The Clinical Neuropsychologist

ISSN: 1385-4046 (Print) 1744-4144 (Online) Journal homepage: https://www.tandfonline.com/loi/ntcn20

COVID-19 and clinical neuropsychology: A review

of neuropsychological literature on acute and
chronic pulmonary disease

Patrick Riordan, Monica Stika, Joshua Goldberg & Michelle Drzewiecki

To cite this article: Patrick Riordan, Monica Stika, Joshua Goldberg & Michelle Drzewiecki
(2020) COVID-19 and clinical neuropsychology: A review of neuropsychological literature on
acute and chronic pulmonary disease, The Clinical Neuropsychologist, 34:7-8, 1480-1497, DOI:
10.1080/13854046.2020.1810325

To link to this article: https://doi.org/10.1080/13854046.2020.1810325

Published online: 03 Sep 2020.

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THE CLINICAL NEUROPSYCHOLOGIST
2020, VOL. 34, NOS. 7–8, 1480–1497
https://doi.org/10.1080/13854046.2020.1810325

COVID-19 and clinical neuropsychology: A review of

neuropsychological literature on acute and chronic
pulmonary disease
Patrick Riordana,b, Monica Stikab, Joshua Goldbergb and Michelle Drzewieckib
a
Mental Health Service, Hines VA Medical Center, Hines, IL, USA; bDepartment of Neurology, Loyola
University Medical Center, Maywood, IL, USA

ABSTRACT ARTICLE HISTORY

Objective: The illness resulting from Severe Acute Respiratory Received 15 April 2020
Syndrome Coronavirus 2 (SARS-CoV-2), better known as COVID-19, Accepted 10 August 2020
has quickly escalated to a worldwide pandemic. Although under- Published online 4 Septem-
standing of the short and long-term manifestations of COVID-19 ber 2020
remains incomplete, there is a preponderance of respiratory path-
KEYWORDS
ology in COVID-19 and potential for chronic loss of pulmonary COVID-19; pulmonary
function in recovered patients, raising concerns for associated disease; ARDS; COPD;
cognitive impacts. SARS; MERS
Method: We conducted a narrative review of the existing litera-
ture on neuropsychological variables in acute/severe respiratory
disease and various forms of chronic pulmonary disease to inform
expectations about potential cognitive manifestations of
COVID-19.
Results: Cognitive dysfunction is common but not inevitable in
acute and chronic pulmonary disease, although unique predictors
and symptom trajectories appear to be associated with each.
Conclusions: Although the full scope of neuropathophysiology
associated with COVID-19 remains to be established, pulmonary
insults associated with the disease are likely to produce cognitive
dysfunction in a substantial percentage of patients.

Introduction
Coronavirus Disease 2019 (COVID-19) refers to the clinical disease state caused by the
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Empirical knowledge
regarding the epidemiology, pathophysiology, and clinical manifestations of the dis-
ease is rapidly evolving, but some general patterns have already taken shape. COVID-
19 was declared a pandemic by the World Health Organization on March 11, 2020, by
early April cases had been reported in nearly every country worldwide (CDC, 2020a;
WHO, 2020), and the outbreak is projected to last well into 2021 (Mahase, 2020).
Available data generally show elevated rates of disease symptomology and severity in
older adults and consistently show increased morbidity and mortality in individuals

CONTACT Patrick Riordan Patrick.Riordan@va.gov Hines VA Medical Center, Hines, IL, USA.
ß 2020 Informa UK Limited, trading as Taylor & Francis Group
 THE CLINICAL NEUROPSYCHOLOGIST 1481

with chronic health conditions like hypertension, diabetes, and coronary artery disease
(CDC, 2020b; Zhou et al., 2020). Importantly, however, significant international and
regional differences in epidemiological data have been observed, raising questions
about the influence of host genetics, cultural factors, health care system characteris-
tics, and government policies on disease dynamics and generalizability of research
findings (Dudley & Lee, 2020).
Coronaviruses are known to predominantly target the human respiratory system, as
previously observed in Severe Acute Respiratory Syndrome (SARS-CoV) and Middle
East Respiratory Syndrome (MERS-CoV) outbreaks (Rothan & Byrareddy, 2020). The
SARS-CoV-2 virus accesses host cells through the ACE2 enzyme, which is present in
multiple organ systems but is most prevalent in the type II alveolar cells within the
lungs (Letko et al., 2020). Failure of these cells, which help maintain alveolar homeo-
stasis through a variety of support roles, has previously been linked to numerous pul-
monary diseases (Beers & Moodley, 2017). Consistent with these mechanisms and prior
coronavirus outbreaks, pneumonia is reported to be the most frequent serious clinical
manifestation of COVID-19, and symptoms like dry cough, dyspnea, and ‘ground-glass’
opacities on lung CT are characteristic (Huang et al., 2020).
Early estimates of disease severity from the initial outbreak in Wuhan showed 81%
of patients experiencing mild or negligible symptoms of the disease (i.e., nonpneumo-
nia or mild pneumonia),
15% experiencing severe disease with symptoms like dys-
pnea, hypoxia, or >50% pulmonary infiltrates, and another 5% experiencing critical
symptoms like respiratory failure, septic shock, and multiple organ dysfunction (Wu &
McGoogan, 2020). While morbidity and mortality rates have varied substantially in
other countries (KCDC, 2020; Onder et al., 2020), pneumonia is consistently the most
frequent serious manifestation of COVID-19, with up to 20–40% of patients hospital-
ized for COVID-19 pneumonia reported to develop acute respiratory distress syndrome
(ARDS: Wang, Hu, et al., 2020; Wu, Chen, et al., 2020). Furthermore, lung abnormalities
have been observed in asymptomatic patients (Shi et al., 2020) and there are reports
of chronically reduced lung function and pulmonary fibrosis in somepatients who
have recovered from COVID-19 (Wang, Wang, et al., 2020). While long-term COVID-19
data remain to be seen, existing literature has demonstrated significant rates of
chronic lung injury and pulmonary dysfunction in survivors of ARDS (Heyland et al.,
2005) and evidence of pulmonary fibrosis in survivors of the 2003 SARS outbreak
(Antonio et al., 2003). There is also mounting evidence of high potential for delirium
(Kotfis et al., 2020) and other neurological manifestations in some patients with
COVID-19, including anosmia (Gane et al., 2020), stroke (American Academy of
Neurology, 2020), and other atypical neuropathology (e.g., Poyiadji et al., 2020). This
topic is covered in detail elsewhere in this issue (Rabinovitz et al., 2020).

Implications for clinical neuropsychology

Sequelae of COVID-19 infection are likely to have significant implications for the practice
of clinical neuropsychology, both in terms of potential cognitive manifestations and
associated mental health and quality of life factors. Although formal neuropsychological
test data do not appear to have been reported anywhere, high rates of subjective
1482 P. RIORDAN ET AL.

cognitive complaints (Sheng et al., 2005), cases of mental status change (Saad et al.,
2014), and other acute and chronic neurological symptoms (e.g., Algahtani et al., 2016;
Hung et al., 2003; Kim et al., 2017; Lau et al., 2004) were reported in the literature on
the prior SARS and MERS outbreaks. Additionally, significant rates of associated mental
health issues were documented amongst patients, providers, and even non-infected
individuals living under quarantine during that time (e.g., Jeong et al., 2016; Kim et al.,
2018; Sheng et al., 2005; Um et al., 2017). The emerging COVID-19 literature also high-
lights growing concern for delirium as a frequent and easily overlooked manifestation of
the disease. Although delirium is notoriously underdocumented, even early data from
Wuhan included reports of “impaired consciousness” in 7.5% of patients (Kotfis et al.,
2020). Furthermore, several case studies have reported delirium as the presenting mani-
festation of COVID-19 infection in some older adult patients (Alkeridy et al., 2020; Beach
et al., 2020). Additionally, multiple features of COVID-19 hospital care (e.g., social isola-
tion, prolonged ventilator use) are noted to increase the risk of delirium and underscore
the importance of assessing for and addressing modifiable risk factors for delirium
(Kotfis et al., 2020; O’Hanlon & Inouye, 2020).
Direct CNS infection, systemic and neuroinflammation, and prolonged hypoxia have
been proposed as likely underlying causes of both acute and chronic cognitive mani-
festations of COVID-19 (Steardo et al., 2020). Although multiple pathophysiological
processes may ultimately prove to contribute to cognitive dysfunction in patients with
COVID-19, there can be little doubt that neuropsychologists are or will soon be
encountering sequelae of acute and chronic pulmonary dysfunction caused by the dis-
ease. While potential for cognitive changes due to pulmonary disease is intuitive, the
dynamics of this relationship in terms of predictors, trajectories, and specific manifesta-
tions are much less clear. Accordingly, here we review the existing literature on neuro-
psychological outcomes associated with pneumonia, ARDS, and chronic pulmonary
disease to help inform initial expectations for neuropsychologists working with
patients recovering from COVID-19.

Pneumonia
Pneumonia is one of the most common causes of hospital admission and mortality in
the United States (Ramirez et al., 2017). In basic terms pneumonia refers to an infection
in one or both lungs, but it can be caused by a wide range of viral and bacterial agents
and varies substantially in severity, from mild to life-threatening. Pneumonia is broadly
classified as community-acquired versus hospital-acquired and, notably in the context of
COVID-19, the latter is frequently associated with ventilator use (Bassetti et al., 2012).
However, the emerging literature highlights the difficulty of distinguishing between
pneumonia due to COVID-19 itself versus ventilator-associated pneumonia (François
et al., 2020) and between COVID-19 pneumonia and ARDS (Gattinoni et al., 2020).

Pneumonia & cognition/mental health/quality of life outcomes

Although more research has been directed at cognitive outcomes in ARDS and chronic
pulmonary disease, a number of studies have demonstrated that pneumonia may
 THE CLINICAL NEUROPSYCHOLOGIST 1483

impact cognitive functioning, especially in certain patient populations and clinical con-
texts. Population-based research has demonstrated a bidirectional relationship
between cognitive impairment and pneumonia, with incidence of each shown to
increase the likelihood of the other (Shah et al., 2013). Similarly, pre-existing cognitive
impairment is associated with increased rates of pneumonia mortality (Salive et al.,
1993). Pneumonia is shown to increase the risk of developing dementia amongst eld-
erly patients (Tate et al., 2014). Even in non-elderly populations without major medical
comorbidities or other recent hospitalizations, a single episode of pneumonia is associ-
ated with substantially increased risk of cognitive impairment (Davydow et al., 2013).
While much of this research was based on brief cognitive screening measures, a study
using a broader neuropsychological test battery (RBANS, Trails, DKEFS Tower Test)
reported significant, lasting cognitive impairment after hospitalization for pneumonia
in approximately one third of adults >65 and in approximately one fifth of younger
patients (Girard et al., 2018). A single episode of hospitalization for pneumonia is also
associated with increased risk of depression and functional impairment in ADLs/IADLs
(Davydow et al., 2013).

Acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is characterized by severe dyspnea, tachyp-
nea, cyanosis, diffuse alveolar infiltration, pulmonary edema, and hypoxemia
(Ashbaugh et al., 1967; Bernard et al., 1994). ARDS can result from pneumonia and
multiple other precipitating etiologies including viral infection, severe trauma, sepsis,
transfusion, and other medical/surgical conditions (Ashbaugh et al., 1967; Hopkins,
Key, et al., 2010). Dysfunction of pulmonary surfactants, which are produced by the
type II alveolar cells that are susceptible to COVID-19, has also been identified as a
potential cause of ARDS (Fanelli & Ranieri, 2015). ARDS can produce multiple system
dysfunction and failure, including the central nervous system (Hopkins, Suchyta, et al.,
2010). ARDS course and recovery can be further complicated by shock, hypoxia, aspir-
ation, fluid overload, acidosis, steroid use, delirium, coma, trauma, infection, and
residual polyneuropathy and myopathy (Ashbaugh et al., 1967; Herridge et al., 2016;
Hsieh et al., 2015). Research suggests that most patients without pre-existing lung dis-
ease prior to an episode of ARDS largely return to baseline structural physiology with
mildly reduced diffusion, and this appears to be stable up to five years post-ARDS epi-
sode (Herridge et al., 2016). However, significant neuropsychological, psychiatric, and
functional sequelae of ARDS are well documented across a range of studies.

ARDS & cognition

ARDS is extensively linked to acute and chronic changes in cognitive functioning.
Acutely, intubated patients with ARDS are reported to exhibit higher prevalence of
delirium (73%) compared to other intubated patients without ARDS (52%) and non-
intubated ICU patients (21%; Hsieh et al., 2015). In terms of long-term cognitive
change, a review by Wilcox et al. (2013) reported the prevalence of ARDS-related cog-
nitive impairment ranged from 70 to 100% at discharge and remained around 46–78%
1484 P. RIORDAN ET AL.

at one year, 25–47% at two years, and approximately 20% after five years. Domains
most highly affected included attention, concentration, memory, and executive
functioning. Although the accumulated literature demonstrates clear potential for
ARDS-related impairment in major domains of cognitive functioning, review of several
individual studies is instructive for understanding the general patterns and trajectories
of this phenomenon.
Hopkins et al. (1999) reported the first formal neuropsychological data in ARDS, with
testing completed at time of discharge and again at a one-year follow-up. Using a test bat-
tery consisting of the WAIS-R, WMS-R, RAVLT, RCFT, Verbal Fluency (CFL), and Trail Making
Tests A & B, they evaluated a series of post-ARDS patients without any history of CNS dis-
ease, severe chronic disease, immunosuppression, and other complicating characteristics.
Compared to population normative data, they found that 100% of patients scored outside
of normal ranges on at least one neuropsychological measure pre-discharge and reported
mean WAIS-R scores of VIQ ¼ 92.1, PIQ ¼ 85.8, and FSIQ ¼ 89.7 at this assessment. At 1-
year follow-up significant improvement was observed on most measures, with mean
WAIS-R scores of VIQ ¼ 98.4, PIQ ¼ 98.1, and FSIQ ¼ 97.8. However, 30% of patients still
exhibited deficits on the WAIS-R, 48% were observed to display decreased mental process-
ing speed, and 78% of patients exhibited atypical performance on at least one test of other
cognitive functions such as memory, attention, and concentration.
In subsequent 2004 study, Hopkins and colleagues reported additional ARDS cogni-
tive outcome data using stricter inclusion criteria (including thorough screening for
pre-existing cognitive impairment, neurologic disease, psychotic disorder, or medical
conditions known to cause cognitive dysfunction), normatively corrected neuropsycho-
logical test scores, and well-defined criteria for cognitive ‘impairment’ (i.e., at least two
or more neuropsychological test scores >1.5 SD below population mean, or at least
one test score >2 SD below the population mean). Using the same battery of meas-
ures, they found that 69.7% of participants who completed the entire study exhibited
cognitive impairment at time of discharge and 45.5% at 1-year follow-up. In terms of
symptom trajectories, 33.3% of participants exhibited impairment at discharge but not
on 1-year follow-up testing, slightly higher than the 22% identified in their 1999 study.
Conversely, 9.1% of participants did not display cognitive impairment at discharge but
did on follow-up testing. On discharge testing, mean demographically-adjusted T
scores > 1 SD deviation below normal expectations were observed on the WAIS-R
PIQ, WAIS-R FSIQ, Object Assembly, Digit Symbol, Rey Figure Immediate and Delayed
Recall, and WMS-R Delay Recall Index, while mean scores for Trails A and B fell > 1.5
SD below expectations. At 1-year follow-up, no mean demographically-adjusted T
scores fell below 40, with the WMS-R Delay Recall Index (T ¼ 41.5), Rey Immediate
Recall (T ¼ 43.1), and WAIS-R Comprehension (T ¼ 43.2) representing the lowest mean
scores at that time. Hopkins et al. (2005) reported 2-year follow-up data on these par-
ticipants, finding evidence of cognitive impairment in 47% of participants using the
same measures and criteria, and concluding that there was no evidence of improve-
ment in neurocognitive sequelae of ARDS from 1–2 years.
The authors of the prior studies noted narrow representation of frontal/executive
functioning (EF) as a limitation of their test battery (Hopkins et al., 1999), but some
facets of executive functioning have been shown to be vulnerable to ARDS/acute lung
 THE CLINICAL NEUROPSYCHOLOGIST 1485

injury (ALI) in theirs and others’ work. As described above, impaired performance on
Trails B was observed in a number of ARDS studies and reported in other research on
survivors of ARDS and other forms of critical illness (Pandharipande et al., 2013). In an
ALI study evaluating cognitive functioning with a telephone administered test battery,
approximately 49% of patients exhibited impaired performance on an EF measure of
response initiation and response suppression, the Hayling Sentence Completion Test
(HSCT), with a particularly strong association observed between hypoxemia and EF
outcomes (Mikkelsen et al., 2012). In a drug study using the same measure at 6- and
12-month follow-ups after sepsis-related ARDS, 30% and 16% of patients scored in the
impaired range, respectively (Needham et al., 2016). In a cross-sectional telephone
based study of self-selected survivors of ARDS at varying lengths of time since illness
(Mikkelsen et al., 2009), impaired HSCT performance was observed in 29% of patients,
while much lower rates of impaired performance were reported on measures of judg-
ment (Neurobehavioral Cognitive Status Examination[NCSE]: Judgment, <5% impaired)
and abstract reasoning (WAIS-III Similarities, 10% impaired).
A variety of factors appear to be associated with increased likelihood of ARDS-
related cognitive impairment. In terms of patient history variables, pre-existing depres-
sion, lower premorbid intelligence, self-reported memory difficulties, and pre-existing
cognitive impairment are risk factors for increased cognitive morbidity post-ARDS
(Herridge et al., 2016; Larson et al., 2007; Wilcox et al., 2013). With regard to illness-
related variables, findings have been mixed. Hopkins et al. (1999) reported significant
negative correlations between duration of hypoxemia and performance on a range of
neuropsychological tests, including Trails B, Rey Figure Recall, Digit Span, Block
Design, Digit Symbol Coding, and overall WAIS IQ Scores. However, an overall measure
of disease severity (APACHE-II  18) did not predict cognitive outcome differences in
this study. In their subsequent 2004 study, however, overall disease severity (APACHE-
II score) was correlated with lower cognitive performance on one measure (delayed
visual memory), while oxygen saturation <90% did not significantly correlate with
neuropsychological test scores. Other studies have identified hypoxemia and hypoxia
as mechanisms of neuronal atrophy, subsequent ventricular enlargement, and associ-
ated cognitive impairment, particularly in memory (Herridge et al., 2016; Mikkelsen
et al., 2012). This relationship may be due to the demonstrated sensitivity of hippo-
campal neurons to oxygen deprivation (Cervos-Navarro & Diemer, 1991). In a study of
15 patients post-ARDS, brain CT scans showed generalized cerebral atrophy and bilat-
eral temporal horn enlargement relative to matched controls (Hopkins et al., 2006).
Additional factors reported to predict cognitive impairment following ARDS include
duration of hypotension, venous pressure, hyperglycemia, and amnesia for ICU admis-
sion (Herridge et al., 2016; Hopkins, Suchyta, et al., 2010; Hopkins et al., 2005; Larson
et al., 2007). Delirium is also recognized as a potentially modifiable risk factor for long-
term cognitive dysfunction following critical illness (Hopkins & Jackson, 2006).

ARDS & mental health/quality of life outcomes

A range of acute and post-acute psychiatric symptomology is associated with ARDS.
Chronic mental health conditions including depression, generalized anxiety, and PTSD
1486 P. RIORDAN ET AL.

are observed in significant numbers of ARDS survivors (Davydow et al., 2008), a topic
addressed in greater detail elsewhere in this issue (Kaseda, 2020). Research has also
demonstrated reduced health-related quality of life (HRQOL) amongst ALI/ARDS survi-
vors (Davydow et al., 2008; Dowdy et al., 2006; Hsieh et al., 2015). Many of the same
illness and treatment variables that predict psychopathology (e.g., longer lengths of
ICU stay and increased duration of both sedation and mechanical ventilation) are also
predictive of diminished HRQOL, (Davydow et al., 2009; Dowdy et al., 2006) and con-
siderable symptom overlap has been reported. For example, pre-ARDS depression is
negatively associated with patients returning to work (Adhikari et al., 2009), and pre-
morbid generalized anxiety is associated with greater impairments in physical func-
tioning and reduced HRQOL (Herridge et al., 2016).

Chronic pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) and other chronic pulmonary diseases
can also inform expectations for COVID-19 outcomes. COPD is a common and fre-
quently preventable respiratory disease characterized by airflow limitations due to air-
way and/or alveolar abnormalities, most often caused by exposure to noxious particles
or gases (GOLD, 2020). Chronic airway obstructions are caused by a variety of patho-
logically-distinct conditions such as chronic bronchitis (characterized by bronchial
inflammation and mucus overproduction), emphysema (characterized by alveolar dam-
age and impaired gas exchange), and refractory asthma (characterized by airway
inflammation and constriction). COPD currently affects approximately 16 million
Americans and represents the 4th leading cause of death in the United States (NHLBI,
2018). Risk factors include lifestyle (especially tobacco smoking), environment, and
genetics. A range of viral infections, including coronaviruses, have also been impli-
cated in the pathogenesis and exacerbation of COPD (Frickmann et al., 2012). COPD is
classified as an incurable disease but treatment options include medications (e.g. bron-
chodilators, inhaled steroids, anti-inflammatory agents), pulmonary rehabilitation, oxy-
gen supplementation, surgery, and lifestyle related changes (NHLBI, 2019).

Chronic pulmonary disease& cognition

Similar to ARDS, a range of neuropsychological impairments have been reported in
patients with various forms of chronic pulmonary disease. Reported areas of cognitive
dysfunction include motor functioning, abstraction, executive functioning, learning
and memory, processing speed, and working memory (Favalli et al., 2008; Grant et al.,
1982; Prigatano et al., 1983). While minimal or absent cognitive findings have been
reported in some studies of patients with COPD (e.g., Fix et al., 1982; Kozora et al.,
1999), measurable cognitive impairment is common in those with hypoxemia
(Prigitano et al., 1983) and has been observed in non-hypoxemic COPD as well.
Although they characterized the magnitude of the weaknesses as “small,” Fix et al.
(1982) found reduced performances on measures of simple attention, working mem-
ory, processing speed, and executive functioning in a COPD sample predominantly
comprised of emphysema patients. Patients with both COPD and non-obstructive
 THE CLINICAL NEUROPSYCHOLOGIST 1487

chronic bronchitis have demonstrated lower cognitive performance relative to norma-

tive reference values and asymptomatic smokers (Dal Negro et al., 2014), and neuro-
psychological impairments have also been reported in studies pooling patients with
chronic bronchitis and other chronic respiratory diseases (e.g., Jelicic & Kempen, 1997;
Stuss et al., 1997). In asthma studies, impairments in attention, processing speed,
learning and memory, and visual-spatial functioning have been identified (Irani et al.,
2017; Moss et al., 2005). Additionally, older adults with refractory asthma have exhib-
ited elevated rates of executive dysfunction and associated difficulty with treatment
compliance (O’Conor et al., 2015). Cognitive impairments have also been reported in
other chronic pulmonary diseases like idiopathic pulmonary fibrosis (IPF). Bors et al.
(2015) found that patients with severe IPF performed significantly worse than controls
and patients with mild to moderate IPF on a range of neuropsychological tests (Trails
A & B, Stroop Color-Word, HVLT Delayed Recall, Boston Naming Test, and
Grooved Pegboard).
The extent to which there is a prototypical neuropsychological performance profile
for COPD has been debated, but potential for impairment in most general areas of
cognitive functioning is reported (Dodd et al., 2010). However, performances on lan-
guage measures have appeared relatively resistant to COPD-related cognitive change
in some studies (Dodd et al., 2010). For example, Stuss et al. (1997) found strong cor-
relations between arterial oxygen and CO2 pressures and performance on tests of
memory (WMS) and complex attention (Trails B, PASAT) in a sample of patients with
COPD. However, they did not find significant correlations between blood gas levels
and verbal fluency (FAS) or naming (Boston Naming Test) performance, and even
observed ceiling levels of BNT performance. Additionally, several studies comparing
neuropsychological test performances across patients with COPD, Alzheimer’s disease
(AD), and healthy controls reported distinct and typically less severe patterns of per-
formance impairment in COPD versus AD (Kozora et al., 1999; Morris et al., 2019).
Liesker et al. (2004) compared performance on a range of neuropsychological tests in
patients with non-hypoxemic COPD and controls matched for age, education, and
NART-estimated IQ. In spite of a relatively small sample size, they found significantly
lower performance in the COPD group on 3/9 neuropsychological test scores (Trail
Making Test B, WAIS Digit-Symbol, and a rote addition test), but did not identify sig-
nificant performance differences on any Stroop trials or on learning or delayed recall
trials of a story memory test.
Interms of predictors of cognitive dysfunction in COPD, much like the ARDS data,
many of the findings are mixed. Although findings on the degree of correlation
between arterial oxygen and cognitive function have varied (Dodd et al., 2010), the
presence of hypoxemia is generally associated with increased risk of impairment in a
range of cognitive functions. In a studycomparing performance of patients with COPD
with mild hypoxemia against matched controls on a broad range of neuropsycho-
logical tests (Halstead-Reitan, WAIS, WMS subtests, and other measures), “modest”
impairments in abstract reasoning, memory, and processing speed were reported
(Prigatano et al., 1983). In later work comparing performance on a similar test battery
across groups of patients with COPD with varying levels of hypoxemia severity, Grant
et al. (1987) reported increasing levels of impairment on a composite measure of
1488 P. RIORDAN ET AL.

overall test performance with increased disease severity. Here, a 27% rate of impaired
performance was reported for the mild hypoxemia group, 44% in the moderate hyp-
oxemia group, and 61% in the severe group. Cerebral perfusion has also been
observed to correlate with presence of hypoxemia and degree of cognitive impairment
in a SPECT study of patients with hypoxemic COPD, non-hypoxemic COPD, and
healthy controls (Ortapamuk & Naldoken, 2006). Here, the greatest breadth and sever-
ity of cognitive impairment (on verbal learning, recall, and attention tests) and ROI
perfusion abnormalities was observed in the hypoxemic COPD group, with the non-
hypoxemic COPD group exhibiting significant but less extreme differences relative to
controls. Despite the generally irreversible nature of COPD and the extensive findings
demonstrating significant potential for cognitive impairment, a number of studies
have suggested potential for cognitive improvement/protection with various forms of
COPD intervention, including supplemental oxygen therapy (Krop et al., 1973; Thakur
et al., 2010), exercise programs (Emery et al., 2003), comprehensive rehabilitation pro-
grams (Kozora et al., 2002), and lung volume reduction surgery (Kozora et al., 2008).

COPD & mental health/quality of life outcomes

In addition to its cognitive manifestations, patients with COPD also often experience
psychological distress, mood symptoms, and functional/quality of life limitations
(Ouellette & Lavoie, 2017; Yohannes et al., 2000). Estimates vary, but persons with
COPD are reported to be at approximately 60% and 85% higher risk of developing
depression and anxiety, respectively, than the general population (Yohannes &
Alexopoulos, 2014). Elevated rates of psychological dysfunction have been reported
across major COPD etiologies, including emphysema (TenVergert et al., 2001), chronic
bronchitis (Wagena et al., 2005), and refractory asthma (Pakhale et al., 2011). Diagnosis
of mood disorders in patients with COPD is complicated by symptom overlap, and
high rates of undiagnosed/untreated depression and anxiety are reported (Yohannes &
Alexopoulos, 2014). Impairments across major areas of health-related quality of life are
also reported in this group, with both COPD and its common comorbidities reported
to account for various aspects of these impairments (van Manen et al., 2003). High
rates of functional disability are also observed in patients with COPD, especially those
with comorbid mood disorder, with one study reporting a 46.5% rate of functional dis-
ability in non-depressed individuals and 68.2% in patients with depression (Egede,
2007). Additionally, anxiety and depression are associated with poorer treatment
adherence in some COPD populations (Pakhale et al., 2011).

Conclusions
The COVID-19 pandemic will have significant implications for the practice of clinical
neuropsychology for many years to come. While available evidence indicates potential
for direct or secondary neurological manifestations of the disease, the rapidly evolving
literature on COVID-19 indicates that the majority of severe pathology is respiratory in
nature. It may be years before we have a firm understanding of the neuropsycho-
logical ramifications of COVID-19, but the existing literature on acute and chronic
 THE CLINICAL NEUROPSYCHOLOGIST 1489

respiratory illness is instructive and strongly implies significant potential for cognitive
impairment following COVID-19 infection. Neuropsychological findings across and
even within pulmonary illnesses are notably mixed, but some instructive takeaways
can be drawn.
General Pneumonia/ARDS findings:

 The causes and severity of pneumonia can vary widely, but research demonstrates
substantial potential for development or exacerbation of cognitive dysfunction fol-
lowing hospitalization for pneumonia.
 Delirium is common during ARDS.
 Measurable cognitive impairment following ARDS is typical but not inevitable, with
data suggesting that roughly 70–100% of patients exhibit impaired performance on
initial neuropsychological testing at hospital discharge.
 Substantial improvement in neuropsychological test performance is common in the
first year following an episode of ARDS, with some patients’ scores returning to
normal, but cognitive recovery is likely to plateau after this point.
 There appears to be potential for impairment across domains of cognitive function-
ing, but the literature suggests that chronic memory impairment is especially com-
mon following ARDS.
 Hypoxemia/hypoxia appear to be the primary factors underlying chronic cognitive
dysfunction, although the strength of this relationship varies across studies and
other variables are contributory.
 Limited imaging data show evidence of general cerebral atrophy and bilateral tem-
poral horn enlargement, as well associated cognitive impairment, in patients
post-ARDS.
 Acute anxiety and depression frequently occur in ARDS, and chronic mood disor-
ders, PTSD, and decreased life quality are common findings post-ARDS. These
findings underscore the need for neuropsychological and mental health evalu-
ation and treatment in routine post-ARDS care during hospitalization and
after discharge.

General Chronic Pulmonary Disease Findings:

 Similar to ARDS, significant potential for cognitive impairment has been reported
across the major forms of COPD and in multiple other chronic pulmonary condi-
tions, including pulmonary fibrosis. However, significant differences in acuity of
symptom onset, symptom trajectory, and treatment potential are present.
 Hypoxemia/hypoxia is also believed to be the primary etiology of cognitive dys-
function in COPD, and hypoxemia/hypercapnia severity is broadly predictive of
severity of cognitive dysfunction. As with ARDS, the strength of correlation
between hypoxemia and cognitive impairment varies across studies, and cognitive
impairment has been reported in non-hypoxemic COPD as well.
 Potential for impairment across domains of neuropsychological functioning appears
possible, but some studies have suggested that language impairments due to
COPD may be less common.
1490 P. RIORDAN ET AL.

 Various forms of COPD treatment are associated with improved performance on

cognitive testing.
 As with ARDS, mood/psychological symptoms, quality of life limitations, and
impaired role functioning are frequently reported in patients with chronic pulmon-
ary disease, with some studies suggesting that untreated mood symptoms predict
treatment non-adherence and potential disease exacerbation.

Overall, the existing literature on acute and chronic pulmonary disease helps inform
expectations regarding the practice of clinical neuropsychology with patients recover-
ing from COVID-19. While this literature demonstrates that there is not a well-defined
prototype for cognitive dysfunction following pneumonia, ARDS, or development of
chronic pulmonary disease, it does illustrate clear trends in terms of potential impair-
ments, symptom trajectories, and predisposing factors like advanced age and medical
comorbidities. Future research will be necessary to improve our understanding of the
ways in which COVID-19 both overlaps with and differs from what we already know
about neuropsychological outcomes in pulmonary disease and prior coronavirus epi-
demics, with early data suggesting significant potential for unique pathology and out-
comes. However, the existing literature strongly implies that many hospitalized with
COVID-19 will develop appreciable cognitive and mental health symptoms that may
improve with time and treatment but may never fully recover. Clinical neuropsycholo-
gists will be in a unique position to evaluate and address the potentially devastating
impacts of these symptoms, symptoms that may understandably be overlooked in the
context of a global, life-threatening pandemic. As in so many areas of modern life,
COVID-19 has already dictated drastic changes in the practice of clinical neuropsych-
ology. Providers have had to postpone patients, close clinics, and/or rapidly shift to
telehealth assessment models. Here too a turn back to existing literature is instructive,
with, for example, a telephone-administered battery of neuropsychological tests hav-
ing been developed and validated for use with patients with ARDS (Christie et al.,
2006) and chronic pulmonary disease (Taichman et al., 2005), in addition to the grow-
ing body of studies evaluating remote video administration of neuropsychological
tests (e.g., Cullum et al., 2014). Nonetheless, additional research is needed to better
understand the validity and reliability of these methodologies in the significantly less
controlled circumstances we may now need to apply them in. Ultimately, clinical
neuropsychology has a long way to go in terms of understanding and adapting to the
new reality of COVID-19. However, while this pandemic gives us many new things to
learn, it also demonstrates that there is much to learn from what we already have.

Disclosure statement
All authors have no conflicts of interest to declare.

Funding
There was no formal funding support for this work.
 THE CLINICAL NEUROPSYCHOLOGIST 1491

References
Adhikari, N. K. J., McAndrews, M. P., Tansey, C. M., Matt
e, A., Pinto, R., Cheung, A. M., Diaz-
Granados, N., Barr, A., & Herridge, M. S. (2009). Self-reported symptoms of depression and
memory dysfunction in survivors of ARDS. Chest, 135(3), 678–687. https://doi.org/10.1378/
chest.08-0974
Algahtani, H., Subahi, A., & Shirah, B. (2016). Neurological complications of Middle East respira-
tory syndrome coronavirus: A report of two cases and review of the literature. Case Reports in
Neurological Medicine, 2016, 3502683–3502686. https://doi.org/10.1155/2016/3502683
Alkeridy, W. A., Almaghlouth, I., Alrashed, R., Alayed, K., Binkhamis, K., Alsharidi, A., & Liu-
Ambrose, T. (2020). A unique presentation of delirium in a patient with otherwise asymptom-
atic COVID-19. Journal of the American Geriatrics Society, 68(7), 1382–1384. https://doi.org/10.
1111/jgs.16536
American Academy of Neurology. (2020, April 6). COVID-19: Neurologists in Italy to colleagues in
US: Look for poorly-defined neurologic conditions in patients with the coronavirus. https://jour-
nals.lww.com/neurotodayonline/blog/breakingnews/pages/post.aspx?PostID=920
Antonio, G. E., Wong, K. T., Hui, D. S. C., Wu, A., Lee, N., Yuen, E. H. Y., Leung, C. B., Rainer, T. H.,
Cameron, P., Chung, S. S. C., Sung, J. J. Y., & Ahuja, A. T. (2003). Thin-section CT in patients
with severe acute respiratory syndrome following hospital discharge: Preliminary experience.
Radiology, 228(3), 810–815. https://doi.org/10.1148/radiol.2283030726
Ashbaugh, D. G., Ohio, M. D., Boyd Bigelow, D., Colorado, M. D., Petty, T. L., Levine, B. E., &
Michigan, M. D. (1967). Acute respiratory distress in adults. The Lancet, 290, 319–323.
Bassetti, M., Taramasso, L., Giacobbe, D. R., & Pelosi, P. (2012). Management of ventilator-associ-
ated pneumonia: epidemiology, diagnosis and antimicrobial therapy. Expert Review of anti-
Infective Therapy, 10(5), 585–596. https://doi.org/10.1586/eri.12.36
Beach, S. R., Praschan, N. C., Hogan, C., Dotson, S., Merideth, F., Kontos, N., Fricchione, G. L., &
Smith, F. A. (2020). Delirium in COVID-19: A case series and exploration of potential mecha-
nisms for central nervous system involvement. General Hospital Psychiatry, 65, 47–53. https://
doi.org/10.1016/j.genhosppsych.2020.05.008
Beers, M. F., & Moodley, Y. (2017). When is an alveolar type 2 cell an alveolar type 2 cell? A con-
undrum for lung stem cell biology and regenerative medicine. American Journal of Respiratory
Cell and Molecular Biology, 57(1), 18–27. https://doi.org/10.1165/rcmb.2016-0426PS
Bernard, G. R., Artigas, A., Brigham, K. L., Carlet, J., Falke, K., Hudson, L., Lamy, M., Legall, J. R.,
Morris, A., Spragg, R., Cochin, B., Lanken, P. N., Leeper, K. V., Marini, J., Murray, J. F.,
Oppenheimer, L., Pesenti, A., Reid, L., & Rinaldo, J. (1994). The American-European consensus
conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordin-
ation. American Journal of Respiratory and Critical Care Medicine, 149(3 Pt 1), 818–824. https://
doi.org/10.1164/ajrccm.149.3.7509706
Bors, M., Tomic, R., Perlman, D. M., Kim, H. J., & Whelan, T. P. M. (2015). Cognitive function in
idiopathic pulmonary fibrosis. Chronic Respiratory Disease, 12(4), 365–372. https://doi.org/10.
1177/1479972315603552
Center for Disease Control (CDC). (2020a, April 5). Coronavirus disease 2019 (COVID-19): World
map. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/world-map.html
Center for Disease Control (CDC). (2020b, April 6). Preliminary estimates of the prevalence of
selected underlying health conditions among patients with coronavirus disease 2019—United
States, February 12–March 28, 2020. https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e2.
htm?s_cid=mm6913e2_w
Cervos-Navarro, J., & Diemer, N. H. (1991). Selective vulnerability in brain hypoxia. Critical
Reviews in Neurobiology, 6(3), 149–182.
Christie, J. D., Biester, R. C. P., Taichman, D. B., Shull, W. H., Jr, Hansen-Flaschen, J., Shea, J. A., &
Hopkins, R. O. (2006). Formation and validation of a telephone battery to assess cognitive
function in acute respiratory distress syndrome survivors. Journal of Critical Care, 21(2),
125–132. https://doi.org/10.1016/j.jcrc.2005.11.004
1492 P. RIORDAN ET AL.

Cullum, C. M., Hynan, L. S., Grosch, M., Parikh, M., & Weiner, M. F. (2014). Teleneuropsychology:
Evidence for video teleconference-based neuropsychological assessment. Journal of the
International Neuropsychological Society: JINS, 20(10), 1028–1033. https://doi.org/10.1017/
S1355617714000873
Dal Negro, R. W., Bonadiman, L., Tognella, S., Bricolo, F. P., & Turco, P. (2014). Extent and preva-
lence of cognitive dysfunction in chronic obstructive pulmonary disease, chronic non-
obstructive bronchitis, and in asymptomatic smokers, compared to normal reference values.
International Journal of COPD, 9, 675–683. https://doi.org/10.2147/COPD.S63485
Davydow, D. S., Desai, S. V., Needham, D. M., & Bienvenu, O. J. (2008). Psychiatric morbidity in
survivors of the acute respiratory distress syndrome: A systematic review. Psychosomatic
Medicine, 70(4), 512–519. https://doi.org/10.1097/PSY.0b013e31816aa0dd
Davydow, D. S., Katon, W. J., & Zatzick, D. F. (2009). Psychiatric morbidity and functional impair-
ments in survivors of burns, traumatic injuries, and ICU stays for other critical illnesses: A
review of the literature. International Review of Psychiatry (Abingdon, England), 21(6), 531–538.
https://doi.org/10.3109/09540260903343877
Davydow, D. S., Hough, C. L., Levine, D. A., Langa, K. M., & Iwashyna, T. J. (2013). Functional dis-
ability, cognitive impairment, and depression after hospitalization for pneumonia. The
American Journal of Medicine, 126(7), 615–624. https://doi.org/10.1016/j.amjmed.2012.12.006
Dodd, J. W., Getov, S. V., & Jones, P. W. (2010). Cognitive function in COPD. The European
Respiratory Journal, 35(4), 913–922. https://doi.org/10.1183/09031936.00125109
Dowdy, D. W., Eid, M. P., Dennison, C. R., Mendez-Tellez, P. A., Herridge, M. S., Guallar, E.,
Pronovost, P. J., & Needham, D. M. (2006). Quality of life after acute respiratory distress syn-
drome: A meta-analysis. Intensive Care Medicine, 32(8), 1115–1124. https://doi.org/10.1007/
s00134-006-0217-3
Dudley, J. P., & Lee, N. T. (2020). Disparities in age-specific morbidity and mortality from SARS-
CoV-2 in China and the Republic of Korea. Clinical Infectious Diseases, 71(15), 863–865. https://
doi.org/10.1093/cid/ciaa354
Egede, L. E. (2007). Major depression in individuals with chronic medical disorders: Prevalence,
correlates and association with health resource utilization, lost productivity and functional dis-
ability. General Hospital Psychiatry, 29(5), 409–416. https://doi.org/10.1016/j.genhosppsych.
2007.06.002
Emery, C. F., Shermer, R. L., Hauck, E. R., Hsiao, E. T., & MacIntyre, N. R. (2003). Cognitive and psy-
chological outcomes of exercise in a 1-year follow-up study of patients with chronic obstruct-
ive pulmonary disease. Health Psychology, 22(6), 598–604. https://doi.org/10.1037/0278-6133.
22.6.598
Fanelli, V., & Ranieri, V. M. (2015). Mechanisms and clinical consequences of acute lung injury.
Annals of the American Thoracic Society, 12(Supplement 1), S3–S8. https://doi.org/10.1513/
AnnalsATS.201407-340MG
Favalli, A., Miozzo, A., Cossi, S., & Marengoni, A. (2008). Efficacy and safety of donepezil, galant-
amine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and
meta-analysis. Clinical Interventions in Aging, 3(2), 211–225. https://doi.org/10.1002/gps
Fix, A. J., Golden, C. J., Daughton, D., And, I. K., & Bell, C. W. (1982). Neuropsychological deficits
among patients with chronic obstructive pulmonary disease. The International Journal of
Neuroscience, 16(2), 99–105. https://doi.org/10.3109/00207458209147610
François, B., Laterre, P. F., Luyt, C. E., & Chastre, J. (2020). The challenge of ventilator-associated
pneumonia diagnosis in COVID-19 patients. Critical Care, 24(1), 289. https://doi.org/10.1186/
s13054-020-03013-2
Frickmann, H., Jungblut, S., Hirche, T. O., Groß, U., Kuhns, M., & Zautner, A. E. (2012). The influ-
ence of virus infections on the course of COPD. European Journal of Microbiology &
Immunology, 2(3), 176–185. https://doi.org/10.1556/EuJMI.2.2012.3.2
Gane, S. B., Kelly, C., & Hopkins, C. (2020). Isolated sudden onset anosmia in COVID-19 infection.
Rhinology Journal, 58(3), 299–301. https://doi.org/10.4193/Rhin20.114
Gattinoni, L., Chiumello, D., & Rossi, S. (2020). COVID-19 pneumonia: ARDS or not? Critical Care
(London, England), 24(1), 154. https://doi.org/10.1186/s13054-020-02880-z
 THE CLINICAL NEUROPSYCHOLOGIST 1493

Girard, T. D., Self, W. H., Edwards, K. M., Grijalva, C. G., Zhu, Y., Williams, D. J., Jain, S., & Jackson,
J. C. (2018). Long-term cognitive impairment after hospitalization for community-acquired
pneumonia: A prospective cohort study. Journal of General Internal Medicine, 33(6), 929–935.
https://doi.org/10.1007/s11606-017-4301-x
GOLD. (2020). Global strategy for chronic obstructive pulmonary disease. Global Initiative for
Chronic Obstructive Lung Disease. https://goldcopd.org/wp-content/uploads/2019/12/GOLD-
2020-FINAL-ver1.2-03Dec19_WMV.pdf
Grant, I., Heaton, R. K., Mcsweeny, A. J., Adams, K. M., & Timms, R. M. (1982). Neuropsychologic
findings in hypoxemic chronic obstructive pulmonary disease. Archives of Internal Medicine,
142(8), 1470–1476. https://doi.org/10.1001/archinte.1982.00340210062015
Grant, I., Prigatano, G. P., Heaton, R. K., McSweeny, A. J., Wright, E. C., & Adams, K. M. (1987).
Progressive neuropsychologic impairment and hypoxemia: Relationship in chronic obstructive
pulmonary disease. Archives of General Psychiatry, 44(11), 999–1006. https://doi.org/10.1001/
archpsyc.1987.01800230079013
Herridge, M. S., Moss, M., Hough, C. L., Hopkins, R. O., Rice, T. W., Bienvenu, O. J., & Azoulay, E.
(2016). Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in
patients and their family caregivers. Intensive Care Medicine, 42(5), 725–738. https://doi.org/10.
1007/s00134-016-4321-8
Heyland, D. K., Groll, D., & Caeser, M. (2005). Survivors of acute respiratory distress syndrome:
Relationship between pulmonary dysfunction and long-term health-related quality of life.
Critical Care Medicine, 33(7), 1549–1556. https://doi.org/10.1097/01.CCM.0000168609.98847.50
Hopkins, R. O., Gale, S. D., & Weaver, L. K. (2006). Brain atrophy and cognitive impairment in sur-
vivors of acute respiratory distress syndrome. Brain Injury, 20(3), 263–271. https://doi.org/10.
1080/02699050500488199
Hopkins, R. O., & Jackson, J. C. (2006). Assessing neurocognitive outcomes after critical illness:
are deliriu and long-term cognitive impairments realted. Current Opinion in Critical Care, 12(5),
338–394.
Hopkins, R. O., Key, C. W., Suchyta, M. R., Weaver, L. K., & Orme, J. F. (2010). Risk factors for
depression and anxiety in survivors of acute respiratory distress syndrome. General Hospital
Psychiatry, 32(2), 147–155. https://doi.org/10.1016/j.genhosppsych.2009.11.003
Hopkins, R. O., Weaver, L. K., Pope, D., Orme, J. F., Jr, Bigler, E. D., & Larson-Lohr, V. (1999).
Neuropsychological sequelae and impaired health status in survivors of severe acute respira-
tory distress syndrome. American Journal of Respiratory and Critical Care Medicine, 160(1),
50–56. https://doi.org/10.1164/ajrccm.160.1.9708059
Hopkins, R. O., Suchyta, M. R., Snow, G. L., Jephson, A., Weaver, L. K., & Orme, J. F. (2010). Blood
glucose dysregulation and cognitive outcome in ARDS survivors. Brain Injury, 24(12),
1478–1484. https://doi.org/10.3109/02699052.2010.506861
Hopkins, R. O., Weaver, L. K., Collingridge, D., Parkinson, R. B., Chan, K. J., & Orme, J. F. (2005).
Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syn-
drome. American Journal of Respiratory and Critical Care Medicine, 171(4), 340–347. https://doi.
org/10.1164/rccm.200406-763OC
Hsieh, S. J., Soto, G. J., Hope, A. A., Ponea, A., & Gong, M. N. (2015). The association between
acute respiratory distress syndrome, delirium, and in-hospital mortality in intensive care unit
patients. American Journal of Respiratory and Critical Care Medicine, 191(1), 71–78. https://doi.
org/10.1164/rccm.201409-1690OC
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu,
T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., … Cao, B. (2020). Clinical features of
patients infected with 2019 novel coronavirus in Wuhan. The Lancet, 395(10223), 497–506.
https://doi.org/10.1016/S0140-6736(20)30183-5
Hung, E. C. W., Chim, S. S. C., Chan, P. K. S., Tong, Y. K., Ng, E. K. O., Chiu, R. W. K., Leung, C.-B.,
Sung, J. J. Y., Tam, J. S., & Lo, Y. M. D. (2003). Detection of SARS coronavirus RNA in the cere-
brospinal fluid of a patient with severe acute respiratory syndrome. Clinical Chemistry, 49(12),
2108–2109. https://doi.org/10.1373/clinchem.2003.025437
1494 P. RIORDAN ET AL.

Irani, F., Barbone, J. M., Beausoleil, J., & Gerald, L. (2017). Is asthma associated with cognitive
impairments? A meta-analytic review. Journal of Clinical and Experimental Neuropsychology,
39(10), 965–978. https://doi.org/10.1080/13803395.2017.1288802
Jelicic, M., & Kempen, G. I. J. M. (1997). Cognitive function in community-dwelling elderly with
chronic medical conditions. International Journal of Geriatric Psychiatry, 12(10), 1039–1041.
https://doi.org/10.1002/(SICI)1099-1166(199710)12:10<1039::AID-GPS678>3.0.CO;2-Z
Jeong, H., Yim, H. W., Song, Y. J., Ki, M., Min, J. A., Cho, J., & Chae, J. H. (2016). Mental health sta-
tus of people isolated due to Middle East respiratory syndrome. Epidemiology and Health, 38,
e2016048. https://doi.org/10.4178/epih.e2016048
Kaseda, E. (2020). Post-traumatic stress disorder: A differential diagnostic consideration for
COVID-19 survivors. The Clinical Neuropsychologist, 34(7–8), 1498–1514. https://doi.org/10.
1080/13854046.2020.1811894
KCDC. (2020, March 14). Updates on COVID-19 in Korea. https://www.cdc.go.kr/board/board.
es?mid=a30402000000&bid=0030
Kim, J. E., Heo, J. H., Kim, H. O., Song, S. H., Park, S. S., Park, T. H., Ahn, J. Y., Kim, M. K., & Choi,
J. P. (2017). Neurological complications during treatment of Middle East respiratory syndrome.
Journal of Clinical Neurology (Seoul, Korea), 13(3), 227–233. https://doi.org/10.3988/jcn.2017.13.
3.227
Kim, H. C., Yoo, S. Y., Lee, B. H., Lee, S. H., & Shin, H. S. (2018). Psychiatric findings in suspected
and confirmed middle east respiratory syndrome patients quarantined in hospital: A retro-
spective chart analysis. Psychiatry Investigation, 15(4), 355–360. https://doi.org/10.30773/pi.
2017.10.25.1
Kotfis, K., Williams Roberson, S., Wilson, J. E., Dabrowski, W., Pun, B. T., & Ely, E. W. (2020).
COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Critical Care, 24(1), 1–9.
https://doi.org/10.1186/s13054-020-02882-x
Kozora, E., Emery, C., Kaplan, R. M., Wamboldt, F. S., Zhang, L., & Make, B. J. (2008). Cognitive
and psychological issues in emphysema. Proceedings of the American Thoracic Society, 5(4),
556–560. https://doi.org/10.1513/pats.200708-123ET
Kozora, E., Filley, C. M., Julian, L. J., & Collum, C. M. (1999). Cognitive functioning in patients with
chronic obstructive pulmonary disease in mild hypoxemia compared with patients with mild
Alzheimer disease and normal controls. Neuropsychiatry, Neuropsychology, & Behavioral
Neurology, 12(3), 178–183.
Kozora, E., Tran, Z. V., & Make, B. (2002). Neurobehavioral improvement after brief rehabilitation
in patients with chronic obstructive pulmonary disease. Journal of Cardiopulmonary
Rehabilitation and Prevention, 22(6), 426–430.
Krop, H. D., Block, A. J., & Cohen, E. (1973). Neuropsychologic effects of continuous oxygen ther-
apy in chronic obstructive pulmonary disease. Chest, 64(3), 317–322. https://doi.org/10.1378/
chest.64.3.317
Larson, M. J., Weaver, L. K., & Hopkins, R. O. (2007). Cognitive sequelae in acute respiratory dis-
tress syndrome patients with and without recall of the intensive care unit. Journal of the
International Neuropsychological Society: JINS, 13(4), 595–605. https://doi.org/10.1017/
S1355617707070749
Lau, K. K., Yu, W. C., Chu, C. M., Lau, S. T., Sheng, B., & Yuen, K. Y. (2004). Possible central ner-
vous system infection by SARS coronavirus. Emerging Infectious Diseases, 10(2), 342–344.
https://doi.org/10.3201/eid1002.030638
Letko, M., Marzi, A., & Munster, V. (2020). Functional assessment of cell entry and receptor usage
for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology, 5(4), 562–569.
https://doi.org/10.1038/s41564-020-0688-y
Liesker, J. J. W., Postma, D. S., Beukema, R. J., ten Hacken, N. H. T., Van Der Molen, T.,
Riemersma, R. A., van Zomeren, E. H., & Kerstjens, H. A. M. (2004). Cognitive performance in
patients with COPD. Respiratory Medicine, 98(4), 351–356. https://doi.org/10.1016/j.rmed.2003.
11.004
Mahase, E. (2020). Covid-19: outbreak could last until spring 2021 and see 7.9 million hospital-
ised in the UK. BMJ (Clinical Research ed.), 368, m1071. https://doi.org/10.1136/bmj.m1071
 THE CLINICAL NEUROPSYCHOLOGIST 1495

Mikkelsen, M. E., Christie, J. D., Lanken, P. N., Biester, R. C., Thompson, B. T., Bellamy, S. L.,
Localio, A. R., Demissie, E., Hopkins, R. O., & Angus, D. C. (2012). The adult respiratory distress
syndrome cognitive outcomes study: Long-term neuropsychological function in survivors of
acute lung injury. American Journal of Respiratory and Critical Care Medicine, 185(12),
1307–1315. https://doi.org/10.1164/rccm.201111-2025OC
Mikkelsen, M. E., Shull, W. H., Biester, R. C., Taichman, D. B., Lynch, S., Demissie, E., Hansen-
Flaschen, J., & Christie, J. D. (2009). Cognitive, mood and quality of life impairments in a select
population of ARDS survivors. Respirology (Carlton, Vic.), 14(1), 76–82. https://doi.org/10.1111/j.
1440-1843.2008.01419.x
Morris, C., Mitchell, J. W., Moorey, H., Younan, H.-C., Tadros, G., & Turner, A. M. (2019). Memory,
attention and fluency deficits in COPD may be a specific form of cognitive impairment. ERJ
Open Research, 5(2), 1–9. https://doi.org/10.1183/23120541.00229-2018
Moss, M., Franks, M., Briggs, P., Kennedy, D., & Scholey, A. (2005). Compromised arterial oxygen
saturation in elderly asthma sufferers results in selective cognitive impairment. Journal of
Clinical and Experimental Neuropsychology, 27(2), 139–150. https://doi.org/10.1080/
13803390490515450
National Heart, Lung, and Blood Institute (NHLBI). (2018). Chronic cough, shortness of breath,
wheezing? What you should know about COPD. https://www.nhlbi.nih.gov/health-topics/all-
publications-and-resources/quick-guide-copd.
National Heart, Lung, and Blood Institute (NHLBI). (2019). What you should know about COPD.
https://www.nhlbi.nih.gov/health-topics/education-and-awareness/copd-learn-more-breathe-
better/publications-health-providers.
Needham, D. M., Colantuoni, E., Dinglas, V. D., Hough, C. L., Wozniak, A. W., Jackson, J. C., Morris,
P. E., Mendez-Tellez, P. A., Ely, E. W., & Hopkins, R. O. (2016). Rosuvastatin versus placebo for
delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associ-
ated acute respiratory distress syndrome: An ancillary study to a randomised controlled trial.
The Lancet. Respiratory Medicine, 4(3), 203–212. https://doi.org/10.1016/S2213-2600(16)00005-9
O’Conor, R., Wolf, M. S., Smith, S. G., Martynenko, M., Vicencio, D. P., Sano, M., Wisnivesky, J. P.,
& Federman, A. D. (2015). Health literacy, cognitive function, proper use, and adherence to
inhaled asthma controller medications among older adults with asthma. Chest, 147(5),
1307–1315. https://doi.org/10.1378/chest.14-0914
O’Hanlon, S., & Inouye, S. K. (2020). Delirium: A missing piece in the COVID-19 pandemic puzzle.
Age and Ageing, 49(4), 497–498. https://doi.org/10.1093/ageing/afaa094
Onder, G., Rezza, G., & Brusaferro, S. (2020). Case-fatality rate and characteristics of patients
dying in relation to COVID-19 in Italy. JAMA - Journal of the American Medical Association,
323(18), 1775–1776. https://doi.org/10.1001/jama.2020.4683
Ortapamuk, H., & Naldoken, S. (2006). Brain perfusion abnormalities in chronic obstructive pul-
monary disease: comparison with cognitive impairment. Annals of Nuclear Medicine, 20(2),
99–106. https://doi.org/10.1007/BF02985621
Ouellette, D. R., & Lavoie, K. L. (2017). Recognition, diagnosis, and treatment of cognitive and
psychiatric disorders in patients with COPD. International Journal of Chronic Obstructive
Pulmonary Disease, 12, 639–650. https://doi.org/10.2147/COPD.S123994
Pakhale, S., Mulpuru, S., & Boyd, M. (2011). Optimal management of severe/refractory asthma.
Clinical Medicine Insights. Circulatory, Respiratory and Pulmonary Medicine, 5, 37–47. https://doi.
org/10.4137/CCRPM.S5535
Pandharipande, P. P., Girard, T. D., Jackson, J. C., Morandi, A., Thompson, J. L., Pun, B. T.,
Brummel, N. E., Hughes, C. G., Vasilevskis, E. E., Shintani, A. K., Moons, K. G., Geevarghese,
S. K., Canonico, A., Hopkins, R. O., Bernard, G. R., Dittus, R. S., & Ely, E. W. (2013). Long-term
cognitive impairment after critical illness. The New England Journal of Medicine, 369(14),
1306–1316. https://doi.org/10.1056/NEJMoa1301372
Poyiadji, N., Shahin, G., Noujaim, D., Stone, M., Patel, S., & Griffith, B. (2020). COVID-19–associated
Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology, 296(2),
E119–E120. https://doi.org/10.1148/radiol.2020201187
1496 P. RIORDAN ET AL.

Prigatano, G. P., Parsons, O., Wright, E., Levin, D. C., & Hawryluk, G. (1983). Neuropsychological
test performance in mildly hypoxemic patients with chronic obstructive pulmonary disease.
Journal of Consulting and Clinical Psychology, 51(1), 108–116. https://doi.org/10.1037/0022-
006X.51.1.108
Rabinovitz, B., Jaywant, A., & Fridman, C. (2020). Neuropsychological Functioning in Severe
Acute Respiratory Disorders Caused by the Coronavirus: Implications for the Current COVID-
19 Pandemic. The Clinical Neuropsychologist, 34(7–8), 1453–1479. https://doi.org/10.1080/
13854046.2020.1803408.
Ramirez, J. A., Wiemken, T. L., Peyrani, P., Arnold, F. W., Kelley, R., Mattingly, W. A., Nakamatsu,
R., Pena, S., Guinn, B. E., Furmanek, S. P., Persaud, A. K., Raghuram, A., Fernandez, F., Beavin,
L., Bosson, R., Fernandez-Botran, R., Cavallazzi, R., Bordon, J., Valdivieso, C., Schulte, J., &
Carrico, R. M. (2017). Adults hospitalized with pneumonia in the United States: Incidence, epi-
demiology, and mortality. Clinical Infectious Diseases: An Official Publication of the Infectious
Diseases Society of America, 65(11), 1806–1812. https://doi.org/10.1093/cid/cix647
Rothan, H. A., & Byrareddy, S. N. (2020). The epidemeology and pathogensis of coronavirus
(Covid-19) outbreak. Journal of Autoimmunity, 109(1), 102433. https://doi.org/10.1016/j.jaut.
2020.102433
Saad, M., Omrani, A. S., Baig, K., Bahloul, A., Elzein, F., Matin, M. A., Selim, M. A. A., Mutairi, M., Al
Nakhli, D., Al Aidaroos, A. Y. A., Sherbeeni, N., Al Al-Khashan, H. I., Memish, Z. A., & Albarrak,
A. M. (2014). Clinical aspects and outcomes of 70 patients with Middle East respiratory syn-
drome coronavirus infection: A single-center experience in Saudi Arabia. International Journal
of Infectious Diseases, 29, 301–306. https://doi.org/10.1016/j.ijid.2014.09.003
Salive, M. E., Satterfield, S. U. Z. A. N. N. E., Ostfeld, A. M., Wallace, R. B., & Havlik, R. J. (1993).
Disability and cognitive impairment are risk factors for pneumonia-related mortality in older
adults. Public Health Reports, 108(3), 314.
Shah, F. A., Pike, F., Alvarez, K., Angus, D., Newman, A. B., Lopez, O., Tate, J., Kapur, V., Wilsdon,
A., Krishnan, J. A., Hansel, N., Au, D., Avdalovic, M., Fan, V. S., Barr, R. G., & Yende, S. (2013).
Bidirectional relationship between cognitive function and pneumonia. American Journal of
Respiratory and Critical Care Medicine, 188(5), 586–592. https://doi.org/10.1164/rccm.201212-
2154OC
Shi, H., Han, X., Jiang, N., Cao, Y., Alwalid, O., Gu, J., Fan, Y., & Zheng, C. (2020). Radiological find-
ings from 81 patients with COVID-19 pneumonia in Wuhan, China: A descriptive study. The
Lancet Infectious Diseases, 20(4), 425–434. https://doi.org/10.1016/S1473-3099(20)30086-4
Sheng, B., Cheng, S. K. W., Lau, K. K., Li, H. L., & Chan, E. L. Y. (2005). The effects of disease sever-
ity, use of corticosteroids and social factors on neuropsychiatric complaints in severe acute
respiratory syndrome (SARS) patients at acute and convalescent phases. European Psychiatry:
The Journal of the Association of European Psychiatrists, 20(3), 236–242. https://doi.org/10.
1016/j.eurpsy.2004.06.023
Steardo, L., Steardo Jr, L., Zorec, R., & Verkhratsky, A. (2020). Neuroinfection may contribute to
pathophysiology and clinical manifestations of COVID-19. Acta Physiologica, 229(3), e13473.
https://doi.org/10.1111/apha.13473
Stuss, D. T., Peterkin, I., Guzman, D. A., Guzman, C., & Troyer, A. K. (1997). Chronic obstructive
pulmonary disease: effects of hypoxia on neurological and neuropsychological measures.
Journal of Clinical and Experimental Neuropsychology, 19(4), 515–524. https://doi.org/10.1080/
01688639708403741
Taichman, D. B., Christie, J., Biester, R., Mortensen, J., White, J., Kaplan, S., Hansen-Flaschen, J.,
Palevsky, H. I., Elliott, C. G., & Hopkins, R. O. (2005). Validation of a brief telephone battery for
neurocognitive assessment of patients with pulmonary arterial hypertension. Respiratory
Research, 6(1), 39. https://doi.org/10.1186/1465-9921-6-39
Tate, J. A., Snitz, B. E., Alvarez, K. A., Nahin, R. L., Weissfeld, L. A., Lopez, O., … Williamson, J. D.
(2014). Infection hospitalization increases risk of dementia in the elderly. Critical Care
Medicine, 42(5), 1037.
TenVergert, E. M., Vermeulen, K. M., Geertsma, A., Van Enckevort, P. J., De Boer, W. J., Van Der
Bij, W., & Ko€eter, G. H. (2001). Quality of life before and after lung transplantation in patients
 THE CLINICAL NEUROPSYCHOLOGIST 1497

with emphysema versus other indications. Psychological Reports, 89(3), 707–717. https://doi.
org/10.2466/pr0.2001.89.3.707
Thakur, N., Blanc, P. D., Julian, L. J., Yelin, E. H., Katz, P. P., Sidney, S., Iribarren, C., & Eisner, M. D.
(2010). COPD and cognitive impairment: The role of hypoxemia and oxygen therapy.
International Journal of Chronic Obstructive Pulmonary Disease, 8, A4125. www.dovepress.com
https://doi.org/10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A4125
Um, D. H., Kim, J. S., Lee, H. W., & Lee, S. H. (2017). Psychological effects on medical doctors
from the Middle East Respiratory Syndrome (MERS) outbreak: A comparison of whether they
worked at the MERS occurred hospital or not, and whether they participated in MERS diagno-
sis and treatment. Journal of Korean Neuropsychiatric Association, 56(1), 28. https://doi.org/10.
4306/jknpa.2017.56.1.28
van Manen, J. G., Bindels, P. J. E., Dekker, F. W., Bottema, B. J. A. M., van der Zee, J. S., Ijzermans,
C. J., & Schad
e, E. (2003). The influence of COPD on health-related quality of life independent
of the influence of comorbidity. Journal of Clinical Epidemiology, 56(12), 1177–1184. https://
doi.org/10.1016/S0895-4356(03)00208-7
Wagena, E. J., van Amelsvoort, L. G. P. M., Kant, I., & Wouters, E. F. M. (2005). Chronic bronchitis,
cigarette smoking, and the subsequent onset of depression and anxiety: Results from a pro-
spective population-based cohort study. Psychosomatic Medicine, 67(4), 656–660. https://doi.
org/10.1097/01.psy.0000171197.29484.6b
Wang, D., Hu, B., Hu, C., Zhu, F., Liu, X., Zhang, J., Wang, B., Xiang, H., Cheng, Z., Xiong, Y., Zhao,
Y., Li, Y., Wang, X., & Peng, Z. (2020). Clinical characteristics of 138 hospitalized patients with
2019 Novel coronavirus-infected pneumonia in Wuhan, China. Jama - Jama, 323(11),
1061–1069. https://doi.org/10.1001/jama.2020.1585
Wang, J., Wang, B. J., Yang, J. C., Wang, M. Y., Chen, C., Luo, G. X., & He, W. F. (2020). Advances
in the research of mechanism of pulmonary fibrosis induced by corona virus disease 2019
and the corresponding therapeutic measures. Zhonghua Shao Shang za Zhi ¼ Zhonghua
Shaoshang Zazhi ¼ Chinese Journal of Burns, 36, E006. https://doi.org/10.3760/cma.j.cn501120-
20200307-00132
Wilcox, M., Brummel, N. E., Archer, K., Wesley Ely, E., Jackson, J. C., & Hopkins, R. O. (2013).
Cognitive dysfunction in ICU patients: Risk factors, predictors, and rehabilitation interventions.
Critical Care Medicine, 41(9 SUPPL.1), S81–S98. https://doi.org/10.1097/CCM.0b013e3182a16946
World Health Organization (WHO). (2020, April 6). COVID disease 2019 (COVID-19): Situation
Report – 75. https://www.who.int/docs/default-source/coronaviruse/situation-reports/
20200404-sitrep-75-covid-19.pdf?sfvrsn=99251b2b_4
Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., Du, C., Zhang, Y.,
Song, J., Wang, S., Chao, Y., Yang, Z., Xu, J., Zhou, X., Chen, D., Xiong, W., … Song, Y. (2020).
Risk factors associated with acute respiratory distress syndrome and death in patients with
coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Internal Medicine, 180(7), 934.
https://doi.org/10.1001/jamainternmed.2020.0994
Wu, Z., & McGoogan, J. M. (2020). Characteristics of and important lessons from the coronavirus
disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the
Chinese center for disease control and prevention. Jama - Jama, 323(13), 1239. https://doi.
org/10.1001/jama.2020.2648
Yohannes, A. M., & Alexopoulos, G. S. (2014). Depression and anxiety in patients with COPD.
European Respiratory Review: An Official Journal of the European Respiratory Society, 23(133),
345–349. https://doi.org/10.1183/09059180.00007813
Yohannes, A. M., Baldwin, R. C., & Connolly, M. J. (2000). Mood disorders in elderly patients with
chronic obstructive pulmonary disease. Reviews in Clinical Gerontology, 10(2), 193–202. https://
doi.org/10.1017/S0959259800002100
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., Guan, L., Wei,
Y., Li, H., Wu, X., Xu, J., Tu, S., Zhang, Y., Chen, H., & Cao, B. (2020). Clinical course and risk fac-
tors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort
study. The Lancet, 395(10229), 1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3