Cross-sectional analysis of clinical aspects in patients with long-COVID and post-COVID syndrome

Abstract

Objective: Regarding pathogenesis, clinical manifestations, at-risk individuals, and diagnostic methods for stratifying patients for therapeutic approaches, our understanding of post-COVID syndrome is limited. Here, we set out to assess sociodemographic and clinical aspects in patients with the long-COVID and post-COVID syndrome.

Methods: We performed a cross-sectional analysis of patients presenting at our specialized university hospital outpatient clinic. We assessed patients' clinical presentation, fatigue, symptoms of depression and anxiety, and impairment of smell.

Results: A total of 101 patients were included (73.3% female), of whom 78.2% had a mild course of COVID-19. At presentation, 93.1% suffered from fatigue, 82.2% from impaired concentration, and 79.2% from impaired memory, 53.5% had impaired sleep. The most common secondary diagnosis found in our cohort was thyroid disease. Fatigue analysis showed that 81.3% of female and 58.8% of male patients had severe combined fatigue. Female gender was an independent risk factor for severe fatigue (severe cognitive fatigue OR = 8.045, p = 0.010; severe motor fatigue OR = 7.698, p = 0.013). Males suffered from more depressive symptoms, which correlated positively with the duration of symptom onset. 70.3% of patients with anamnestic smell impairment had hyposmia, and 18.9% were anosmic.

Interpretation: Most long-COVID patients suffered from severe fatigue, with the female sex as an independent risk factor. Fatigue was not associated with symptoms of depression or anxiety. Patients with long-COVID symptoms should receive an interdisciplinary diagnostic and therapeutic approach depending on the clinical presentation.

Keywords: COVID-19; SARS-CoV-2; anxiety; depression; fatigue; post-COVID syndrome; smell disorder.

Figure 1

Comorbidities, self-reported cognitive impairment, and cardiovascular risk factors prior to acute COVID-19 infection. Data were derived from a self-questionnaire, covering previous comorbidities from various organ systems as well as the most important cardiovascular risk factors. Impairment of cognition or concentration was self-assessed by patients. Differences between females and males were analyzed using a nonparametric two-tailed Mann-Whitney test, which showed no differences.

Figure 2

Females are affected by more severe motor fatigue. Fatigue was assessed using the FSMC score. (A) The majority of patients had severe fatigue (81.3% females, 58.8% males). Females were affected more severely compared to males (p < 0.05). This effect was driven by motor fatigue since (B) cognitive fatigue was not dependent on sex (p = 0.12). (C) Females were affected by more severe motor fatigue (p = 0.02). (D) Total fatigue using the FSMC was not depending on age (r = 0.15, p = 0.22; n = 65). (E) The latency between onset of COVID-19 and presentation did not affect the severity of total fatigue, cognitive fatigue or motor fatigue in females (total: r=0.07, p = 0.66; cognitive: r=0.07, p = 0.66; motor: r = –0.03, p = 0.84) or f) males (total: r = −0.14, p = 0.62; cognitive: r = –0.14, p = 0.61; motor: r = –0.16, p = 0.56). n = 65 total, n = 48 females, n = 17 males. Data are shown as mean ± standard deviation (SD) (A–C) or mean with a 95% confidence interval (D–F). Data were analyzed using a two-tailed Mann–Whitney U-test (A–C) and nonparametric two-tailed Spearman correlation (D–F). * p < 0.05.

Figure 3

The severity of symptoms of depression or anxiety was not dependent on age or psychiatric comorbidity. We performed a HADS to assess symptoms of depression and anxiety. Scores were regarded as: 0–7 = negative, 8–10 = indifferent, >10 = positive. (A) The majority of patients had a negative or indifferent HADS regarding depressive symptoms (85.1% females, 68.2% males) or symptoms of anxiety (77.7% females, 72.7% males). (B) The severity of depressive symptoms was not affected by a previous psychiatric or psychosomatic disease in females (n = 14 with comorbidity, n = 53 women without comorbidity) or (C) males (n = 3 men with comorbidity, n = 19 men without comorbidity). Data are shown as mean ± standard deviation (SD). Data were analyzed using a nonparametric two-tailed Kruskal-Wallis test.

Figure 4

Impairment of smell is not affected by duration from symptom onset. The smell was assessed using Sniffin' Sticks^®. The following thresholds were used: 0–7 = anosmia, 8–12 = hyposmia, >12 = normosmia. (A) Most patients suffered from hyposmia (71.4% females, 66.7% males), while there was no difference depending on gender. (B) Impaired smelling was not associated with age (r = –0.09, p = 0.59; n = 37 with all 16 odors tested. None of the patients recognized all 16 odors, while the maximum number of odors detected was 14 out of 16. (C) Duration (days) from symptom onset of acute COVID-19 infection to presentation to our clinic did not correlate (r = –0.12, p = 0.46, n = 40; the result of the test in percent because of varying total number of odors tested). (A) Data are shown as mean ± standard deviation (SD) and (B,C) mean with 95% confidence interval. Data were analyzed using (A) nonparametric two-tailed Mann-Whitney U test or (B,C) nonparametric two-tailed Spearman correlation.