Brain Fog following COVID-19 infection may be due to post-traumatic stress disorder (PTSD)

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A new report suggests that lingering “brain fog” and other neurological symptoms after COVID -19 recovery may be due to post-traumatic stress disorder (PTSD), an effect observed in past human coronavirus outbreaks such as SARS and MERS.

People who have recovered from COVID-19 sometimes experience lingering difficulties in concentration, as well as headaches, anxiety, fatigue or sleep disruptions. Patients may fear that the infection has permanently damaged their brains, but researchers say that’s not necessarily the case.

A paper co-authored by clinical professor and neuropsychologist Andrew Levine, MD, of the David Geffen School of Medicine at UCLA, and graduate student Erin Kaseda, of Rosalind Franklin University of Medicine and Science, in Chicago, explores the historical data on survivors of previous coronaviruses, which caused severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).

The paper was published in The Clinical Neuropsychologist.

“The idea is to raise awareness among neuropsychologists that PTSD is something you might want to consider when evaluating persistent cognitive and emotional difficulties among COVID- 19 survivors,” said Dr. Levine.

“When we see someone for neuropsychological testing, we expect them to be at their best, relatively speaking,” Dr. Levine said.

“If we identify a psychiatric illness during our evaluation, and if we believe that condition’s symptoms are interfering with their ability to perform at their best, we would want that treated first, and then retest them once it’s under control.”

If the symptoms are due, even partially, to a psychiatric condition such as PTSD, treatment will help manage those symptoms, and provide a clearer view of any underlying brain issues.

“Once they have treatment, and hopefully have some remission of their psychiatric symptoms, if the cognitive complaints and the deficits on neuropsychological tests are still there, then that’s more evidence that something else is going on,” Kaseda said.

“It’s going to be important for clinicians across the board to be keeping up with the literature that’s coming out, to make sure they have the most up to date information as these survivors are starting to present for neuropsychological testing.”

Kaseda began pursuing this question based on her experience working with patients with mild traumatic brain injury, such as concussion.

“When these symptoms persist for months or years after the original injury, it’s much more likely to be due to the presence of a psychiatric disorder,” she said.

A review of data from the SARS and MERS outbreaks showed that those survivors had heightened risk for PTSD.

In the case of COVID-19, the symptoms of PTSD may arise in response to the invasive measures needed to treat the patients, including intubation and ventilation, which can be traumatic for fearful patients.

Other times, delirium causes patients with COVID-19 to suffer hallucinations, and the memory of these terrifying sensations continues to plague the recovered patient.

In addition to patients who have been hospitalized, frontline health-care providers can be similarly affected due to the constant stress and fear they face at work. And for some people, the anxiety of living through a pandemic, being isolated from friends, and battling the constant fear of an invisible threat can deliver a similar blow to thinking and memory skills.

While a PTSD diagnosis might not sound like good news, there are many available treatments for the disorder, including psychotherapy and medications.

By comparison, researchers are still working to understand the direct neurological effects of COVID-19. “Treatment options (for COVID) are still quite a way’s out, because it’s still an evolving situation,” Kaseda said.

“We don’t actually know anything yet from survivors of COVID-19,” Kaseda said. “Until we have that data, it’s very hard to say what actual percentage of patients are going to have cognitive complaints because of direct effects of the virus, because of medical intervention, or because of psychiatric concerns.”


IMMUNOSUPPRESSION OF PTSD
PTSD is defined as a stress‐related disorder with subsequent autoimmune disease that may arise after exposure to a serious traumatic event or injury.3

It is suggested that PTSD conforms with a bi‐phasic stress response model: Acute stress may reflect an enhancement of the immune response while chronic stress may reflect a suppression of the immune response with increased susceptibility to infections. Therefore, these correlations pose a complex question regarding the conversion from T‐helper 1 cells (Th1) to T‐helper 2 cells (Th2).

A study showed that chronic stress elicits the simultaneous suppression and enhancement of the immune response via alteration of the cytokine expression pattern.4 In the chronic stress model, CD4+ Th1 subsets release Th1 cytokines that activate the inflammatory cellular immune response.

The response involves IL12 and IFN‐G, which is strongly suppressed by IL10. This action helps to shift the cellular immune response from anti‐inflammatory process of Th1 to Th2 via adrenergic agonists as a result of stress.

Moreover, the immunosuppressive effect is specific to the inflammatory cellular immune system. A shift from Th1 to Th2 cellular is strongly enhanced through the suppression of IL12, which is a major Th1 agonist within humoral immunity. However, the shift occurs proportionately rather than quantitatively.

These effects above are observed over both the short and long term in PTSD. This decreased reaction of the immune system is also observed due to senescence with the chronic down‐regulation of cortisol receptors sites.

The down‐regulation of cortisol receptors may reduce the capacity of lymphocytes to respond to anti‐inflammatory signals and allow other cytokine‐mediated processes to dominate in patients with PTSD.

IMMUNOSUPPRESSION AND SUSCEPTIBILITY TO COVID‐19
Many clinical observations have shown that elderly patients, those with an underlying chronic disease and treated with immunosuppressants, or patients otherwise in an immunosuppressed state could suffer from a decreased immune response and greater susceptibility to life‐threatening virus infections.

Such infections show rapid national and international spread, such as in the case of SARS‐CoV‐2, which is currently posing a global health emergency.5, 6

The results of studies are particularly important for individuals who might be at a higher risk of developing complications that are associated with respiratory virus infections, such as the elderly, for whom the increased susceptibility to pathogens is a serious public health problem. Influenza and pneumonia are the fifth leading cause of mortality in individuals aged 50 or older who might have lower immunity.

Another clue has been showed that pregnancy is an independent risk factor to develop severe virus pneumonia under immune tolerance. The pregnancy bias toward Th2 system dominance which left pregnant woman vulnerable to viral infections might bring a challenge for the prevention of SARS‐CoV‐2 infection.7

In addition, it has been showed that immunosuppression (secondary to disease or treatment) is by far the most identified risk factor to develop severe viral pneumonia by different respiratory virus families.8

Green ML has demonstrated that the profound and prolonged immunosuppression experienced by the patients undergoing hematopoietic cell transplantation and intensive chemotherapy for hematologic malignancy resulted in high rates of viral pneumonia that far surpassed the incidence in the general population.9

What is more, the rates of progression to pneumonia increase even depending on the risk factors of patients relating to the degree of immunosuppression (ie, lymphopenia, early post‐transplant, and use of immunosuppressive agents). SARS‐CoV‐2 causes COVID‐19 around the world accompaing with multiple psychological problems, such as PTSD in particular, in infected and healthy individuals. Subsequently, a vicious circle involving immunosuppression between COVID‐19 and PTSD may be engaged (Figure 1).

image
figure 1 : A vicious circle involving immunosuppression between COVID‐19 and PTSD

POSSIBLE STRATEGIES
During such a stressful period, psychological services and crisis interventions are needed at an early stage in almost all groups to reduce PTSD and in order to alleviate the current acute stress responses of individuals and patients and reduce the incidence of PTSD to prevent immunosuppression, thus breaking the vicious circle.

Evidence‐based medicine is of great importance to conduct population‐based psychiatric surveys on the symptomatology of PTSD.10

Furthermore, neuroimaging can provide a heuristic framework for bridging gaps between thalamocortical neurocircuitry and depressive symptoms in PTSD.11, 12

Then, we can take appropriate psychological crisis intervention efficiently following the experience of China.13

References

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World Health Organization declared the 2019 coronavirus disease (COVID-19) outbreak a pandemic. As to May 11, 2020, 4, 006, 257 confirmed cases of COVID-19 and 278, 892 deaths have been reported to the World Health Organization (WHO), from more than 200 countries and territories [1].

It is still too early to predict how many people will be infected with the virus all over the world as the number of cases and deaths continue to rise. Meanwhile, millions of people are scared and even panic of the possible loss of health, life, and wealth.

Experiencing or witnessing the suffering related to COVID-19 may result in high prevalence of posttraumatic disorder (PTSD), a mental disorder leading to serious distress and disability among survivors, family members, people who provide first aids and care (medical and public health professionals, police officers, etc.), and even among the general public. While control of the epidemic and care of patients with COVID-19 are still the dominant task of the whole world, this commentary calls for attention to early intervention and prevention of PTSD among affected populations.

PTSD is a common pathological outcome of a wide variety of traumatic events, from wars and disasters to individual events such as road traffic or work accidents [2].

Patients with PTSD live under the shadow of past trauma. Core symptoms of PTSD, as defined by the Diagnostic and Statistics of Mental Disorders, the fifth edition (DSM-5) [3] of the America Psychiatric Association, include persistent intrusion symptoms, persistent avoidance of stimuli, negative alterations in cognition or mood, and marked alterations in arousal and reactivity, all associated with the experienced traumatic event.

PTSD results in clinically significant distress or impairment in social, occupational, or other important areas of functioning. Epidemiological data indicate that the median time for PTSD to remit is 36 months for individuals who sought help for any mental health problem (not necessarily for PTSD) and about 64 months for individuals who never sought help for a mental health problem.

Approximately one-third of those who diagnosed with PTSD had a chronic course [4].

Infectious disease epidemic and PTSD
Exposure to infectious disease epidemics results in a particular type of psychological trauma, which could be categorized into three groups.

The first is directly experiencing and suffering from the symptoms and traumatic treatment. For example, dyspnea, respiratory failure, gatism, alteration of conscious states, threatening of death, tracheotomy, etc. are major trauma of patients with severe COVID-19.

The second is witnessing of patients who suffer from, struggle against and die of the infectious disease, which has a direct impact on fellow patients, family members of patients, or people who directly provide aids and care for the patients. The third is experiencing the realistic or unrealistic fear of infection, social isolation, exclusion, and stigmatization.

This directly affects patients, family members, care and help providers, or even the general public.

Epidemiological studies have demonstrated a rather high prevalence of mental health problems among survivors, victim families, medical professionals, and the general public after an epidemic of infectious disease, such as SARS, MERS, Ebola, flu, HIV/AIDS.

While most of these mental health problems will fade out after the epidemic, symptoms of PTSD may last for a prolonged time and result in serious distress and disability. A systematic review of psychological consequences of infectious disease outbreak (after 2003 SARS outbreak, the H1N1 outbreak in 2009, and occupational exposure to HIV) indicates that the average prevalence of PTSD among health professionals was approximately 21% (ranging from 10 to 33%), and 40% of them reported persistently high PTSD symptoms 3 years after post exposure.

PTSD symptoms were also significantly higher among exposed healthcare workers (HCWs) than unexposed control group, particularly among allied HCWs, followed by nurses and physicians [5]. A study of the long-term psychiatric morbidities among SARS survivors revealed that PTSD was the most prevalent long-term psychiatric condition.

The cumulative proportion of patients with PTSD was 47.8%, while 25.5% continued to meet PTSD criteria at 30 months post-SARS [6]. Of the 116 people who survived from Ebola in Liberia, 76 (66%) met the DSM-IV diagnostic criteria of posttraumatic stress disorder 3 years after the outbreak (Nyanfor SS, Xiao SY: The Psychological Impact of the Ebola epidemic among Survivors in Liberia: a retrospective cohort study, submitted).

The feature and level of exposure to psychological trauma seems to be the most reliable predictor of PTSD after an infectious disease epidemic. Most epidemiological studies indicate the survivors reported highest prevalence of PTSD, followed by victim families, medical professionals providing care to patients with infectious diseases, and others.

The female, the elderly, children, less educated, low-income groups are more vulnerable to PTSD, while comorbidity of chronic mental and somatic disorders, neurotic personality, lack of social connection and social support, etc. are possible risk factors, early psychosocial interventions are possible protective factors of PTSD [7].

Prevention of PTSD after infectious disease epidemic
The importance of providing mental health service to people affected by the epidemic of infectious diseases are highly recognized by the academic society and the general public. In 2007, the Inter-Agency Standing Committee (IASC) announced Guidelines on Mental Health and Psychosocial Support in Emergency Settings [8], which has been widely adapted to direct mental health service after disasters, including infectious disease epidemics.

The IASC guidelines are organized around a 4-tiered intervention pyramid: (1) restoring basic services and security for the affected population, (2) strengthening family and community networks, (3) providing distressed individuals with psychosocial support, and (4) providing specialized mental health intervention for severely affected survivors. Other strategies or models of intervention have also been practiced in various of settings [9]. However, systematic and well-designed intervention studies targeted at the prevention of PTSD after disasters are unavailable until now.

References

1. World Health Organization: Coronavirus disease 2019 (COVID-19) Situation Report-112. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed 12 May 2020.

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Source: UCLA

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