In our cohort of SARS-CoV-2 positive tested and almost entirely still unvaccinated HEs during the first three waves (wild-type and alpha variant of SARS-CoV-2), a standardized interview revealed a high proportion of HEs with long lasting symptoms. Only twelve percent reported no symptoms at all, whilst 73% had symptoms longer than 28 days and 47% longer than 90 days. This goes in line with the work of Carvalho-Schneider et al., based on a prospective follow-up of 150 adults with noncritical COVID-19, that 68% of adults reported at least one lasting symptom at day 30 after symptom onset [16].
Comparison of different observational studies upon long lasting symptoms after non–severe SARS-CoV-2 infection revealed differences in the studied cohorts, the items of the interviews and the follow up. Whereas the first studies included patients who were asked for convalescent plasma donation or patients who were surveyed in the context of a quality management system [7, 9], here we included all employees of the Cologne Municipal Hospitals, representing the group of employees of working age in the healthcare sector in Cologne, Germany. Employees were not only tested for SARS-CoV-2 if symptoms were present, but also all direct contact persons were actively screened for SARS-CoV-2 for 14 days after the documented contact. Hence, we were able to also include HEs with an asymptomatic course. Interestingly, only twelve percent of the employees included in the survey had no symptoms at all. Compared to large register studies like Roessler et al. where disease diagnoses were recorded [17], in the present study we were able to capture symptoms that were not necessarily linked to a physician’s disease diagnosis. These symptoms may nevertheless be essential to understand the burden of post-COVID conditions [6].
In comparison to the work of Augustin et al. with a prevalence of 35% for six months lasting symptoms [7], in our cohort the prevalence of long-lasting symptoms after three months was at 47% of hospital employees, hence, being comparable.
A nationwide cross-sectional study in the Danish population with over 60.000 SARS-CoV-2 positive persons revealed significant risk differences for anosmia, fatigue/exhaustion, dyspnoea and reduced strengths in legs/arms compared to a SARS-CoV-2 negative control group [6]. Our data, which do not include control groups, are consistent with the findings of the Danish questionnaire study.
Our study showed the development of symptom complexes. Different symptom complexes following SARS-CoV-2 infection may be linked to different pathologies [18]. Thus, Zazhytska et al. reported that damaged cerebral cells with persistent viral loads in some individuals being possibly the cause for mental disorders, or a disruption of nuclear architecture may be a cause of anosmia [19]. Etter et al. showed signs of neurodegeneration associated to autoimmunity and peripheral immune signatures as possible causes for concentration and memory disorders or other central neurological symptoms [20]. Persistent infection or inflammation of heart cells may be the reason for palpitation and breathlessness [21, 22]. Furthermore, data of the electronic database of the US Department of Veterans Affairs indicated that individuals with COVID-19 had an increased risk for different cardiovascular diseases in comparison to controls [23].
It must be mentioned that our study may be limited by a small sample size as well as a missing control group in our study design. Considering whether long-lasting symptoms were caused by SARS-CoV-2 infection or occurred incidentally, post-COVID symptoms need to be compared between SARS-CoV-2 positive and negative groups. The Danish cross-sectional study by Vedel Sørensen et al. as well as the findings of Roessler et al. confirm our data [6, 17]. Another limitation of our study is that we only asked about subjectively perceived symptoms. However, the work of Roessler et al. confirms our results and shows that also more severe conditions diagnosed by a trained physician are more common in the COVID-19 cohort than in the control cohort [17]. Cohen et al. detected an increased risk of 11% for SARS-CoV-2 infected patients over 65 years for persistent long-term symptoms [24]. In our questionnaire, we explicitly asked only about new onset symptoms. Nevertheless, we cannot rule out the possibility that some employees may have overstated their reported symptoms.
The socioeconomic impact of long lasting symptoms after a SARS-CoV-2 infection was early described by the surrogate sick leave of working people in Sweden. Westerlind et al. found out in their study that the median leave time from work was 35 days and 9% were absent from work for at least four months due to COVID-19 [10].
For both medical and socioeconomic reasons, predictors for long lasting symptoms are essential. Predictors were first identified by the Swedish study investigating sick leaves, which were older age and sick leaves within the year prior to infection in a first rough analysis [10]. Through the identification of risk factors for long-lasting COVID-19 course, individuals who are at increased risk can be selected and medically treated at an early stage [5]. An early identification of risk factors is important because drug therapy for COVID-19, for example monoclonal antibody therapy or antiviral therapy with Nirmatrelvir/Ritonavir (Paxlovid®), for example, should be carried out within the first 5 days after beginning of COVID-19 symptoms [25].
Kuodi et al. examined the effectiveness of COVID-19 vaccines against long-term COVID-19 symptoms and showed, that vaccination with at least two doses of COVID-19 vaccine reduced the odds for post-COVID symptoms substantially and even bringing it to the same baseline like individuals reporting no previous SARS-CoV-2 infection [26]. Therefore, the importance of full vaccination against COVID-19 must be emphasized also with regard to the prevention of long-lasting COVID-19 symptoms.