Higher anxiety and perceived trauma among COVID-19 patients: a prospective comparative study

The respiratory system is the primary site of infection by the COVID-19 virus. However, many studies have shown that CNS(central nervous system) involvement is a common feature in affected cases of COVID infection. Coronavirus attacks CNS and causes a variety of neuropsychiatric manifestations. This virus in its nature is neurotropic, neuro-invasive, and neurovirulent and it can enter CNS through hematogenous or direct neuron pathways [1]. The olfactory bulb is the most predisposed site of CNS infection as it has a common axonal connection to the nasopharynx and nasal cribriform plate, so the orbitofrontal cortex is affected and because of the constitutional inflammation, the blood barrier’s function will be damaged [1]. physiological factors such as interleukin-1β and medical conditions have been reported to cause neuropsychiatric problems as well [2]. Studies have shown that more than one-third of infected people in the acute phase developed neurologic symptoms and 34% of them showed brain abnormalities such as microhemorrhages, hypodensities, hyperintensities, and infarcts [2].

Remembering the experiences of previous coronavirus pandemics rings the warning bell for the need to pay attention to neuropsychiatric disorders. From 2002-to 2003, the SARS outbreak variety of mental problems including OCD, post-traumatic stress disorder (PTSD), depression, anxiety, somatization, and hostility were reported to increase among other disorders [3, 4]. However, there are no clear and reliable statistics about the influence of Covid-19 and its preventive or curative measures on the general population, but what emerged from reviews describe psychological distresses, sleep disturbances, and affected well-being to a great extent. Goerge Salanti et al. also claim that depression and anxiety are two main domains of mental disorders during the Covid-19 pandemic, have a linear association with the number of SARS CoV-2 infection rates and the stringency of Quarantine, with no regard to age, gender, and country. They also emphasized that the response to the psychological stress generated by the pandemic varied across different populations as they experienced different severity following controlling measures. [5].

Health care protocols such as lockdown, isolation, and emotional distresses have posed a great concern to the mental health of different populations. Therefore, it is understandable that PTSD or traumatic-related stress may occur during the pandemic as we have seen the same circumstances in other disasters [3, 6, 7]. Previous medical conditions predispose patients to experience a more severe form of the disease and in some cases even predict intensive care unit admission so the risks of mental disorders grow to higher levels [8]. Somatic illnesses can increase depression, especially in predisposed subjects; and the severity of this disorder is associated with the severity of the primary disease. In this way, diseases like cancer, coronary syndromes, and stroke, tend to cause a more severe form of depression. This may result in a lower quality of life, social dysfunction, and higher levels of mortality. Appropriate and timely interventions can be helpful and decrease the severity of the problem [9].

Anxiety as the anticipated sequel of illnesses, can be the result of direct effects of the disease on the body or it can be the mental response to the illness, other explanations are that this disorder is the side effect of treatment or it happened by chance [10]. Anxiety not only affects the patients in their acute phase of the illness but also can cause prolonged sequels as we have seen from our previous study that 34.58% of patients presented with anxiety even 9 months after the recovery [7].

However, it is not yet clear whether psychiatric presentation during COVID-19 is a consequence of experiencing a potentially life-threatening disease or the result of the neuro-invasion nature of COVID-19 [11], or what the general population experience due to isolation and all the trauma that happened during COVID-19 pandemic [12].Therefore, in this study, we aimed to compare depression, anxiety, perceived trauma, and obsession in three groups of COVID-19 patients, healthy control, and patients with orthopedic complications. We tried to eliminate the trace of hospitalization on the outcome by having a control group with lower connections to distracting factors on normal brain functions, so we chose orthopedic patients as they have minimal obvious neurological impairments affecting the brain and its functions with a mass burden itself [13].

This study compared the severity of mental health conditions such as depression, anxiety, perceived trauma, and obsession among three groups of COVID-19, orthopedic patients and healthy subjects during the 4^th and 5^th coronavirus peaks in Iran to find out whether COVID-19 patients are at higher risk of mental health disorders than other medical conditions and healthy subjects.

COVID-19 patients showed a much higher level of anxiety and perceived stress compared to university staff and orthopedic patients. However, the university staff group reported a higher level of trauma and anxiety respected to orthopedic patients, level of depression and obsession were similar among these three groups. Most of the participants of the orthopedic group were those with lower educational and socio-economic levels as 60% of them were uneducated.University staff (healthy subjects) consisted of younger subjects than the two other groups and the COVID-19 patients’ group had higher co-morbidities than the two other collections. Few studies have reported the effect of educational levels and socio-economic properties on the coping styles with the disease as Lee et al. expressed that depression has an inverse relation to the literacy rate [19]. E. Gonzalo pointed at celibacy and unemployment as the risk factors for higher mental health morbidity besides the female gender and younger ages [20]. However, in our study gender and age did not have any effect on the outcome. informational bias could influence the outcome of the university staff group as some of them were in very close connection with healthcare workers and may have direct access to uncensored news and data about the burden of the disease.

A higher level of anxiety in COVID-19 patients compared to the other two groups, can explain that COVID-19’s anxiety is more than a mere disease's anxiety, and it may suggest involving a neuro-invasion pattern of the virus as previous studies such as one described by Mazza et al., have outlined that according to clinical, laboratory data from cell culture, invitro and those from animal studies, the virus can cause neuroinflammation via direct invasion to CNS or through cytokine storm mechanisms. These findings, besides the concerns of disease confrontations, uncertainty about the future, and traumatic memories from a severe experiment of the illness, can cause disorders ranging from simple mood disorders to anxiety and even psychosis in susceptible subjects. Cytokine disturbances like dysregulation of IL-6, IL-1, IFN-ϒ, and TNF-α have been reported to be influencing these conditions [21].

However higher level of perceived trauma can also explain that COVID-19 is a traumatic disease with an unknown outcome that could impact mental health gravely. Consistent with previous studies, perceived trauma was observed highly in the infected group and most of them showed avoidance presentation. Buthaina Al Falasi et al. did a study on Italian citizens by using Startle physiological arousal and anger numbness and they showed 43.8% of PTSD symptoms (compared to ours, 7.14%). They also endorsed that their estimation of the prevalence of PTSD was higher than an actual percentage as they used a screening tool instead of the diagnostic one. They pointed to female sex and younger ages as the risk factors for developing PTSD [3]. Buthaina Al Falasi in another study mentioned quarantine and suffering a family member or close friend from COVID-19 infection as another precipitating factor in developing PTSD at younger ages [22]. Zhang L and Cénat JM reported a prevalence of 15% to 22% for PTSD after the pandemic [23, 24]. Another study in Italy stated 23.5 percent for the prevalence of PTSD among the general population in the early COVID-19 era [25]. The difference between our findings from other studies could be firstly attributed to the different societies in which the experiments were done, next explanation is that the fear of people from the burden of COVID-19 reduced after 3 to 4 waves of the disease. Mona Salehi et al. reported the prevalence of PTSD as 1.1% for the general population in 2014 in the normal non-pandemic era. They also endorsed the prevalence of definite PTSD as 36%, 18%, and 9% for MERS, SARS, and COVID-19 accordingly. At last, they estimated that near 29% of people who survive from the infection experience levels of PTSD symptoms [26]. In a study close to ours, E. Seyahi et.al in turkey assessed the effect of Covid-19’s burden on patients with rheumatoid diseases versus hospital workers and high school teachers during the first months of the outbreak. They claimed that rheumatoid patients (like school teachers) faced less anxiety, depression and PTSD symptoms compared to hospital workers. In their study, they did not discriminate between COVID and non-COVID subjects as there were 21 subjects with Covid 19 infection distributed in those 3 groups. They emphasized that despite lower levels of psychiatric symptoms in rheumatoid patients against hospital workers, there is a significant concern over the traumatic impact of COVID-19 on those patients as the mean score of IES-R score was higher than expected [27].In another study, F. Ingegnoli et al., stated that Covid-19 with IES-R score of 29.7 was considered responsible for a massive psychosocial burden on rheumatoid patients with a prevalence of 41% PTSD symptoms. They stressed the role of socioeconomic on the subjects and claimed that the higher income is associated with lower levels of stress apprehended after the pandemic [28].

However, depression symptoms were observed similarly between three groups of people, with an overall rate of 21.9%, and most of them experienced mild symptoms. One might say that we assessed patients in the acute phase and it may take time that patients to develop depressive symptoms but stress reaction and anxiety to the disease will develop sooner. We also can correlate this insignificance to the ceiling effect and the nationwide prevalence of depression as the low social support for the whole community has stressed the general population. Another explanation is the low sensitivity of our screening tool to distinguish between acute onset depression and chronic forms of it. A 1-month cohort study done by Mazza et al. demonstrated that COVID-19 patients are at higher risk of developing depressive disorders [21], so the need for a follow-up study is sensed.

Our patients did not show many differences in their obsessional symptoms either, however their range of obsessive symptoms was high. OCD symptoms were observed in 85.7% of all three groups with no superiority for any of them, 80% of COVID-19 patients showed at least one OCD-related symptom with the majority of 67.1 for pollution-related symptoms such as environmental dirt or even body-related discharges. Two other Subgroups of the study showed about the same percentages. Higher rates of symptoms associated with washing are reasonable because such habits are more encouraged by social pressure to limit the transition pathways. Accordingly Adam abba aji et al., did a study to evaluate the prevalence of OCDs in the general population of Canada during the recent outbreak; they conducted an online survey by using a brief obsessive–compulsive scale (BCOS) which showed 60.3% of participants with new presentations of symptoms, 53.8 had compulsion of hand washing. This was beside 25.1 percent of the population with prior symptoms. So, the overall percentage equaled 85.4% which was too similar to our study with 85.7%. The authors declared that the population of their study was more exposed to general anxiety disorders (GAD) and major depressive disorders (MDD) [29]. A review done by Mina Soleimani and her colleague suggests that an increase in cleaning activities and a decrease in physician visits regarding lowering contamination risks puts a higher danger of worsening mental disorders, especially OCD. This article estimates the total definite OCD prevalence as defined by the criteria, is about 2% with variations by ages as young adults experience a higher rate than other group ages. Accordingly GAD and panic attacks were seen more in women with OCD during the corona pandemic. Therefore, fear of contamination, continues and repetitive hand washing, isolation, uncertainty about future, need for doing routine orders of daily tasks that may be not possible during the pandemic, and aggressive thoughts about harming the nearby people could be suggested as the base for incidence of OCD [30].

Our study in line with the literature, confirms that COVID-19 causes mental disturbances such as anxiety and trauma in the infected people compared to the controlled groups, but it is not yet clear whether an organic pathology is underway for the CNS involvement or these processes are because of the fear and burden of the disease or both. Perceived trauma and anxiety symptoms are significantly higher in COVID-19 patients and the symptoms of OCD and depression do not differ between COVID-19 and non-COVID-19 people. Therefore, all COVID-19 patients should be screened for psychological complications and preventive measures such as a positive atmosphere in the corona ward and psychological counseling for vulnerable patients should be implemented. Treatment of psychologic complications in patients with COVID-19 should be kept in mind.