Quality of life and ability to work of patients with Post-COVID syndrome in relation to the number of existing symptoms and the duration since infection up to 12 months: a cross-sectional study

The pandemic, which has been going on for almost two years now and is caused by the new SARS-COV-2 virus, has more and more influence, also on people who are not ill and not infected. High loads in health service, increased care expenditure of children at home and the partial long isolation of friends and relatives is accompanied with impairments for all parts of the population [1‐3].

For individuals who have experienced COVID-19-disease, there may be additional health-related problems. A number of studies have now shown that infection with the SARS-CoV-2 virus can lead to severe acute respiratory syndrome (SARS) and long-lasting symptoms [4‐9]. The cause for the development of a so-called Post-COVID syndrome is still unclear, but recent evidence suggests a possible association with sustained activation of pulmonary endothelial cells as well as the entire immune system, and aberrant immune responses or autoimmunity are also postulated [10‐12]. Moreover, an internationally recognized naming of the persistent symptoms does not yet exist. However, a system is increasingly emerging that designates occurring symptoms 4 up to 12 weeks after the acute illness with “Long-COVID” and symptoms that persist over a period of more than 12 weeks with “Post-COVID-syndrome” [13, 14]. Because 98.1% of the cohort presented here were interviewed more than 12 weeks after infection, the term “Post-COVID-syndrome” is used.

In addition to the development of therapeutic concepts and the assessment of needs of the affected persons, the restoration of social and occupational participation of the large number of patients must also be taken into account [15‐17]. Many sufferers are unable to work for months after infection, with both socioeconomic and individual consequences [18]. This can have influences on health-related quality of life (HRQoL).

Longer-lasting symptoms after acute infections with coronaviruses are also known in Middle East respiratory syndrome and other forms of SARS [19‐21]. These include, similar to Post-COVID-syndrome, fatigue, muscle pain, and mental dysfunction [20‐22]. Research have shown that HRQoL decreases further as the disease progresses [19]. Hui et al. studied recovered patients after hospitalized SARS for 3, 6, and 12 months after symptom onset. They showed that some scores of the HRQoL questionnaire (SF-36) improved over time (role physical, social function, role emotional) while others showed no change over time (physical function, bodily pain, vitality and mental health) and remained below normal values until the end. The general health score even showed a significant deterioration over time. A significant difference after 12 months between patients who were treated in an intensive care unit and those who did not require this therapy could not be found [23]. Influenza virus infections (H1N1) can also lead to acute respiratory distress syndromes (ARDS) [24, 25]. Studies on HRQoL showed that quality of life continued to increase 6 months after discharge from the hospital and that even patients who required intensive care therapy returned to approximately the values of the normal population after one year [24, 25]. Irrespective of the pathogen, patients with ARDS treated with intensive care continued to show limitations in functioning and HRQoL even five years after critical illness [26]. Consequently, the development of a post-intensive care syndrome may be considered to be the cause of the limitations [27]. To our knowledge, there are no data on HRQoL for mild courses of influenza, as no long-term symptoms occur.

Therefore, the question arises to what extent persistent symptoms after SARS-CoV-2 virus infection also lead to a reduction in HRQoL, both in hospitalized and non-hospitalized patients. Malik et al. conducted a systematic review with meta-analysis on this question. A total of twelve studies were included with a total of 4828 patients who reported continued symptoms after a period of up to 180 days after infection. 558 of the patients studied received intensive care. The prevalence of impaired quality of life measured by the visual analogue scale (EQ-VAS) was 59% across the entire sample. Furthermore, it was shown that patients who received intensive care and had fatigue as an existing symptom had a significantly worse outcome than those to whom these two things did not apply [28]. In addition, Meys et al. showed that HRQoL values are still below normal population levels three months after infection, even in non-hospitalized patients. [29]

This raises the question of whether patients who had COVID-19 and still have symptoms of Post-COVID syndrome are affected differently in their health-related quality of life depending on how long ago the infection occurred. In addition, the aim of the study is to analyse predictors that may affect HRQol. These include ability to work, number of existing symptoms, and received therapies.

The cross sectional study included all patients presenting to the Post-COVID outpatient clinic at Jena University Hospital between first of March and 29th October 2021. Each patient completed the SF-36 and the COVID-19 Rehabilitation Needs Questionnaire (RehabNeQ) as part of the structured baseline assessments described elsewhere [17, 30‐32]. The SF-36 is a valid and reliable assessment tool for HRQoL with reliability coefficients above 0.70 for each subscale and even above 0.80 for the summary scales [33, 34]. The RehabNeQ, a structured self-report assessment of COVID-related health information, is also reliable by means of dichotomous answer options of the present cohort with a reliability coefficient of 0.6 or higher (Kuder-Richardson reliability coefficient) [35]. As part of the assessment described, patients consented to the use of their data for research purposes. The only condition for an appointment was to have had PCR-confirmed SARS-CoV-2 infection.

Additional inclusion criteria were as follows:

The following data of the RehabNeQ were extracted:

384 patients presented to the Post-COVID outpatient clinic at Jena University Hospital within the study period, 336 of them met the inclusion criteria, 46 patients were excluded, as they were older than 65 years, 2 patients were already unable to work before COVID-19.

After reviewing the questionnaires, further exclusions of 18 individuals were made because the SF-36 was not completed (n = 12), too much information was missing in the area of symptom burden or statements about work ability (n = 4), or the time since infection was not reported (n = 2). Thus, in conclusion, 318 patients were included whose questionnaires were fully completed (detailed information is shown in Fig. 1).

68.9% (n = 219) of the included patients reported being female and were on average 46.9 (± 10,9) years old. 56.9% (n = 181) of the respondents were married. 18.6% (n = 59) were living in a partnership. The information on other forms of family status was distributed among single (13.2%, n = 42), separated/divorced (8.5%, n = 27) and widowed (1.9%, n = 6). 2 respondents did not answer.

The majority of respondents reported having been infected with the SARS-CoV-2 virus between 6 and 12 months ago (56.0%, n = 178). In some cases, the time of infection was already more than 12 months ago (14.8%, n = 47). A total of 93 persons indicated periods of up to 6 months since infection, of which 87 (27.4%) indicated 3 or more months and 6 (1.9%) less than 3 months. Of the respondents who participated in the study, 75 (23.6%) stated that they had been hospitalized. Of these, 13 (17.3%) persons had received mechanical ventilation. The correlation with the time of infection is shown in Table 1

The study provides indications that especially the number of remaining symptoms with regard to the post-COVID syndrome has an impact on HRQoL. However, unlike Malik et al., there was no difference between hospitalized and non-hospitalized patients in the acute infection phase. Nevertheless, it should be noted that in the sample studied, only a very small proportion was severely ill and therefore required inpatient hospitalization. In addition, the analysis showed that there is a correlation between the perceived ability to work and the quality of life, which is comprehensible. The overall cohort showed a significant reduction in HRQoL compared to the normal German population [31]. This was also independent of the duration of infection. A reduction in HRQoL after COVID-19 disease has also been demonstrated by other authors, although the number of studies is still very small, especially in the longer follow-up [28, 37]. Poudel et al. could show in the three analysed studies, which included patients with a time since infection of more than four weeks, that the values of the PCS were slightly higher than those of the MCS [37]. This is contrary to our results. Reasons may lie in the smaller sample or in the different long follow-up (Poudel et al., max 12 weeks follow up). Also, the composition of the sample could provide an explanation, as it was especially the older (> 65 years) patients who showed particularly strong deficits in HRQoL according to Poudel et al. For this study, only patients of working age (up to 65 years) were included. Finally, the time of the survey could also have an influence. The studies included by Poudel et al. were collected in 2020 [37]. The cohort of this sample became infected for the most part at the end of 2020 until May/June 2021. In March, the delta variant of the SARS-CoV-2 virus was detected for the first time in a polymerase chain reaction test in Germany. Compared to the wild type, slightly altered symptoms were observed in non-research publication during the acute course [38, 39]. Whether this also applies to the Post-COVID syndrome remains to be seen and should be investigated in more detail.

The symptoms most frequently reported by respondents were fatigue, sleep disturbances and memory impairment, similar to other studies [6, 17, 40, 41]. These may influence HRQoL, although other pandemic-related aspects, such as loss of social contacts, job insecurities, and limitations in daily life, should not be ignored in this consideration [42].

The analysis of the data presented here showed that the values of the MCS of those affected, in whom the infection has already occurred more than 12 months ago, are again at the physiological standard level. It is interesting to note that this is independent of the number of symptoms still present.

Thus, there seems to be adaptation through coping skills, self-efficacy as a way to maintain a psychological “steady state”. Further research on how a patient recalibrates their self-assessment of health-related quality of life or their cognitive appraisal processes is needed [43]. In contrast, the number of existing symptoms seems to have more of an influence on the physical aspects of the HRQoL. Only a few lingering symptoms show a return to normal levels in affected individuals with at least 6 months interval from infection. The greater the number of symptoms, the worse the scores in the PCS. A limitation in function and participation, and thus a rehabilitation need, can therefore be postulated [7, 8].

Overall, however, it appears that there may be improvement in psychological and physical function over the course of one year, similar to Huang et al. [42]. Comparable analyses in survivors of SARS still showed limitations in almost all SF-36 scales at both 12 and 24 months [23, 44]. How HRQoL develops in patients with Post-COVID syndrome remains to be seen and should be studied in detail scientifically. This is necessary according to our results with special focus on the still existing symptoms. How the number of symptoms and their severity develops in the course of the disease is still unclear, although an improvement of some of them can be assumed, which is also shown by our data [42]. Davis et al. showed similar results [45]. He divided the existing symptoms into three clusters: Cluster 1: Symptoms that are very frequent at the beginning of the infection and occur less frequently over time (e.g. dry cough, fever). Cluster 2: Symptoms that are relatively stable in their probability of occurrence over a period of up to 7 months (e.g. muscle aches, shortness of breath, dizziness) and cluster 3 with symptoms where the probability of occurrence only increases in the course of the disease and the further course is variable (e.g. brain fog, tinnitus, palpitations) [45]. A variability of the temporal course must therefore be assumed. A meta-analysis showed that from the 60th day after infection there was an increase in symptom burden [40]. Here it is necessary to observe the course of the severity of individual symptoms over a longer period of time and to investigate which influences the patients are exposed to.

The study was also able to show that HRQoL correlates with real and perceived incapacity to work. Almost 40% of the respondents stated that they were unable to work, as was already found in other studies at a similar level [18]. 70% of them were even permanently unable since the infection and thus partly more than 1 year. Although our results, similar to those of Huang et al., show that between the 6th and 12th month after infection there is often a return to work, however, the perceived ability to work increases only slightly in comparison [42]. A restriction in work performance therefore remains. This is also confirmed once again by the results of this analysis. More than half of those able to work have deficits in the PCS of the HRQoL. Therefore, it can be assumed that the productivity of these present employees is reduced by the still existing health problems. The cost of this is similar to that of actual absenteeism [46]. In contrast to the deficits in the physical sum scale of those able to work, the values of the mental sum scale were mostly within the normal range. This could indicate that mental health is more important than physical health for the ability to work. A survey of employed persons in Germany showed that mental stressors in particular were reported by around 30% of respondents. A high level of concentration and attention is required to cope with these tasks [47]. Restrictions, such as concentration disorders, stand in the way of this and thus also of returning to work. According to our analysis, the majority of patients who are unable to work still show deficits in both scales. Economic aspects, such as continued payment of wages in the event of illness, must also be taken into account in this analysis. The financial losses caused by long absences are not bearable for some in the long run, so that mental recovery, as a first step, could have an important influence here [48‐50]. However, there is no data yet on this particular angle of view, how it affects patients with Post-COVID syndrome.

More than half of the respondents reported problems obtaining outpatient therapies. Although the analysis could not show that this has an influence on HRQoL, Therapeutic interventions, also in the context of multidisciplinary phase-specific (tele-) rehabilitative measures, are necessary to alleviate symptom severity and to promote activity and participation again [51‐53]. The clinics and therapists must be prepared and specially trained for this [54, 55].

The HRQoL of patients with Post-COVID syndrome is reduced for months after infection, and so is their occupational performance. The presented normalization of the subdomains of HRQoL and the reduction of the remaining symptoms gives hope for the recovery of the patients and the return to the baseline level of activities and participation that existed before the COVID-19 disease. Further research in this area is needed to detect further positive or negative factors influencing HRQoL. Subgroups should also be considered. The results should be used to optimize therapeutic rehabilitative measures. A consideration of the symptoms depending on the virus variant leading to the infection may help to explain differences in studies and to establish therapy approaches even more individual.