after the end of the epidemic, three to four years after the epidemic. We repeated the meta-analysis on scores used to assess PTSD such as on IES and its dimension (IES-total, IES-intrusive, IES-avoidance and IES-hyperarousal). When possible (sufficient sample size), we computed meta-regressions to assess the relation between prevalence (or score) of PTSD, and sociodemographic (such as age, gender, marital status), and health condition before the start of the epidemic (such as chronic disease). Results were expressed as prevalence (%) or scores and 95% confidence intervals (95CI) for meta-analysis, and as regression coefficients and 95CI for meta-regressions. P-values less than 0.05 were considered statistically significant. Finally, results heterogeneity of the meta-analysis was evaluated by examining forest plots, 95CI and I-squared (I\u003csup\u003e2\u003c/sup\u003e). I\u003csup\u003e2\u003c/sup\u003e is commonly used to assess heterogeneity between studies. I\u003csup\u003e2\u003c/sup\u003e ranges from 0 to 100%: I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u003cem\u003e\u0026lt;\u003c/em\u003e\u0026thinsp;25% for low heterogeneity, between 25 and 50% for modest heterogeneity and \u0026gt;\u0026thinsp;50% for high heterogeneity. We also assessed publication bias by examining metafunnels of previous meta-analyses and aimed to verify the strength of our results by conducting further meta-analyses after exclusion of studies not evenly distributed around the base of the metafunnels.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAn initial search produced a possible 367 articles (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Removal of duplicates and use of the selection criteria reduced the number of articles reporting PTSD in survivors of the SARS-CoV-1 epidemic to 10 articles (\u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) for the systematic review and 8 articles for the meta-analysis \u0026ndash; we excluded two studies because there was no prevalence or scores of PTSD (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). All included articles were written in English. All studies are described in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and we will only refer to the studies included in our meta-analysis below.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDesign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAge,\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSex,\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003ePTSD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eMeasurement\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eyears\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e% men\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cb\u003eScale\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cb\u003eTime\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e7 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHong 2009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBeijing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e10 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e20 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e46 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKwek 2006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingapore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLam 2009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHong-Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.3\u0026thinsp;\u0026plusmn;\u0026thinsp;13.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e41 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLau 2006\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHong-Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e818\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003en per age group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e49.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e129\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMak 2009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHong-Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSCID, IES-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e30 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMak 2010\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHong-Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSCID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e30 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eWu 2005a\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHong-Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e41.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 month\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3 months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWu 2005b\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHong-Kong\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCross-sectional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eIES-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1 month\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eQuality and study design of included studies\u003c/h2\u003e \u003cp\u003eAll studies were cross-sectional except three cohort studies (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Using the NOS scales, the overall quality of the included articles was good. The mean score was 80\u0026thinsp;\u0026plusmn;\u0026thinsp;16% for cross-sectional studies (\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), ranging from 62.5 (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) to 100% (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). They performed worst for selection bias, more specifically sample size, and representativeness. The three cohort studies (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) had a score of 87.5%, and performed worst for the selection of the non-exposed cohort (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Using the STROBE checklist, the quality was also good, with a mean score of 71.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1%, ranging from 65.6 (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) to 81.3% (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). How missing data was addressed, the absence of flow-chart, and addressing potential bias were poorly reported (Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). All studies were conducted in South-East Asia and were published from 2005 to 2010.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAims of included articles\u003c/h3\u003e\n\u003cp\u003eAll studies shared the main objective of assessing the psychological or psychiatric impact of the SARS-CoV-1 epidemic of 2003 in survivors, except one study in which it was the secondary objective (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) \u0026ndash; the main objective of this study was to investigate how the Hong Kong population perceived the SARS epidemic and would react to a possible resurgence (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). More specifically, four studies aimed to assess the psychological impact of the SARS-CoV-1 epidemic (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), three studies assessed the psychiatric morbidity of the 2003 epidemic (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), and one study aimed to identify predictors of chronic PTSD (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eInclusion and exclusion criteria of included studies\u003c/h3\u003e\n\u003cp\u003eAll studies included SARS-CoV-1 survivors, on a voluntary basis. Only four studies had exclusion criteria: age\u0026thinsp;\u0026lt;\u0026thinsp;18 or \u0026gt;\u0026thinsp;65 years old or being abroad (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), neurological or pituitary disease (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), and severe communication problems or being treated and followed for SARS-CoV-1 in different hospitals (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePopulation\u003c/h2\u003e \u003cp\u003eSample size ranged from 63 (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) to 818 (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) survivors, for a total of 1769 survivors. Age was reported in all studies but one (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e); mean age was 39.4 years old (95CI 29.5 to 49.2). Gender was reported in all studies; proportion of men was 35% (25 to 46%), ranging from 16 (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) to 50% (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Marital status was described in four studies (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Other parameters were reported in less than three studies, or differently between studies, precluding further analysis: duration of hospitalization (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), education level (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), chronic disease (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), percentage of health-care workers (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e), and steroids treatment (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Other parameters were only reported in one study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of PTSD\u003c/h2\u003e \u003cp\u003ePTSD was measured by self-reported questionnaires in all studies. Questionnaires were administered on hospital grounds during the follow-up of the SARS-CoV-1 infection in four studies (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), via postal survey in three studies (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), and via telephone in one study (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Patients were also interviewed by clinicians in the four studies on hospital grounds (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeven of the included studies assessed PTSD with the \u003cb\u003eIES\u003c/b\u003e scale (15 items) (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) or its revised version (IES-R) (22 items) (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). The IES assesses two dimensions: \u003cem\u003eintrusion\u003c/em\u003e i.e. ideas disturbing the normal thinking, and \u003cem\u003eavoidance\u003c/em\u003e i.e. actions to avoid a situation. The IES-R added a third dimension: \u003cem\u003ehyperarousal\u003c/em\u003e i.e. trouble concentrating, anger, irritability, and hypervigilance. All items were scored on a 5-point Likert scale ranging from 0 (\u0026ldquo;not at all\u0026rdquo;) to 4 (\u0026ldquo;extremely\u0026rdquo;). Total score is the sum of all items, thus ranging from 0 to 60 for the IES, and from 0 to 88 for the IES-R; whereas score for each dimension is the average score, thus from 0 to 4. The higher the IES score, the higher the PTSD risk, but cut-off for PTSD is under debate and varied between included studies: total score\u0026thinsp;\u0026gt;\u0026thinsp;26 (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), the three dimension\u0026thinsp;\u0026gt;\u0026thinsp;2 (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), or not reported (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTwo of the included studies assessed PTSD using the \u003cb\u003eStructured Clinical Interview for DSM-IV\u003c/b\u003e (SCID) (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). The SCID is a semi-structured and clinician-administered interview coding each symptom reported in the DSM-IV as present, subthreshold, or absent. A diagnosis of PTSD is made following the PTSD diagnostic algorithm. The study that used both the IES-R and the SCID retained the SCID to diagnose PTSD (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAll studies reported prevalence of SARS-CoV-1 survivors suffering from PTSD (six using the IES/IES-R and two using the SCID), two reported the mean IES scores (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), and four reported the mean IES subscale scores (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTime from the epidemic\u003c/h2\u003e \u003cp\u003eTime from the epidemic was reported in all studies: less than one year after the epidemic (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), one to two years after the epidemic (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), two to three years after the epidemic (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) and three to four years after the epidemic (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). The longest follow-up in included studies was 46 months (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMeta-analysis of prevalence of PTSD in survivors\u003c/h2\u003e \u003cp\u003eThe overall prevalence of PTSD was 25% (95CI 19 to 32%) in SARS-CoV-1 survivors, with a high heterogeneity between studies (I\u0026sup2;=94%). More specifically, the prevalence was 22% (14 to 29%) less than a year after the epidemic, 40% (28 to 53%) between one and two years after the epidemic, 26% (19 to 32%) between two and three years after the epidemic, and 27% (21 to 32%) between three and four years after the epidemic (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eMeta-analysis of IES score in survivors\u003c/h2\u003e \u003cp\u003eAll studies that reported a total score at IES used a 0 to 60 scale. \u003cb\u003eIES total\u003c/b\u003e score was 39.1 (95CI 26.5 to 51.7). More specifically, IES total was 38.7 (24.2 to 53.1) less than one year after the epidemic, 41.2 (8.66 to 73.7) one to two years after the epidemic, 39.0 (-1.96 to 80.0) three to four years after the epidemic. If the two studies that used IES reported only total score (from 0 to 60), the five studies using the IES-R reported only score by dimensions (from 0 to 4) and not the total score (from 0 to 88). One study summed the score of each item for each dimension (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e); we converted these scores on a 0 to 4 scale to pool data with other studies. \u003cb\u003eIES avoidance\u003c/b\u003e score was 1.08 (95CI -0.09 to 2.26) less than one year after the epidemic: 0.93 (-0.42 to 2.28) one month after the epidemic (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), 1.55 (-0.80 to 3.90) three months after the epidemic (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). \u003cb\u003eIES intrusive\u003c/b\u003e score was 1.09 (0.32 to 1.86), less than one year after the epidemic: 1.11 (-0.30 to 2.52) (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) and 1.12 (-0.31 to 2.55) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) one month after the epidemic, and 0.91 (-0.52 to 2.34) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) and 1.36 (-0.83 to 3.54) (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e) three months after the epidemic. \u003cb\u003eIES hyperarousal\u003c/b\u003e score was 0.97 (95CI 0.10 to 1.85) less than one year after the epidemic: 1.05 (-0.50 to 2.60) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) and 1.04 (-0.53 to 2.61) (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) one month after the epidemic, 0.85 (-0.60 to 2.30) three months after the epidemic (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). IES total was not reported between two and three years after the epidemic, and IES avoidance, IES intrusive and IES hyperarousal were never reported more than one year after the epidemic. All I\u003csup\u003e2\u003c/sup\u003e were null (Figure S2 and 3).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eMeta-regression and sensitivity analyses\u003c/h2\u003e \u003cp\u003ePTSD following SARS-CoV-1 infection was more frequent in younger (Coefficient \u0026minus;\u0026thinsp;0.64 per 10 years, 95CI -0.93 to -0.33, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and in female patients (-0.20, -0.24 to \u0026ndash; 0.08, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant effect of marital status (0.02, -0.02 to 0.05, p\u0026thinsp;=\u0026thinsp;0.133) or chronic disease before the outbreak (-0.03, -0.12 to 0.05, p\u0026thinsp;=\u0026thinsp;0.284) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There was no significant effect of time, age, gender, marital status, or chronic disease before the epidemic on IES scores (total, intrusive, avoidance, hyperarousal) (Figure S4). Because of lacking data, meta regressions on PTSD in healthcare workers, education level and duration of hospitalization were impossible. The funnel plots for these meta-analyses demonstrated a high heterogeneity, precluding any sensitivity analyses (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Figure S5).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main findings were that the prevalence of PTSD after the SARS-CoV-1 epidemic in 2003 among survivors is high, around 25%. Prevalence remained high even more than one year after the end of the epidemic. Younger age and female survivors seem to be more at risk of PTSD.\u003c/p\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003ePTSD in survivors: a public health issue\u003c/h2\u003e \u003cp\u003eWe found a 25% prevalence of PTSD in survivors from the SARS-CoV-1 epidemic, which is higher than the prevalence in the general population, usually reported to be around 5 and 10% (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This is an issue that needs to be considered, given the ongoing COVID-19 pandemic (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). The intensity and duration of the current pandemic are much more important than the 2003 epidemic, which may result in a higher rate of PTSD in survivors (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Healthcare systems in several countries may be at risk after the Covid-19 pandemic (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). PTSD is an underlying mechanism of the development of several psychiatric and medical consequences, such as neurocognitive disorders (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) and dementia (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e), inflammation (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e) and cardiometabolic diseases (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Strokes have been described even in younger patients (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). Considering the probably high prevalence of PTSD following the pandemic (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e), management of survivors should not solely focus on treating the infection, but also on prevention, detection and management of psychological sequalae of infectious disease outbreaks. PTSD is treatable, with psychological therapies such as trauma-focused cognitive behavioural therapy or eye movement desensitisation (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e), or pharmacological treatment such as selective serotonin reuptake inhibitors (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Mental health professionals should be part of multidisciplinary teams that assess and manage infectious outbreaks (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Although several meta-analysis being previously published (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e), they focused on the Covid pandemic or covered a wide range of psychological disorders without detailing temporal, sociodemographic and other characteristics that could have influenced the onset of PTSD (meta-regression). In their general overview, they also did not analyze scores of PTSD, both in short- nor long term.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eLong-term PTSD\u003c/h2\u003e \u003cp\u003eLong-term PTSD has initially been described in traumatism caused by war, terrorism, or environmental catastrophes. For example, 15% of veterans still suffered from PTSD fifty years after the Korean war (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e); 39% of survivors of terrorist attacks still had PTSD two years after the events (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e), 14.1% in residents of restricted access areas in Fukushima eighteen months after the nuclear accident (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). Our study found a high prevalence of PTSD in SARS-CoV-1 survivors up to four years after the epidemic (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). These findings complement those in the literature about the long-term psychological impact of infectious diseases. A longitudinal study of survivors of Legionnaires\u0026rsquo; disease reported that 15% of patients had PTSD seventeen months after the disease (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e). Another study of survivors of acute respiratory distress syndrome found that 24% still had PTSD during an eight year follow-up (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e). PTSD is reported between 30% (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e) and 35% (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e) of HIV patients six to fourteen months after receiving the diagnosis. PTSD can become a lifelong disorder (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), as it can remain high up to decades after the initial trauma (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). A third of patients with PTSD may experience a chronic form that can last for years (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The consequences of PTSD are very costly both to healthcare systems and to society (\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e). The onset of PTSD can be delayed (\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e), and thus be overlooked in the acute stage of epidemics (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eGender and age: risk factors for PTSD\u003c/h2\u003e \u003cp\u003eGender and age were the two only factors which had a significant effect on the prevalence of PTSD in our study. Females were more likely to have PTSD, which is consistent with other studies. The prevalence of PTSD is approximately twice that found in men (\u003cspan additionalcitationids=\"CR60\" citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e). This is observed both across nations and cultures (\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e). Besides being more prevalent, PTSD in females seems to be more severe, chronic, and have higher comorbidity rates (\u003cspan additionalcitationids=\"CR64 CR65\" citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e). Gender and sex both affect trauma and PTSD in different ways, including combinations of genetic predisposition and hormonal influences and fluctuations along with individual gender-roles. Most of these different areas and functions seem to put women at a particular risk of PTSD (\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e). In our study, PTSD was more common in younger patients. This is consistent with other findings in literature (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan additionalcitationids=\"CR68\" citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e). Younger age could also be a risk factor for PTSD in Covid-19 survivors (\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e). Age at trauma is a risk factor for some populations, but not for others (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Among factors listed in our meta-analysis, we did not find any significant effect of marital status and chronic disease on prevalence of PTSD. Marital status is not linked with PTSD in some studies (\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e, \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e), whereas in others married women are less likely to develop PTSD (\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e, \u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e). Chronic disease is associated with PTSD in some cases (\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e). No conclusive evidence was found to support the co-occurrence of PTSD and COPD, although there was evidence implicating PTSD as an important comorbidity affecting COPD management (\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e). Chronic pain and PTSD can be considered as mutually maintaining conditions, (\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e), and personality may also be a risk factor for PTSD (\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eOther influencing factors for PTSD\u003c/h2\u003e \u003cp\u003eBesides aforementioned factors that were analysed in our meta-analysis, other factors have been reported in the literature to influence the prevalence of PTSD. Due to the massive number of Covid-19-related hospitalizations in the current pandemic, healthcare workers, more specifically in emergency care settings, are particularly exposed to the highly stressful work-related situations, therefore are at risk of developing PTSD (\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e, \u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e). PTSD rates of 10 to 20% have been reported (\u003cspan additionalcitationids=\"CR81 CR82\" citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR83\" class=\"CitationRef\"\u003e83\u003c/span\u003e) for healthcare workers, with an even higher rate (13 to 40%) in Intensive Care Unit staff (\u003cspan additionalcitationids=\"CR85\" citationid=\"CR84\" class=\"CitationRef\"\u003e84\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR86\" class=\"CitationRef\"\u003e86\u003c/span\u003e). The unprecedented numbers of critically ill patients, with an often-unpredictable course of the disease, high mortality rates and lack of effective treatment, or initial treatment guidelines may increase the risk of developing PTSD for healthcare workers (\u003cspan citationid=\"CR87\" class=\"CitationRef\"\u003e87\u003c/span\u003e, \u003cspan citationid=\"CR88\" class=\"CitationRef\"\u003e88\u003c/span\u003e). It is likely that healthcare workers involved in the diagnosis, care and treatment of SARS-CoV patients are at risk of developing PTSD (\u003cspan citationid=\"CR89\" class=\"CitationRef\"\u003e89\u003c/span\u003e, \u003cspan citationid=\"CR90\" class=\"CitationRef\"\u003e90\u003c/span\u003e). Marital status and pre-existing chronic disease didn\u0026rsquo;t have a significant effect on PTSD prevalence in our study. Obesity frequently accompanies PTSD (\u003cspan additionalcitationids=\"CR92\" citationid=\"CR91\" class=\"CitationRef\"\u003e91\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR93\" class=\"CitationRef\"\u003e93\u003c/span\u003e), and is associated with emotional eating among veterans seeking treatment for overweight/obesity (\u003cspan citationid=\"CR94\" class=\"CitationRef\"\u003e94\u003c/span\u003e). While physical activity may not cure PTSD, it has a positive impact on the severity of its symptoms (\u003cspan citationid=\"CR95\" class=\"CitationRef\"\u003e95\u003c/span\u003e) and may be a useful adjunct to usual care to improve the health of people with PTSD (\u003cspan citationid=\"CR96\" class=\"CitationRef\"\u003e96\u003c/span\u003e). Exposure to trauma and PTSD are risk factors for smoking (\u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e97\u003c/span\u003e), and there is a two-to five-fold increased risk of PTSD or nicotine dependence given the occurrence of the other (\u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e). Patients with PTSD smoke more heavily, experience more severe withdrawal symptoms, and have lower quit rates than those without PTSD (\u003cspan citationid=\"CR97\" class=\"CitationRef\"\u003e97\u003c/span\u003e, \u003cspan additionalcitationids=\"CR100\" citationid=\"CR99\" class=\"CitationRef\"\u003e99\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR101\" class=\"CitationRef\"\u003e101\u003c/span\u003e); they may attempt to self-medicate PTSD symptoms (hyperarousal, re-experiencing) (\u003cspan citationid=\"CR98\" class=\"CitationRef\"\u003e98\u003c/span\u003e) or reduce negative affect (\u003cspan citationid=\"CR102\" class=\"CitationRef\"\u003e102\u003c/span\u003e) by smoking. Smoking among patients with PTSD contributes to their poorer physical health and greater healthcare costs (\u003cspan citationid=\"CR103\" class=\"CitationRef\"\u003e103\u003c/span\u003e, \u003cspan citationid=\"CR104\" class=\"CitationRef\"\u003e104\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur study has some limitations. We conducted our meta-analyses only on published articles, which theoretically exposes our results to publication bias. Meta-analyses inherit the limitations of each study of which they are composed: varying quality of studies and multiple variations in study protocols and evaluation (\u003cspan citationid=\"CR105\" class=\"CitationRef\"\u003e105\u003c/span\u003e). Both the selection procedure and literature search may have introduced biases, as we only studied articles written in English. The sample size may seem low, but the first epidemic of SARS-CoV-1 took place mostly in South-East Asia and Canada (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), which renders generalizability of our results impossible. Most included studies were based on self-report questionnaires, which induce declarative bias (\u003cspan citationid=\"CR106\" class=\"CitationRef\"\u003e106\u003c/span\u003e), with only two using a clinician-administered interviews (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). However, self-report questionnaires enable comparisons between studies. It is possible that some survivors were included twice, as several authors published two studies (\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), which might introduce some bias. Selection bias is likely present, as most survivors were females (\u003cspan citationid=\"CR107\" class=\"CitationRef\"\u003e107\u003c/span\u003e). Response rate within those studies was heterogeneous, and ranged from 27.5% (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) to 96.8% (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Data collection and inclusion/exclusion criteria were similar but not identical between studies, which may have affected our results. Most studies were cross-sectional, giving us data only at a precise point in time. The lack of data for long-term prevalence for PTSD suggest implementing longitudinal studies for several years to assess psychological impact on long term.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe overall prevalence of PTSD was high (25%) in survivors after the 2003 SARS-CoV-1 epidemic and remained high in the following years (27% between three and four years after the epidemic). Females and younger patients seem to be more impacted. Considering the current Covid-19 pandemic and the massive number of subsequent hospitalisations, worldwide, this article may be a warning for long-term psychological and psychiatric aftermath in severe infectious diseases survivors.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u003c/strong\u003eWe are very thankful to Ms Nathalie Pi\u0026ntilde;ol-Domenech who helped us to retrieve articles through all the databases.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFrederic Dutheil\u003c/strong\u003e: Conceptualization, Investigation, Project Administration, Resources, Supervision, Validation, Writing - Original Draft Preparation. \u003cstrong\u003eHenry Thai\u003c/strong\u003e: Data Curation, Formal Analysis, Methodology, Software, Visualization, Writing - Original Draft Preparation. \u003cstrong\u003eGeorges Brousse\u003c/strong\u003e: Data Curation, Investigation, Writing - Review \u0026amp; Editing. \u003cstrong\u003eJulien Baker\u003c/strong\u003e: Validation, Writing - Review \u0026amp; Editing. \u003cstrong\u003eMartial Mermillod\u003c/strong\u003e: Methodology, Investigation, Writing - Review \u0026amp; Editing. \u003cstrong\u003eMarek Zak\u003c/strong\u003e: Methodology, Writing - Review \u0026amp; Editing. \u003cstrong\u003eUkadike Chris Ugbolube\u003c/strong\u003e: Validation, Writing - Review \u0026amp; Editing. \u003cstrong\u003eReza Bagheri\u003c/strong\u003e: Formal analysis, Validation, Software, Writing - Review \u0026amp; Editing. \u003cstrong\u003eJean-Baptiste Bouillon-Minois\u003c/strong\u003e: Data curation, Methodology, Validation, Writing - Review \u0026amp; Editing. \u003cstrong\u003eLuc Vialatte\u003c/strong\u003e: Validation, Visualization, Writing - Original Draft Preparation.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll relevant data, including the studies, datasets, and any additional supporting information that contributed to the analysis, have been compiled from publicly available sources, previously published studies, and databases. The raw data used and/or analysed in this study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eDeclaration of ethics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis meta-analysis is based solely on data from published studies, all of which have followed the appropriate ethical guidelines.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAl Jowf GI, Ahmed ZT, An N, Reijnders RA, Ambrosino E, Rutten BPF, et al. A public health perspective of post-traumatic stress disorder. 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Fam Med. 1997;29(2):132‑6. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Public health, mental health, occupation, infection, predictive strategy, stress disorders","lastPublishedDoi":"10.21203/rs.3.rs-6345541/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6345541/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDrawing lessons from the past may help us to face long term mental health consequences of pandemic. The systematic review and meta-analysis examine the prevalence of post-traumatic stress disorder (PTSD) in survivors of the first SARS-CoV epidemic in 2003. PubMed, Embase, Science Direct, PsycInfo and Cochrane were searched until March 2025, for articles reporting prevalence or scores of PTSD in survivors following the SARS-CoV-1 epidemic. Random-effects meta-analysis were stratified by time of follow-up. We included 10 studies for the systematic review and 8 for the meta-analysis, i.e. a total of 1769 survivors (39.4 years old, 65% women). Overall prevalence of PTSD was 25% (95CI 19 to 32%). The longest follow-up was 46 months after the epidemic, with a PTSD prevalence of 42% in survivors. Younger patients and female were more at risk of PTSD following a SARS-CoV-1 infection (coefficient \u0026minus;\u0026thinsp;0.64 per 10-year, 95CI -0.93 to -0.33; and \u0026minus;\u0026thinsp;0.20 per 10%-male, 95CI -0.24 to -0.08, respectively). Prevalence of PTSD in survivors was high (25%) during the first SARS-CoV-1 epidemic in 2003 and remained high in long-term. Exploring the SARS-CoV-1 epidemic\u0026rsquo;s effects on mental health may help us to build efficient preventive strategies to face the long-term consequences of the COVID-19 pandemic.\u003c/p\u003e","manuscriptTitle":"Prevalence of post-traumatic stress disorder (PTSD) in survivors following the first SARS-CoV epidemic of 2003: A systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 01:52:04","doi":"10.21203/rs.3.rs-6345541/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"90c83bd4-748b-43dc-9af2-db31ff60219d","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48085407,"name":"Health sciences/Diseases/Infectious diseases/Viral infection"},{"id":48085408,"name":"Biological sciences/Psychology/Human behaviour"}],"tags":[],"updatedAt":"2025-06-19T11:08:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 01:52:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6345541","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6345541","identity":"rs-6345541","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}