Persistence of Cognitive, Psychiatric, and Functional Declines following COVID‐19

Tracy D. Vannorsdall, PhD, ABPP/CNMid-Atlantic Regional Conference in Occupational and Environmental Medicine

10.16.2021

Objectives

• Neuropsychological and neuropsychiatric symptoms and methods

• JH PACT outcomes

• Management of cognitive and neuropsychiatric changes following COVID‐19 illness

WHO Post‐COVID‐19 Case Definition

Cognitive and neuropsychiatric symptoms• Reduce quality of life • May limit participation in rehabilitative interventions • Can hinder return to work efforts 

Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others* and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.

Functional Limitations Post‐COVID‐19

Up to 67% of non‐hospitalized patients report functional limitations 3 to 6 months following COVID‐19 illness (*survey data*)

Self‐care ADLs Return to Work

https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/prevalenceofongoingsymptomsfollowingcoronaviruscovid19infectionintheuk/7october2021https://pubmed.ncbi.nlm.nih.gov/32932582/https://pubmed.ncbi.nlm.nih.gov/34308300/https://www.medrxiv.org/content/10.1101/2021.03.21.21253968v2

Functional Limitations Post‐COVID‐19

Roughly 20%  to > 50% of patients report functional limitations up to 8 months following COVID‐19‐related hospitalization

Risk factors: ICU, length of stay, female sex, age

https://www.journalofinfection.com/article/S0163‐4453(21)00391‐1/fulltexthttps://www.journalofinfection.com/article/S0163‐4453(20)30784‐2/fulltext

Self‐care ADLs Return to Work

Post-COVID Neuropsychiatric Conditions

• Marked variability in symptoms across patients

• Multiple plausible biological mechanisms

• Unclear trajectory

• Possibility of unmasking previously undetected cognitive and psychiatric issues

• Reactions to pandemic-related stress, social isolation, etc.

• Effects of the virus vs pre-existing conditions vs treatmentsChallenges

⁍ Direct and indirect mechanisms affecting brain health:⁍ Systemic inflammatory response

⁍ Inflammatory cascade

⁍ Hypoxia

⁍ Delirium/encephalopathy

⁍ Acute respiratory distress syndrome

⁍ Prothrombotic state / Stroke

Assessing CognitionNeuropsychological assessment – performance‐based method to determine cognitive functioning and abilities across domains• Traditional neuropsychological exam

• Pros – Structured, objective, norm‐derived outcomes, comprehensive, tailored to the individual and referral question, sensitive to dysfunction, provides intervention targets

• Cons – time, availability  • Screeners (e.g., MMSE, MOCA)

• Pros – quick, free/inexpensive, objective • Cons – lack sensitivity, not tailored to the individual 

Assessing CognitionSelf‐report instruments(e.g., Perceived Deficits Questionnaire – Dep’n, 5‐item; PDQ‐D‐5; Patient‐Reported Outcomes Measurement Information System; PROMIS Cognitive Function 4a)

• Pros – quick, free/inexpensive, subjective• Cons – subjective, may not correlate with cognitive ability, can be driven by psychiatric issues, sleep/fatigue, stress, personality, etc. 

Assessing Neuropsychiatric Symptoms

Domain Instruments

Depression  PHQ‐9Beck Depression Inventory IIHADS

Anxiety  GAD‐7Beck Anxiety InventoryHADS

PTSD/Trauma‐related  Impact of Events Scale‐6 (IES‐6) PTSD Checklist for DSM 5 (PCL‐5)

https://www.cdc.gov/coronavirus/2019‐ncov/hcp/clinical‐care/post‐covid‐assessment‐testing.html

Domain Finding (n = 12 studies; n = 8‐185 patients)

Global Cognitive Functioning  Deficits in 100% of n = 12 studies15 – 80% of patients

Attention & Executive Function Deficits reported in 100% of n = 7 studies 

Memory  Deficits in 3 of 4 studies

Language  Deficits in 100% of n = 4

Visuospatial Function Deficits in 2 of 4 studies 

Conclude: Patients with recent SARS-CoV-2 infection appear to experience global cognitive impairment, impairment in memory, attention and executive function, and in particular verbal fluency.

Johns Hopkins Post-Acute COVID-19 Team

Brigham et al. American Journal of Medicine, 2021

JH PACT Telephone Battery

Test DomainRAVLT

Verbal learningDelayed recall

Oral Trail Making Test Part APart B

Processing speedExecutive functioning

Number SpanForward

BackwardAttentionWorking memory

Verbal FluencyLetter-cued

Category-cuedExecutive functioningLanguage retrieval

Mild/Moderate Impairment:  ≥1.5 SD below age‐adjusted means (i.e. <7th%ile)Severe Impairment: ≥2 SD below age‐adjusted means (i.e., <2nd %ile

JH PACT Telephone Battery

Domain Instrument

Depression PHQ-9

Anxiety GAD-7

Trauma/PTSD Impact of Events Scale-6

Functional Decline Quick Dementia Rating Scale

JH PACT 4-month Outcomes

NON-ICU(N= 34)

Post-ICU(N = 48)

Age (Mean (SD) years) 49.5 (13) 58.0 (15)*

Male (%) 11 (32) 23 (48)

Race (%)WhiteBlack or African Am.Asian or other

47449

276010

Education (Mean (SD) years) 15.7 (3) 14.0 (3)*

Estimated WAIS-IV FSIQ 101 (9) 96 (8)*

Age-adjusted Standard Scores

To ask a question: please use the Q&A feature to direct any questions to one of the moderators, Julia Maietta or Alexander Tan.

75

80

85

90

95

100

105

110

115

RAVLTAcquisition

(n = 82)

RAVLTDelayedRecall

(n = 82)

Oral TrailMaking Test

Part A(n = 82)

Oral TrailMaking Test

Part B(n = 77)

Number SpanForward(n = 82)

Number SpanBackward(n = 82)

Letter-cuedVerbal Fluency

(n = 81)

Category-cuedVerbal Fluency

(n = 81)

CognitiveComposite

(n = 82)

Non-ICU Post-ICU

Rates of Low Scores

To ask a question: please use the Q&A feature to direct any questions to one of the moderators, Julia Maietta or Alexander Tan.

0

10

20

30

40

50

60

70

80

90

100

Learning(n = 82)

Memory(n = 82)

ProcessingSpeed

(n = 82)

ExecutiveFunction(n = 77)

Attention(n = 82)

WorkingMemory(n = 82)

Letter-cuedVerbal Fluency

(n = 81)

Category-cuedVerbal Fluency

(n = 81)

CognitiveComposite

(n = 82)

Severe Mild/Moderate Normal

67% of PACT patients showed mild/moderate cognitive deficit on ≥ 1 test

≥2 scores mild/mod impaired:32% Non‐ICU58% Post‐ICU

≥2 scores severely impaired:15% Non‐ICU31% Post‐ICU

Mental Health & Functional Decline

To ask a question: please use the Q&A feature to direct any questions to one of the moderators, Julia Maietta or Alexander Tan.

NON-ICU(N= 34)

Post-ICU(N = 48)

Domain Tool % above threshold % above threshold

Mild Moderate Mild Moderate

Depression PHQ-9 68 29 67 19

Anxiety GAD-7 53 15 48 15

PTSD IES-6 -- -- 25

Fx Decline QDRS 62 18 69 13

78% reported mild elevations on ≥ 1 measure35% reported moderate elevations on ≥ 1 Measure

JH PACT Key Findings at ~4 months post-COVID-19

⁍ 67% show dysfunction in ≥1 domain of cognition⁍ Processing speed, verbal fluency, learning, memory deficits are

common

⁍ Dysfunction frequently occurs in both Post-ICU & Non-ICU pts⁍ Post-ICU impairments are more severe and broad relative to non-ICU

⁍ Substantial mental health and functional impairments⁍ Clinically meaningful levels of psychiatric distress and/or decline

reported by ≥35% of patients

• Cross-sectional, retrospective study of 88 clinically-referred patients

• Across 4 sites (3 US, 1 European) and 3 languages (English, Spanish, German)

• Excluded those with prior dementia & low effort

Under Review

• 48%-71% were unable to return to work at baseline capacity (mean 7 mos. post-COVID-19)

• 0% to 71% lost employment

Long-term neuropsychological outcomes of COVID-19: A multicenter, cross-cultural study

Christina D. Kay, PhD*1, Ana Sofia Costa, PhD*2,3, Tracy D. Vannorsdall, PhD4,5, Paula Aduen,PhD6, Clara Vila-Castelar, PhD6, Sarah M. Burstein, BA1, Lauren Pollak, PhD1, Daniel K. Leibel, PhD4, Janet C. Sherman, PhD1, Julia Bungenberg, MD2, Kathrin Reetz, MD2,3, Yakeel T. Quiroz, PhD6

WHO Recommendations for Clinical Management of Cognitive & Neuropsychiatric Symptoms

• Cognition• Education should be provided, and advice on strategies to help establish expectations and to alleviate stress and anxiety

• Cognitive restorative rehabilitation may support with cognitive exercises and compensation tools and breaking down activities

• Encourage participation in daily activities that are meaningful for the patient

• Psychiatric symptoms• Basic mental health and psychosocial support by appropriately trained health or non‐health workers should be provided.

Management of Neuropsychiatric Symptoms Post‐COVID‐19

Very little COVID‐specific research thus far

• The critical illness literature suggests that multi‐modal rehab (including cognitive rehab) improves executive functioning and disability following hospitalization (e.g., Jackson et al, Critical Care Med, 2012)

• A 6‐week rehabilitation program starting 125 days post‐COVID‐19 diagnosis(Daynes et al., Chronic Respiratory Disease, 2021)

• Psychoeducation on emotional and cognitive changes, sleep, etc. from https://www.yourcovidrecovery.nhs.uk/

• Pre‐rehab MoCA 25/30 (SD 3), Post‐rehab = 27/30 (SD = 2), p < 0.01, exceeds minimal important difference for pulmonary rehab patients

Psychoeducation Behavioral activation 

Cognitive approaches 

Goal setting  Diaries Relaxation training 

Self‐care

Increase understanding and setting expectations 

Scheduling enjoyable and important  activities

Reframing exercises 

SMARTSpecific MeasurableAttractive/action orientedRealisticTime‐bound 

Aid understanding of patterns of antecedents, behaviors, and consequences

Progressive muscle relaxationMindfulness mediation

Sleep hygieneNutrition, Physical activitySocialization 

Management of Cognitive & Neuropsychiatric Symptoms Post‐COVID‐19

Cognitive and Mental Health Referral Resources

American Academy of Clinical Neuropsychology • https://theaacn.org/directory/

Rehabilitation Psychology• https://abpp.org/Directory

Future Work

⁍ Characterization ⁍ Large, longitudinal studies of neuropsychological and functional

outcomes relative to well-matched controls are ongoing ⁍ https://c4r‐nih.org⁍ https://g2aging.org⁍ https://hrs.isr.umich.edu⁍ https://www.recovercovid.org/

⁍ Treatment studies⁍ What cognitive remediation and mental health interventions work? ⁍ For whom? ⁍ When?⁍ What are the critical elements?

Acknowledgements

Ann Parker, MD PHDAlly Gorgone, MSKostas Lyketsos, MD MHSEsther Oh, MD PhDAnupama Kumar, MBBSDaniel Leibel, PhDEmily Duggan, PhDNeuroCOVID International Neuropsychology Taskforce

NIH: K23ES029105, K23HL138206, K12HL143957, R01AG057725

Johns Hopkins Alzheimer’s Disease Research Center (P30AG066507)

The Richman Precision Medicine Center of Excellence in Alzheimer’s Disease