quantitative critque
( FYI the step by step doc is just a GUIDE on how to go by. you dont have used it if you dont want to)
Step’by-step guide to critiquing
research. Part 1: quantitative research
Michaei Coughian, Patricia Cronin, Frances Ryan
Abstract
When caring for patients it is essential that nurses are using the
current best practice. To determine what this is, nurses must be able
to read research critically. But for many qualified and student nurses
the terminology used in research can be difficult to understand
thus making critical reading even more daunting. It is imperative
in nursing that care has its foundations in sound research and it is
essential that all nurses have the ability to critically appraise research
to identify what is best practice. This article is a step-by step-approach
to critiquing quantitative research to help nurses demystify the
process and decode the terminology.
Key words: Quantitative research
methodologies
Review process • Research
]or many qualified nurses and nursing students
research is research, and it is often quite difficult
to grasp what others are referring to when they
discuss the limitations and or strengths within
a research study. Research texts and journals refer to
critiquing the literature, critical analysis, reviewing the
literature, evaluation and appraisal of the literature which
are in essence the same thing (Bassett and Bassett, 2003).
Terminology in research can be confusing for the novice
research reader where a term like ‘random’ refers to an
organized manner of selecting items or participants, and the
word ‘significance’ is applied to a degree of chance. Thus
the aim of this article is to take a step-by-step approach to
critiquing research in an attempt to help nurses demystify
the process and decode the terminology.
When caring for patients it is essential that nurses are
using the current best practice. To determine what this is
nurses must be able to read research. The adage ‘All that
glitters is not gold’ is also true in research. Not all research
is of the same quality or of a high standard and therefore
nurses should not simply take research at face value simply
because it has been published (Cullum and Droogan, 1999;
Rolit and Beck, 2006). Critiquing is a systematic method of
Michael Coughlan, Patricia Cronin and Frances Ryan are Lecturers,
School of Nursing and Midwifery, University of Dubhn, Trinity
College, Dublin
Accepted for publication: March 2007
appraising the strengths and limitations of a piece of research
in order to determine its credibility and/or its applicability
to practice (Valente, 2003). Seeking only limitations in a
study is criticism and critiquing and criticism are not the
same (Burns and Grove, 1997). A critique is an impersonal
evaluation of the strengths and limitations of the research
being reviewed and should not be seen as a disparagement
of the researchers ability. Neither should it be regarded as
a jousting match between the researcher and the reviewer.
Burns and Grove (1999) call this an ‘intellectual critique’
in that it is not the creator but the creation that is being
evaluated. The reviewer maintains objectivity throughout
the critique. No personal views are expressed by the
reviewer and the strengths and/or limitations of the study
and the imphcations of these are highlighted with reference
to research texts or journals. It is also important to remember
that research works within the realms of probability where
nothing is absolutely certain. It is therefore important to
refer to the apparent strengths, limitations and findings
of a piece of research (Burns and Grove, 1997). The use
of personal pronouns is also avoided in order that an
appearance of objectivity can be maintained.
Credibility and integrity
There are numerous tools available to help both novice and
advanced reviewers to critique research studies (Tanner,
2003). These tools generally ask questions that can help the
reviewer to determine the degree to which the steps in the
research process were followed. However, some steps are
more important than others and very few tools acknowledge
this. Ryan-Wenger (1992) suggests that questions in a
critiquing tool can be subdivided in those that are useful
for getting a feel for the study being presented which she
calls ‘credibility variables’ and those that are essential for
evaluating the research process called ‘integrity variables’.
Credibility variables concentrate on how believable the
work appears and focus on the researcher’s qualifications and
ability to undertake and accurately present the study. The
answers to these questions are important when critiquing
a piece of research as they can offer the reader an insight
into \vhat to expect in the remainder of the study.
However, the reader should be aware that identified strengths
and limitations within this section will not necessarily
correspond with what will be found in the rest of the work.
Integrity questions, on the other hand, are interested in the
robustness of the research method, seeking to identify how
appropriately and accurately the researcher followed the
steps in the research process. The answers to these questions
658 British Journal of Nursing. 2007. Vol 16, No II
RESEARCH METHODOLOGIES
Table 1. Research questions – guidelines for critiquing a quantitative research study
Elements influencing the beiievabiiity of the research
Elements
Writing styie
Author
Report titie
Abstract
Questions
Is the report well written – concise, grammatically correct, avoid the use of jargon? Is it weil iaid out and
organized?
Do the researcher(s’) quaiifications/position indicate a degree of knowledge in this particuiar field?
Is the title clear, accurate and unambiguous?
Does the abstract offer a clear overview of the study including the research problem, sample,
methodology, finding and recommendations?
Elements influencing the robustness of the research
Elements
Purpose/research
Problem
Literature review
Theoreticai framework
Aims/objectives/
research question/
hypotheses
Sampie
Ethicai considerations
Operational definitions
Methodology
Data Anaiysis / results
Discussion
References
Questions
Is the purpose of the study/research problem clearly identified?
Does the research report foilow the steps of the research process in a iogical manner? Do these steps
naturally fiow and are the iinks ciear?
is the review Iogicaily organized? Does it offer a balanced critical anaiysis of the iiterature? is the majority
of the literature of recent origin? is it mainly from primary sources and of an empirical nature?
Has a conceptual or theoretical framework been identified? Is the framework adequately described?
is the framework appropriate?
Have alms and objectives, a research question or hypothesis been identified? If so are they clearly
stated? Do they reflect the information presented in the iiterature review?
Has the target popuiation been cieariy identified? How were the sample selected? Was it a probability
or non-probabiiity sampie? is it of adequate size? Are the indusion/exciusion criteria dearly identified?
Were the participants fuiiy informed about the nature of the research? Was the autonomy/
confidentiaiity of the participants guaranteed? Were the participants protected from harm? Was ethicai
permission granted for the study?
Are aii the terms, theories and concepts mentioned in the study dearly defined?
is the research design cieariy identified? Has the data gathering instrument been described? is the
instrument appropriate? How was it deveioped? Were reliabiiity and validity testing undertaken and the
resuits discussed? Was a piiot study undertaken?
What type of data and statisticai analysis was undertaken? Was it appropriate? How many of the sampie
participated? Significance of the findings?
Are the findings iinked back to the iiterature review? if a hypothesis was identified was it supported?
Were the strengths and limitations of the study including generalizability discussed? Was a
recommendation for further research made?
Were ali the books, journais and other media aliuded to in the study accurateiy referenced?
will help to identify the trustworthiness of the study and its
applicability to nursing
practice.
Critiquing the research steps
In critiquing the steps in the research process a number
of questions need to be asked. However, these questions
are seeking more than a simple ‘yes’ or ‘no’ answer. The
questions are posed to stimulate the reviewer to consider
the implications of what the researcher has done. Does the
way a step has been applied appear to add to the strength
of the study or does it appear as a possible limitation to
implementation of the study’s findings? {Table 1).
Eiements influencing beiievabiiity of the study
Writing style
Research reports should be well written, grammatically
correct, concise and well organized.The use of jargon should
be avoided where possible. The style should be such that it
attracts the reader to read on (Polit and Beck, 2006).
Author(s)
The author(s’) qualifications and job title can be a useful
indicator into the researcher(s’) knowledge of the area
under investigation and ability to ask the appropriate
questions (Conkin Dale, 2005). Conversely a research
study should be evaluated on its own merits and not
assumed to be valid and reliable simply based on the
author(s’) qualifications.
Report title
The title should be between 10 and 15 words long and
should clearly identify for the reader the purpose of the
study (Connell Meehan, 1999). Titles that are too long or
too short can be confusing or misleading (Parahoo, 2006).
Abstract
The abstract should provide a succinct overview of the
research and should include information regarding the
purpose of the study, method, sample size and selection.
Hritislijourn.il of Nursing. 2007. Vol 16. No 11 659
the main findings and conclusions and recommendations
(Conkin Dale, 2005). From the abstract the reader should
be able to determine if the study is of interest and whether
or not to continue reading (Parahoo, 2006).
Eiements influencing robustness
Purpose of the study/research problem
A research problem is often first presented to the reader in
the introduction to the study (Bassett and Bassett, 2003).
Depending on what is to be investigated some authors will
refer to it as the purpose of the study. In either case the
statement should at least broadly indicate to the reader what
is to be studied (Polit and Beck, 2006). Broad problems are
often multi-faceted and will need to become narrower and
more focused before they can be researched. In this the
literature review can play a major role (Parahoo, 2006).
Logical consistency
A research study needs to follow the steps in the process in a
logical manner.There should also be a clear link between the
steps beginning with the purpose of the study and following
through the literature review, the theoretical framework, the
research question, the methodology section, the data analysis,
and the findings (Ryan-Wenger, 1992).
Literature review
The primary purpose of the literature review is to define
or develop the research question while also identifying
an appropriate method of data collection (Burns and
Grove, 1997). It should also help to identify any gaps in
the literature relating to the problem and to suggest how
those gaps might be filled. The literature review should
demonstrate an appropriate depth and breadth of reading
around the topic in question. The majority of studies
included should be of recent origin and ideally less than
five years old. However, there may be exceptions to this,
for example, in areas where there is a lack of research, or a
seminal or all-important piece of work that is still relevant to
current practice. It is important also that the review should
include some historical as well as contemporary material
in order to put the subject being studied into context. The
depth of coverage will depend on the nature of the subject,
for example, for a subject with a vast range of literature then
the review will need to concentrate on a very specific area
(Carnwell, 1997). Another important consideration is the
type and source of hterature presented. Primary empirical
data from the original source is more favourable than a
secondary source or anecdotal information where the
author relies on personal evidence or opinion that is not
founded on research.
A good review usually begins with an introduction which
identifies the key words used to conduct the search and
information about which databases were used. The themes
that emerged from the literature should then be presented
and discussed (Carnwell, 1997). In presenting previous
work it is important that the data is reviewed critically,
highlighting both the strengths and limitations of the study.
It should also be compared and contrasted with the findings
of other studies (Burns and Grove, 1997).
Theoretical framework
Following the identification of the research problem
and the review of the literature the researcher should
present the theoretical framework (Bassett and Bassett,
2003). Theoretical frameworks are a concept that novice
and experienced researchers find confusing. It is initially
important to note that not all research studies use a defined
theoretical framework (Robson, 2002). A theoretical
framework can be a conceptual model that is used as a
guide for the study (Conkin Dale, 2005) or themes from
the literature that are conceptually mapped and used to set
boundaries for the research (Miles and Huberman, 1994).
A sound framework also identifies the various concepts
being studied and the relationship between those concepts
(Burns and Grove, 1997). Such relationships should have
been identified in the literature. The research study should
then build on this theory through empirical observation.
Some theoretical frameworks may include a hypothesis.
Theoretical frameworks tend to be better developed in
experimental and quasi-experimental studies and often
poorly developed or non-existent in descriptive studies
(Burns and Grove, 1999).The theoretical framework should
be clearly identified and explained to the reader.
Aims and objectives/research question/
research hypothesis
The purpose of the aims and objectives of a study, the research
question and the research hypothesis is to form a link between
the initially stated purpose of the study or research problem
and how the study will be undertaken (Burns and Grove,
1999). They should be clearly stated and be congruent with
the data presented in the literature review. The use of these
items is dependent on the type of research being performed.
Some descriptive studies may not identify any of these items
but simply refer to the purpose of the study or the research
problem, others will include either aims and objectives or
research questions (Burns and Grove, 1999). Correlational
designs, study the relationships that exist between two or
more variables and accordingly use either a research question
or hypothesis. Experimental and quasi-experimental studies
should clearly state a hypothesis identifying the variables to
be manipulated, the population that is being studied and the
predicted outcome (Burns and Grove, 1999).
Sample and sample size
The degree to which a sample reflects the population it
was drawn from is known as representativeness and in
quantitative research this is a decisive factor in determining
the adequacy of a study (Polit and Beck, 2006). In order
to select a sample that is likely to be representative and
thus identify findings that are probably generalizable to
the target population a probability sample should be used
(Parahoo, 2006). The size of the sample is also important in
quantitative research as small samples are at risk of being
overly representative of small subgroups within the target
population. For example, if, in a sample of general nurses, it
was noticed that 40% of the respondents were males, then
males would appear to be over represented in the sample,
thereby creating a sampling error. The risk of sampling
660 Britishjournal of Nursing. 2007. Vol 16. No II
RESEARCH METHODOLOGIES
errors decrease as larger sample sizes are used (Burns and
Grove, 1997). In selecting the sample the researcher should
clearly identify who the target population are and what
criteria were used to include or exclude participants. It
should also be evident how the sample was selected and
how many were invited to participate (Russell, 2005).
Ethical considerations
Beauchamp and Childress (2001) identify four fundamental
moral principles: autonomy, non-maleficence, beneficence
and justice. Autonomy infers that an individual has the right
to freely decide to participate in a research study without
fear of coercion and with a full knowledge of what is being
investigated. Non-maleficence imphes an intention of not
harming and preventing harm occurring to participants
both of a physical and psychological nature (Parahoo,
2006). Beneficence is interpreted as the research benefiting
the participant and society as a whole (Beauchamp and
Childress, 2001). Justice is concerned with all participants
being treated as equals and no one group of individuals
receiving preferential treatment because, for example, of
their position in society (Parahoo, 2006). Beauchamp and
Childress (2001) also identify four moral rules that are both
closely connected to each other and with the principle of
autonomy. They are veracity (truthfulness), fidelity (loyalty
and trust), confidentiality and privacy.The latter pair are often
linked and imply that the researcher has a duty to respect the
confidentiality and/or the anonymity of participants and
non-participating subjects.
Ethical committees or institutional review boards have to
give approval before research can be undertaken. Their role
is to determine that ethical principles are being applied and
that the rights of the individual are being adhered to (Burns
and Grove, 1999).
Operational definitions
In a research study the researcher needs to ensure that
the reader understands what is meant by the terms and
concepts that are used in the research. To ensure this any
concepts or terms referred to should be clearly defined
(Parahoo, 2006).
Methodology: research design
Methodology refers to the nuts and bolts of how a
research study is undertaken. There are a number of
important elements that need to be referred to here and
the first of these is the research design. There are several
types of quantitative studies that can be structured under
the headings of true experimental, quasi-experimental
and non-experimental designs (Robson, 2002) {Table 2).
Although it is outside the remit of this article, within each
of these categories there are a range of designs that will
impact on how the data collection and data analysis phases
of the study are undertaken. However, Robson (2002)
states these designs are similar in many respects as most
are concerned with patterns of group behaviour, averages,
tendencies and properties.
Methodology: data collection
The next element to consider after the research design
is the data collection method. In a quantitative study any
number of strategies can be adopted when collecting data
and these can include interviews, questionnaires, attitude
scales or observational tools. Questionnaires are the most
commonly used data gathering instruments and consist
mainly of closed questions with a choice of fixed answers.
Postal questionnaires are administered via the mail and have
the value of perceived anonymity. Questionnaires can also be
administered in face-to-face interviews or in some instances
over the telephone (Polit and Beck, 2006).
Methodology: instrument design
After identifying the appropriate data gathering method
the next step that needs to be considered is the design
of the instrument. Researchers have the choice of using
a previously designed instrument or developing one for
the study and this choice should be clearly declared for
the reader. Designing an instrument is a protracted and
sometimes difficult process (Burns and Grove, 1997) but the
overall aim is that the final questions will be clearly linked
to the research questions and will elicit accurate information
and will help achieve the goals of the research.This, however,
needs to be demonstrated by the researcher.
Table 2. Research designs
Design
Experimental
Qucisl-experimental
Non-experimental,
e.g. descriptive and
Includes: cross-sectional.
correlationai.
comparative.
iongitudinal studies
Sample
2 or more groups
One or more groups
One or more groups
Sample
allocation
Random
Random
Not applicable
Features
• Groups get
different treatments
• One variable has not
been manipuiated or
controlled (usually
because it cannot be)
• Discover new meaning
• Describe what already
exists
• Measure the relationship
between two or more
variables
Outcome
• Cause and effiect relationship
• Cause and effect relationship
but iess powerful than
experimental
• Possible hypothesis for
future research
• Tentative explanations
Britishjournal of Nursing. 2007. Vol 16. No 11 661
If a previously designed instrument is selected the researcher
should clearly establish that chosen instrument is the most
appropriate.This is achieved by outlining how the instrument
has measured the concepts under study. Previously designed
instruments are often in the form of standardized tests
or scales that have been developed for the purpose of
measuring a range of views, perceptions, attitudes, opinions
or even abilities. There are a multitude of tests and scales
available, therefore the researcher is expected to provide the
appropriate evidence in relation to the validity and reliability
of the instrument (Polit and Beck, 2006).
Methodology: validity and reliability
One of the most important features of any instrument is
that it measures the concept being studied in an unwavering
and consistent way. These are addressed under the broad
headings of validity and reliability respectively. In general,
validity is described as the ability of the instrument to
measure what it is supposed to measure and reliability the
instrument’s ability to consistently and accurately measure
the concept under study (Wood et al, 2006). For the most
part, if a well established ‘off the shelf instrument has been
used and not adapted in any way, the validity and reliability
will have been determined already and the researcher
should outline what this is. However, if the instrument
has been adapted in any way or is being used for a new
population then previous validity and reliability will not
apply. In these circumstances the researcher should indicate
how the reliability and validity of the adapted instrument
was established (Polit and Beck, 2006).
To establish if the chosen instrument is clear and
unambiguous and to ensure that the proposed study has
been conceptually well planned a mini-version of the main
study, referred to as a pilot study, should be undertaken before
the main study. Samples used in the pilot study are generally
omitted from the main study. Following the pilot study the
researcher may adjust definitions, alter the research question,
address changes to the measuring instrument or even alter
the sampling strategy.
Having described the research design, the researcher should
outline in clear, logical steps the process by which the data
was collected. All steps should be fully described and easy to
follow (Russell, 2005).
Analysis and results
Data analysis in quantitative research studies is often seen
as a daunting process. Much of this is associated with
apparently complex language and the notion of statistical
tests. The researcher should clearly identify what statistical
tests were undertaken, why these tests were used and
what •were the results. A rule of thumb is that studies that
are descriptive in design only use descriptive statistics,
correlational studies, quasi-experimental and experimental
studies use inferential statistics. The latter is subdivided
into tests to measure relationships and differences between
variables (Clegg, 1990).
Inferential statistical tests are used to identify if a
relationship or difference between variables is statistically
significant. Statistical significance helps the researcher to
rule out one important threat to validity and that is that the
result could be due to chance rather than to real differences
in the population. Quantitative studies usually identify the
lowest level of significance as PsO.O5 (P = probability)
(Clegg, 1990).
To enhance readability researchers frequently present
their findings and data analysis section under the headings
of the research questions (Russell, 2005). This can help the
reviewer determine if the results that are presented clearly
answer the research questions. Tables, charts and graphs may
be used to summarize the results and should be accurate,
clearly identified and enhance the presentation of results
(Russell, 2005).
The percentage of the sample who participated in
the study is an important element in considering the
generalizability of the results. At least fifty percent of the
sample is needed to participate if a response bias is to be
avoided (Polit and Beck, 2006).
Discussion/conclusion/recommendations
The discussion of the findings should Oow logically from the
data and should be related back to the literature review thus
placing the study in context (Russell, 2002). If the hypothesis
was deemed to have been supported by the findings,
the researcher should develop this in the discussion. If a
theoretical or conceptual framework was used in the study
then the relationship with the findings should be explored.
Any interpretations or inferences drawn should be clearly
identified as such and consistent with the results.
The significance of the findings should be stated but
these should be considered within the overall strengths
and limitations of the study (Polit and Beck, 2006). In this
section some consideration should be given to whether
or not the findings of the study were generalizable, also
referred to as external validity. Not all studies make a claim
to generalizability but the researcher should have undertaken
an assessment of the key factors in the design, sampling and
analysis of the study to support any such claim.
Finally the researcher should have explored the clinical
significance and relevance of the study. Applying findings
in practice should be suggested with caution and will
obviously depend on the nature and purpose of the study.
In addition, the researcher should make relevant and
meaningful suggestions for future research in the area
(Connell Meehan, 1999).
References
The research study should conclude with an accurate list
of all the books; journal articles, reports and other media
that were referred to in the work (Polit and Beck, 2006).
The referenced material is also a useful source of further
information on the subject being studied.
Conciusions
The process of critiquing involves an in-depth examination
of each stage of the research process. It is not a criticism but
rather an impersonal scrutiny of a piece of work using a
balanced and objective approach, the purpose of which is to
highlight both strengths and weaknesses, in order to identify
662 Uritish Journal of Nursinii. 2007. Vol 16. No II
RESEARCH METHODOLOGIES
whether a piece of research is trustworthy and unbiased. As
nursing practice is becoming increasingly more evidenced
based, it is important that care has its foundations in sound
research. It is therefore important that all nurses have the
ability to critically appraise research in order to identify what
is best practice. HH
Russell C (2005) Evaluating quantitative researcli reports. Nephrol Nurs J
32(1): 61-4
Ryan-Wenger N (1992) Guidelines for critique of a research report. Heart
Lung 21(4): 394-401
Tanner J (2003) Reading and critiquing research. BrJ Perioper Nurs 13(4):
162-4
Valente S (2003) Research dissemination and utilization: Improving care at
the bedside.J Nurs Care Quality 18(2): 114-21
Wood MJ, Ross-Kerr JC, Brink PJ (2006) Basic Steps in Planning Nursing
Research: From Question to Proposal 6th edn. Jones and Bartlett, Sudbury
Bassett C, B.issett J (2003) Reading and critiquing research. BrJ Perioper
NriK 13(4): 162-4
Beauchamp T, Childress J (2001) Principles of Biomedical Ethics. 5th edn.
O.xford University Press, Oxford
Burns N, Grove S (1997) The Practice of Nursing Research: Conduct, Critique
and Utilization. 3rd edn.WB Saunders Company, Philadelphia
Burns N, Grove S (1999) Understanding Nursing Research. 2nd edn. WB
Saunders Company. Philadelphia
Carnell R (1997) Critiquing research. Nurs Pract 8(12): 16-21
Clegg F (1990) Simple Statistics: A Course Book for the Social Sciences. 2nd edn.
Cambridge University Press. Cambridge
Conkin DaleJ (2005) Critiquing research for use in practice.J Pediatr Health
Care 19: 183-6
Connell Meehan T (1999) The research critique. In:Treacy P, Hyde A, eds.
Nursing Research and Design. UCD Press, Dublin: 57-74
Cullum N. Droogan J (1999) Using research and the role of systematic
reviews of the literature. In: Mulhall A. Le May A. eds. Nursing Research:
Dissemination and Implementation. Churchill Livingstone, Edinburgh:
109-23-
Miles M, Huberman A (1994) Qualitative Data Analysis. 2nd edn. Sage,
Thousand Oaks. Ca
Parahoo K (2006) Nursing Research: Principles, Process and Issties. 2nd edn.
Palgrave Macmillan. Houndmills Basingstoke
Polit D. Beck C (2006) Essentials of Nursing Care: Methods, Appraisal and
Utilization. 6th edn. Lippincott Williams and Wilkins, Philadelphia
Robson C (2002) Reat World Research. 2nd edn. Blackwell Publishing,
O.xford
KEY POINTS
I Many qualified and student nurses have difficulty
understanding the concepts and terminology associated
with research and research critique.
IThe ability to critically read research is essential if the
profession is to achieve and maintain its goal to be
evidenced based.
IA critique of a piece of research is not a criticism of
the wori<, but an impersonai review to highlight the
strengths and iimitations of the study.
I It is important that all nurses have the ability to criticaiiy
appraise research In order to identify what is best
practice.
Critiquing Nursing Research
2nd edition
Critiquing
Nursing Research
2nd edition
ISBN-W; 1- 85642-316-6; lSBN-13; 978-1-85642-316-8; 234 x 156 mm; p/back; 224 pages;
publicatior) November 2006; £25.99
By John R Cutdiffe and Martin Ward
This 2nd edition of Critiquing Nursing Research retains the features which made the original
a ‘best seller’ whilst incorporating new material in order to expand the book’s applicability. In
addition to reviewing and subsequently updating the material of the original text, the authors
have added two further examples of approaches to crtitique along with examples and an
additonal chapter on how to critique research as part of the work of preparing a dissertation.
The fundamentals of the book however remain the same. It focuses specifically on critiquing
nursing research; the increasing requirement for nurses to become conversant with research,
understand its link with the use of evidence to underpin practice; and the movement towards
becoming an evidence-based discipline.
As nurse education around the world increasingly moves towards an all-graduate discipline, it
is vital for nurses to have the ability to critique research in order to benefit practice. This book
is the perfect tool for those seeking to gain or develop precisely that skill and is a must-have
for all students nurses, teachers and academics.
John Cutclitfe holds the ‘David G. Braithwaite’ Protessor of Nursing Endowed Chair at the University of Texas (Tyler); he is
also an Adjunct Professor of Psychiatric Nursing at Stenberg College International School of Nursing, Vancouver, Canada.
Matin Ward is an Independent tvtental Health Nurse Consultant and Director of tvlW Protessional Develcpment Ltd.
To order your copy please contact us using the details below or visit our website
www.quaybooks.co.yk where you will also tind details ot other Quay Books otters and titles.
John Cutcliffe and Martin Ward
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MAHbUTHCASIUMITED
Uritishjoiirnnl of Nursinji;. 2OO7.V0I 16. No 11 663
O R I G I N A L A R T I C L E
Smell dysfunction: a biomarker for
COVID-19
Shima T. Moein, MD, PhD1, Seyed MohammadReza Hashemian, MD, FCCM2, Babak Mansourafshar, MD2,
Ali Khorram-Tousi, MD1, Payam Tabarsi, MD3 and Richard L. Doty, PhD, FAAN4
Background: Severe acute respiratory syndrome-
coronavirus-2 (SARS-CoV-2), the virus that causes coro-
navirus disease 2019 (COVID-19), is responsible for the
largest pandemic since the 1918 influenza A virus subtype
H1N1 influenza outbreak. The symptoms presently recog-
nized by the World Health Organization are cough, fever,
tiredness, and difficulty breathing. Patient-reported smell
and taste loss has been associated with COVID-19 infection,
yet no empirical olfactory testing on a cohort of COVID-19
patients has been performed.
Methods: The University of Pennsylvania Smell Identifica-
tion Test (UPSIT), a well-validated 40-odorant test, was ad-
ministered to 60 confirmed COVID-19 inpatients and 60
age- and sex-matched controls to assess the magnitude and
frequency of their olfactory dysfunction. A mixed effects
analysis of variance determined whether meaningful differ-
ences in test scores existed between the 2 groups and if the
test scores were differentially influenced by sex.
Results: Fi�y-nine (98%) of the 60 patients exhibited some
smell dysfunction (mean [95% CI] UPSIT score: 20.98 [19.47,
22.48]; controls: 34.10 [33.31, 34.88]; p < 0.0001). Thirty-
five of the 60 patients (58%) were either anosmic (15/60;
25%) or severely microsmic (20/60; 33%); 16 exhibited mod-
erate microsmia (16/60; 27%), 8 mild microsmia (8/60; 13%),
and 1 normosmia (1/60; 2%). Deficits were evident for all 40
UPSIT odorants. No meaningful relationships between the
test scores and sex, disease severity, or comorbidities were
found.
Conclusion: Quantitative smell testing demonstrates that
decreased smell function, but not always anosmia, is a
major marker for SARS-CoV-2 infection and suggests the
possibility that smell testing may help, in some cases, to
identify COVID-19 patients in need of early treatment or
quarantine. C© 2020 ARS-AAOA, LLC.
Key Words:
chronic rhinosinusitis; olfactory disorders; olfaction; olfac-
tory test; UPSIT; COVID-19; biomarker
How to Cite this Article:
Moein ST, Hashemian SM, Mansourafshar B, Khorram-
Tousi A, Tabarsi P, Doty RL. Smell dysfunction: a biomarker
for COVID-19. Int Forum Allergy Rhinol. 2020;10:944–950.
1School of Biological Sciences, Institute for Research in Fundamental
Sciences, Tehran, Iran; 2Chronic Respiratory Diseases Research Center,
National Research Institute of Tuberculosis and Lung Diseases
(NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran;
3Clinical Tuberculosis and Epidemiology Research Center, National
Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid
Beheshti University of Medical Sciences, Tehran, Iran; 4Smell & Taste
Center, Department of Otorhinolaryngology-Head and Neck Surgery,
Perelman School of Medicine, University of Pennsylvania, Philadelphia,
PA
Correspondence to: Richard L. Doty, PhD, FAAN, Smell & Taste Center,
Department of Otorhinolaryngology–Head and Neck, Surgery, Perelman
School of Medicine, University of Pennsylvania, Philadelphia, PA; e-mail:
doty@pennmedicine.upenn.edu
Potential conflicts of interest: R.L.D. is a consultant to Acorda Therapeutics,
Eisai Co, Ltd, Merck Pharmaceuticals, the Michael J. Fox Foundation for
Parkinson’s Research, and Johnson & Johnson; receives royalties from
Cambridge University Press, Johns Hopkins University Press, and John Wiley
& Sons, Inc.; he is president of, and a major shareholder in, Sensonics
International, a manufacturer and distributor of smell and taste tests,
R ecently there have been numerous reports in the mediathat anosmia occurs in persons who have contracted
coronavirus disease 2019 (COVID-19) by exposure to the
severe acute respiratory syndrome-coronavirus-2 (SARS-
CoV-2) virus. These include 1 published single case report,1
and self-report surveys from Germany,2 Great Britain,3
Iran,4 Italy,5 and the United States,6 with smell loss re-
ports ranging from 34% to 68% of COVID-19–positive pa-
tients. Otorhinolaryngology authorities have warned that
loss of smell and taste, in combination with other symp-
toms, appears to be a strong predictor of COVID-19
infection.7,8
To date, validated quantitative olfactory testing has not
been performed in a cohort of COVID-19 patients to
including the test used in this study. A. K-T. is a medical advisor to Cobel
Darou in Iran. The other authors have nothing to disclose.
Received: 9 April 2020; Revised: 15 April 2020; Accepted: 15 April 2020
DOI: 10.1002/alr.22587
View this article online at wileyonlinelibrary.com.
944 International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020
http://crossmark.crossref.org/dialog/?doi=10.1002%2Falr.22587&domain=pdf&date_stamp=2020-06-18
Smell dysfunction: a biomarker for COVID-19
verify or determine the true magnitude of their deficits
and whether less-than-total loss occurs in some patients.
Moreover, the proportion of COVID-19 patients exhibit-
ing true olfactory disturbances is unknown. Most studies
suggest that, in general, a significant number of persons
with smell loss are unaware of their deficit until formal
testing9 and that self-reports of both smell and taste abil-
ities correlate poorly with the results of quantitative smell
and taste tests.10,11
In this case-control study, we administered the Persian
version of the 40-item University of Pennsylvania Smell
Identification Test (UPSIT)12 to 60 confirmed COVID-19
patients and 60 age- and sex-matched controls to assess
the presence, magnitude, and frequency of their olfactory
dysfunction. We determined whether the smell loss was
related to the sex of the subjects and inquired, for those
patients who were aware of their dysfunction before testing,
when they first noticed their chemosensory disorder.
Patients and methods
Subjects
The age, sex, comorbidities, smoking status, and com-
plaints of chemosensory dysfunction of the 120 study par-
ticipants are presented in Table 1. The 60 SARS-COV-
2–positive subjects had been admitted with the symptoms
of COVID-19 to the Masih Daneshvari Hospital, Tehran,
Iran, between March 21, 2020, and March 23, 2020, or
March 31, 2020, and April 5, 2020. At the time of the ol-
factory testing, all were inpatients in the recovery period of
the disease and were ready to be discharged within 4 days.
The study was explained in detail to 68 such patents, of
which 8 declined to participate (ie, the participation rate
was 88%).
The control subjects were from a database of 141 subjects
collected in Iran for an earlier study. They were tested in the
olfactory laboratory of the Institute for Research in Fun-
damental Sciences, Tehran, Iran, and comprised a conve-
nience sample obtained from e-mail lists, flyers, and word of
mouth. None had influenza or common cold symptoms at
the time of testing. The recruitment period for this database
(August 8, 2019, to February 13, 2020) preceded the first
reported confirmed cases of COVID-19 in Iran (February
19, 2020). A control subject was individually matched as
closely as possible to each COVID-19 patient. Exact age
matches were possible for 34 subjects, 1-year differences
for 22 subjects, and 2-year differences for 4 subjects. In
cases where >1 match was possible, the first match in the
database sequence was used.
Informed written consent was obtained from each patient
and control, and the study protocol was approved by the
local ethics committee and the Iranian Ministry of Health
(license number IR.SBMU.NRITLD.REC.1399.013).
All testing was performed with the highest regard for
examiner safety with appropriate personal protective
equipment.
TABLE 1. Patient and control subject demographics
*
Parameter
COVID-19
patients Controls
p
(Fisher exact
probability
test)
Sample size, n 60 60
Age (years), mean ± SD 46.55 ± 12.17 46.55 ± 12.07
Gender (male/female), n 40/20 40/20
Smoker (current/never), n 2/58 11/49 0.016
Taste/smell complaints, n 21 0 0.001
Comorbidities, n
Asthma 3 0 0.244
Atherosclerosis 0 2 0.496
Autoimmune disease 4
a
0 0.119
Carcinoma 2
b
0 0.496
Congenital melanocytic nevi 1 0 1.000
Diabetes 8
c
0 0.007
Hemophilia 0 1 1.000
Hepatic failure 0 1 1.000
Hyperlipidemia 1 1 1.000
Hypertension 6
c
5 1.000
Hypothyroidism 4
c
2 0.679
Migraine 0 1 1.000
Osteoporosis 0 1 1.000
Sinusitis 2 0 0.496
*Significant p differences indicated in bold.
aAutoimmune disease included Behcet’s disease in combination with Crohn’s
disease (n = 1), multiple sclerosis (n = 2), and rheumatoid arthritis (n = 1).
bProstate and cervical cancers.
c
Although, in rare cases, changes in dosage and medications may have occurred
during the course of inpatient treatments, most patients remained on their pread-
mission medications.
COVID-19 = coronavirus disease 2019; SD = standard deviation.
Diagnosis and clinical severity classification
of COVID-19 patients
COVID-19 diagnosis was based on the COVID-19 detec-
tion protocol of Masih Daneshvari Hospital. All of the
patients underwent 16-slice chest computed tomography
(CT) imaging (Scope Power Siemens CT Scan, Munich, Ger-
many) and had positive chest CT findings.13 Subsequently,
the diagnosis of COVID-19 disease was confirmed by quan-
titative detection of SARS-CoV-2 RNA using the real-time
reverse-transcription polymerase chain reaction (rRT-PCR)
in respiratory specimens.14 The RT-PCR assays were per-
formed using Sansure Biotech’s 2019-nCoV 30-Minute Nu-
cleic Acid Reagent Kits (Sansure Biotech, Inc., Development
Zone, Changsha, China). The respiratory specimens were
International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020 945
Moein et al.
collected from the patients’ nasopharyngeal wash/aspirate
or nasal aspirate.
COVID-19 clinical severity was classified as mild, mod-
erate, or severe according to the Massachusetts General
Hospital COVID-19 treatment guidance algorithm.15 Mild
clinical COVID-19 presentation was defined as having oxy-
gen saturation (SpO2) >90% along with or without risk
factors. Moderate clinical COVID-19 presentation was
considered for patients who had at least 1 epidemiolog-
ical risk factor along with a risk factor in vital signs or
laboratory findings at the admission point of time. Pa-
tients in the intensive care unit (ICU) or with progres-
sive disease were classified as having severe clinical pre-
sentation of COVID-19. Epidemiological risk factors in-
cluded age >55 years or preexisting pulmonary disease,
chronic kidney disease, diabetes with glycated hemoglobin
(A1c) >7.6%, history of hypertension or cardiovascular
disease or transplant, or immunosuppression or human
immunodeficiency virus (HIV). Risk factors of vital signs
comprised respiratory rate >24 breaths/minute, heart rate
>125 beats/minute, and SpO2 <90% on ambient air. In
laboratory findings, fibrin degradation product D-dimer
>1000 ng/mL, creatine phosphokinase (CPK) more than
twice the upper limit of normal, C-reactive protein (CRP)
>100 mg/L, lactate dehydrogenase (LDH) >245 U/L, el-
evated troponin, admission absolute lymphocyte count
<0.8, and ferritin >300 μg/L. For COVID-19 patients
with mild disease with SpO2 >90%, supportive care
was provided and hydroxychloroquine administration was
started (200 mg twice per day [BID] × 2 doses, then
100 mg BID for 5 days). For the patients with moder-
ate to severe COVID-19 presentations, lopinavir/ritonavir
200/50 mg BID for up to 10 days) was prescribed.
In patients with progressive COVID-19 disease admit-
ted to the ICU, intravenous immunoglobulin (IVIG) at
standard dose of 0.5 g/kg/day daily for 5 days was
administered.16
Olfactory testing
A modified and validated Persian version of the UPSIT was
administered in this study (Sensonics International, Had-
don Heights, NJ). The UPSIT is a well-validated and reliable
(test-retest r = 0.94) test that employs microencapsulated
“scratch and sniff” odorants.11,12,17,18 It provides an in-
dex of absolute dysfunction (ie, anosmia, severe microsmia,
moderate microsmia, mild microsmia, normosmia, malin-
gering), as well as relative dysfunction based upon age-
and gender-adjusted normative percentile ranks. The to-
tal number of odorant stimuli out of 40 that is correctly
identified serves as the test measure. Scores on this test
correlate well with other types of olfactory tests, includ-
ing threshold tests.19 Although the UPSIT is designed to be
self-administered, to be certain that the COVID-19 patients
correctly performed the test during the limited clinical time
window, the testing was assisted by a trained examiner.
FIGURE 1. UPSIT scores of the COVID-19 patients compared to those of
healthy controls. The distribution of the participants’ scores in each group
is depicted in violin plot. The white circles indicate the median of the score
for each group. COVID-19 = coronavirus disease 2019; UPSIT = University
of Pennsylvania Smell Identification Test.
Statistical analyses
Statistical analyses were performed using either SYSTAT 13
(Systat Software, Inc., San Jose, CA)20 or MATLAB 2019b
(The MathWorks, Inc., Natick, MA). A subject group by
gender mixed factor analysis of variance (ANOVA) was
used to determine whether the UPSIT scores differed signif-
icantly between the patient and control groups and whether
gender influenced the test scores. Standard ANOVAs were
used to compare other means. Differences in frequencies
were assessed using the Fisher’s exact probability test.
Results
The COVID-19 patients’ non-mutually exclusive present-
ing symptoms were fever (n = 46, 77%), cough (n = 35,
58%), shortness of breath (n = 31, 52%), headache (n =
22, 37%), myalgia (n = 5, 8%), sweating (n = 2, 3%),
shivering (n = 2, 3%), anorexia (n = 2, 3%), stomachache
(n = 1, 2%), and tinnitus (n = 1, 2%). The mean (95%
CI) time between the onset of symptoms and the olfactory
testsing was 12.76 (11.47, 14.06) days.
The UPSIT testing revealed that, relative to controls and
published normative data, the COVID-19 patients exhib-
ited marked olfactory dysfunction. Thus, as illustrated in
Figure 1, the mean (95% confidence interval [CI]) UP-
SIT score for the COVID-19 patients was 20.98 (19.47,
22.48), reflecting severe microsmia,21 whereas the mean
UPSIT score (95% CI) for the age- and sex-matched con-
trols fell within the normal range (34.10 [33.31, 34.88];
ANOVA group main effect F [1,58] = 232.99, p < 0.0001,
η2 = 0.80). The COVID-19 deficit was not specific to any
1 UPSIT odorant, being evident for all 40 stimuli (Fig. 2).
Importantly, all but 1 of the 60 patients with COVID-19
had some degree of measured olfactory dysfunction (98%).
Thirty-five of the 60 patients (58%) were either anosmic
946 International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020
Smell dysfunction: a biomarker for COVID-19
FIGURE 2. Performance on individual UPSIT odorants for the COVID-19
patients and matched healthy controls. Note that dysfunction was evident
for all 40 UPSIT odorants. Performance for each group is calculated as the
percent of individuals having correctly identified the odorant. COVID-19 =
coronavirus disease 2019; UPSIT = University of Pennsylvania Smell Identi-
fication Test.
TABLE 2. Classification of olfactory function of the UPSIT
scores of COVID-19 patients and matched controls
UPSIT function category
COVID-19
patients n
(%)
Controls n
(%)
UPSIT score
range
Normosmia 1 (2) 49 (82) 31–40
Mild microsmia 8 (13) 11 (18) 28–30
Moderate microsmia 16 (27) 0 24–27
Severe microsmia 20 (33) 0 17–23
Anosmia 15 (25) 0 6–16
Probable malingering 0 0 0–5
COVID-19 = coronavirus disease 2019; UPSIT = University of Pennsylvania Smell
Identification Test.
(15/60; 25%) or severely microsmic (20/60; 33%); 16/60
(27%) exhibited moderate microsmia, 8/60 (13%) mild mi-
crosmia, and 1/60 (2%) normosmia according to Persian-
adjusted UPSIT norms (Table 2).21 This contrasts markedly
from the controls, of which 49 of 60 (82%) were normal
with the remaining 11 of 60 (18%) having only mild bor-
derline dysfunction. Relative to the normal controls, the
11 controls with mild borderline dysfunction tended to be
disproportionately men (10/11 [91%] vs 30/49 [61%]; p =
0.08) of older age (respective mean ages [95% CIs] = 51.18
[42.63, 59.73] and 45.51 [42.11, 48.90]; p = 0.18). Even
though there was a tendency for women, overall, to outper-
form men on the UPSIT (respective mean [95% CI] UPSIT
scores: 22.55 [20.13, 24.97] and 20.20 [18.27, 22.13]; F
[1,58] = 3.82, p = 0.055, η2 = 0.06), this was unrelated
to COVID-19 (sex by group interaction F [1,58] = 0.396,
p = 0.53).
Thirty-five percent (21/60) of the COVID-19 patients re-
ported a loss in either smell or taste function, with 12%
(7/60) reporting smell loss only, 7% (4/60) taste loss only,
TABLE 3. Relationship between COVID-19 clinical disease
severity and mean (95% CI) scores on the UPSIT
COVID-19 disease severity n (%)
UPSIT score
mean (95%CI)
Mild 25 (42) 22.04 (20.11–24.72)
Moderate 29 (48) 19.69 (17.24–21.99)
Severe 6 (10) 22.83 (17.65–25.77)
CI = confidence interval; COVID-19 = coronavirus disease 2019; UPSIT = Univer-
sity of Pennsylvania Smell Identification Test.
and 17% (10/60) both taste and smell loss. There was no
significant difference between UPSIT scores of patients who
were aware or unaware of their chemosensory loss (p =
0.28). All 21 reported that the onset of the olfactory dys-
function occurred at the same time or immediately after the
onset of their other COVID-19 symptoms. None reported
recognizing any smell or taste deficits prior to their other
COVID-19 symptoms, namely fever, cough, or shortness
of breath. In the healthy control group, none of the partic-
ipants reported any smell or taste problems.
As shown in Table 1, significantly fewer smokers were
present in the COVID-19 group than in the control group
(2/60 vs 11/60; p = 0.016). Eight patients with diabetes
were present in the COVID-19 group, unlike the control
group (8/60 vs 0/60; p = 0.007). However, the respective
mean (95% CI) UPSIT scores for COVID-19 patients with
and without diabetes did not differ (21.38 [18.18, 24.56]
vs 20.92 [19.32, 22.62], respectively; F [2,57] = 1.43,
p = 0.24, η2 = 0.05). No association of UPSIT scores with
disease severity, as per the Massachusetts General Hospi-
tal COVID-19 treatment guidance algorithm, was apparent
(Table 3; F [2,57] = 1.45, p = 0.24, η2 = 0.05).
Discussion
This study quantitatively evaluated olfaction in a sizable
cohort of patients diagnosed with the SARS-CoV-2 virus
infection. By employing a well-validated 40-item smell test,
COVID-19 patients were able to be classified into dis-
tinct categories of olfactory dysfunction, with 35 of 60
(58%) exhibiting either anosmia or severe microsmia. In
the present study, only 35% of the patients were aware
of their olfactory deficit before testing, a percentage near
to that of 34% reported in an interview with COVID-19
inpatients in Italy,5 but lower than those reported in 2 on-
line surveys (59%3 and 68%6). This difference between
self-report rate and quantified smell assessment conceiv-
ably reflects a disproportionate sampling of hospital ad-
mitted cases and/or the well-documented underestimation
of self-reported smell and taste dysfunction present for the
general population9,10 and for such diseases as Alzheimer’s
disease (AD)11 and Parkinson’s disease (PD).22,23 In gen-
eral, smell loss is most noticeable when marked loss, such
as anosmia, is present.11,22 It should be pointed out that
International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020 947
Moein et al.
the present study’s sample resembles the demographic and
clinical characteristics of COVID-19 patients reported in
a compilation of 43 studies involving 3600 patients,24
implying it is likely representative of COVID-19 patients
in general.
The basis for the smell loss due to SARS-CoV-2 is not
entirely clear, although it is well established that viruses
and other xenobiotics can damage the olfactory neuroep-
ithelium. Indeed, acute viral upper respiratory viral infec-
tions that damage this epithelium are the major cause of
chronic olfactory dysfunction and numerous viruses are
known to enter the brain through cellular and pericellular
transport via this epithelium.25 In North America, the peak
period of non-influenza–related smell loss, including that
possibly due to coronaviruses, occurs during the months of
April, May, and June, whereas influenza-related smell loss
peaks in December, January, and February.26 Currently,
the prevalence of COVID-19 in North America seems to
follow a similar function to that observed for olfactory
deficits due to other viruses, including other coronaviruses.
What seems unique, however, is that nearly everyone who
contacts COVID-19 appears to exhibit measurable loss of
smell seemingly independent of severe nasal congestion or
inflammation.
Although SARS-CoV-2 has the ability to enter epithe-
lial cells by directly binding to the angiotensin converting
enzyme 2 (ACE2) protein on the cell surface,27 olfactory
receptor cells do not express ACE2, as well as another
gene involved in SARS-CoV-2 entry (TMPRSS2), unlike
epithelial sustentacular and stem cells.28 Thus, damage to
the olfactory receptors may be mediated indirectly through
SARS-CoV-2 uptake into other cells critical for sustain-
ing the olfactory receptor cell population. For example,
olfactory ensheathing glial cells that surround the olfac-
tory receptor cell axons and form the olfactory fila are 1
candidate by which ACE2-independent virus transfer can
occur into olfactory receptor neurons by way of exosomes.
A possible scenario suggests that at this point olfactory re-
ceptor neurons may initiate a rapid immune response in
the host with the manifestation of olfactory dysfunction.29
That being said, the olfactory neuroepithelium has con-
siderable propensity for regeneration if the stem cell layer
is not markedly damaged30-32 – regeneration that is likely
related to spontaneous improvement in olfactory function
over time.33
It is of interest that significantly fewer smokers were
found in our COVID-19 cohort than in the control co-
hort. Our findings correspond with studies that report cur-
rent smokers as rare as 1.4% and 1.3% in Chinese34 and
U.S.35 COVID-19 patient populations, respectively. A re-
cent study reported that smoking upregulated the expres-
sion of ACE-2 in the airways, potentially predisposing
individuals to increased risk of coronavirus infection
but, paradoxically, protecting the host against acute lung
injury.36 Interestingly, nonsmokers appear to be much more
susceptible than smokers to olfactory dysfunction from
industrial exposures to acrylate and methacrylate37 and
smoking appears to protect, to some degree, against the
olfactory loss of PD.38 Future research is needed to deter-
mine to what degree the reported low frequency of smok-
ers in COVID-19 populations is impacted by selection bias
(eg, more smokers may have died before reaching the hos-
pital) and reverse causation (ie, cessation of smoking in
patients with severe symptoms prior to entering the hos-
pital, thereby being counted as nonsmokers). The latter is
unlikely in our study, however, because each patient was
specifically asked whether they currently smoked or had
smoked in the past.
The complaint of taste loss by a small number of our
COVID-19 patients most likely reflects, to a significant de-
gree, damage to the olfactory system, rather than damage
to the taste buds or taste afferents, per se. Thus, the vast
majority of individuals who clinically present with com-
plaints of taste loss actually exhibit smell dysfunction, in-
cluding those with a viral etiology.39 Taste bud–mediated
sensations are largely limited to the basic taste qualities of
sweet, sour, bitter, salty, and umami. With the exception
of such sensations, all “tastes” are flavor sensations from
olfactory receptor stimulation by volatiles entering from
the nasopharynx during deglutition.40 This tendency for
many persons with smell loss to misconstrue their prob-
lem as taste loss39 must be considered in studies relying
only on self-report. Future research employing quantitative
taste tests is clearly needed to definitively establish whether
SARS-CoV-2 also can damage taste afferents or, in rare
cases, more central taste-related brain regions.
More men than women were present in our sample, in
accord with the reported demographic and clinical charac-
teristics of COVID-19 patients.24 However, the magnitude
of olfactory dysfunction, as measured by the UPSIT, was
essentially the same in both sexes. This implies that there is
little or no protection from being a female in terms of the
degree to which SARS-CoV-2 damages the olfactory sys-
tem, in accord with some other studies of postviral olfac-
tory deficits.41 If this observation is confirmed with larger
samples, it would appear that the olfactory dysfunction of
COVID-19 differs from that of AD and PD, where women
significantly outperform men.11,22,38
It is important to note that the COVID-19–positive pa-
tients evaluated in this study had severe enough symptoms
to be admitted to the hospital. It is unknown whether less
severe cases also exhibit the same degree of smell dysfunc-
tion as documented in this study, although within our hos-
pitalized cohort no relationship was evident between the
olfactory test scores and disease severity. This is similar to
what is seen in the smell loss of PD, where no clear associa-
tion is present between the magnitude of the classic motor
signs and the amount of olfactory dysfunction.22
Even though the COVID-19 patients in this study were
undergoing drug treatments for their disease, it is unlikely
that the involved drugs were a meaningful cause of their ol-
factory dysfunction. Despite the fact that a significant num-
ber of medications are reported to have taste side effects,42
alterations in smell function are relatively rare and have
948 International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020
Smell dysfunction: a biomarker for COVID-19
not been associated with hydroxychloroquine, lopinavir-
ritonavir, or IVIG. Because the same degree of smell func-
tion was evident among patients with COVID-19 taking
each of these medications, it is improbable that any one
medication would have produced the smell deficits observed
in this study.
Although RT-PCR was by far the frontline response to
the SARS-CoV-2 outbreak, the accuracy and conditions
under which the results of RT-PCR were achieved must
be kept in context, because a false-negative rate of at least
15% has been reported.43-45 The present findings, along
with the wealth of anecdotal data, suggest that quantita-
tive testing of the sense of smell might serve as a rapid
and inexpensive alternative diagnostic means to screen for
COVID-19 in large numbers of individuals. Indeed, the
sensitivity and specificity of olfactory tests for COVID-19–
positive patients under the age of 65 years would seem to be
quite strong, because age-related changes in smell function
occur mainly after the age of 65 years.17
The present study has both strengths and weaknesses.
Among its strengths are (1) the use of a sensitive test of
olfactory function that allows for determining different de-
grees of olfactory function, (2) testing of well-validated
COVID-19 patients whose clinical severity was well doc-
umented, and (3) the use of controls matched closely to
those of the patients on the basis of age and sex who were
sampled outside of the period in which COVID-19 was
first identified in Iran. Its major limitation is the sampling
of the study population at only 1 point in time relative
to the onset of COVID-19 symptoms. Future studies are
needed to establish (1) the exact time of onset of smell
symptoms, (2) whether the olfactory dysfunction is tran-
sient, long-lasting, or permanent, (3) whether such symp-
toms are evident in those who fail to develop other COVID-
19 symptoms, and (4) whether the deficits follow seasonal
patterns such as those noted for other virus-related cases
of smell dysfunction.26 Information as to permanency is of
considerable significance, because loss of the ability to smell
significantly impacts quality of life, the flavor of foods, and
beverages, and safety from spoiled food, fire, and leaking
natural gas. Importantly, smell loss can be a harbinger of
a number of neurological diseases, most notably AD and
PD—diseases which, in some cases, have been associated
with a number of viruses.46,47 Although the reasons are
poorly understood, older persons with smell loss are 3 times
more likely to die over the course of an ensuring half-decade
than older persons with a normal sense of smell.48,49
Conclusion
The present study provides a quantitative assessment of the
olfactory function of a cohort of patients with COVID-
19. Its findings strongly suggest that some degree of loss
of smell function is present in nearly all COVID-19 pa-
tients near the end of their acute recovery period. However,
anosmia, per se, was present in only about one-quarter of
COVID-19 positive patients in our sample, with about one-
third evidencing severe microsmia. In light of the current
findings and pandemic environment, and the widespread
anecdotal evidence of smell dysfunction in COVID-19,
it does not seem unreasonable that testing the olfaction
of persons who may be at risk or have subtle COVID-
19 signs, such as low-grade fevers, may aid in identifying
COVID-19 patients who are in need of early treatment or
quarantine.
Acknowledgments
We thank Mr. Iraj Fotouhi for his invaluable help in as-
sisting patients during smell testing, Ms. Crystal Wylie for
comments on a draft of the paper, and Dr. Kambiz Pour-
rezaei for insightful discussions of the research.
References
1. Eliezer M, Hautefort C, Hamel AL, et al. Sud-
den and complete olfactory loss function as a pos-
sible symptom of COVID-19. JAMA Otolaryngol
Head Neck Surg. (in press). Epub 08 April 2020.
https://doi.org/10.1001/jamaoto.2020.0832.
2. Luers JC, Klussmann JP, Guntinas-Lichius O.
[The Covid-19 pandemic and otolaryngol-
ogy: what it comes down to?]. Laryngorhi-
nootologie. 2020;99(5):287–291. https://doi.org/
10.1055/a-1095-2344. German.
3. Menni C, Valdes A, Freydin MB, et al. Loss of
smell and taste in combination with other symp-
toms is a strong predictor of COVID-19 infec-
tion. medRxiv. 2020.04.05.20048421. Epub 07 April
2020. https://doi.org/10.1101/2020.04.05.20048421.
4. Bagheri SHR, Asghari AM, Farhadi M, et al. Coin-
cidence of COVID-19 epidemic and olfactory dys-
function outbreak. medRxiv. 2020.03.23.20041889.
Epub 27 March 2020. https://doi.org/10.1101/2020.
03.23.20041889.
5. Giacomelli A, Pezzati L, Conti F, et al. Self-reported ol-
factory and taste disorders in SARS-CoV-2 patients: a
cross-sectional study. Clin Infect Dis. (in press). Epub
26 March 2020. https://doi.org/10.1093/cid/ciaa330.
6. Yan CH, Faraji M, Prajapati DP, Boone CE. Associ-
ation of chemosensory dysfunction and Covid-19 in
patients presenting with influenza-like symptoms. Int
Forum Allergy Rhinol. (in press). Epub 12 April 2020.
https://doi.org/10.1002/alr.22579.
7. American Academy of Otolaryngology–Head and
Neck Surgery Foundation. ENT Health. Hyposmia
and anosmia. Alexandria, VA: American Academy of
Otolaryngology–Head and Neck Surgery Foundation;
2020. https://www.enthealth.org/conditions/hyposmi
a-and-anosmia/. Accessed May 14, 2020.
8. Hopkins C, Kumar N. Loss of sense of smell as marker
of COVID-19 infection 2020. London, UK: ENT UK,
The Royal College of Surgeons of England; 2020.
https://www.entuk.org/loss-sense-smell-marker-covid
-19-infection-0. Accessed May 14, 2020.
9. Wehling E, Nordin S, Espeseth T, Reinvang I,
Lundervold AJ. Unawareness of olfactory dysfunc-
tion and its association with cognitive functioning in
middle aged and old adults. Arch Clin Neuropsychol.
2011;26:260-269.
10. Soter A, Kim J, Jackman A, Tourbier I, Kaul A, Doty
RL. Accuracy of self-report in detecting taste dysfunc-
tion. Laryngoscope. 2008;118:611-617.
11. Doty RL, Reyes PF, Gregor T. Presence of both odor
identification and detection deficits in Alzheimer’s dis-
ease. Brain Resh Bull 1987;18:597-600.
12. Doty RL, Shaman P, Dann M. Development of the
University of Pennsylvania Smell Identification Test: a
standardized microencapsulated test of olfactory func-
tion. Physiol Behav. 1984;32:489-502.
13. Chung M, Bernheim A, Mei X, et al. CT imaging fea-
tures of 2019 novel coronavirus (2019-nCoV). Radi-
ology. 2020;295:202-207.
14. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral
load in upper respiratory specimens of infected pa-
tients. N Engl J Med. 2020;382:1177-1179.
15. Massachusetts General Hospital. Massachusetts
General Hospital COVID-19 Treatment Guidance.
Boston, MA: Massachusetts General Hospital; 2020.
https://www.massgeneral.org/assets/MGH/pdf/news/
coronavirus/covid-19_domID_treatmentGuide .
Accessed May 14, 2020.
16. Jamaati H DF, Tabarsi P, Marjani M, Saffaei A,
Hashemian SM. A fourteen-day experience with coro-
navirus disease 2019 (COVID-19) induced acute res-
piratory distress syndrome (ARDS): an Iranian treat-
ment protocol. Iran J Pharm Res 2020;19(1):31–36.
17. Doty RL, Shaman P, Applebaum SL, Giberson R,
Siksorski L, Rosenberg L. Smell identification ability:
changes with age. Science 1984; 226: 1441-1443.
18. Doty RL, Frye RE, Agrawal U. Internal consistency
reliability of the fractionated and whole university
of Pennsylvania smell identification test. Percept Psy-
chophys 1989;45(5): 381-384.
19. Doty RL, Wylie C, Potter M, Beston R, Cope B, Ma-
jam K. Clinical validation of the olfactory detection
threshold module of the Snap & Sniff(R) olfactory test
system. Int Forum Allergy Rhinol 2019;9(9): 986-992.
20. Wilkinson L. SYSTAT: The System for Statistics.
Evanston, IL: SYSTAT, Inc.; 1990.
International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020 949
https://doi.org/10.1001/jamaoto.2020.0832
https://doi.org/10.1055/a-1095-2344
https://doi.org/10.1055/a-1095-2344
https://doi.org/10.1101/2020.04.05.20048421
https://doi.org/10.1101/2020.03.23.20041889
https://doi.org/10.1101/2020.03.23.20041889
https://doi.org/10.1093/cid/ciaa330
https://doi.org/10.1002/alr.22579
https://www.enthealth.org/conditions/hyposmia-and-anosmia/
https://www.enthealth.org/conditions/hyposmia-and-anosmia/
https://www.entuk.org/loss-sense-smell-marker-covid-19-infection-0
https://www.entuk.org/loss-sense-smell-marker-covid-19-infection-0
https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/covid-19_domID_treatmentGuide
https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/covid-19_domID_treatmentGuide
Moein et al.
21. Doty RL. The Smell Identification TestTM Administra-
tion Manual. 3rd ed. Haddon Heights, NJ: Sensonics,
Inc.; 1995.
22. Doty RL, Deems DA, Stellar S. Olfactory dysfunction
in parkinsonism: a general deficit unrelated to neuro-
logic signs, disease stage, or disease duration. Neurol-
ogy. 1988;38:1237-1244.
23. Doty RL, Perl DP, Steele JC, et al. Odor identifi-
cation deficit of the parkinsonism-dementia complex
of Guam: equivalence to that of Alzheimer’s and id-
iopathic Parkinson’s disease. Neurology. 1991;41(5
Suppl 2):77-80.
24. Fu L, Wang B, Yuan T, et al. Clinical character-
istics of coronavirus disease 2019 (COVID-19) in
China: a systematic review and meta-analysis. J In-
fect. 2020;80:656-665.
25. Doty RL. The olfactory vector hypothesis of neu-
rodegenerative disease: is it viable? Ann Neurol.
2008;63:7-15.
26. Potter MR, Chen JH, Lobban N-S, Doty RL.
Olfactory dysfunction from acute upper respira-
tory infections: relationship to season of onset.
Int Forum Allergy Rhinol. 2020;10(6):706–712.
https://doi.org/10.1002/alr.22551.
27. Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA se-
quencing of 13 human tissues identify cell types and
receptors of human coronaviruses. Biochem Biophys
Res Commun. 2020;526:135-140.
28. Brann DH, Tsukahara T, Weinreb C, et al.
Non-neural expression of SARS-ClV-2 entry
genes in the olfactory epithelium suggests mech-
anisms underlying anosmia in COVD-19 patients.
bioRxiv 2020.03.25.009084. Epub 09 April 2020.
https://doi.org/10.1101/2020.03.25.009084.
29. Butowt R, Bilinska K. SARS-CoV-2: olfaction, brain
infection, and the urgent need for clinical samples al-
lowing earlier virus detection. ACS Chem Neurosci.
2020;11:1200-1203.
30. Chang SY, Glezer I. The balance between efficient
anti-inflammatory treatment and neuronal regenera-
tion in the olfactory epithelium. Neural Regen Res.
2018;13:1711-1714.
31. Choi R, Goldstein BJ. Olfactory epithelium: cells,
clinical disorders, and insights from an adult
stem cell niche. Laryngoscope Investig Otolaryngol.
2018;3:35-42.
32. Joiner AM, Green WW, McIntyre JC, Allen BL,
Schwob JE, Martens JR. Primary cilia on horizon-
tal basal cells regulate regeneration of the olfactory
epithelium. J Neurosci. 2015;35:13761-13672.
33. London B, Nabet B, Fisher AR, White B, Sammel MD,
Doty RL. Predictors of prognosis in patients with ol-
factory disturbance. Ann Neurol. 2008;63:159-166.
34. Zhang JJ, Dong X, Cao YY, et al. Clinical charac-
teristics of 140 patients infected with SARS-CoV-2 in
Wuhan, China. Allergy. (in press). Epub 19 February
2020. https://doi.org/10.1111/all.14238.
35. CDC COVID-19 Response Team. Preliminary esti-
mates of the prevalence of selected underlying health
conditions among patients with coronavirus disease
2019 – United States, February 12-March 28, 2020.
MMWR Morb Mortal Wkly Rep. 2020;69:382-386.
36. Leung JM, Yang CX, Tam A, et al. ACE-2 expression
in the small airway epithelia of smokers and COPD
patients: implications for COVID-19. Eur Respir J.
2020;55:2000688.
37. Schwartz BS, Doty RL, Monroe C, Frye R, Barker
S. Olfactory function in chemical workers exposed to
acrylate and methacrylate vapors. Am J Public Health.
1989;79:613-618.
38. Sharer JD, Leon-Sarmiento FE, Morley JF, Weintraub
D, Doty RL. Olfactory dysfunction in Parkinson’s dis-
ease: positive effect of cigarette smoking. Mov Disord.
2015;30:859-862.
39. Deems DA, Doty RL, Settle RG, et al. Smell and taste
disorders, a study of 750 patients from the University
of Pennsylvania Smell and Taste Center. Arch Oto-
laryngol Head Neck Surg. 1991;117:519-528.
40. Burdach KJ, Doty RL. The effects of mouth move-
ments, swallowing, and spitting on retronasal odor
perception. Physiol Behav. 1987;41:353-356.
41. Tian J, Wei YX, Li L, Sun ZF, Wang BQ. [Analysis of
clinical characteristics of 141 patients with postviral
olfactory dysfunction]. Lin Chung Er Bi Yan Hou Tou
Jing Wai Ke Za Zhi. 2017;31:749-752. Chinese.
42. Schiffman SS. Influence of medications on taste and
smell. World J Otorhinolaryngol Head Neck Surg
2018;4:84-91.
43. Li D, Wang D, Dong J, et al. False-negative results
of real-time reverse-transcriptase polymerase chain re-
action for severe acute respiratory syndrome coron-
avirus 2: role of deep-learning-based CT diagnosis and
insights from two cases. Korean J Radiol. 2020;21:
505-508.
44. Ai J-W, Zhang H-C, Xu T, et al. Optimizing di-
agnostic strategy for novel coronavirus pneumonia,
a multi-center study in Eastern China. medRxiv.
2020.02.13.20022673. Epub 17 February 2020.
https://doi.org/10.1101/2020.02.13.20022673.
45. Liang Y, Liang J, Zhou Q, et al. Prevalence and
clinical features of 2019 novel coronavirus disease
(COVID-19) in the Fever Clinic of a teaching hos-
pital in Beijing: a single-center, retrospective study.
medRxiv. 2020.02.25.20027763. Epub 28 February
2020. https://doi.org/10.1101/2020.02.25.20027763.
46. Balin BJ, Hudson AP. Herpes viruses and Alzheimer’s
disease: new evidence in the debate. Lancet Neurol.
2018;17:839-841.
47. Olsen LK, Cairns AG, Aden J, et al. Viral mimetic
priming enhances alpha-synuclein-induced degenera-
tion: implications for Parkinson’s disease. Brain Behav
Immun. 2019;80:525-535.
48. Pinto JM, Wroblewski KE, Kern DW, Schumm
LP, McClintock MK. Olfactory dysfunction pre-
dicts 5-year mortality in older adults. PLoS One.
2014;9:e107541.
49. Devanand DP, Lee S, Manly J, et al. Olfactory deficits
predict cognitive decline and Alzheimer dementia in
an urban community. Ann Neurol. 2015;84:182-189.
950 International Forum of Allergy & Rhinology, Vol. 10, No. 8, August 2020
https://doi.org/10.1002/alr.22551
https://doi.org/10.1101/2020.03.25.009084
https://doi.org/10.1111/all.14238
https://doi.org/10.1101/2020.02.13.20022673
https://doi.org/10.1101/2020.02.25.20027763
Rubric to Critique Quantitative Research Article
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Introduction and Literature Review |
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What was the general issue, topic, or question being investigated? |
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What was the purpose of the study? Is the phenomenon to be studied clearly articulated and delimited? |
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3 |
Clearly identifies how the literature justifies the problem and leads to the research question(s) |
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| Method | |||||||||||
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Which purposeful sampling technique was used? What was the sample size? How were people selected for interviews or observations? |
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What was the research role assumed by the researcher? What was the person’s training and background? |
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What was the design selected? |
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| Results and Discussion | |||||||||||
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What data collection strategies were used? Were multiple strategies employed? |
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What strategies did the researcher use to minimize potential bias and to help extend the findings (internal and external validity)? |
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Were the limitations of the study discussed? If yes, what were some of the recognized limitations? If no, provide your own opinions as to any limitations of the study. |
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What ethical considerations were addressed? Did the researcher specify how informed consent, confidentiality, etc. were handled in the field? |
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What do you think of this study in general and why? That is, do you think the study is good/bad, important/not important, and interesting/not interesting, makes sense/does not make sense? Would you act based on this study? Why? |