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Evaluation and Care Long COVID

Patients

Aluko A. Hope, MD, MSCE Associate Professor, Department of Medicine, Division of PACCM

9/23/2021

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Disclosures

• No commercial financial interests

• NIH (NHLBI and NINR) funding OHSU

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Outline

1. Case

2. Pathophysiology & Epidemiology

3. Medical evaluation & treatment

4. Case

5. ReferencesOHSU

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ED55 year old with PMHx of hypertension, pre-diabetes, obesity and depression who got COVID-19 in April 2020

Acute COVID-19 symptoms included: shortness of breath, cough, fatigue, fever, anosmia lightheadedness, sleepiness,

myalgia

She works a nurse

She presents 9 months after her COVID-19 illness for evaluation and treatment:

like she is wearing a lead weight on her body

she suffers profound exhaustion for days, and her heart races on occasion

difficulty finding words, staying focused, multi-tasking, mentally exhaustion from doing IADLs.

unrestful sleep

Impact on Life Activities

She is unable to work

feels like a burden on her family

feels dismissed by the medical community

she has spent through her savings

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What is Happening to ED?She is Experiencing Manifestations of Long COVID

Reported Problems

• Wearing a lead weight on her body, after

doing household chores she suffers profound

exhaustion for days

• Heart races on occasion.

• Difficulty finding words, staying focused,

multi-tasking, and is mentally exhausted when

going to the market.

• She has unrestful sleep every night.

• Scared she could die, and contemplates if life

is worth living.

Manifestations of Long COVID

• Physical Fatigue

• Post-Exertional Malaise

• Dysautonomia

• Brain Fog

• Sleep Disturbances

• Depression; PTSD

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What is Long COVID?NICE Guidance

Acute COVID-19: signs and symptoms of COVID-19 for up to 4 weeksOngoing symptomatic COVID-19: signs and symptoms for COVID-19 from 4-12 weeksPost COVID-19 syndrome: signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis

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Epidemiology• COVID-19

– Global: 183 million infected and 4 million deaths– US: 35 million and 0.6 million deaths

• Case definition of Long COVID? – A failure to return to baseline state of health

• Long COVID prevalence may range from 10-30% of all COVID-19 cases– Conservative Estimate: 18 million globally, 3.5 million in US– Only small percentage, yet the public health effects are significant

*Berger Z et al. Long COVID and Health Inequities: The Role of Primary Care. Milbank Q. 2021.

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What are the some of the characteristic symptoms in Long COVID?

• Fatigue • Dyspnea on Exertion• “Post-Exertional Malaise”• Neuropathic Pain• Cognitive Impairment• Palpitations / tachycardia• Sleep disruption• GI problems

• Depression / Anxiety / PTSD• Anosmia/Ageusia• Headache• Joint & muscle pain• Many others – less frequentOHSU

Symptom Burden and Health Impairments in Adults with Long COVID who present for evaluation and treatment

• LC clinic at a tertiary care center in New York

• 64% had not been hospitalized

• Female predominant• 13 symptoms via modified

Edmonton Symptom Assessment (scale of 0-10)– Median (IQR) #

symptoms, 7 (4-9)• Hospitalized patients had

more mobility impairment & physical disability despite similar degree of symptoms

Characteristics Total (N=183)Hospitalized

(N=65)

Not Hospitalized

(N=118)p-

Demographics and comorbidities

Age, mean (SD) 52.5 (14.2) 56.4 (13.8) 50.2 (14.0) 0.004

Female Gender, n (%) 131 (71.6) 40 (61.5) 90 (76.9) 0.028

Race/Ethnicity, n (%) 0.284

White, Not Hispanic 21 (11.5) 5 (7.7) 16 (13.7)

Black, Not Hispanic 50 (27.3) 19 (29.2) 31 (26.5)

Hispanic 81 (44.3) 33 (50.8) 47 (40.2)

Other 31 (16.9) 8 (12.3) 23 (20.0)

BMI, kg/m2, mean (SD) 31.9 (9.0) 32.1 (6.7) 31.8 (10.1) 0.843

Diabetes, n (%) 47 (25.7) 24 (36.9) 22 (18.8) 0.007

Hypertension, n (%) 82 (44.8) 36 (55.4) 45 (38.5) 0.028

Stroke, n (%) 6 (3.3) 5 (7.7) 1 (0.9) 0.013

Congestive heart failure 9 (4.9) 3 (2.6) 6 (9.2) 0.047

Lessen S et al. Under review (DO NOT TWEET)

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Continuing Cardiopulmonary Symptoms, Disability, and Financial Toxicity 1 Month After Hospitalization for Third-Wave COVID-19: Early Results From a US Nationwide Cohort

• Adult patients hospitalized for COVID-19 across PETAL network without substantial pre-COVID disability

• 253 adults • 54.9% new or worsened

cardiopulmonary symptom• 84.2% not feeling back to their pre-

COVID function• On a scale of 1-100, with 100 being

all the way back to what you could do before COVID, how close to being back are you?– Median (IQR) 80 (64-95)

Iwashyna TJ, Kamphuis LA et al. J Hosp Med 2021

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Characterizing long COVID in an international cohort: 7 months of symptoms and their impact

• Patient led research collaborative– patient-led research group organized by people across the

world connected by social media and digital tools like Slack• They conducted survey research on patient symptoms

– 3,752 participants from 56 countries. – 205 symptoms. – Average of 14.5 symptoms in an average of 9 organ systems.

Davis H et al. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact. EclinicalMedicine 2021.

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Davis H et al. Characterizing Long COVID in an International Cohort: 7 Months of Symptoms and Their Impact.

EclinicalMedicine 2021.

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Long COVID Recovery & Prognosis

• Most patients improve and will recover in time– Symptoms are unpredictably remitting and relapsing

• Recovery timeline is variable– Weeks– Months– Beyond 12 Months = ‘Long Long Haulers’

• Unable to predict a person’s recovery timeline

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Pathophysiology of Long Covid

• Persistent hyperinflammatory state or immune dysregulation?

• Persistent viral replication (reservoir)?

• Inadequate antibody response

Viral-dependent mechanisms

• Residual organ damage from acute infection?

• Unmasking of underlying comorbidities after infection?

• Post-hospital or post-ICU syndromes

Viral-independent mechanisms

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Multi-organ complications of covid-19 and Long Covid

Harry Crook et al. BMJ 2021;374:bmj.n1648

©2021 by British Medical Journal Publishing Group

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Mitochondrial Dysfunction• SARS-CoV-2 known to target mitochondrial matrix and

disrupt normal function

– Decreases energy production– Decreases anti-viral signaling and immune response– Hijacked for viral replication and proliferation– Increases inflammatory responses and reactive oxygen species

– Impairs ability to support immune response– Impaired mitochondrial dynamics (fusion, fission, mtDNA

release)– Loss of mitochondrial integrity and death

Singh KK, Chaubey G, Chen JY, Suravajhala P. Decoding SARS-CoV-2 hijacking of host mitochondria in COVID-19 pathogenesis. Am J Physiol Cell Physiol. 2020

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Evaluation and ManagementKnowledgeable clinicians, earning trust, providing thoughtful, high-quality care

1. Pathophysiology2. Best Practices3. Management for Characteristic Symptoms

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Best Practices

• Most States have at least one Long COVID clinic

• CDC, AAPM&R, NICE have published clinical guidelines

• Yet, there is distinct lack of evidence and clinical pathwaysEarly Stages

• Majority of issues can be well-managed without drugs and procedures

• We can improve the trajectory and severity of their recovery

• Transparent, well-coordinated, trauma-informed care is essential

Supportive Care

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Integrative Model for Evaluation & Management Long COVID

César Fernández-de-las-Peñas, Lidiane L. et al., Proposed integrative model for post-COVID symptoms, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 2021,

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Considerations for the Evaluation and Management of Long Covid• Most conditions can be diagnosed by history and exam

• Ordering of laboratory tests and imaging is guided by the

duration and severity of complaints and is guided by the

presenting symptoms or conditions.

• Work-up focuses on ruling out other causes and elucidating

contributory factors

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History of Present Illness

• Method of SARS-CoV-2 diagnosis: PCR, Antibody, Antigen,

Confirmed Exposure, Presumed

• Time and intensity of symptoms since SARS CoV-2 exposure

• Illness course – including treatment trials

• Energy window

• Nutrition and hydration

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Past Medical History

• Prior Conditions impact the severity of COVID-19

disease and symptoms of Long Covid

– Asthma, Mood disorders, trauma or stress-related

disorders, Headache, Sleep disorders, chronic pain

– Allergies, COPD, diabetes, fibromyalgia, autoimmune

disorders, kidney disease, oncology, obesity, etc.

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Social History Considerations (Pre / Post COVID)

• Finances, employment disability (FMLA)

• Baseline daily activities (ADLs, iADLS)

• Social support and caretaker responsibilities.

• SDoH: Housing, food security, transportation, etc.

• Family-related COVID-19 illness or death, bereavementOHSU

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Medication Review

• Drugs that cause side effects similar to

reported symptoms e.g. sedating,

psychogenic side effects

– BEERS

– Polypharmacy

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Measuring Health via Surveys• Quality Of Life: PROMIS, PCFS, EQ-5D

• Respiratory: mMRC

• Neuro: MoCA, MMSE, Compass 31, Neurobehavioral Symptom Survey

• Psych: GAD-7, PHQ-9, PTSD Screen, IESR

• Fatigue: Modified Fatigue Impact Scale, Wood Mental Fatigue Inventory, Fatigue Severity

Scale

• Insomnia - Insomnia Severity Index (ISI)

• Disability effects: Visual Analog Scale

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Exercise Capacity AssessmentsCan play important role in evaluating and monitoring

• Examples include– 1 minute sit to stand– 2 minute step test– 6 minute walk test– 10 meter walk test– Short Physical Performance Battery (SPPB)

• Be mindful of post-exertional malaise, prepare home supportsOHSU

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Physical Exam• Vital Signs:

– BP, HR, Respiratory rate, oxygen saturation, Temperature, BMI

– Orthostatic vitals, oxygen saturation after activity

• Focused Exam:

– Pulmonary (wheeze, ronchi)

– Cardiovascular (dysautonomia, POTS)

– Neurologic Exam (tremors, impaired balance, walking while talking test)

– Skin (hair loss – telogen effluvium)

– Psych (difficulty finding words, memory, mood)

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Diagnostic Studies

• Positive COVID test is not required to establish the diagnosis

– Testing capacity was limited, many false negatives

• There is no “Long COVID test”

• Review records in advance

• Be clear about goals before ordering

– Diagnostic testing is primarily to rule out other etiologies

– Negative Test ≠ symptoms are not important

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Lab Testing – Basic Evaluation

• CBC, CMP, UA

• CRP, ESR, Ferritin

• TSH and free T4

• Vit D, Vit B12

• Chest X-Ray, EKG

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Laboratory Testing - Directed

• Further testing directed towards ruling out specific etiologies:

– Endo: Cortisol and ACTH, A1c

– Rheum: ESR/CRP, ANA, RF, anti-CCP, anti-cardiolipin, CPK

– Coag: D-Dimer, PT/INR, CK, fibrinogen

– Myocardial injury: troponin

– Cardiac vs. Pulm: BNP

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Additional Diagnostic Testing

• Tests contingent on history, exam, clinical findings:

– Spirometry (pre-and post Albuterol), can include DLCO and Lung Volumes when there

is concern for restrictive lung disease

– Echocardiogram

• Not recommended routinely:

– MRI Brain (red flag headache symptoms, not brain fog)

– Cardiac MRI (abnormalities in echo, consider in consultation with specialty care)

– CT chest (abnormal CXR, PFTs, O2)

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Management of 2 Characteristic Symptoms

Physical Fatigue and Post-Exertional

Malaise

Neuropsychiatric

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Fatigue and Post-exertional Malaise

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Short of breath• Feels weighed down by a lead weight• Severe exhaustion after minimal exertion,

with prolonged post-exertional malaise and recovery

• “Crash” after “good day”

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Fatigue and Post-exertional Malaise

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Multifactorial (mitochondrial dysfunction, mood, stress, deconditioning, autonomic dysfx, immune dysregulation, etc.)

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Fatigue and Post-exertional Malaise

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Basic labs, CXR, EKG• Level of Physical Activity Level• Depression screening• Assess sleepOHSU

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Fatigue and Post-exertional Malaise

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Individualized, structured, return to activity program

• 4 Ps – Prioritize, Planning, Pace, Posture• Healthy nutrition and hydration• Treat co-existing conditionsOHSU

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Neuropsychiatric Symptoms

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Brain fog: difficulties finding words, attention, short-term memory, train of thought, dividing attention.

• Mood disorders: Depression, Anxiety, PTSD• Insomnia• Headache (migraine)

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Neuropsychiatric Symptoms

Common Signs and Symptoms

Pathophysiology

Testing Treatment

Multifactorial:• Immune dysregulation, systemic and neuroinflammation,

microvascular thrombosis, iatrogenic effects of Rx, psychosocial impacts of infection and isolation, and neurodegeneration, ImmunosenescenceOHSU

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Neuropsychiatric Symptoms

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Cognitive screening• Consider Neuropsychologic testing• Screen for psychiatric co-morbidities• Assess sleep• Brain imaging for headaches with “red

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Neuropsychiatric Symptoms

Common Signs and Symptoms

Pathophysiology

Testing Treatment

• Brain fog: Individualized cognitive rehab program (Speech / OT)

• Headaches: Consider steroids / normal mgt.• Mood Dxs: Monitor for improvement as symptoms

get better. Role for pharmacologic n of 1 trials. Severe Insomnia: role for pharmacologic n of 1 trials; Consider CBTiOHSU

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Rationale Behind Physical Therapy Treatment Approach• Not an ‘aerobic exercise’ program• By understanding exercise physiology, we can

– Individualize the optimal level of activity and exertion– Systematically titer the progression of activity

• It is a function of– Breathing test: Awareness of understanding how breathing patters

link directly to maximal effort – Heart Rate

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Ventilatory Threshold

• During incremental exercise, there are two distinct changes in breathing patterns:• VT1 - first ventilatory threshold• VT2 - second ventilatory threshold

• VT1 represents the breathing correlate of the body beginning to engage anaerobic fermentation in addition to oxidative metabolism • Can be identified using the “talk test.” (Point at which it

becomes difficult to speak in complete sentences.”• Pushing past VT1 can lead to PEM• Above VT1 Blood lactate levels begin to rise from baseline but

if work levels are held steady a lactate plateau may be held for a time as the body has some ability to clear lactate.”

• VT2 occurs at the point the body must rely almost entirely upon anaerobic fermentation to deal with further increases in workload

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PT Program Principles

• Long COVID patients with physical fatigue should not exceed VT1– This is hard because often VT1 is severely left-shifted

• Increasing duration of physical Activity levels (exercise) below VT1 can improve physical fatigue

• Patients learn the breathing test as best gauge of appropriate level of activity and avoid going over VT1– We also couple with ranges of heart rate (Easily monitored)

• Patients gradually titer their level of exertion as VT1 improves

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Cognitive Therapy for Cognitive Impairment

• Speech Language Therapist– Initially 1x / week then biweekly

• Evaluate: Language, attention, memory, energy, sleep, other• Measure repeatable outcomes: Memory, attention, executive

functioning, visuospatial processing (e.g. RBANS, MoCA) • Monitor: Processing speed, word errors, metacognition • Recommendations: sleep, diet, exercise, brain / body connection

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Example Strategies in SLT

•WRAP (write, repeat, associate, picture), associating word lists

•Calendars, important items in the same place, follow directionsMemory

•Limit multitasking and distractions

•Self-talk and self-cues and goal setting

•Increase attention from sustained, selective, alternatingAttention

•Face speaker, ask for attention, talk the word

•Pause / think / speak,

•Tell others how they can help (‘give me a second or can you offer a guess’)Communication

•Avoid caffeine, alcohol, fatty meals, screen time

•Bedtime rituals, sleep environment, sunlightSleep

•Extra time to think, describe what you’re thinking, scan alphabet for start letter

•Draw, gestures, words with same meaningLanguage

•STOP (Stop, Think, Organize, Plan)

•Self-talk, repetition, visualization, self-monitoring, puzzles, logic tasksExec Function

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The role of specialty referral

• Specialized centers can provide experienced evaluations

• PCPs can manage most symptoms early

• As symptoms become chronic (≥ 3 months) a multidisciplinary team

approach or a referral may be appropriate

• Telemedicine can play a critical role for a population that is fatigued

and overwhelmed

• No matter where, listening and validation is essential

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What Happened to ED?She is unequivocally overwhelmed!!

Fatigue

Physical therapy 1/wk

Daily, titeredactivity program

Dysautonomia

Nutritionist

Every other week

Disciplined with daily diet, fluids,

salt levels

Brain Fog

Speech Therapy 1/wk

Home exercises and

accommodations

Pending neuropsychiatry

consult in 3m

Sleep Problems

Focus on daily sleep routines

Depression & PTSD

Counseling every other week

Pending consultation for

CBTi

Traumatized, fearful of dying

and worried that her identity as a

nurse is lost

Dependent on Others

Unable to drive to appts

Feels shame and regret

Unemployed

Eating up her savings

Uncertain if she can ever return to

work

Social Injustices

Experiences structural racism ,

testimonial & hermeneutic

injustices

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Support For Disability & Work AccommodationsLikely the 2nd most important thing we can do!

• All patients need to time to recover

• Relapses are common

• Working, stress, pushing themselves too hard is the most

common trigger for relapses and PEM

• Facilitating respite and / or reasonable reentry back to work is

enormously beneficial for quality of life faster recovery

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Accommodations & Disability for Fatigue & Brain FogReturn to 100% work will fail 100% of the time!

Possible Disability Accommodations:• Work from home• Limited hours• Alternating work days• Frequent breaks• Avoid standing• Temporary disabled parking permits• Limit tasks with divided attention• Optimize range of movements• Limit environments with multiple

sensory inputs• Graduated return to work activities

For Disability Applications, Document • Activity levels pre/post infection• Symptoms that are remitting and

relapsing• Specific work activities will result in

physical and mental fatigue• Environmental settings that result in

sensory overload (markets, etc) • Work-ups that rule out other

associated causes including pre-existing conditions

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Managing PASC in Your PracticeTop 10 Essential Components

1. Knowledge Toolkit – CDC Guidelines, AAPM&R Guidelines, Scientific literature (e.g Nature), PT protocol

2. Empathetic clinicians with committed interest

– Dynamic & complex condition requiring thoughtful, supportive management

– PCPs, Neuro, Sleep Med, Cards, Behavioral Health, Neuropsychology,

3. Rehabilitation team familiar key principles (PT/SLT/PM&R)

4. Extended visit for a dedicated comprehensive assessment with records in advance

5. Determine the right health measurement tools for your practice

6. Develop an agreed documentation template or clinical approach for initial assessment

7. Patient instructions for most common symptoms

8. Team members to support SDoH, care navigation, FMLA

9. If possible, access to virtual visits

10. Set expectations clearly, Be patient

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Thank You

Aluko A. Hope, MD, MSCEAssociate Professor, Department of Medicine

hopeal@ohsu.eduTwitter: @hopealukoOHSU

Resources for Patients and

ProvidersOHSU

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Provider Resources• CDC - Evaluating and Caring for Patients with Post-COVID Conditions: Interim Guidance

https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-index.html

• Nature Medicine – Post Acute COVID-19 Syndromehttps://www.nature.com/articles/s41591-021-01283-z

• Annals of Internal Medicine - Toward Understanding COVID-19 Recovery: National Institutes of Health Workshop on Postacute COVID-19https://www.acpjournals.org/doi/10.7326/M21-1043

• Long COVID Speech Therapy – OHSU Powerpoint embedded in this slide deck

• Online CME (OHSU): https://rise.articulate.com/share/7Z5i0jOWRACIdVf3LlOMb4HCT6Ed8RIc#/

• Guidelines for Multidisciplinary Care Centers (Survivor Corps): https://static1.squarespace.com/static/5e8b5f63562c031c16e36a93/t/605a8a3262f0191b99584df0/1616546355297/PCCC+Standard+of+Practice+3_23.pdf

• WHO Post COVID-19 CRF: https://cdn.who.int/media/docs/default-source/3rd-edl-submissions/who_crf_postcovid_feb9_2021.pdf?sfvrsn=76afd14_1&download=true

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Patient Support Groups

• Body Politic• Survivor Corps• Long COVID Alliance• Long COVID KidsOHSU

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Patient Resources• ADA and Long COVID:

– White House fact sheet

– Guidance on Long COVID as a Disability Under ADA

• Post-COVID information Pack (4Ps)

• Breathing Coaching Online Resources:– https://stasisperformance.com– https://www.pulmonaryhealthcoaching.com– https://pulmonarywellness.org/covid-19/

• OHSU Long Covid Clinic: OHSU COVID-19 Connected Care Center hotline at 833-OHSU-CCC, or 833-647-8222.

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