Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19

This cross-sectional, survey study was conducted in the Netherlands and Flanders (Belgium) between June 4th and June 11th 2020. Members of two Facebook groups for COVID-19 subjects with persistent complaints [12, 13] and subjects who registered at a website of the Lung Foundation Netherlands (www.​coronalongplein.​nl) received a web link with an invitation to fill out questionnaires.

Subjects were asked one-off to provide information regarding anthropometric/sociodemographic characteristics and medical history (gender, age, height, body weight, date of onset of symptoms, hospitalization at the time of the infection, type of COVID-19 diagnosis, number of pre-existing comorbidities, marital and smoking status). Subjects were stratified into four groups according to the type of COVID-19 diagnosis: (1) hospitalized with confirmed COVID-19 (regular ward, no admission to intensive care unit (ICU); (2) non-hospitalized with confirmed COVID-19 (based on reverse transcription polymerase chain reaction (RT-PCR) test and/or computed tomography (CT) scan of the thorax); (3) non-hospitalized with symptom-based diagnosis of COVID-19 (established by a doctor, no formal COVID-19 testing); and (4) non-hospitalized with presumed COVID-19 (no formal diagnosis at the time of the presumed infection).

The medical ethics committee of Maastricht University stated that the Medical Research Involving Human Subjects Act (WMO) does not apply for this study and that an official approval of this study by the committee was not required (METC2020-1978). The medical ethics committee of Hasselt University formally judged and also approved the study (MEC2020/041). All subjects gave digital informed consent at the start of the survey. Data from this study on persistent symptoms and care dependency have been published before [14‐16].

The present study adopted the definition of one of the three domains of validity (construct validity) described in the COSMIN study—which aimed to clarify and standardize terminology and definitions of measurement properties that are relevant and should be evaluated for health-related patient-reported outcomes (HR-PRO) [17]. Construct validity is defined as the degree to which the scores of a HR-PRO instrument are consistent with hypotheses (for instance with regard to relationships to scores of other instruments) based on the assumption that the HR-PRO instrument validly measures the construct to be measured [17]. For this reason, we opted to investigate the construct validity of the PCFS Scale by testing whether the PCFS Scale is a simple tool that can be used for measuring the impact of symptoms on the functional status of subjects. Our hypothesis is that the PCFS Scale is related with instruments used to assess the number and intensity of symptoms as well as with instruments which assess the impairment in HrQoL and in work and usual activities. In order to test this hypothesis, we explored the level of impairment in these outcomes (see below) after stratifying subjects according to the PCFS Scale.

To assess the level of impairment in functional status subjects were asked to fill in the PCFS Scale [8]. The PCFS Scale stratification is composed of five scale grades: grade 0 (No functional limitations); grade 1 (Negligible functional limitations); grade 2 (Slight functional limitations); grade 3 (Moderate functional limitations) and grade 4 (Severe functional limitations). The final scale grade 5 ‘death’, which is required to be able to use the scale as outcome measure in clinical trials, was left out for this self-administered questionnaire. Additionally, the following questionnaires were completed: the Utrecht Symptom Diary (USD), an adapted Dutch version of the Edmonton Symptom Assessment System [18, 19], to assess symptom intensity ranging from 0 (no symptom) to 10 points (worst possible); the 5-level version of the EQ-5D questionnaire (EQ-5D-5L) to assess HrQoL [20]. This questionnaire is composed by five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and a visual analogue scale (VAS) ranging from 0 (the worst imaginable health) to 100 points (the best imaginable health). From the scores of each domain, an index can be calculated (ranging from − 0.329 to 1) with higher scores representing a better HrQoL [21]; and the Work Productivity and Activity Impairment (WPAI) questionnaire from which four main outcomes can be generated and expressed in percentages: (1) percent work time missed due to health (absenteeism); (2) percent impairment while working due to health (presenteeism); (3) percent overall work impairment due to health; (4) percent activity impairment due to health. The recall period is 7 days and higher scores represent more impairment in outcomes, the questionnaire has shown to be valid and reproducible and has been extensively used in different common chronic diseases [22, 23].

From the initial 2159 respondents, 15 were excluded because of ICU admission during the infection, 22 were excluded because of reported onset of symptoms before January 1, 2020 or within the previous 21 days, and 183 were excluded due to incomplete surveys. Therefore, a total of 1939 subjects (85% women, 46 ± 11 years, body mass index (BMI): 25.2[22.6–28.8]kg/m²) were included in the analyses. The general characteristics of these subjects are presented in Table 1. The time from onset of symptoms to the day of the participation in the study was on average 79 ± 17 days. The majority of the subjects was diagnosed based on symptoms (42%), whereas 17% were diagnosed based on CT/RT-PCR and 36% had no formal COVID-19 diagnosis. Five percent of the subjects were hospitalized with confirmed COVID-19. In addition, the majority of subjects were married or living together (71%), reported no previous comorbidities (61%), and had no previous smoking habits (82%). Most of the subjects reported moderate-to-slight functional limitations according to the PCFS Scale (85%) while only 3% of the subjects reported to currently have no limitations in daily life.

The gender distribution, type of COVID-19 diagnosis, presence of self-reported pre-existing comorbidities and marital status were different among the PCFS Scale categories. Interestingly, no differences in the proportion of smoking status were presented (Table 1). Additional file 1: Fig. 1 displays the odds of being in a higher grade of the PCFS Scale according to gender, BMI category, type of COVID-19 diagnosis, marital status, presence of self-reported pre-existing comorbidities and smoking status. Additional file 1: Table 1 displays the prevalence of each specific pre-existing comorbidities according to the different groups of the PCFS Scale grades.

Subjects with no functional limitations were older compared to subjects presenting slight, moderate and severe functional limitations. Subjects with severe functional limitations (Grade 4 on the PCFS Scale) presented lower BMI compared to all other groups (Table 1). Notably, other factors associated with poorer functional status were marital status (prevalence of category ‘alone’ highest in Grade 4) and presence of comorbidities (prevalence of ‘≥ 2 comorbidities’ highest in Grade 4). Interestingly, subjects with severe functional limitations also had the highest prevalence of a ‘symptom-based’ COVID-19 diagnosis.

The most intense symptoms reported were fatigue, muscle weakness and sleeping problems while the least were fever, nausea and dysphagia. Subjects classified as experiencing slight, moderate and severe functional limitations presented a gradual increase in the number and intensity of symptoms (Table 1 and Fig. 1). No differences were found between subjects with negligible functional limitations and no functional limitations concerning the number and intensity of symptoms (Fig. 1).

HrQoL was comparable between subjects with negligible functional limitations and no functional limitations, while all other pairwise comparisons including the subjects with slight, moderate and severe functional limitations showed worsening of HrQoL for increasing categories of the PCFS Scale (Fig. 2a). We found weak-to-strong associations between functional status and all domains of HrQoL (r: 0.233–0.661; P < 0.01) (Fig. 2b). Notably, the strongest association found was with the ‘usual activities’ domain of the 5-level EQ-5D questionnaire.

Figure 3 displays the comparison of the level of impairment in work and usual activities as assessed by the WPAI questionnaire. Absenteeism, presenteeism and work impairment were different considering all pairwise comparisons with exception of the comparison between subjects with no and negligible functional limitations and between subjects with moderate and severe functional limitations. Activity impairment increased gradually according to the decrease in functional status.