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Part 3.  Crisis

In the previous installments of this series, the symptoms of COVID-19 were described, especially as they relate to their mental health impact. In Part 1, Aren’t We Scared Enough?, the effects of the novel coronavirus, SARS-CoV-2, on the respiratory system were described, including how the virus might affect our lungs in ways that may result in a more prolonged recovery process. In Part 2, Aftermath, the implications of the respiratory problems associated with COVID-19 were reviewed, particularly with regard to how those might affect our thinking and emotions. In this part of the series, the focus is on the most serious negative outcomes that have been documented with this illness: cytokine storms, ischemic cascade and cerebral hemorrhage. These conditions are the most life-threatening and most likely to result in complex prolonged recovery. For mental health providers, it will be important to have some awareness and accurate information about the physical and mental health issues involved in the long-term recovery process for the most severely affected COVID-19 survivors.

As was discussed previously, what we know about SARS-CoV-2 is that it thrives particularly in our lungs. Most people know that the lungs are two air-filled organs with hollow lobes used for breathing. The interior surface of each lobe is made up of a number of specialized cells. Some of these, goblet cells, secrete the layer of mucus that lines and protects our respiratory system by trapping invasive particles and preventing the cells from becoming dried out and irritated.  Other cells have minuscule hair-like structures called cilia that move to keep the mucus circulating. Clusters of squamous epithelial cells, like the cells in our mouths and salivary glands, form grape-like clusters called alveoli.

Throughout these tissues are two microscopic networks made up of capillaries and bronchioles.  The capillaries bring deoxygenated blood into the lungs where they meet up with the flexible bronchioles, which are the terminal, microscopic branches of the bronchi–the tubes that carry air into the lungs from the trachea. The capillaries and bronchioles are both distributed around the alveolar sacs. Their extremely thin walls meet and create the respiratory membrane where the key chemical transfers of respiration take place: O2 in and CO2 out. Oxygen is transferred from incoming bronchioles to arterial capillaries that then travel to the heart and from there to the body’s tissues. The venous capillaries arrive from the heart and transfer their CO2 to outgoing bronchioles, which release it when we breathe out.

The cellular biology of lung tissue has been well described for many years. More recently, though, improvements in microbiology have allowed scientists to observe more carefully how lung tissue functions, including hemodynamics (changes in blood flow distribution) and localized immune response. That research has shown that our lung tissue defends itself against molecular intruders in part by excreting the mucosal layer and by circulating that layer around and then out of the lung using the cilia. In addition, however, advanced molecular biology has shown that the lung’s epithelial cells have a proactive defense system, which can detect potential pathogens and initiate an immune response, including immune effector cells that link to leukocyte-mediated defenses. This active defense system that detects and then destroys invasive bacteria or viruses is mediated by blood-borne molecule messengers known as cytokines.

The most common health impacts of COVID-19 are due to the initial SARS-CoV-2 infection, represented in Figure 1 below in Stages I and II. These stages reflect the onset of viral infection, with clinical symptoms including fever, cough and headache. In Stage II, the direct effects of the viral infection are slowly overtaken by the onset of the individual’s own immune reaction (inflammatory response), which is reflected in increased dyspnea (shortness of breath), hypoxemia (decreased blood O2) and hypoxia (O2 deprivation and anaerobic cellular metabolism in all tissues).

Figure 1. COVID-19 Phases and Potential Therapeutic Targets

Weathering the Storm: COVID-19 and Mental Health

Nile, S.H., Nile, A., Qiu, J., Li, L., Xu, J and Kai, G. (2020). COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Review. May 7. Elsevier Public Health Emergency Collection.

In Part 2 of this series, we reviewed the neurocognitive and behavioral manifestations of hypoxia. These are common to many if not most individuals with COVID-19. For a significant subset of patients, however, the illness will progress to Stage III when the body’s own immune response is triggered but then overreacts. The excessive activation of the immune response is what is referred to as a cytokine storm (see Figure 2). It is the biological equivalent of having the fire department respond to a house fire by unleashing a flood of water that washes away the whole town. In the body, the equivalent is that the immune cells overreact, and instead of restricting their attack to those respiratory cells that contain the virus, they begin to attack healthy cells in the lungs, the vascular system and in other organs. This can damage the heart and liver, invariably cause blood vessel walls to become more porous and include a rapid decrease in blood pressure and an increase in blood clots, exacerbating the condition of an already compromised system.

Figure 2. COVID-19 pathogenesis and cytokine storm and effects.

Weathering the Storm: COVID-19 and Mental Health

Key: ACE2 = angiotensin-converting enzyme; PMN = polymorphonuclear granulocyte; AC = alveolar cell; NK = natural killer

Because this excessive immune reaction was a known feature of both MERS and SARS-CoV-1, the medical treatment anticipated this reaction for cytokine storms in COVID-19. Unfortunately, as can be seen in Figure 1, the introduction of treatment for COVID-19 cytokine storm symptoms has to be timed very carefully. If the administration of immunosuppressive agents (e.g. corticosteroids) is done too early, the virus may continue to spread. If the immunosuppressant treatment is offered too late, the patient may have excessive cellular organ damage and be unable to recover from the combined impact of hypoxia and multi-organ failure.

Patients with more severe respiratory symptoms, including Acute Respiratory Distress Syndrome (ARDS), are typically placed on a ventilator and may even need further extreme cardiovascular intervention, such as extracorporeal membrane oxygenation (ECMO). In addition to the injury to the respiratory epithelium caused by the invasive virus itself and followed by exacerbating injuries due to the host’s immune overreaction, the use of mechanical ventilators and ECMO to save a patient can also cause injury to the respiratory and vascular systems.

As was discussed in Part 2, normal breathing in medicine is known as “negative pressure respiration” because the person’s diaphragm and chest muscles open outwards, creating a vacuum into which the lungs expand, drawing air into them. Mechanical ventilation is known as “positive pressure ventilation” because the system uses a pump to push pressurized air into the lung and then uses a vacuum to draw the air back out. This is usually done in conjunction with keeping a patient lying prone to allow easier expansion of the chest cavity. The main problem with mechanical ventilation is that the air pressure and gas mixture has to be very finely calibrated and adjusted to the conditions of the lung tissue. If the pressure is even a little too high, the fragile alveoli, weakened by the virus and/or immune overreaction, will react like soft bread soaked in broth and easily pull apart. But without enough pressure, the fluid-filled lungs and alveolar sacs will not get enough air into them to allow for the inflation of the compressed and weakened bronchioles.

Aside from the increased risk of other airborne pathogens that cause additional infections in the lungs, the use of prolonged positive pressure in the lungs will result in increased intracranial pressure, which increases the risk of cerebrovascular accidents (strokes) and causes negative effects on the heart by changing the normal blood pressure in the chambers. Other organs are also affected by alterations in blood flow caused by the pressure changes in the lungs. In the end, while patients with COVID-19 who receive mechanical ventilation have a greater chance for survival, the long-term consequences can be serious.

In some cases, patients with severe ARDS may be so compromised by the virus and their body’s immune responses that they are not able to benefit from positive pressure ventilation. In that case, the WHO has recommended starting ECMO as soon as possible for critically ill patients whose pulse oxygenation levels are not sustained at acceptable levels. Needless to say, there are significant risks associated with both implementing ECMO as well as not implementing it. Persisting hypoxia is the main risk for not starting a patient on ECMO. As we covered in Part 2, hypoxia can cause widespread organ damage, including damage to the brain as well as the positive pressure effects.

However, the risks of starting ECMO can be equally daunting. The main risk with all forms of extracorporeal life support is brain injury, including seizures, intracranial hemorrhage, infarcts and wide-spread neuronal necrosis. The main risk when drawing blood from the body to increase O2 and decrease CO2 is with coagulation. When blood is drawn and sent through an oxygenator, there is a high risk that blood clots will form in the tubing or in the patient, requiring the use of anticoagulants. Unfortunately, decreasing the blood’s clotting potential increases the rate of blood flow, and therefore, the likelihood of hemorrhaging. In most of the body, small hemorrhages are fairly harmless, but in the brain, they can be very damaging. As discussed previously, when blood flow problems (ischemia) occur, the tissues downstream from a hemorrhage (or clot) quickly suffer from hypoxia, and our brain’s cells are the most vulnerable.

The bursting of small blood vessels in the brain, or the occlusion of small vessels due to a clot or other air bubble, are known risks when using ECMO. When working with COVID-19 survivors, it will be important to be aware of any history of ischemic illness, including both transient ischemia as well as cerebral vascular accidents (CVA, or strokes). Many patients who have been on either ventilation or ECMO will need to be evaluated by neurology, neuropsychiatry and neuropsychology to clarify the nature of any residual cognitive, emotional or psychomotor deficits. These patients will also need to be screened for ongoing hypoxemia and/or epileptiform conditions.

Unfortunately, once a patient has been started on any type of ventilator or ECMO, it can be complicated and risky to get them back to breathing on their own again. Consequently, patients with COVID-19 who are intubated and on a ventilator, or who progress to needing ECMO, are unlikely to be breathing independently again soon. Regarding patients with other acute health care crises, we know that the body’s skeletal antigravity muscles and respiratory musculature begin to significantly weaken after about five days. It is not surprising to learn that over 50% of these patients do not survive.

But 50% of patients do survive, and they will be struggling back against very challenging circumstances. It is common for patients to be supine and on a ventilator for weeks, and during much of this time, due to the discomfort and risk of agitation, they are sedated. COVID-19 survivors will be a large number of people who will need intensive, general physical and respiratory rehabilitation as well as emotional support and cognitive rehabilitation. These patients will need to overcome both hypoxemia due to weak respiratory muscles and lung tissue scarring as well as decreased muscle strength and poor balance from being in a bed for weeks or months. This would be like waking up from a coma on top of a mountain with a wicked chest cold. You would have all the effects of elevation sickness on top of the deconditioning and dizziness due to being unconscious for weeks, plus respiratory tissue scarring from pneumonia. And then you would be told to get up and exercise or you could die.

For those recovering from a life-threatening illness and prolonged hospitalization, there are a number of unexpected hurdles. Aside from the motor problems and weakness due to deconditioning, your brain chemistry is suddenly off. This is a condition in cardiac rehabilitation known as “cardiac depression.” The onset of depressed mood after cardiac surgery has been well studied for decades now, and there appears to be a strong vicious cycle effect. Individuals with pre-existing depression are known to have worse overall outcomes from cardiac surgery, but that is also true of other surgical procedures, including back surgery, joint replacements and gastrointestinal surgery. Similar to postpartum depression, the experience of being on a respirator and/or under anesthesia can exacerbate the stressful impact of hospitalization, physical pain, discomfort and anxiety about recovery.

Extreme, life-threatening experiences are known to cause PTSD in many individuals, even when the person has been sedated or unconscious for much of the experience. It turns out that just hearing about the procedure or re-imagining a trauma while feeling the residual pain in affected tissues can result in PTSD. One of the unfortunate implications of prolonged physical recovery from COVID-19 is the necessity for being re-exposed to medical settings, equipment and personnel, which is likely to elicit negative affect, re-traumatization experiences (“triggering”) and nightmares. Just as with other PTSD patients who experience symptoms in association with being in rehabilitation settings, non-compliance and avoidance of treatment can be significant factors as well as poor motivation, negative mood states and complications due to sleep disturbance.

Aside from psychological trauma, individuals recovering from severe COVID-19 can experience severe feelings of guilt and shame about having survived when others around them, or whom they may have met in the hospital or even knew pre-morbidly, may not have survived. This is called survivor guilt, and it is especially a problem for survivors who have lost family members, including parents, spouses, children or other immediate family members.

Overall, the COVID-19 patient who is recovering from severe illness will likely be exhibiting at least some of the following:

  • Decreased respiratory efficiency, resulting in hypoxemia and related generalized fatigue, decreased alertness and concentration, poor task focus and task persistence;
  • Dizziness and headache with unstable posture (increasing fall risk);
  • Severe deconditioning;
  • Anxiety, especially with somatic fears, or fears of hospitalization and medical procedures;
  • PTSD, including exaggerated startle responses and fear reactions to environmental stimuli associated with the original trauma (e.g. hospitals and staff, PPE, oxygen tanks and masks), nightmares and sleep disturbance;
  • Residual neurocognitive, motor or neuropsychiatric conditions from either transient ischemic attacks or cerebral vascular accidents (strokes);
  • Epilepsy;
  • Grief and loss issues;
  • Psychosocial stressors (financial losses, loss of employment, loss of health and physical strength, etc).

When reaching out to clients under these extreme conditions, it will be important to offer both a strong treatment alliance – a commitment to being part of their recovery process – as well as a sense of hope. Being knowledgeable about the conditions facing them physically and psychologically is just the start.

Final Common Pathway, the final article of this four-part series, will focus on assessment and intervention strategies that emphasize overcoming issues common to all victims of COVID-19, from the stressed-out observer and battle-weary health-care provider to those who are barely but still standing.

Dr. LeGoff is a licensed neuropsychologist with more than 25 years of clinical experience, having held many prestigious clinical and teaching positions at Ivy League universities and government and healthcare institutions nationwide. A world-renowned speaker, author and expert in personal development and cognitive behavioral therapy, Dr. LeGoff has conducted professional trainings worldwide.

IMCS – Integrated Medical Case Solutions – is the premier behavioral medicine network for pain and trauma response with evidence-based outcomes and a proven track record for transforming workers’ compensation cases. IMCS makes intervention efficient with a national network of 1,200+ psychologists and psychiatrists in all 50 states.