Short-time Behavioural Intervention in Post-Covid Syndrome (SIPCOV): A Pragmatic Randomised Controlled Trial
Phase: NA
Conditions: COVID-19
Sponsor: University Hospital, Akershus

SIPCOV protocol, February 2022 
 
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Short-time behavioural intervention in post-Covid 
syndrome (SIPCOV): A pragmatic randomised 
controlled trial 
 
NCT05196451 
February 21., 2022 
 

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1. Introduction 
Persistent post-infectious symptoms (PPIS) after Covid-19, often referred to as post-Covid 
syndrome, may be considered as an epidemic in its own right 
The Covid-19 pandemic is an unprecedented threat to health and welfare globally. It is increasingly 
clear that Covid-19 may result in disabling long-term sequelae often referred to as post-Covid 
syndrome or “Long Covid”, being equally common among hospitalized and non-hospitalized 
patients.29,30 Evidence suggests that most post-Covid syndrome cases fit within the label of Persistent 
post-Infectious Symptoms (PPIS), encompassing chronic fatigue, pain and other symptoms, but with 
scarce findings on standard clinical examination.6,24,27,31 
PPIS is a common sequel after several acute infections with a diverse array of pathogens, ranging 
from infectious mononucleosis (IM) caused by Epstein-Barr virus, to Q-fever caused by the bacterium 
Coxiella burnetii, and gastroenteritis caused by the parasite Giardia lamblia,10,12 or as an adverse 
effect following vaccination.9 PPIS is a pathogen-independent phenomenon that phenotypically 
appears as an abnormal perpetuation of the acute sickness response (ASR), which is a stereotyped 
collection of physiological, behavioral and psychological manifestations to an infectious event.1 
Across multiple prospective cohort studies, almost one half of subjects report PPIS six months after 
the infectious event, and 10-15 % satisfy diagnostic criteria for chronic fatigue syndrome (CFS) (often 
also referred to as myalgic encephalomyelitis (ME)).5,10,12,23,28 Although late recovery may occur 
chronic disability is common, with strong negative impact upon employment prospects and family 
networks, and with high societal costs.13 Given the total number of Covid-19 cases globally 
(approximately 140 million by April 2021),37 post-Covid syndrome may be considered as an epidemic 
in its own right (Fig. 1).   
 
 
Figure 1. Covid-19 weekly incidence37 and a conservative estimate of post-Covid syndrome prevalence (based on 10 % and 5 % case 
rate, respectively, 6 and 12 months after the acute infection).12 Recent evidence suggests that the numbers may be even higher.35  
 
Functional brain alterations may be a central disease mechanism of post-Covid syndrome 
The underlying disease mechanisms of post-Covid syndrome remain poorly understood. However, 
studies of PPIS following other infections have revealed a complex blend of genetic/epigenetic25 and 
psychosocial7 vulnerabilities, in concert with autonomic,40,41 hormonal,22 and immunological21 
alterations.  
A prominent model of PPIS consider functional brain alterations to be a central 
pathophysiological element, possibly explaining other documented aberrations.11,26,42 This 
assumption is supported by functional brain imaging studies,38,39 clinical trial outcomes,17,32 and 
fundamental neurobiological concepts,3,18 and is also intimately related to more comprehensive 
theories on sustained activation of biological stress responses.33,42  
 
A rehabilitation program aiming to counteract functional brain alterations in post-Covid 
syndrome may be effective, but has not been systematically studied 
If functional brain alteration is important in the pathogenesis of PPIS (including post-Covid 
syndrome), it is conceivable that mental and behavioural interventions may have a beneficial effect. 
Indeed, cognitive behavioral therapy (CBT) is of documented value in PPIS following other 
infections.15,17 As for more extensive and multidisciplinary rehabilitation, little is known regarding 

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efficacy. To the best of our knowledge, no specific rehabilitation program has been systematically 
studied among post-Covid syndrome sufferers.  
 
1.1 Needs description 
The present study addresses urgent needs for the health care services as well as the scientific 
community 
 Patient treatment. This project directly addresses a strong need to develop effective treatment 
strategies for a large patient group suffering from post-Covid syndrome disability. Thus, it 
significantly improve health care services. Of note, the pragmatic approach ensures strong 
external validity and generalizability of the results.     
 Relevance and benefit to society. This project addresses a highly challenging health problem 
nationally and internationally, which may have substantial negative impact upon employment 
issues, social security systems, family networks etc.  
 Scientific relevance. The project addresses a prominent knowledge gap. Also, as the intervention 
builds upon a specific pathophysiological model, the study results will provide increased insight 
in disease mechanisms, and may eventually foster similar studies in PPIS following other 
infections.  
 
2. Hypotheses, aims and objectives 
We hypothesise that a short-time outpatient-based rehabilitation program will be beneficial as 
compared to usual care in post-Covid syndrome  
The aim of the present study is to assess the efficacy of a short-time outpatient-based rehabilitation 
program (the intervention) as compared to usual care (non-intervention) in post-Covid syndrome. The 
objectives are:  
a) To determine the effect on physical functioning immediately after completion of the intervention. 
We hypothesises better physical functioning in the intervention group than in the non-intervention 
group.  
b) To determine the effect on other post-Covid syndrome symptoms (such as fatigue, cognitive 
difficulties, dyspnoea, pain, sleeping problems) and quality of life (QoL) immediately after 
completion of the intervention. We hypothesise a beneficial effect of the intervention across all 
these domains.  
c) To determine adverse effects of the intervention. We hypothesis no differences in the frequency 
nor seriousness of adverse effects in the intervention group as compared to the non-intervention 
group. 
d) To determine the effect of the intervention on a long-term basis. We hypothesise that a beneficial 
effect of the intervention is sustained six months after its delivery.  
e) To explore predictors of intervention effect, including differential effects across subgroups. We 
hypothesise that time since diagnosis of acute Covid-19 and hospitalization is negatively 
associated with intervention effect. Furthermore, we hypothesise equal effect of the intervention 
in the subgroup fulfilling diagnostic criteria for chronic fatigue syndrome/myalgic 
encephalomyelitis (CFS/ME).  
f) To determine the cost-benefit and cost-effectiveness of the intervention. We hypothesise cost- 
benefit  and cost-effectiveness to be better in the intervention as compared to the non-intervention 
group.  
 
3. Project methodology 
3.1. Project arrangements, method selection and analyses 
Design, recruitment, inclusion/exclusion 
The proposed study is a 2-arm pragmatic randomised controlled trial (RCT) in which 310 patients 
who suffer from post-Covid syndrome are randomised to either a short-time outpatient-based 
rehabilitation program (the intervention) or care as usual in a 1:1 ratio (Fig. 2). Assessments will take 

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place immediately before randomisation (T0), after intervention or care as usual (T1), and 12 months 
after T0 (T2). Of note, the timing of T1 will vary in the intervention group, due to the individualized 
therapy approach (cf. below); TI in the non-intervention group will be matched accordingly. Patients 
will be recruited from General Practitioners (GP’s) as well as social media and self-referral to the 
involved institutions, and included based upon the criteria listed in Table 1.  
 
Table 1. Criteria for inclusion and exclusion  
Inclusion criteria 
  Exclusion criteria 
Fulfils pragmatic diagnostic criteria of idiopathic post-Covid 
syndrome (Sandler 2021): 
 Confirmed acute Covid-19 by a positive PCR or self-test for 
SARS-CoV-2. 
 Persistent symptoms at least 3 months following acute Covid-
19 without symptom-free interval.  
 Functional disability to an extent that interrupts all or a majority 
of normal activities (such as work/school attendance, physical 
exercise, social activities, etc.) 
Other chronic illnesses or demanding life situations 
that might explain persistent symptoms and 
disability 
 
Sustained organ damage (lung, heart, brain) 
following acute, serious Covid-19 
Age ≥ 16 years  
Bedridden 
Lives in one of the following Norwegian counties: Oslo, Viken, 
Innlandet, Vestfold og Telemark, Agder 
 
Insufficient command of Norwegian language 
Informed consent to participation 
  
 
 
 
 
Randomisation and blinding 
Patients eligible for the present study are randomized to either intervention or care as usual in a 1:1 
probability by a computer-based routine for block randomization; block size will vary randomly 
between 4 and 6. Allocation will be stratified by severity of illness during the acute stage of Covid-
19, operationalized as (1) no admission to hospital, (2) admission to hospital. Allocation concealment 
will be ensured using sequentially numbered, opaque, sealed envelopes. It is not possible to blind for 
treatment due to the nature of the intervention. However, during endpoint-evaluation, the responsible 
researchers will be blinded for group allocation.  
 
Intervention 
The intervention consists of an individualized numbers of outpatient encounters (min. 2, max. 8) with 
medical doctors and physiotherapists at Kysthospitalet. The first meeting is always with a medical 
doctor. At least one of the encounters has to be face-to-face; the remaining encounters may be 
organized by video link for patients living far away. The encounters aim to foster a two-stage 
rehabilitation process:  
 
Stage 1: This first meeting is with a medical doctor. The intervention aims to eliminate serious 
pathology with a good anamnesis and clinical examination and to give patients` knowledge and 
understanding of their condition. The main focus is psychoeducation, based upon the theoretical 
framework of the Cognitive Activation Theory of Stress (CATS) and the Sustained Arousal-
model of PPIS development. These models regard PPIS to be a product of functional brain 
alterations, which initially are an integrated part of the physiological acute sickness response,1 but 
may become inappropriately sustained because of mechanisms such as unconscious 
expectancies/predictions, worrying tendencies and associative learning processes.18,33,34,42 This 
sustainment causes persistent changes of autonomic nervous activity, hormonal activity and 
immunological responses, which in turn may explain patients’ symptoms and occasional findings 
(such as high heart rate). Thus, the symptoms and functional disability of patients does not 
indicate a chronic infectious or autoimmuine disorders, and efforts are made to counteract 
patients’ worries.  
 
Stage 2: The individual follow-up with physiotherapists starts with a repetition of the information 
given in stage 1, based on patients understanding of their condition and experienced symptoms. 

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The aim is to counteract patients` worries and subsequent symptom monitoring, and to reassure 
them that desired activities and graded exercise are both beneficial and safe. Over time, the overall 
aim is to increase activity levels and normalize activity tolerance by ‘uncoupling’ an unconscious 
association between activity and neurobiological stress response activation. The use of both 
cognitive talking therapy and behavioral modifications (included graded exercise) are important 
intervention components, and all the health care workers providing the intervention are educated 
in cognitive behavioral therapy (CBT). Stage 2 is highly individualized based upon the patients’ 
symptom burden and personal preferences. A total of 120 patients` with post-Covid syndrome 
have received the intervention so far. The number of encounters needed as well as the interval 
between encounters is highly individual. It is considered important that the number of encounters 
is based on patients` individual needs, as a fixed number may delay recovery because of 
unnecessary treatments and result in overuse of health services.  
The intervention share some resemblance with Cognitive Behavioral Therapy (CBT) for PPIS.15,17 
The rationale behind the intervention is explained in detail to the patients’ family doctors, ensuring 
compliant follow-up in primary health care. The cost (in monetary units) will be calculated for both 
stages of the intervention.  
 
 
 
Figure 2. Overview of study design. 

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Effect monitoring 
Effect monitoring is primarily based on patient reported outcome measures (PROM), applying a web-
based questionnaire composed of several validated instruments. The questionnaire will be distributed 
to the participants at T0, T1 and T2. It will chart clinical symptoms as well as background, 
psychological and social variables, and will be used for subgrouping according to different case 
definitions of CFS/ME. The most important inventories are (cf. appendix 1 for a complete overview):  
 The 36-Item Short-Form Survey (SF-36) comprises a total of 36 items on subjective mental, social 
and physical health, which are assigned to 8 dimensions. Scale ranging from 0 (poor quality of 
life) to 100 (best).36,43 The SF-36 instrument was recently recommended as a useful tool to assess 
rehabilitation needs in post-Covid syndrome sufferers, and is generally recognized as a valid and 
reliable measurement for intervention trials.20 
 The Chalder Fatigue Questionnaire (CFQ) charts subjective experience of physical and mental 
fatigue. In this study, the CFQ total linear score (i.e. the sum across all 11 items, each item scored 
on a zero to three Likert scale) will be applied. Furthermore, fatigue caseness is defined as a CFQ 
total dichotomous score of 4 or higher (each item scored 0-0-1-1).  
 The Hospital Anxiety and Depression Scale (HADS) is a validated questionnaire for charting 
symptoms of depression and anxiety. It consists of 14 items rated zero to three on Likert scales, 
allowing computation of sub-scores for depression and anxiety symptoms. In the present study, 
these sub-scores as well as total sum score will be applied.  
 Adverse effects: A self-invented questionnaire will address possible adverse effect related to the 
intervention. 
In addition, employment status, usage of social security-systems (i.e. short and long-term sick leave), 
and usage of health care services (i.e. the number of GP and specialist contacts, hospitalisations, 
medications, usage of rehabilitation services, etc.) will be charted trough register linkage (cf. below) 
as well as questionnaires to the study participants.   
 
Unexpected findings of other health problems 
The questionnaire may reveal unexpected findings of other health problems, such as serious 
depressive symptoms, substance abuse, etc. We will implement Standard Operating Procedures to 
ensure that such health problems are identified and that appropriate measures are instituted, such as 
immediate notifying of the patient’s general practitioner/family doctor.  
 
Linkage with health registries 
In order to explore predictors of intervention effects (point 2.e), above), linkage with existing health 
registries will be considered, such as ‘Norsk pasientregister’, ‘Mor-Barn-studien’, ‘Vaksine-registeret 
Sysvak’, ‘Reseptregisteret’, ‘Intensivregisteret’ og ‘Pandemiregisteret’. Also, previously recorded 
medical information from hospital and family doctor records will be exploited for the same purpose.  
A primary prediction analyses will use the following variables, based upon previous evidence from 
other studies of PPIS:10,12,23  
 Previous infectious diseases: COVID-19 diagnosed by PCR-test (date, genetic variant), other 
infectious events one year prior to inclusion 
 Previous immunizations: Vaccination against COVID-19 (date(s), type(s)), other vaccinations one 
year prior to inclusion. 
 Previous and current medical history: Diagnoses of other chronic diseases, current medication 
 Severity of acute COVID-19: Hospitalization (days), intensive care unit admission (days), 
respiratory support, cardiovascular support, neurological sequels, thromboembolic events, 
immunological and infectious markers during hospital stay (CRP, viral replication numbers). 
Other possible predicting factors, such as genetic traits, will not be explored under the current 
protocol.  
 

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Population and sample size calculation 
As of July 2021, a total of approximately 103,000 Covid-19 cases have been reported from the 
geographical areas (five Norwegian counties) from which patient are recruited to the present study. 
Assuming a 5 % case rate of post-Covid syndrome (cf. Figure 1) of whom 1/5 is eligible and willing 
to participate, a total of 1,300 patients could potentially be included.  
 
The SF-36 subscale Physical Functioning (SF-36-PFS) will serve as the primary endpoint in 
the present study. A difference of 10 points is considered clinically significant.43 Similarly, in a study 
of CFS/ME which shares similarities with post-Covid syndrome, the minimally clinically important 
difference of SF-36-PFS was reported to be 10.4 The scatter of SF-36-PFS scores among post-Covid 
syndrome sufferers are unknown, but two large Norwegian surveys reported a Standard Deviation 
(SD) of 20 across all age groups.8,14 If SD is set to be 25 in the population under study, and assuming 
20 % drop-out rate, the study should aim to include a total of 310 participants. This yields a power 
of 90 % (α=0.05) to detect a small to medium effect size.   
 
Statistical analyses 
The ‘full analysis set’ (all randomized participants) will be used for intention-to-treat analyses of 
efficacy. Missing values will be imputed applying multiple imputation techniques. The ‘per protocol 
analysis set’ is defined as all patients in the ‘full analysis set’ that completed the treatment period 
without any of the following protocol deviations: Interruption of therapy; Lost to follow-up; Primary 
endpoint measurements missing; Diagnosed with another chronic disorder during the study period; 
Experiencing a severe illness or trauma during the study period; Commencing other treatment for 
post-Covid syndrome during the study period.  
Variables will be reported with parametric or non-parametric descriptive statistics, eventually 
frequency tabulation, as appropriate. General linear models (ANCOVA) will be used for analyses of 
treatment effect; the baseline values of each efficacy endpoint will be included as covariates. For each 
statistical analysis, the net intervention effect (the mean change in the intervention group minus the 
mean change in the usual care group) will be calculated from the parameters of the fitted general 
linear model and reported with 95 % confidence interval. All statistical tests will be carried out two-
sided. A p-value ≤ 0.05 is considered statistically significant. Safety data will be summarized 
descriptively through appropriate data tabulations and descriptive statistics. No interim analysis will 
be carried out. A statistical analysis plan will be developed. 
 
3.2. Participants, organization and collaborations 
Principal investigator and research group 
The present project is hosted by the PAEDIA research group at Akershus University Hospital (Ahus), 
which has extensive experience in translational as well as clinical research on post-Covid syndrome 
and other PPIS, and a strong track record of result dissemination and implementation. The group has 
established a well-working infrastructure for patient flow and data acquisition, and a large 
collaborative network with national and international experts on various methodological aspects.  
The PAEDIA research group is headed by Prof. Vegard Wyller, who is also the PI of the 
present project, and Chair of the COFFI collaborative (cf. below). Prof. Wyller is the most published 
and cited PPIS researcher in Norway. Other members of PAEDIA include two postdoctoral fellows, 
six PhD fellows, two master students, and three clinical consultants. The local research support staff 
consists of one laboratory engineer, two research nurses and two research secretaries. An internal 
learning program for PhD fellows has been established, encompassing a) one-to-one supervision 
sessions; b) regular in-group discussions; c) invited lecturers; d) oral presentation training and 
practice; e) seminars on selected topics (statistics, ethics). A total of five PhD fellows have 
successfully graduated over the past four years. 
 
Steering Committee, collaborating partners and networks 
A Steering Committee consisting of Prof. Vegard Wyller (Head, Universituy of Oslo); Prof. Guri 
Rørtveit (University of Bergen); Prof. Signe Flottorp (Norwegian Institute of Public Health); Profs. 

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Silje Endresen Reme and  Henrik Børsting Jacobsen (Dept. of Psychology, University of Oslo) and 
Drs. Annika Jordbru, Andreas Horsdal, Gro Aasland, and Tom Farmen Nerli (Kysthospitalet Stavern) 
will oversee all stages of the project. The main collaborating partner is Kysthospitalet Stavern, where 
the intervention under study has already been established for other patient groups. In addition, the 
project will be intimately linked to an international consortium of researchers on post-infectious 
complications (Collaborative of Fatigue Following Infection, COFFI), encompassing highly reputed 
research groups from five countries (US, UK, Australia, The Netherlands and Norway), and with 
Prof. Wyller as the chair of the consortium (www.coffi-collaborative.com). A total of 15 post-
infectious cohort studies (including 3 COVID-19 cohorts) have joined the collaborative so far, 
summing up to a total of about 6000 patients.  
Important measures to ensure integration between all collaborators encompass a) Regular 
meetings (video link) to discuss scientific and strategic challenges; b) Hosting of seminars and 
workshops; and c) Face-to-face meetings. 
 
The work tasks of a potential PhD fellow 
A PhD fellow in the present project will be included in the team of researchers and managers 
responsible for participant investigations and data gathering. Thus, he will get first-hand knowledge 
of all parts of the investigational program described above. Furthermore, in close collaboration with 
his supervisors and the rest of the research team, he is expected to carry out data analyses, interpret 
the results and draft a total of four scientific papers.  
 
Infrastructure  
As the intervention under study has already been developed, the necessary research infrastructure is 
primarily related to a) administrative and coordinating tasks regarding patient flow, allocation, data 
management, etc;  and b) patient recruitment from GPs. For the former, the project will exploit already 
established routines and personnel within the PAEDIA research group. For the latter, the project will 
benefit from using ‘Praksisnett’ – a collaborative network of GPs providing established routines and 
payment procedures for the recruitment of patients in clinical trials.  
 
3.3. Plan for activities, visibility and dissemination 
A PhD-dissertation can be completed within three years from project onset; the entire project 
period is estimated at a maximum of 10 years  
A PhD-fellow focusing on research questions a) – c) will be able to complete a dissertation within 
approximately three years from project onset. However, extensive analyses related to research 
questions d) – f) are estimated to take longer time, and is also dependent on external funding of 
additional researchers (PhD and/or postdoctoral positions). Thus, the total project period is estimated 
at a maximum of 10 years.  
 
Results will be disseminated widely; scientific dissemination is prioritized 
Given the seriousness of post-Covid syndrome and the urgent need for scientific knowledge, rapid 
and continuous dissemination or project results will receive high attention. The target for 
dissemination is not restricted to the scientific community, but includes a wide range of health-care 
workers, politicians, policy makers, health care administrators, and the general public.  
Several means of dissemination will be exploited, including scientific papers; popular science 
newspaper articles; giving interviews; meetings with politicians, public health providers and other 
stakeholders; social media. Dissemination to researchers and the scientific community includes 
publications in international, peer-reviewed, open access medical journals. The main results will be 
offered to journals of high impact. Negative findings will also be reported.  
 
3.4. Plan for implementation 
Based upon the research results, the Steering Committee will contribute actively to the establishment 
for clinical guidelines for post-Covid syndrome, in strong collaboration with health administrators, 

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patients’ organizations, and other stakeholders. A Working Group of should be established with the 
specific task of scrutinizing existing guidelines, revising them, and disseminating the revised 
guidelines. 
 
4. User involvement 
An advisory board of two user representatives is the most important user involvement 
For the present project, an advisory board of users will formally established, consisting of a) One 
representative from the Consumer Advisory Committee at Ahus; and b) One representative from the 
organization Recovery Norway, consisting of individuals having recovered from PPIS and similar 
conditions. The advisory board will meet quarterly with the PI; important themes for discussions are 
results’ interpretation and practical impact, ethical issues, considerations regarding further research, 
and dissemination/implementation strategies. 
 
5. Ethical considerations 
Ethics 
Participation in the project is based upon informed consent, and thorough information will be 
provided orally as well as in writing to the participants. All data will be treated and stored without 
personal identifying information, and in accordance with national directives. Generally, 
investigational methods are neither harmful nor painful. Approval will be sought from the Regional 
Committees for Medical and Health Research Ethics. If the intervention is found to be beneficial, 
participants in the non-intervention group who suffer from a sustained post-Covid syndrome 
diagnosis will be offered a referral to Kysthospitalet for treatment after completion of the study (Fig. 
2). 
 
Gender perspectives 
Severe COVID-19 appears to be more common in males than in females. post-infectious 
complications, however, such as PPIS, are more common among females than males, the ratio being 
about 3:1. Thus, such complications strongly impact on women’s health, but have traditionally 
received low attention. In this project, possible gender differences will be scrutinized in the analyses.  
 
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Appendix  
 
Overview of inventories  
Category 
Inventory 
Characteristics 
References 
 
BACKGROUND/DEMOGRAPHICS 
 
 
 
 
Household, socioeconomic level 
 
Household members; parents work/education; 
chronic disease in family 
 
 
Smoking, alcohol, drugs 
 
Alcoholic beverages, illicit drugs, smoking; 5-
point Likert scale (never to each day) 
 
 
SYMPTOMS AND FUNCTIONS 
 
 
 
 
Fatigue  
Chalder Fatigue Scale 
11 items; 4-point Likert scale; each item scored 
0-3; total sum score range 0 to 33.  
Chalder T, Berelowitz G, Pawlikowska T, et 
al. J Psychosom Res 1993;37:147-53. 
 
Chronic Fatigue Syndrome diagnosis 
and related symptoms 
CDC symptom inventory for CFS 
 
28 items addressing frequency of symptoms on 
5-point Likert scale; each item scored 1-5 (never 
to each day/always).  
Wagner D, et al. Popul Health Metr 
2005;3:8 
 
post-exertional malaise (PEM) 
PEM items from DePaul Symptom Questionnaire 
5 items addressing frequency of symptoms on 5 
point Likert scale; each item scored 0-4 (never to 
each day/always). Average, then multiply with 
25 to get a 100 point scoring scale.  
Bedree H, et al. Fatigue 2019; 7: 166-79 
 
Sleep disturbances 
Karolinska sleep questionnaire (KSQ) 
12 items addressing frequency of sleep related 
problems; 6-point Likert scale scored 1 – 6; 
lower score means more symptoms. Indexes for 
insomnia, awakening problems, and sleepiness 
Akerstedt T, Ingre M, Broman JE, Kecklund 
G. Chronobiol Int 2008;25:333-48 
 
Pain 
Brief Pain Inventory (BPI) 
4 items; 10 point Likert scale score 1 - 10 (no 
pain to worst pain possible) 
Klepstad P, et al. J Pain Symptom Manage 
2002;24:517-25. 
 
Dyspnoea 
Medical Research Council dyspnoea scale  
 
1 item; 5 options (from “breathless during 
strenuous exercise” to “too breathless to leave 
the house”).  
Bestall JC, et al. Thorax 1999; 54: 581-6. 
 
Depression/Anxiety symptoms 
Hospital Anxiety and Depression Symptoms 
(HADS) 
14 items; 4 point Likert scale scored 0 – 3 (8 
items with reversed scoring). Indexes for anxiety 
symptoms and depressive symptoms, also total 
sum score range 0 to 42. 
Zigmond AS, Snaith RP. Acta Psychiatr 
Scand 1983;67:361-70. 
 
Negative affect 
Positive and Negative Affect Schedule (PANAS-
SF) 
5 items addressing negative affects (ashamed, 
anxious, nervous, hostile, upset); 5-point Likert 
scale scored 1-5. Total sum score range 5-25 
Thompson ER. J of Cross-Cultural 
Psychology 2016; 38: 227-42. 
 

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Illness perception 
Brief Illness Perception Questionnaire  
8 items; 10 point Likert scale, scoring 1 – 10. 
Broadbent E, et al. J Psychosom Res 
2006;60:631-7 
 
Work related self-efficacy 
Return-to-work self-efficacy scale (RTWSE-11) 
11 items; 6-point Likert scale, scored 1-6 
(reverse scoring item 2 and 6). Total sum score 
range 11 to 66 (higher scores means high work-
related self- efficacy).  
Shaw WS, Reme SE, Linton SJ, et al. Scand 
J Work Environ Health 2011; 37: 109-19. 
 
Quality of life  
36-Item Short Form Survey (SF-36).  
36 items, scored on Likert scales and recoded to 
achieve 100 point scales (higher score means 
better health); average score reported. Eight 
subdomains: Physical functioning; Role 
limitations due to physical health; Role 
limitations due to emotional problems; 
Energy/fatigue; Emotional well-being; Social 
functioning; Pain; General health  
Ware JE, Sherbourne CD. Med Care 1992; 
30: 473-83. 
 
Health related quality of life 
EuroQoL 5L (EQ-5D-5L) 
5 items; 5 point Likert scale, scored 1 to 5. A 
summary index with a maximum score of 1 (best 
health status) can be derived from these five 
dimensions by conversion with a table of 
scores. In addition: 200 mm VAS scale for 
assessment on global health status. A score of 
100 indicates best health status.  
Herdman M, Gudex C, Lloyd A, Janssen 
MF, Kind P, Parkin D, et al. Quality of Life 
Research. 2011; 20: 1727-36. 
 
Interoception 
Body Vigilance Scale (BVS) 
4 items; 11 point Likert scales 0 – 10. Score on 
item 3 should be devided by 10. Scores on item 
4: average among 15 sensations. Total sum score 
range 0 to 40. 
Schmidt NB, et al. J Consult Clin Psychol 
1997; 65: 214-20. 
 
Miscellaneous/hypotheses generating 
 
a) 1 item addressing avoidance behavior: “To 
what degree do you avoid everything that may 
worsen your symptoms”?  
b) 1 item addressing school/work absenteeism. 
 
 
CONSTITUTIONAL 
 
 
 
 
Neuroticism 
NEO-FFI-30 
6 items making up the neuroticism axis; 5-point 
Likert scale scored 0 – 4. Total sum score range 
0 – 24. 
Körner A, et al. Psychother Psychosom Med 
Psych. 2008; 58: 238-245 
 
Worrying tendencies 
Penn State Worry Questionnaire (PSWQ) 
16 items; 5-point Likert scale scored 1 – 5 
(reversed scoring of item1,3,8,10,11). Total sum 
score range 16 to 80 
Pallesen, S, et al. Scandinavian Journal of 
Psychology 2006, 47, 281–291 
 
Emotional awareness 
Toronto Alexithymia Scale (TAS-20) 
7 items making up the index of Difficult 
identifying feelings. 5-point Likert scale scored 
1-5, total sum score range 7 to 49. 
Bagby RM, et al.. J Psychosom Res 
1994;38:33-40. 
 

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Loneliness 
UCLA loneliness scale 
20 items; 4-point Likert scale scored 1 – 4 
(reverse scoring of item 1,5,6,9,10,15,16,19,20). 
Total sum score from 20 to 80. 
Russell, D., et al. Journal of Personality and 
Social Psychology 1980, 39(3), 472–480 
 
Self-efficacy 
General Self-Efficacy Scale, short form 
6 items; 4-point Likert scale scored 1 – 4. Total 
sum score from 6 to 24.  
Romppel M, et al. Psychosoc Med 2013; 10: 
Doc01.