About five million people worldwide have died from COVID-19 so far. A substantially greater number of patients required inpatient or intensive care treatment to overcome COVID-19. Nevertheless, most infections present with only mild symptoms and do not require inpatient treatment. Previous reports have shown that patients with severe COVID-19 often suffer from persisting symptoms even months after the acute disease (1). Data on patients treated out of hospital as well as reliable information on whether or not less severe COVID-19 results in lower prevalences of persisting symptoms are sparse (1).
In this study, we aimed to determine the general prevalence of persisting COVID-19 symptoms in a cohort of COVID-19 patients treated on an outpatient basis.
Footnotes
Conflict of interest statement The authors declare that no conflict of interest exists.
Methods
The “Medizinisches Versorgungszentrum Dachau” (MVZ Dachau) is a medical care center in Bavaria, Germany, that encompasses a total of eight locations with 46 family doctors and 38 medical specialists. During the study period (03/20–02/21), 69 141 patients underwent PCR testing for SARS-CoV-2. From March 2021 onward, all patients tested positive for COVID-19 underwent standardized follow-up, consisting of a standardized telephone survey conducted by a qualified nurse. The standardized questionnaire used in the interviews incuded typical persisting symptoms as published in the available literature at that time (2).
Results
A total of 1673 patients was tested positive for COVID-19 during the study period. 723 patients could not be followed up as these had been tested as part of screening, e.g. in nursing homes. The remaining 950 patients were tested at MVZ. None of them died. 29 patients were excluded from our survey because they required inpatient treatment. A total of 896 patients underwent follow-up resulting in completed questionnaires. The mean follow-up time after diagnosis was 6.9 month (95% confidence interval: [6.6; 7.1]; at least 3 months follow-up in >97% of all patients]. The mean age was 41.7 [40.6; 42.9] years. About half of patients (54.1%) had at least one pre-existing condition. In 117 patients (13.1%), COVID-19 infection was asymptomatic. At least one persisting symptom was present in 305 patients (34.0%). In addition to non-specific symptoms such as fatigue or headache, the persistence of typical acute symptoms of COVID-19 such as anosmia/ageusia and shortness of breath were common (n = 198; 22.1%) (table 1). 13 patients (1.5%) were newly diagnosed with other medical conditions when presenting with persisting symptoms of COVID-19. The majority (n = 203) of patients indicated in the telephone interview that they would be willing to accept the offer of a further diagnostic workup for their persisting symptoms. In a multivariate regression analysis, patients with persisting symptoms were significantly older, more often female, and experienced more symptoms in the acute disease (table 2).
Table 1. Persisting symptoms (mean, proportion in percent/ 95% confidence interval).
| Persisting symptoms | n = 896 |
| At least one symptom | 305 (34.0%) |
| At least one specific symptom | 198 (22.1%) |
| Fatigue | 116 (12.9%) |
| Agosmia/ageusia* | 112 (12.5%) |
| Shortness of breath* | 112 (12.5%) |
| Headache | 30 (3.3%) |
| Hair loss | 26 (2.9%) |
| Concentration disorder | 22 (2.4%) |
| Memory disorder | 22 (2.4%) |
| Cough | 20 (2.2%) |
| Chest pain | 20 (2.2%) |
| Sleep disturbance | 17 (1.9%) |
| Limb pain | 15 (1.7%) |
| Vertigo | 14 (1.6%) |
| Anxiety | 11 (1.2%) |
| Joint pains | 10 (1.1%) |
| Total (mean/patient) | 0.7 [0.6; 0.8] |
* specific symptoms
Table 2. Predictors of persisting symptoms in COVID-19, based on a multivariate logistic regression model (mean, proportion in percent/95% CI).
| Persisting Symptoms | Multivariable | |||
| yes (n = 305) | no (n = 591) | aOR [95% CI] | p-value | |
| Age (years) | 46.4 [44.5– 48.3] | 39.5 [38– 40.9] | 1.02 [1.01– 1.03] | <0.01 |
| BMI (kg/m²) | 26.3 [25.7– 26.9] | 26.3 [25.9– 26.7] | ||
| Follow-up time (months) | 6.6 [6.4– 6.9] | 7.2 [6.8– 7.7] | 1.02 [0.98– 1.07] | 0.4 |
| Female sex | 198 (64.9%) | 264 (44.7%) | 1.92 [1.4– 2.7] | <0.01 |
| Symptoms during acute phase | ||||
| – At least one COVID-19 symptom | 288 (94.4%) | 480 (81.2%) | 4.2 [1.7– 10.6] | <0.01 |
| – Cough | 167 (54.8%) | 246 (41.6%) | ||
| – Anosmia/ageusia | 160 (52.5%) | 189 (32.0%) | 1.8 [1.3– 2.6] | <0.01 |
| – Fever | 135 (44.3%) | 185 (31.3%) | ||
| – Headache | 128 (42.0%) | 192 (32.5%) | ||
| – Limb pain | 129 (42.3%) | 183 (31.0%) | ||
| – Rhinitis | 81 (26.6%) | 146 (24.7%) | ||
| – Sore throat | 75 (24.6%) | 139 (23.5%) | ||
| – Shortness of breath | 88 (28.9%) | 71 (12.0%) | 2.1 [1.4– 3.2] | <0.01 |
| – Abdominal pain/diarrhoea | 50 (16.4%) | 50 (8.5%) | ||
| – Fatigue | 21 (6.9%) | 11 (1.9%) | ||
| – Total (mean/patient) | 3.5 [3.3– 3.7] | 2.5 [2.3– 2.6] | 1.1 [1.0– 1.3] | 0.048 |
An aOR of 1.02 for “age” translates to a 2% increased risk of persisting symptoms, an aOR of 4.2 for “at least one COVID-19 symptom” translates to a 320% increased risk of persisting symptoms in patients with symptomatic vs. those with asymptomatic COVID-19 infection.
BMI, body mass index; aOR, adjusted odds ratio; CI, confidence interval
Discussion
Our study represents the first analysis of the prevalence of persisting symptoms more than six months after mild or moderately severe COVID-19 infection in patients with COVID-19 who were treated on an outpatient basis. This is of particular importance, as most patients have a mild or moderate clinical course.
The comparability of the available data is limited; however, the prevalence of persisting symptoms in patients treated in the outpatient setting is reported to be in the range of 5.2 to 26% one to three months after diagnosis and between 2.3% and 62% after three to six months (1). The prevalences found in our study lie within this rather broad range reported in the literature. Nevertheless, our results do not seem to support the hope that persisting symptoms after COVID-19 are self-limiting: the prevalences of persisting symptoms in our cohort did not decline with longer follow-up. Several studies have aimed to measure the association of risk factors and persisting symptoms after COVID-19 infection. In summary, the evidence is sparse and data are controversial as a consequence of the high heterogeneity of the cohorts studied (1). Our finding of an increased risk of persisting symptoms in older patients and in women after COVID-19 are in line with pre-existing data (1, 3, 4).
Most patients with persisting symptoms did either not actively seek medical advice or diagnostic workup did not yield a cause for their symptoms. This finding of ours is consistent with earlier findings reporting that patients with persisting symptoms of COVID-19 either failed or were unable to seek specialized medical care or reported not feeling being taken seriously by their physicians (5, 6). Nevertheless, in our cohort, about two thirds of patients with persisting symptoms accepted our offer to undergo diagnostic workup.
Limitations
The interpretation of our data is primarily limited by the cross-sectional nature of our study and by the lack of a control group. Symptoms such as fatigue, headache, or depression have commonly been reported during the pandemic in patients without preceding COVID-19 infection as well. Incomplete follow up (53.6% of cases in our study) might have lead to an (up to two-fold) overestimation of symptom persistence.
Conclusion
Persistent symptoms months after outpatient treatment for COVID-19 are common. The majority of patients did not actively seek medical advice. Further research is needed to elucidate the clinical relevance of persisting symptoms after COVID-19 infection.
References
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