Different aspects of frailty and COVID-19: points to consider in the current pandemic and future ones

Abstract

Background
Older adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing, immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly tool for frailty screening in an acute setting as COVID-19 triage.
We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic databases MEDLINE, CINAHL and SCOPUS.
Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of ongoing chronic inflammation and reduced gut microbiota diversity.
Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general population regarding effectiveness and side effects.
Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool.

Conclusion
Older frail adults have a pre-existing immunopathological base that puts them at a higher risk of undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be screened using the CFS.

Full text

R E V I E W Open Access
Different aspects of frailty and COVID-19:
points to consider in the current pandemic
and future ones
Hani Hussien
1,2
, Andra Nastasa
2*
, Mugurel Apetrii
1,2
, Ionut Nistor
1,2
, Mirko Petrovic
3
and Adrian Covic
1,2
Abstract
Background: Older adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute
respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with
other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus
disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing,
immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different
response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of
frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion
for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly
tool for frailty screening in an acute setting as COVID-19 triage.
We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic
databases MEDLINE, CINAHL and SCOPUS.
Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of
COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of
ongoing chronic inflammation and reduced gut microbiota diversity.
Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU
admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general
population regarding effectiveness and side effects.
Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in
COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool.
Conclusion: Older frail adults have a pre-existing immunopathological base that puts them at a higher risk of
undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their
admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be
screened using the CFS.
Keywords: COVID-19, Microbiota, Inflamm-ageing, Immunosenescence, Frailty, Vaccination, SARS co-V2, CFS
© The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
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data made available in this article, unless otherwise stated in a credit line to the data.
* Correspondence: md.hany@yahoo.com
2
Department of Internal Medicine, Nephrology and Geriatrics, Grigore T Popa
University of Medicine and Pharmacy, Faculty of Medicine, Bd Carol nr 50,
Iasi, Romania
Full list of author information is available at the end of the article
Hussien et al. BMC Geriatrics (2021) 21:389
https://doi.org/10.1186/s12877-021-02316-5
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Background
By the end of February 2021, the number of COVID-19
cases has exceeded one hundred million globally [1].
The older adults were the most affected population seg-
ment in terms of hospitalisation, poor outcomes and
mortality due to COVID-19 in Europe [2,3], the United
Kingdom (UK) [4], United States (US) [5] and Canada
[6]. The high risk of mortality and poor outcomes
among older adults diagnosed with COVID-19 is a nat-
ural output of the high prevalence of comorbidities,
weak immune system, and, most importantly, frailty in
this unique population.
Frailty is defined as an age-related clinical disorder,
usually with a decline in multiple organ systems’physio-
logical ability, characterised by a higher degree of vulner-
ability to what appears to be a minor stressor which
exposes frail older adults at a higher risk of poor health
outcomes, including dependence and disability [7].
Frailty is induced by an underlying mechanism inde-
pendent of ageing but most likely to evolve and proceed
with the ageing process; however, frailty is not a neces-
sary element of ageing, and many adults reach advanced
age without becoming frail [8].
During the current COVID-19 pandemic, frailty is im-
portant since it is a common clinical syndrome in older
adults. In a recent meta-analysis, including 1,750,000
adults aged ≥50 years from 62 countries, the overall
prevalence of frailty was 12% [9]. These figures are con-
sistent with 15% as an estimated prevalence of frailty
among Europeans aged ≥65 years [10]. Moreover, almost
¾ of frail persons has multimorbidity [11].
Although the existence of frailty or multimorbidity was
not associated with increased risk of SARS- CoV-2 infec-
tion [12] yet, frail older adults are at higher of developing
severe COVID-19 than pre-frail or non-frail older adults
[13]. Indeed, the presence of frailty necessitates complex
medical care demands, including ICU admission, notwith-
standing the scarce resources of healthcare systems in the
current setting of the SARS-CoV-2 pandemic.
This article reviews the current literature to determine
the impact of frailty on older adults diagnosed with
COVID-19. Also, we explain the causes and mutual
mechanisms (inflamm-ageing, immunosenescence and
reduced microbiota diversity) by which frail adults are
more susceptible to a higher risk of developing a severe
form of COVID-19, adverse outcomes, mortality and a
different response to vaccination. Similarly, we attempt
to highlight the importance of identifying frail older
people using an efficient screening tool before their hos-
pitalisation or ICU admission.
Main text
We performed this narrative review to discuss the im-
pact of frailty on older adults diagnosed with COVID-
19. Also, to underline mutual mechanisms (inflamm-
ageing, immunosenescence and reduced microbiota di-
versity), frail older adults are more susceptible to a
higher risk of developing a severe form of COVID-19,
adverse outcomes, mortality and a different response to
vaccination. Similarly, we attempt to highlight the im-
portance of identifying frail older people using an effi-
cient screening tool before their hospitalisation or ICU
admission.
A literature search was conducted up to March 2021,
using the electronic databases MEDLINE, CINAHL, and
SCOPUS to identify the original articles, review articles,
and editorials that focused on the conceptual or theoret-
ical aspects of frailty in older adults and frail adults diag-
nosed with COVID-19.
We have used the following terms: frailty in older
adults, frailty in elderly, frailty in geriatrics, frailty and
ageing, frailty mechanisms, inflamm-ageing, immunose-
nescence, frailty and SARS-CoV2, frailty screening,
frailty assessment, frailty tools, frailty instruments, frailty
and COVID-19, ICU in frail adults, vaccination in frailty,
reduced microbiota diversity in frailty.
We also included studies of any design, quantitative or
qualitative, and available data from official websites. We
limited the search to articles published in the English
language only between 1990 and 2021.
We have found 2543 papers after removing duplicates
and did not match our search eligibility criteria. Out of
these, 467 papers were considered after the title and ab-
stract assessment. After a full-text review, the final rele-
vant papers were 100 papers.
Inflamm-ageing, immunosenescence and reduced
microbiota diversity: an ominous trinity in frail older
adults diagnosed with COVID-19.
Inflamm-ageing and immunosenescence
As previously explained, older adults are at higher risk
of poor outcomes because of ageing-associated condi-
tions as frailty, multi-comorbidities, and weak immunity.
In general, compared with the young, older adults have a
decrease in their immune systems’capacity to cope with
infection, which is mostly the result of the altered im-
mune response to pathogens [14].. This impairment in
the immune system, which is associated with ageing, is
called immunosenescence.
Notably, and in a close link with COVID-19, it is well
documented that the risk of complications and death
from respiratory infections among seniors rises with
immunosenescence and concomitant lung and heart
health issues [15] and that frailty is associated with lower
recovery rates and significant adverse outcomes in older
adults with acute respiratory infections [16].
In old age, there is impaired crosstalk between the im-
mune system’s innate and adaptive arms and an ongoing
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chronic inflammation known as inflamm-ageing, a
common biological factor responsible for frailty and
the onset of some diseases in older persons [17,18].
Inflamm-ageing is characterised by Chronic Low-
grade Inflammatory Phenotype (CLIP), which is
associated with a concomitant progressive increase in
pro-inflammatory markers, cytokines including inter-
leukin (IL)-6, IL-1b, and tumor necrosis factor (TNF)-
α[19,20]. Moreover, these ongoing inflammatory
processes may impair the host’s ability to identify
pathogensasaharmfulsignal[17,21]. By association,
immunosenescence and inflamm-ageing would signifi-
cantly impact outcome and survival among frail adults
during pandemics.
In addition to CLIP, it is well established that there is
an impairment of naive T cells in terms of numbers and
function in older persons, which results in adaptive im-
munity dysfunction [17,22]. Similar patterns of inflam-
mation were detected in patients with severe COVID-19,
where there is a state of hyper-inflammation [23], with
an increase in the levels of interferon-γ, TNF-α,C-
Reactive Protein (CRP) and cytokines, in particular, IL-
10, IL-6, and IL-17, which correlates with a significant
reduction in T cells population, and even the surviving
T cells are functionally exhausted with impaired prolifer-
ation [24–26].
Previous studies on older adults have shown that
elevated serum IL-6 and CRP levels are associated
with a significant risk of developing frailty and mor-
tality [27,28]. Another aspect of high relevance is
the immunological similarity between COVID-19 and
frailty regarding Cluster of Differentiation (CD)
levels. Studies on autopsies from persons who died
from COVID-19 were positive for immunity cells, in-
cluding CD4, CD8, CD20, and CD38 [29]. Interest-
ingly, immunogerontological studies among frail
patients have shown a chronic increase in the same
CD types [30–34].
Moreover, it is well documented that a higher
serum level of pro-inflammatory cytokines in COVID-
19 patients is associated with poor outcomes. A
plethora of studies has shown that the elevation of
IL-2 and IL-6 is correlated with COVID-19 replica-
tion and disease severity and that patients requiring
ICU admission had higher concentrations of cytokines
than those who were not requiring ICU admission
[35–39]. Also, a higher level of interleukins is an indi-
cator of poor prognosis and high mortality rates in
patients with severe COVID-19 [25,40].
Presumably, in addition to weak immunity in frail
older persons, they have a pre-existing chronic inflam-
matory status with higher pro-inflammatory markers,
which put them at a higher risk of developing a severe
form of COVID-19 and higher mortality rates.
Microbiota: a playmaker in frailty and COVID-19
In addition to inflamm-ageing and immunosenescence,
microbiota diversity reduction contributes to the weak
immune system among frail older adults. The pathogens
interactions with the immune system happen in an en-
vironment that is influenced by its endogenous micro-
biota, owing to their high capacity to regulate many
immunity aspects, including innate and adaptive immun-
ity, locally and at distant sites, in particular in the intes-
tine and lungs [41–43].
Previous research has shown that because of the in-
creased plasma levels of the major pro-inflammatory cy-
tokines, older people’s microbiota reveals a more
substantial interindividual variability than that of youn-
ger adults; also, the reduced gut microbiota diversity is
associated with increased frailty [44–46]. Unsurprisingly,
the grade of frailty is a better indicator of changes in gut
microbiota than chronological age [47].
Studies have recently shown an alteration in gut
microbiota among COVID-19 patients [48] and that the
faecal microbiota alteration is associated with the higher
fecal level of SARS-CoV-2 and a severe form of COVID-
19 [49]. Consistently, biopsies from deceased persons in-
fected with COVID-19 have shown a change in lung
microbiota diversity, especially in those aged ≥65 or with
comorbidities [50].
Thus, among frail older adults, the susceptibility to in-
fections, including SARS-CoV-2, depends on the inter-
play between immune capacity and body microbiota.
Hence, the reduced microbiota diversity accompanied by
immunosenescence and inflamm-ageing would predis-
pose frail adults to develop a severe form of COVID-19.
Therefore, understanding the role of microbiota in the
pathogenesis of frailty and respiratory viral infections
would allow for more targeted therapy for the frail
population during the current pandemic and future
ones. (See Fig. 1, Immunological factors contributing to
developing a severe form of COVID-19 among frail
older adults)
Frailty and COVID-19 vaccination
Another important aspect to consider in frail older
adults is their potential response to the current COVID-
19 vaccines. Although older adults are on the top of the
COVID-19 vaccination list, frail ones were excluded
from COVID-19 vaccines trials [51]. The inflamm-
ageing and immunosenescence, which represent a car-
dinal element in the ageing process, are also associated
with a poor immunological response to vaccination or
previous infections [52], and this poor response would
be worse among frail older adults [53,54]. This known
poor response to vaccination among frail older adults
has triggered doctors, for example, in Norway, to assess
for frailty before deciding whether to proceed with
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COVID-19 vaccination or not [55], particularly after re-
cently 23 frail older adults have died shortly after receiv-
ing a COVID-19 vaccine [56].
Therefore, even after vaccination and because of their
potential poor response to vaccines, it is predicted that
older frail adults will be exposed to the same risk of in-
fection or even, in the best case, a slightly lower risk
than pre-vaccination. Hence, it is recommended to defer
any early relaxation of the current community COVID-
19 policies when dealing with this special population to
maintain their protection.
Critical care for frail older adults in COVID-19 pandemic:
the battle of ventilators
As illustrated before, there is a refined relationship of
frailty with poor outcomes in older adults infected with
SARS-CoV-2, who also are burdened with other ageing-
associated conditions, including the weak immune sys-
tem, reduced gut microbiota, and comorbidities. This
constellation of the ageing-associated conditions and
frailty would attribute to COVID-19 severity, which will
signal the need for ICU admission.
In one recent study from 12 countries, which included
five thousand hospitalised patients diagnosed with
COVID 19 with a median age of 74, the degree of frailty
was associated with high mortality rates and the neces-
sity for a higher level of post-discharge care among sur-
vivors [57]. Consistently, the severe degree of frailty
among COVID-19 patients was associated with pro-
longed hospitalisation, all-cause mortality, and higher
mortality risk in the next 2 weeks following discharge
[58–64]. (See Fig. 2, Frailty is associated with functional
dependence, longer hospitalisation and higher mortality).
During the current pandemic, critical care services are
overwhelmed, and there is a considerable shortage of
ventilators worldwide. Thus, special arrangements
should be taken to avoid disproportionate care, which is
common in ICUs in Europe and North America [65].
Disproportionate care uses advanced life-sustaining mea-
sures in patients with poor long-term outcomes second-
ary to multiple chronic organ dysfunctions,
comorbidities, and/or poor life quality [65]. Hence, the
first goal is to take appropriate steps to optimise ICUs’
capacity by postponing non-emergency patient services
and converting non-critical care units to critical care
ones [66].
In the UK, the Intensive Care National Audit & Re-
search Centre (ICNARC) has published a report on ICU
admission data from England, Wales, and Northern
Ireland, which shows that up to 31 August 2020, about
Fig. 1 This figure shows the pathological mechanisms in older adults which expose frail patients with COVID-19 to undesired outcomes
Fig. 2 This figure shows that frailty in older adults is associated with prolonged hospitalisation, more significant decline in functional
independence and higher mortality after exposure to minor stressors
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34% of patients admitted in ICU due to COVID-19 have
died and that 66% death cases were in those who were ≥
60 years [67]. Also, ICNARC has reported that from Sep-
tember 2020, 35.6% of patients admitted in ICU due to
COVID-19 were aged ≥60 years and that 70% of invasively
ventilated patients aged ≥70 have died in ICU. These fig-
ures confirm that older adults are at higher risk of being
admitted to ICU due to COVID-19 and that they are more
likely to die if they were invasively ventilated.
More than 50% of ICU admissions in the USA because
of COVID-19, and over 80% of deaths were among
adults aged ≥65 years [68]. Similar data were reported
from Mainland China, with 80% of deaths among adults
aged ≥60 years [68]. In a study that included 5700 pa-
tients hospitalised with COVID-19 in the New York City
area, the mortality rate among patients aged ≥65 years
who received mechanical ventilation was 97% compared
to 76.4% aged 18–65 years [69].
Thus, a controversy had arisen over whether the old
patients with COVID-19 should be admitted to ICU or
whether they should be directed to palliative care man-
agement. Currently, there are two opposite strategies for
approaching older adults, aiming to allocate mechanical
ventilators. On the one hand, chronological age alone
was used as exclusion criteria; for instance, doctors in
Italy have opted for a cut-off of 65 years old in the case
of pre-existing comorbidities [70]. Similarly, in
Switzerland, the Swiss Academy of Medical Sciences
(SAMS) [71] has published new guidelines for admission
in ICU, stating that in the context of COVID-19, age is a
risk factor for mortality and should be taken into consid-
eration, yet without specifying a cut-off. SAMS recom-
mends, “For ICU admission, the highest priority is to be
accorded to those patients whose prognosis with regard
to hospital discharge is good with intensive care, but
poor without it”[71].
While, in the USA, the New York state department of
health has chosen “saving the most lives”guidance,
which allocates ventilators according to the presence of
specific exclusion criteria and a cut-off of Sequential
Organ Failure Assessment (SOFA) score [72]. In Spain,
the ministry of health has announced on 03 April 2020,
general criteria for ICU admission; the first criterion was
“Non-discrimination for any reason beyond the patient’s
clinical situation and their objective, evidence-based ex-
pectations of survival “, which makes the patient’s age
out of the picture [73].
However, other stratifying ways have been used; for
instance, in Pennsylvania, USA, allocating ventilators
depends on calculating a specific score, including age
and multi-comorbidities [74]. In the UK, the National
Institute for Health and Care Excellence (NICE) has
updated its guideline on critical care on 25 March
2020 to involve frailty screening for all older adults
who present in COVID-19 triage irrespective of their
COVID-19 status [75].
Meanwhile, in Switzerland, the Board of the Associ-
ation for Geriatric Palliative Medicine (FGPG) has rec-
ommended Advance Care Planning (ACP) when
managing older frail adults diagnosed with COVID-19
[76]. ACP allows frail older adults to opt for either hos-
pitalisation or palliative care before infection or at least
at the time of diagnosis, which respects the patient’s
wishes, and hence, is ethically accepted.
Previous researches have shown that persons dying at an
older age generally have more disability, but not a disease,
than those dying at a younger age, and that a large propor-
tion of their total years spent in the disabled state will con-
tribute to the years just before their end-of-life [77].
Nevertheless, once frailty overlaps with comorbidities
or disability, this is the moment of no return, and frailty
will be a pre-death phase. Consistently, the short-term
survival after admission in ICU of older adults has in-
versely associated with the degree of frailty in advanced
age [78]; also, pre-ICU frailty correlates with a higher
post-ICU disability and new admission in nursing homes
among ICU survivors [79]. Accordingly, and due to es-
calating needs to allocate ventilators to those more likely
to benefit and avoid mechanical ventilation withdrawal,
physicians should proactively participate in conversa-
tions with patients and caregivers concerning do-not-
intubate orders for high-risk subgroups of patients
before their health deteriorates [80].
The COVID-19 in Older PEople (COPE) study, which
included 1564 non-ICU patients diagnosed with
COVID-19 (median age of 74 years), has shown that
COVID-19 outcomes were better predicted by the de-
gree of frailty than either chronological age or comor-
bidity [59]. Similarly, severe frailty is an independent
predictor for mechanical ventilation among older adults
diagnosed with COVID-19 [61]. Therefore, frailty
screening among older adults before ICU admission is of
central importance since it can guide clinicians to the
ICU outcome (See Fig. 2).
Given the connection between frailty and fewer
chances to be home discharged, and the development of
adverse outcomes in the acute care setting, it seems fair
to assume that a COVID-19 older adult with a high de-
gree of frailty or disability is relatively closer to death
than non-frail patients of the same age and are less likely
to benefit from the critical care service.
Hence, it is clear that the potential profit of the admis-
sion of an old patient positive with COVID −19 in crit-
ical care service cannot be rationally taken without
assessing their frailty state before ICU admission. Frailty
as a selection criterion for ICU admission is expected to
deliver a more accurate, rational, yet ethically accepted
choice during the time of pandemics. Ultimately, despite
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the debate on old patients with COVID-19, if they
should receive treatment in ICU or not, there is no dis-
agreement on the catastrophic impact of COVID-19 on
old individuals admitted in the ICU, their families, and
society as a whole.
Frailty screening in COVID-19 triage
In general, all older adults should be assessed for frailty
when encountered with healthcare staff because frailty is
a complex condition that necessitates a particular inter-
vention, yet an individualised one. Ideally, in case of
emergencies, ambulance staff should recognise frail pa-
tients in the community because it would decrease the
number of older adults attending the busy emergency
department (ED). Nevertheless, it is not always applic-
able, in particular during times of pandemics.
The aim of screening for frailty in ED is to understand
the acute manifestations of the present illness regarding
the pre-existing health condition to predict adverse out-
comes during hospitalisation or after discharge and pre-
vent potential adverse outcomes [81]. Also, frailty
screening guarantees more informed medical decision-
making for both patients regarding treatment prefer-
ences and physicians in terms of triaging and therapy
suitability [82]. Moreover, the outcome of frailty assess-
ment in ED will further trigger the clinician’s decision
and the patient and his family, and some patients might
be admitted to the hospital, while others might opt for
palliative care in the home. Even in the case of hospital
admission, the management will be different at a de-
tailed level. For example, deprescribing some of the
current medications, avoiding some new drugs or ma-
noeuvres and subsequently a different individualised ap-
proach in managing the current illness, because some
interventions might be clinically less efficient, not only
that but maybe more harmful.
There is a wide variety of frailty screening instruments,
each with a range of included components. In a system-
atic review that includes 96 studies, 51 frailty tools were
identified for screening and diagnosis of frailty in out-
patient (OPD) and inpatient (IPD) departments [83].
(see supplementary Table 1).
However, besides simplicity and sensitivity, an optimal
screening tool must be efficient in countries with scarce
resources. Indeed, most of the instruments for frailty
assessment are too complicated for use in acute care sit-
uations. Some more straightforward tools involve a type
of manual evaluation approach that may be time-
consuming, prone to inter-operator error and might ex-
pose the assessor to further infection risk. Nevertheless,
recent research, including three hundred thousand
adults, has shown that frailty is associated with more se-
vere COVID-19 and higher mortality rates regardless of
the assessment tool used [84].
A well-validated frailty tool that includes physical as-
sessment is the frailty phenotype score which requires
patients to perform physical maneuvers, such as hand-
grip strength and gait-speed assessments [85], that are
hard to assess during pandemics. Even non-physical
tools could be too long to be used in the triage of pan-
demics, for example, the Edmonton Frail Scale (EFS)
[86] and the Groningen Frailty Indicator (GFI) [87], yet
the former was used for assessment of frailty among
older adults diagnosed with COVID-19 [88].
The Hospital Frailty Risk Score (HFRS) developed by
Thomas Gilbert and colleagues [89] is another validated,
systemic, and low-cost tool to identify hospitalised frail
people at risk for mortality and adverse outcomes. It gen-
erates electronic health record data, and it has the advan-
tage that it can be calculated instantly upon or just before
admission. The HFRS was efficiently used for frailty
screening in eighteen thousand older adults (≥65 years)
diagnosed with COVID-19 [90]; however, one study in-
cluding 4000 adults admitted to ICU has shown that
HFRS did not independently predict the outcome of ICU
patients ≥75 years [91]. Nevertheless, the HRFS needs
electronic health records to be available in a nationwide
health information network that contains the ICD-10
diagnostic codes of all the previous inpatient and out-
patient admissions, which in some limited-resources
health systems is difficult, if not impossible. Similarly, the
Frailty Index (FI) is a well-validated tool for frailty screen-
ing in the general population [92], and it was used with
COVID-19 patients [93]. However, the FI requires labora-
tory tests and some previous medical records, which
might not be available in many health facilities.
Other short tools recommended for frailty screening
in the emergency department include PRISMA-7 [94,
95], FRAIL scale [96], and The Clinical Frailty Scale
(CFS) [97]. PRISMA-7 defines an older adult as frail or
non-frail without referring to the level of frailty. The
FRAIL scale is a self-reporting test [96], and it was used
for frailty assessment among older adults diagnosed with
COVID-19 [13]. (see supplementary Table 2).
The CFS depends on both the assessor’s clinical judg-
ment and information from prior geriatric assessments.
It classifies frailty in old persons to nine grades, where
grade 1 is very fit, and grade 9 is terminally ill. The CFS
considers the cognitive function, mobility, comorbidities,
and functional status combined into a pictograph [97].
Predictably, the CFS was recommended for frailty
screening in the emergency setting and by critical care
staff, owing to its excellent predictability of mortality
and the length of hospitalization, not only that, but also
it was the most comprehensive user-friendly tool, yet
less exigent [94,98–100]. Similarly, the European Very
elderly Intensive Patient (VIP2) study, which included
4000 older adults (≥80 years) admitted to the ICU, has
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shown that the CFS score was inversely associated with
short-term survival [101].
One of CFS’s most significant advantages is that it
does not require any physical evaluation that is challen-
ging to be performed in the ED. Also, it easy to use in
multiple settings, including the acute general medical
setting, even by non-trained junior doctors [102,103].
This Feasibility of CFS gives it ancillary benefits in
health systems with limited means where there is a
lack of experienced doctors, as well as in pandemics
time when rapid decisions are required in busy ED
Recently, the International Conference of Frailty and
Sarcopenia Research (ICFSR) has recommended in
their 2019 guidelines, the CFS, as a screening tool for
frailty [104].
During the current pandemic, the National Institute
for Health and Care Excellence (NICE) has opted for
using the CFS as a screening tool in COVID-19 triage.
NICE has chosen the degree of frailty in older adults as
a filtering criterion for hospitalisation and critical care
admission, where the assessor should ask for a patient’s
capability 2 weeks ago before their presentation in ED.
NICE also recommends that a COVID positive patient
with CFS ≥5 be managed initially outside critical care
[75]. Similarly, Nederland guidelines [105] and the Bel-
gian Society of Intensive care medicine have recom-
mended using the CFS in COVID-19 triage [66].
Therefore, during the current pandemic, many studies
have used CFS to screen frailty among older adults diag-
nosed with COVID-19 [59–61,105–109]. Indeed, many
studies have shown that higher CFS scores were associ-
ated with prolonged hospitalisation, poor outcomes, and
higher mortality rates among older adults diagnosed
with COVID-19 [59,105,109].
It should be noticed that a CFS cut-off ≥5 is not abso-
lute, while it was recommended by NICE [75], studies
from France [109], the COMET study from 11 European
countries has shown that CFS cut-off ≥6 was a more
suitable risk marker for mortality among frail adults
(≥65 years old) diagnosed with COVID-19 [110]. How-
ever, a study from Australia and New Zealand that
includes 10,000 adults (median age 64 years) has shown
that a CFS score of less than 7 was not strongly associated
with mortality [63].
Fig. 3 This figure shows that the allocation of ventilators to non-frail and pre-frail older adults was associated with better outcomes and lower
mortality rates
Hussien et al. BMC Geriatrics (2021) 21:389 Page 7 of 11
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Nevertheless, it is crucial to understand that frailty
does not define futility in older adults and that the deci-
sions to hospitalise a patient or admit them to ICU are
beset with difficulties. Such difficulties are because, to
the best of our knowledge, there is no yet a studied cut-
off of any frailty instrument, which defines the patient
who would benefit from ICU admission. Indeed, the
frontier between “futility”and “worthiness”of ICU ad-
mission for old frail individuals is faint. (See Fig. 3,
Frailty screening and allocation of ventilators in ICU).
Owing to its feasibility and accuracy, the CFS is hence
proposed to be a handy tool in identifying frailty, pre-
dicting the length of stay, and mortality among old
adults who present in emergency settings and presum-
ably, in the triage of COVID-19. Finally, categorising
older adults according to their frailty degree will permit
electing those requiting full therapeutic options and
those who should be managed in the palliative care set-
ting, like nursing homes, without admitting them to the
hospital. Therefore, new guidelines should be con-
structed that address the management of frail old adults
in times of pandemics, mainly when there is a surge in
health care demands, without compromising both ethical
and clinical aspects.
Conclusions
The frail old population is a special segment of the
population with their particularities, distinguishing them
from the rest. Older adults, in particular, frail ones, have
a weaker immune system, reduced gut microbiota diver-
sity, and longstanding inflammatory status than the gen-
eral population. Those factors contribute to the severity
of COVID-19 and the high mortality rate. Moreover,
frailty in patients with COVOD-19 is associated with
poor outcomes, mortality in ICU, re-admission and short
survival post-ICU discharge. Moreover, frailty is associ-
ated with a poor response to vaccination and more side
effects, and hence, as a precautionary measure, it might
be reasonable to screen older adults for frailty before
vaccination.
The allocating of healthcare resources, mainly mech-
anical ventilators, is a wise requisite in times of pan-
demics. Therefore, we suggest that the decision of “NO
ICU “admission for older persons should depend on
their degree of frailty as a primary selection criterion
and that excluding patients based merely on their age is
unreliable. The assessment of frailty in COVID-19 or
any pandemic triage is thus mandatory to define
priorities and actions, and it would provide essential in-
formation to evaluate the efficiency of COVID-19 man-
agement. Owing to its feasibility, user-friendliness and
sensitivity, together with the prediction of poor out-
comes and mortality among COVID-19 frail adults, we
suggest that the Clinical frailty scale is the screening tool
of choice in COVID-19 triage.
Our findings imply that the optimisation of treatment
and management of older adults in COVID-19 and fu-
ture pandemics may differ between frail and non-frail in-
dividuals, and hence, cannot be achieved without proper
frailty assessment before hospital admission. Accord-
ingly, several policy implications should be considered in
dealing with frail old adults in pandemics; additional re-
search is required to delineate more clearly the role of
frailty in pandemics as cause and effect.
Abbreviations
ACP: Advance Care Planning; CFS: Clinical frailty scale; CLIP: Chronic Low-
grade Inflammatory Phenotype; CD: Cluster of Differentiation; COPE: COVID-
19 in Older PEople; COVID-19: Coronavirus disease 2019; CRP: C-reactive
Protein; ED: Emergency department.; HFRS: The Hospital Frailty Risk Score;
ICFSR: International Conference of Frailty and Sarcopenia Research; ICNA
RC: Intensive Care National Audit & Research Centre; ICU: Intensive care unit;
IFN: Interferon; IL: Interleukin; IPD: Inpatient department; NICE: The National
Institute for Health and Care Excellence; OPD: Outpatient department;
SAMS: Swiss Academy of Medical Sciences; SARS-CoV-2: Severe acute
respiratory syndrome coronavirus 2; SOFA: Sequential Organ Failure
Assessment; TNF: Tumor Necrosis Factor
Supplementary Information
The online version contains supplementary material available at https://doi.
org/10.1186/s12877-021-02316-5.
Additional file 1: Supplementary Table 1. The main frailty screening
tools used in clinical practice.
Additional file 2: Table 2. Frailty assessment tools that were used
during the COVOD-19 pandemic.
Acknowledgements
This work was supported by a grant of the Ministry of Research, Innovation
and Digitization, CNCS/CCCDI-UEFISCDI, project number PN-III-P4-ID-PCE-
2020-2393, within PNCDIII.We would like also to thank Jihane Al Echcheikh
from the European Medical Students’Association (EMSA) in Iasi, Romania, for
her contribution in creating the figures for this article.
Authors’contributions
HH and AC were responsible for the article’s concept and design; HH, AC,
MP did literature review; HH, MA and AN wrote the manuscript; MA, AC, IN,
and MP corrected the manuscript. All co-authors have read and have ap-
proved the final version of the manuscript.
Funding
No external source of funding was received for the present article.
Availability of data and materials
Not applicable.
Declarations
Ethical approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
All authors declare that they have no competing interests.
Hussien et al. BMC Geriatrics (2021) 21:389 Page 8 of 11
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Author details
1
Dr C I Parhon University Hospital, Department of Nephrology, Iasi, Romania.
2
Department of Internal Medicine, Nephrology and Geriatrics, Grigore T Popa
University of Medicine and Pharmacy, Faculty of Medicine, Bd Carol nr 50,
Iasi, Romania.
3
Section of Geriatrics, Department of Internal Medicine and
Pediatrics, Ghent University, Ghent, Belgium.
Received: 27 July 2020 Accepted: 6 June 2021
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