Ignoring it bears life-long consequences for brain health.

*Image by Alejandro Guipzot at mixkit.co

Covid-19 Includes Delirium

Delirium means disturbed consciousness in the DSM-IV. The DSM-5 now defines delirium as a disorder of attention, awareness, and cognition, and may share symptoms with psychosis such as hallucinations, paranoia, irrational thoughts, and grotesque dreams. The Atlantic reports that a few delirious Covid-19 patients became psychotic. They “may believe their organs are being harvested, or that nurses are torturing them. A spike in fever might feel like being set on fire. An MRI exam might feel like being fed into an oven.”

About 20–30% of Covid-19 patients experience delirium; in severe cases, the number rises to 60–70% regardless of age. This prevalence is consistent with the literature where delirium occurs to 60–70% in patients admitted to the intensive care unit (ICU).

Covid-19 Delirium Was Overlooked

The first report of Covid-19 delirium dated back to a China study published on April 10, 2020. It is not just Covid-19; about 75% of delirium cases in critically ill patients, in general, were not diagnosed. Why? A reason is that ICU patients undergoing intubation cannot speak, so verbal tests are challenging. Second, delirium is no single disease, but three with a subsyndromal form:

• Hyperactive delirium: restlessness, agitation, hallucinations, and delusions.
• Hypoactive delirium: fatigue, sedation, and slow responses or reactions. This subtype is often misdiagnosed as dementia or depression or just ignored.
• Mixed delirium: having symptoms of both hyper- and hypoactive delirium. This subtype is the most prevalent, followed by hypoactive and then hyperactive delirium.
• Subsyndromal delirium: a borderline phase that may or may not progress into full-blown delirium.

As a result of late reporting, there may have been four to five months of missed diagnoses, wherein delirium is the chief symptom of Covid-19. Also, the prognosis of Covid-19 with delirium might have been undervalued, leading to inadequate supervision and increased mortality. Because delirium might be a sign of impending and sudden respiratory failure from the shut down of the brain’s cardiorespiratory center.

There are guidelines for diagnosing delirium. They are relatively quick as well. But delirium is not apparent, unlike fever or cough. Health professionals either missed it or actively looked for it.

How Covid-19 Causes Delirium

No single brain pathology reflects delirium. Attempts to pinpoint a specific brain region or neurotransmitter responsible for it have failed. A disconnected brain best describes delirium where neurons can no longer comprehend reality properly, said a 2017 review titled “Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.”

A brain disconnected from reality best describes delirium.

One risk factor for delirium is the lack of social contact. It makes one more vulnerable to lose in touch with reality. Particularly so in the context of highly contagious infectious disease, where quarantine measures are mandatory. Deprived social bonding increases the risk of depression, anxiety, anger, apathy, fear, and disorientation — all of which are predictors of delirium.

“In the age of Covid-19, in an attempt to “flatten the curve” and slow the spread of the virus, many hospitals have instituted no-visitation or very limited visitation policy, which may propagate a sense of isolation, ultimately contributing to disorientation and lack of awareness in the patient,” researchers in the U.S. and Poland wrote in a review in Critical Care.

A second risk factor is the prolonged use of sedatives required for mechanical ventilation. A patient is unconscious with anesthesia but falls somewhere between sleepiness and relaxed consciousness with sedation. Regardless, both are independent risk factors for delirium as the brain tries to fill the gap in consciousness.

The third risk factor for delirium is biological brain insults, be it trauma, pathogens, chemicals, hypoxia, or multi-organ damage. Covid-19 delirium, scientists believe, is partly caused by:

• Coronavirus brain invasion via olfactory neurons or blood-brain-barrier. Neuro-Covid is a disease terminology recently coined for this. The lower prevalence of smell loss in severe vs mild-moderate cases supports the olfactory invasion of SARS-CoV-2, given that destruction of renewable olfactory neurons might be a protective mechanism to halt virus spread into the brain. The cytokine hurricane that causes multi-organ damage increases the risk of virus penetrating the compromised blood-brain-barrier.
• Hypoxia and blood clots. Covid-19 is primarily a disease of the lungs, followed by blood vessels. Lung damage endangers gas exchange and, thus, less oxygen would enter the circulation. Blood vessel damage leading to blood clots might restrict blood flow to the brain. The brain could then be deprived of oxygen or blood and malfunction.

The fourth reason includes factors unrelated to Covid-19 disease or treatment procedures. These are existing neurological diseases like dementia or stroke, multiple medical comorbidities, nutritional deficiency, HIV infection, surgery, sleep deprivation, and being older than 65 years or a male.

All these risk factors compound, making delirium difficult to decipher. No single cause means no single solution.

“In the patients with Covid-19, delirium can be a manifestation of direct CNS invasion, induction of CNS inflammatory mediators, secondary effects of other organ system failure, and untoward medical and environmental factors including heavy use of sedatives for prone positioning of the patient and quarantining and social isolation during care,” the review summarized. CNS means central nervous system — that is, the brain and spinal cord

Prevention vs Treatment

Practicing higher-quality health care could prevent 30–40% of delirium cases. Pharmacological treatments for delirium prevention have not worked so far. One effective program is the Hospital Elder Life Program (HELP) that aims to maintain the following:

• Orientation to surroundings (awareness of time, place, and person).
• Nutrition and hydration.
• Sleep and circadian rhythm.
• Mobility that is feasible within limits of physical condition.
• Visual and hearing function, especially in those with sensory deficits.

Another effective preventive guideline recommended for Covid-19 is the ABCDEF bundle: A: Assess, prevent, and manage pain; B: Both spontaneous awakening trials and spontaneous breathing trials; C: Choice of analgesia and sedation; D: Delirium assessment, prevention, and management; E: Early mobility and exercise; F: Family engagement and empowerment.

If prevention failed or unattempted, treatment options for delirium entail re-orientation to surroundings, making frequent eye-contact, lowering the dose of sedatives or neuromuscular blockers, increasing physical mobility, avoiding changes in surroundings including staff, mitigating noises, and taking anti-psychotics drugs. But these interventions do not guarantee success as they have to be tailored to factors causing delirium and delirium subtypes.

Short- and Long-term Consequences

Another reason why prevention is better lies in the aftermath or collateral damage of delirium. Delirium is an end to a critical disease that have involved and involves the brain. Delirium itself is an independent risk factor for one-week longer hospitalization and a two-fold increased risk of hospital death.

Delirium has a heavy financial toll as well. “Total cost estimates attributable to delirium ranged from $16,303 to $64,421 per patient, implying that the national burden of delirium on the health care system ranges from $38 billion to $152 billion each year” in the United States alone.

In addition to these short-term effects, most delirious patients will not have the same brain as before.

Despite the recovery, delirium further poses a two-fold increased rate of cognitive deterioration in a 5-year follow-up, leading to a higher risk of dementia. “At 3-and 12-month follow-up, 79% and 71% of survivors [of delirium] had cognitive impairment, respectively (with 62% and 36% being severely impaired),” a 2010 study found. People who had delirium also had a more imperfect recall of factual events two years later. All these statistics are in comparison to non-delirious patients. Hence, most people experiencing delirium will not have the same brain function as before.

And the same applies to coronaviruses.

Published in The Lancet Psychiatry, a meta-analysis of 65 peer-reviewed and seven pre-print studies analyzed the short- and long-term psychiatric features of coronavirus infections. “Our main findings are that signs suggestive of delirium are common in the acute stage of SARS, MERS, and COVID-19,” they wrote. “There is evidence of depression, anxiety, fatigue, and post-traumatic stress disorder in the post-illness stage of previous coronavirus epidemics, but there are few data yet on COVID-19.”

“SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage,” they made a concluding statement. And “clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term.”

Could We Do Better?

“To prevent is better than to treat,” researchers can’t emphasize this enough about delirium in a 2013 review. “Many risk factors are modifiable by relatively easy and inexpensive interventions, such as…,” as discussed above. And these mitigative strategies “are not widely used in ICUs around the world.” To reiterate, about 75% of delirium cases missed diagnosis.

Sharon K. Inouye, a professor of medicine at Harvard Medical School and director of the Aging Brain Center in the Marcus Institute for Aging Research, played a pivotal role in communicating the prevalence and dire consequences of Covid-19 delirium in early April. “If there is a silver lining to this pandemic, it’s that people are seeing how important delirium is,” she said in an interview. “There may never have been this much delirium all at one time.”

Delirium has always been overlooked, and it is still is.

The WHO only mention altered mental status, and not delirium, as a possible sign of Covid-19. The CDC and Public Health England listed neither altered mental status nor delirium as a Covid-19 symptom, Professor Inouye said in a review published in May titled, “Delirium: a missing piece in the COVID-19 pandemic puzzle.” Delirium has always been overlooked, and it is still is.

This article was published previously here.