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Alzheimer disease (AD) remains one of the most dreaded diagnoses a patient can get. The US Food and Drug Administration (FDA) raised hopes when it approved aducanumab, which promised to be the first disease-modifying drug for AD. But the approval immediately proved controversial. Three FDA board members 

 its patient label, and in mid-July, major hospitals announced that they would not administer the 

, Helen Lavretsky, MD, MS clarifies the issues in the aducanumab debate and offers guidance for clinicians whose patients may ask about it. Going beyond pharmacology, she points out that other treatment options, including mind-body interventions and diet changes, have been shown to slow AD’s progression.

Advice for talking to patients and caregivers about aducanumab and other novel pharmacological options

Mind-body and lifestyle interventions for AD

AD prevention programs, including nutrition, exercise, and stress reduction

Taking care of caregivers, including psychiatrists and other medical professionals

is a professor in-residence in the Department of Psychiatry at the University of California, Los Angeles. Her work on geriatric depression and integrative mental health using mind-body interventions has received national attention, and she has won numerous grants supporting that work. A distinguished fellow of the American Psychiatric Association and a fellow of the American College of Neuropsychopharmacology, she is also on the board of 

Although the new drug aducanumab has grabbed all the headlines, the future of Alzheimer treatment may be just as much about public health campaigns as it is about psychopharmacology. In this episode of Psych Pearls, we find out why.   

What Will the Future of Alzheimer Disease Treatment Look Like? 

It is not new for viruses to have both mental and physical health consequences. 

 is a notable example in recent times, with 38 million individuals currently living with the virus and an estimated 35 million who have died from AIDS-related illnesses.

 As many as half of people living with HIV have at least 

 Today, after more than a year since the pandemic started, the magnitude of the public health impact of the current COVID-19 crisis is not yet fully appreciated, but it will be significant, with more than 

 and counting globally at the time of this writing.

The effects of COVID-19 are expected to last for a long time, with evidence for persistent and/or delayed 

 It has been observed that as many as three-fourths of patients hospitalized with COVID-19 had 

at least 1 ongoing symptom 6 months after 

 and 30% of patients, even those with mild illness, have reported 

persistent symptoms for as long as 9 months

 These long-term consequences include mental health issues, with 

 having persistent neurological and/or psychiatric consequences.

This recognized phase of prolonged illness, referred to by a variety of names including long COVID-19, long-haul COVID-19, and postacute COVID-19, has been recently designated by the National Institutes of Health as 

post-acute sequelae of SARS-CoV-2 infection

Although COVID-19 had initially been most notorious for causing respiratory pathology, with the most vulnerable patients progressing to 

 with an underlying etiology still to be determined but possibly involving dysregulated immune response, inflammation, microvascular thrombosis, and/or cellular damage from the virus.

 Although variable in presentation, PASC most commonly involves a constellation of symptoms (

 range from mild to disabling with significant effects on quality of life, even in patients whose acute course of illness was mild or who were previously healthy and active.

We have much to learn about PASC, due to the multiorgan system effects and the heterogeneity of symptoms in patients who 

. Beth Israel Deaconess Medical Center, a patient care, teaching, and research affiliate of Harvard Medical School in Boston, has recently launched the Critical Illness and COVID-19 Survivorship Program. The program aims to integrate care among pulmonary, critical care, sleep medicine, psychiatry, cognitive neurology, neurology, geriatrics, social work, and physical and occupational therapy clinicians. Although the cases differ, 3 deidentified vignettes demonstrate the core themes for patients presenting with PASC who are referred to psychiatry through the new program.

“Alma,” a woman aged 45 years, presents with a history of hypertension and a 4-week intensive care unit (ICU) stay due to acute respiratory failure, prolonged intubation, and paralysis after contracting COVID-19. Alma’s ICU stay was complicated by a course of delirium. She had been discharged home from a rehabilitation center more than 6 months prior to her appointment.

She has been referred for ongoing symptoms of 

 (PTSD) related to her ICU stay, significantly impaired sleep, and depressed mood. Additionally, Alma continues to struggle with ongoing memory and focus concerns, shortness of breath, and difficulty with weakness. Her cognitive and physical symptoms have improved, but they remain impairing.

The Mental Health Impacts of ICU Admissions

Prior to the COVID-19 pandemic, it had been increasingly recognized that survivors of ICU admissions commonly experience 

long-term physical, psychological, and cognitive impairments

 that adversely impact their quality of life.

 This group of multisystem impairments is referred to as post-intensive care syndrome (PICS). More than 50% of survivors of acute respiratory syndrome suffer from at least 1 feature of PICS a year after their ICU stay.

 are well characterized and persistent manifestations of PICS.

 The differences in characterization and etiologies between PICS and the independent influence of COVID-19 is not yet understood.

After contracting COVID-19, “John,” a man aged 70 years with a history of asthma, obstructive sleep apnea, diabetes, and major depression, was hospitalized for 4 days due to low oxygen levels, which required treatment with steroids.

John presents 3 months after hospitalization with worsening depression, insomnia, breathlessness, and related anxiety. His mood is also influenced by frustration with obstacles in restarting home health services. Due to a lack of assistance, it has been difficult for John to keep up with his many follow-up appointments or go to the pharmacy to pick up medications and other medical supplies. He reports being quite lonely and has not seen his out-of-state family for many months.

Identifying Predisposing Risk Factors for PASC

The outcomes for an individual after contracting COVID-19 will depend not only on the direct influence of the virus, but also on predisposing risk factors (ie, 

preexisting health conditions, socioeconomic factors

), the way their body responds to fighting off the virus (immune activation and/or dysregulation), and iatrogenic complications (ie, adverse effects of such medications as steroids and sedatives; hospital-acquired infections). Additionally, issues arise related to recovering from the virus, which include the onus of having been ill, concern about infecting loved ones, and obstacles in having day-to-day needs met. The 

 due to the pandemic, impacting ability to obtain care for health conditions or engage in preventative care, also are likely to play a role in health outcomes.

 are important risk factors and drive negative health outcomes, especially in older adults.

“Susan” is a woman, aged 40 years, with a prior episode of major depression that had been in remission and mild attention-deficit symptoms that had been well controlled. She presents more than 7 months after contracting COVID-19.

During her acute course, she struggled with fever, cough, headache, shortness of breath, fatigue, and anosmia. Susan was evaluated in the emergency department due to the severity of her symptoms, but she did not require hospitalization. She has had persistent symptoms of breathlessness, profound fatigue, difficulty with concentration and memory, 

, and difficulty performing the duties of her job, which she has held for many years. She is referred for growing depression and feelings of hopelessness.

Symptoms of Lower Severity, but High Persistence

This clinical presentation—a patient who is younger, previously healthy, with milder acute COVID-19 symptoms and persistently impairing symptoms longitudinally—is often referred to as long COVID-19. Earlier in the pandemic, 

this clinical presentation was not fully recognized

 and, indeed, sometimes ignored or discounted.

Long COVID-19 challenges clinicians more than ever to listen to patients and break down the false dichotomy between mental and physical health. The experience of feeling trivialized and frustrated by an overemphasis on the psychological components of illness has been shared by 

 such as severe acute respiratory syndrome (SARS) in early 2000s and Middle East Respiratory Syndrome in 2012.

 It also has been a common experience in patients diagnosed with 

myalgic encephalomyelitis/chronic fatigue syndrome

 (ME/CFS), a complex and disabling illness with features that overlap those of long COVID-19.

The presentation of neuropsychiatric symptoms after COVID-19 are heterogeneous, and to some extent they may reflect variable and multifactorial causes. The 

 by patients, clinicians, and society alike of psychogenic vs organic, psychological vs physiological, functional vs neurological, are all overly simplified and represent 

antiquated views of the brain-body connection

 Breaking down long-standing silos in health care through the use of integrated multidisciplinary teams will be critical to finding more effective treatments. Bridging this divide is urgent, not only to understand and treat the consequences of this pandemic, but also to face the 

longstanding issue of mental health stigmatization

 that serves as an enduring barrier to patients seeking care for their mental health.

 Patients with PASC are at risk of mental health consequences, whether it be from the direct consequence of the virus, indirect consequences of quarantine and the pandemic, exacerbation of preexisting conditions, and/or ongoing challenges of coping with a new, poorly understood, chronic illness.

Issues to Consider in Treatment and Recovery

Many patients slowly recover with supportive measures and symptomatic treatment.

 Much of the initial recovery recommendations focus on physical rehabilitation and support. There are not yet formalized standards of care in treatment of depression and other mental health concerns in PASC. Notably, some patients with PASC may struggle with symptoms of dysautonomia such as persistent tachycardia and/or vulnerability to orthostasis, which may diminish tolerability to some psychotropic medications.

A number of patients with long COVID-19, similar to patients with ME/CFS, have 

 Therefore, pushing themselves to exercise beyond an identified energy envelope may be counterproductive and, in fact, propagate crash-and-burn cycles.

 For that reason, care must be taken in suggesting exercise, an otherwise recommended lifestyle intervention for improving stress, depression, cognition, and insomnia.

In addition to our standard treatments for depression, anxiety, and PTSD, there are some emerging areas of interest. Breathing exercises have been a recommendation of post–COVID-19 clinics and have benefited patients who have persistent feelings of breathlessness. 

, a breathing program, is available online and has been utilized by patients with long COVID-19.

 Respiratory rehabilitation has been suggested, especially when complemented by 

 (ie, tai chi, qigong) that combine conscious breathing in coordination with body movement.

, a form of yoga that combines breathing with humming, has also been recommended, not only because it can be calming, but because it may enhance nitric oxide expression.

 have long been compelling for patients with ME/CFS, but heterogeneity in studies and small sample sizes limit our evidence base.

 There are not yet systematic studies of mind-body interventions in PASC. Of note, 

 provided some relief for survivors of SARS when they did not find adequate support from standard health care.

 has been an important element in the fight against COVID-19.

 The COVID Symptom Study captures and analyzes daily symptom tracking in millions of app users in the United States and United Kingdom.

 It recently provided insight into long COVID-19, identifying the strongest predictor for ongoing illness as having

apps are likely to play an important role in complementing mental health treatment

, allowing for real-time measurement-based care, shared decision-making, and enhanced therapeutic alliances.

We are only just beginning to understand COVID-19 and its consequences. It will take multiyear studies to elucidate long-term sequelae and to understand how to best help patients. Also, this virus has further elucidated the 

inequities in our society and in health care

 Although this has been a time of tribulation, it is also a time that presents an opportunity to understand the trajectory of biological, psychological, and socioeconomic outcomes that will allow us to move toward eroding the stagnancy of mind-body dualism and breaking down siloed care. It also presents the opportunity to find more satisfying outcomes and improved quality of life for those with chronic illnesses.

is a geriatric psychiatrist at Beth Israel Deaconess Medical Center (BIDMC) and an instructor at Harvard Medical School. She is the consulting psychiatrist for the BIDMC Critical Illness and COVID-19 Survivorship Program.

 is Stanley Cobb Professor and Academic Head of Psychiatry at Beth Israel Medical Center and Harvard Medical School.

1. Global statistics. HIV.gov. Updated November 25, 2020. Accessed May 24, 2021. 

https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics

2. Yehia BR, Stephens-Shield AJ, Momplaisir F, et al. 

Health outcomes of HIV-infected people with mental illness

An interactive web-based dashboard to track COVID-19 in real time

4. Nalbandian A, Sehgal K, Gupta A, et al. 

6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

6. Logue JK, Franko NM, McCulloch DJ, et al. 

Sequelae in adults at 6 months after COVID-19 infection

7. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 

6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records

8. Collins FS. NIH launches new initiative to study ‘long COVID.’ National Institutes of Health. February 23, 2021. Accessed May 24, 2021. 

https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-launches-new-initiative-study-long-covid

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

10. Gupta A, Madhavan MV, Sehgal K, et al. 

Extrapulmonary manifestations of COVID-19

11. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. 

Management of post-acute Covid-19 in primary care

12. Marra A, Pandharipande PP, Girard TD, et al. 

Co-occurrence of post-intensive care syndrome problems among 406 survivors of critical illness

Aging and post-intensive care syndrome: a critical need for geriatric psychiatry

14. Wright A, Salazar A, Mirica M, et al. 

The invisible epidemic: neglected chronic disease management during COVID-19

Social isolation and loneliness in older adults: review and commentary of a national academies report

16. Ladds E, Rushforth A, Wieringa S, et al. 

Persistent symptoms after Covid-19: qualitative study of 114 “long Covid” patients and draft quality principles for services

17. Rogers JP, Chesney E, Oliver D, et al. 

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

18. McManimen S, McClellan D, Stoothoff J, et al. 

Dismissing chronic illness: a qualitative analysis of negative health care experiences

19. Perez DL, Keshavan MS, Scharf JM, et al. 

Bridging the great divide: what can neurology learn from psychiatry?

The convergence of neurology and psychiatry: the importance of cross-disciplinary education

The health crisis of mental health stigma

22. Myalgic encephalomyelitis/chronic fatigue syndrome: treatment of ME/CFS. CDC. January 28, 2021. Accessed May 24, 2021. 

https://www.cdc.gov/me-cfs/treatment/index.html

23. O’Rourke M. Unlocking the mysteries of long COVID. The Atlantic. March 8, 2021. Accessed May 24, 2021. 

https://www.theatlantic.com/magazine/archive/2021/04/unlocking-the-mysteries-of-long-covid/618076/

Chinese Association of Rehabilitation Medicine; Respiratory Rehabilitation Committee of Chinese Association of Rehabilitation Medicine; Cardiopulmonary Rehabilitation Group of Chinese Society of Physical Medicine and Rehabilitation

. Recommendations for respiratory rehabilitation in adults with coronavirus disease 2019. 

Modified Bhramari pranayama in Covid 19 infection

Effectiveness of body awareness interventions in fibromyalgia and chronic fatigue syndrome: a systematic review and meta-analysis

Coping with future epidemics: tai chi practice as an overcoming strategy used by survivors of severe acute respiratory syndrome (SARS) in post-SARS Hong Kong

28. Collins F. Predicting ‘long COVID syndrome’ with help of a smartphone app. NIH Director’s Blog. March 23, 2021. 

https://directorsblog.nih.gov/2021/03/23/predicting-long-covid-syndrome-with-help-of-a-smartphone-app/

29. Sudre CH, Murray B, Varsavsky T, et al. 

30. Rodriguez-Villa E, Rauseo-Ricupero N, Camacho E, et al. 

The digital clinic: implementing technology and augmenting care for mental health

The COVID pandemic and the endemic disparities in care across race for psychotic disorders

1 in 3 COVID-19 survivors experience persistent consequences. What can psychiatry do to help?  

Developing a Collaborative Approach to Post-Acute Sequelae of SARS-CoV-2 Infection

When Dawn Sims picks up her curbside groceries, she sanitizes her packaged products with chlorhexidine, a medical-grade disinfectant. Otherwise, she only eats fresh foods that can be washed, zapped in the microwave, or peeled.

Sims, aged 50 years, resides on a 20-acre property with her husband and mother. The property consists of 2 buildings, 30 ft apart. Sims and her husband live in one; her mother, aged 79 years, lives alone in the other. She loved being close to her mother—until 

“I live in terror that I’m going to kill my mother,” Sims said. “That’s my biggest fear: I’m going to bring COVID home to her.”

At the Arkansas Industrial Traffic Association, Sims manages the company’s finances in person for security reasons. Seven individuals work in the office, and masks are not required at their desks, which scares her.

Sims’s concerns are widely shared. Between April and June of 2019, nearly 11% of Americans experienced anxiety and/or depression, according to the 

National Center for Health Statistics National Health Interview Survey

 However, during the same time frame in 2020, when COVID-19 began overwhelming the United States, the Centers for Disease Control and Prevention’s Household Pulse Survey found that 

35.6% of Americans reported symptoms of anxiety and/or depression

,” a recently popularized term, are individuals experiencing long-term symptoms of COVID-19.

 Now, after more than a year of COVID-19 in the United States, data show that long haulers continue to experience both physical and mental symptoms.

The definition of mental long haulers, especially those with mental health issues, is still developing. 

, a psychiatrist and assistant professor at Baylor College of Medicine, told 

 that although he believes that COVID-19 can cause long-term mental health problems, he is awaiting further longitudinal data for proof. Some confirmatory evidence has come in the form of study results published in 

, finding that 1 in 3 patients who recovered from COVID-19 later 

developed neurological or psychiatric conditions

 within 6 months of infection, with anxiety and depression topping the list.

From Nervousness to Mental Health Disorder

What is really happening with these patients? To find out, 

 followed 3 women—Dawn Sims, Heather Scott, and Lisa Germain—from November 2020 to February 2021, the time frame of the pandemic’s second US surge. Although three women is a small sample size, the 

 on these individuals’ mental states was massive. Their 3 stories were very different yet shared certain commonalities.

Mainly, they shared a common distress about the persistent anxiety. In December 2020, that concern overwhelmed Sims. “I am 100% certain that I am going to get it, and I am 100% certain that I’m going to give it to my mother,” she expressed.

From the time Sims was young, she was “a worrier,” but COVID-19 exacerbated her tendencies. “I’m having full-fledged panic attacks,” Sims said. “It’s gone from just being a nervous person, to this.”

Heather Scott, aged 47 years, of Pinconning, Michigan felt the same way as Sims, except her anxiety started when she contracted COVID-19 in November 2020. Two months after her diagnosis and 1 month after her physical symptoms ceased, Scott remained bedridden with depression and anxiety.

“Everything about me changed—not just physically, but mentally,” Scott said. “How does the sickness do that?”

Lisa Germain, aged 51 years, of Milton, Florida, wondered the same thing. She first felt anxious in July 2020, when COVID-19 left her immobilized by pain. Her physical symptoms finally subsided after 6 months, but the disease left behind persistent anxiety.

“I’m now functioning: my heart, my lungs, everything seems to be working. It’s just the mental,” explained Germain.

The association of anxiety with COVID-19 produced a new medical term, 

, coined by psychologists Gordon Asmundson, PhD, and Steven Taylor, PhD, in the March 2020 

 They determined that “intolerance of uncertainty, perceived vulnerability to disease, and anxiety (worry) proneness” can result in a COVID-19–based phobia.

Previous deadly viruses, including severe acute respiratory syndrome and Middle East Respiratory Syndrome, also caused 

, according to “The Long-Term Mental Health Effects of COVID-19,” an analysis published in November 2020.

 Issues included major depressive disorder, anxiety, and phobias—but the problems caused by COVID-19 are distinct.

For instance, in comparing COVID-19 with the Spanish flu, “We have the 2 dimensions of a virus that no virus other than [the Spanish flu of] 1918 has met: contagion and virulence,” Lloyd Sederer, MD, a psychiatrist and adjunct professor at Columbia University’s Mailman School of Public Health, told 

“This is a highly deadly disease that’s pervasive, and no one is spared the risk,” Sederer continued. “Many of the other [viruses] that have come and gone in the past 10 years were controllable; they didn’t have both components of the horror that COVID has.”

Sims’ anxiety peaked in early January, when one of her biggest fears came true: She contracted COVID-19. Still scared of harming her mother, Sims banned her mother from the house. But as the weeks passed, Sims’ anxiety shifted to 

. When she was not asleep, Sims was online reading about other individuals’ lasting symptoms.

All 3 women belong to a coronavirus emotional support group on Facebook. They said they joined the group to vent and share experiences, but they agreed the comments and information shared in the group sometimes make them feel worse.

 during the pandemic in residents of Wuhan, China.

 Investigators found that social media initially provided peer support, but increased exposure to COVID-19–related materials resulted in higher levels of depression.

On Scott’s good days, the group helped her feel less alone. Still, her physical isolation from others overwhelmed her, and she sought help from a psychiatrist.

A Silver Lining: Resilience During COVID-19

All 3 women had not received any therapy before COVID-19. Alana Mendelsohn, MD, PhD, a psychiatry resident at the Columbia University Medical Center, noted that patients with whom she had seen prior to COVID-19 were better able to handle 

“The patients would say, ‘I’ve already been in therapy, working on these issues, developing the skills,’” Mendelsohn explained to 

. Through previous therapy, these patients had increased their mental resilience and acquired the necessary tools to better cope with COVID-19’s uncertainty and chaos.

Individuals who had not been in therapy prior to COVID-19 tend to struggle more, Mendelsohn said. Even individuals who did not previously need mental health care have developed pandemic-induced mental disorders.

Study findings published in the December 2020 

 experienced less mental distress during the pandemic, although those with lower resilience had more difficulty coping.

“As we learned from 9/11 and [superstorm] Sandy, some people are resilient, but not everybody is,” Sederer explained. As the mental hygiene commissioner for New York City, he led the mental health–related responses to the events of September 11, 2001, to superstorm Sandy, and to other disasters.

Factors that predict lower resilience include “having a previous mental health or addiction problem,” said Sederer. “The people most predictable to get sick again were the ones who were sick before.”

“The mental health consequences of [the pandemic] are going to be with us for a very long time, unfortunately,” Mendelsohn added.

That very sentiment is Scott, Germain, and Sims’ biggest fear.

Sitting in her Florida home with self-described “anxiety knots” in her stomach, Germain yearned to feel like she can care for herself. She reported her anxiety was still “so freakin’ high.” Scott still gravitated to her bedroom in Michigan, as her mental health issues persisted. “The mental [part] is the worst part of it all. It’s debilitating,” she said.

Sims fully recovered from COVID-19’s physical symptoms, but she did not recover from her heightened anxiety. “I’ll always feel like there’s potential that someone is carrying a disease that could spread,” she said.

Three women describe the massive impact COVID-19 has had on their lives.

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